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J Epstein

Publications and source records attributed to J Epstein.

At least 55 records · Page 3Linked to original sources
PubMed1999

Oversight and monitoring of blood safety in the United States.

The US blood safety vigilance system is composed of a network of interwoven programs, now organized under a formal structure, with the Assistant Secretary of Health and DHHS Blood Safety Committee bearing overall responsibility. It takes advantage of the breadth of expertise and close collaborative relationship of transfusion medicine and infectious disease scientists within and outside of the government. Core elements include an array of ongoing surveillance programs for monitoring established as well as new and emerging infectious agents that may pose a risk to blood safety, and the existence of historical and contemporary repositories of donor and recipient specimens that enable rapid investigation of putative new risks. This report summarizes the historical events that shaped the US blood safety oversight system, reviews the current organization and decision-making processes related to blood safety issues, and highlights key surveillance systems and research programs which monitor the US and global blood supplies for known and potential emerging risks.

Blood Banks↗
PubMed1999

Rostral and orbital prefrontal cortex dysfunction in the manic state of bipolar disorder.

OBJECTIVE: This study investigated prefrontal cortex function in the manic state of bipolar disorder. METHOD: High-sensitivity [15O]H2O positron emission tomography and a word generation activation paradigm were used to study regional cerebral blood flow in five manic and six euthymic individuals with bipolar disorder and in five healthy individuals. RESULTS: Decreased right rostral and orbital prefrontal cortex activation during word generation and decreased orbitofrontal activity during rest were associated with mania. CONCLUSIONS: The data support the presence of rostral and orbital prefrontal dysfunction in primary mania. These findings, when seen in the context of the human brain lesion and the behavioral neuroanatomic literatures, may help to explain some of the neurobehavioral abnormalities characteristic of the manic state.

Adult↗
PubMed1999

Mannose-binding protein B allele confers protection against tuberculous meningitis.

Inhalation is the principal mode of entry for Mycobacterium tuberculosis in humans. Primary infection is usually restricted to the lungs and contiguous lymph nodes. In a subset of infected individuals, predominantly children, the infection is spread hematogenously to the meninges. The host factors that influence the development of tuberculous meningitis have not been well elucidated. The mannose-binding protein (MBP), a serum protein, is considered as an "ante-antibody." MBP has been shown to bind mycobacteria and acts as an opsonin in vitro. Although MBP plays a role in first-line host defense, it may under certain circumstances be deleterious to the host. In tuberculosis (TB), MBP may assist the spread of this intracellular pathogen. Therefore, we hypothesized that MBP genotypes that result in a phenotype of low MBP levels might be protective. We studied a well-defined South African population in which TB has reached epidemic levels. We found that the MBP B allele (G54D), which disrupts the collagen region of the protein and results in low MBP levels, was found in 22 of 79 (28%) of the TB-negative controls from the same community, compared with 12 of 91 (13%) of the patients with pulmonary TB (p < 0.017), and 5 of 64 (8%) of patients with tuberculous meningitis (p < 0.002). In addition, we found significantly lower serum MBP concentrations in TB-negative controls compared with postacute phase, fully recovered TB patients (p < 0.004). These findings suggest that the MBP B allele affords protection against tuberculous meningitis.

Adult↗
PubMed1998

Primary myeloma cells growing in SCID-hu mice: a model for studying the biology and treatment of myeloma and its manifestations.

Progress in unraveling the biology of myeloma has suffered from lack of an in vitro or in vivo system for reproducible growth of myeloma cells and development of disease manifestations. The SCID-hu mouse harbors a human microenvironment in the form of human fetal bone. Myeloma cells from the bone marrow of 80% of patients readily grew in the human environment of SCID-hu mice. Engraftment of myeloma cells was followed by detectable human Ig levels in the murine blood. Myeloma-bearing mice had high levels of monotypic human Igs, high blood calcium levels, increased osteoclast activity, and severe resorption of the human bones. The human microenvironment was infiltrated with Epstein-Barr virus-negative monoclonal myeloma cells of the same clonality as the original myeloma cells. Active angiogenesis was apparent in areas of myeloma cell infiltration; the new endothelial cells were of human origin. We conclude that the SCID-hu mouse is a favorable host for studying the biology and therapy of myeloma and that a normal bone marrow environment can support the growth of myeloma cells.

Animals↗
PubMed1998

Insulin-like growth factor II and PAX3-FKHR cooperate in the oncogenesis of rhabdomyosarcoma.

The mouse myoblast C2C12 cell line transfected singly with cDNA for Pax-3, PAX3-FKHR, or insulin-like growth factor (IGF) II or cotransfected with IGF-II plus Pax-3 or with IGF-II plus PAX3-FKHR genes showed an altered morphology, a lack of differentiation, and higher proliferation rates in vitro. On s.c. injection into nude mice, tumors grew from transfected cell lines but not from cells transfected with the empty vector. Tumors derived from IGF-II/PAX3-FKHR- and IGF-II-transfected cells grew most rapidly. Cotransfection of IGF-II plus Pax-3 induced tumors comprised highly differentiated striated muscle cells; Pax-3, PAX3-FKHR, or IGF-II transfection produced tumors at varying stages of differentiation. Tumors derived from IGF-II plus PAX3-FKHR-cotransfected cells were composed of undifferentiated cells. This was the only tumor type to infiltrate the underlying muscle. The most angiogenesis and the least apoptosis were observed in the latter tumors. These results support the hypothesis that PAX3-FKHR interacts with IGF-II to play a critical role in the oncogenesis of rhabdomyosarcoma.

Animals↗
PubMed1998

An open-label, dose escalation pilot study of the effect of clonazepam in burning mouth syndrome.

OBJECTIVE: Current treatment for burning mouth syndrome is usually directed at correction of detected organic causes or is empiric, and it often involves the use of tricyclic antidepressants. Recently, there has been renewed interest in the use of benzodiazepines for burning mouth syndrome. The present study was designed to assess the effect of clonazepam in burning mouth syndrome. STUDY DESIGN: Thirty patients, each with a chief complaint of mouth burning without oral mucosal lesions, were entered into the study. All patients underwent routine blood screens. Identified abnormalities were corrected, when possible, before clonazepam was prescribed. The starting dose was 0.25 mg daily, with an increase in dose of 0.25 mg on a weekly basis if symptoms continued. RESULTS: The subject population consisted of 29 women and 1 man. All subjects had been symptomatic (average premorbid burning intensity, 7.0 +/- 1.9 on 10-point scale) for 1 month to 12 years (mean, 3.9 +/- 3.4 years; median, 2.75 years), and 16% had had burning for more than 2 years. Three groups of patients were identified: those who experienced partial to complete relief with clonazepam and who were using the medication at the last follow-up (group 1; 43%); those who found the clonazepam helpful but withdrew from the medication because of side effects--usually drowsiness (group 2; 27%); and those who did not benefit from clonazepam (group 3; 30%). Among the 3 groups, age was found to be significantly lower for group 1 than for group 2 but not significantly lower for group 1 than for group 3. Although the difference did not reach significance, the mean dose of clonazepam appeared lower for group 1 patients than for the other 2 patient groups. The number of patients with burning for less than 2 years was larger in group 1 than in the other groups. CONCLUSIONS: The results suggest that clonazepam may be helpful in burning mouth syndrome, inasmuch as 70% of patients (groups 1 and 2) experienced pain reduction with effects at low doses. These findings suggest that the mechanism of action of clonazepam may be specific and separate from the anxiolytic effect of the benzodiazepines and that clonazepam may represent a useful therapy in a subset of patients with burning mouth syndrome. Double-blind, placebo-controlled trials are warranted.

Aged↗
PubMed1998

Impaired glutathione peroxidase activity accounts for the age-related accumulation of hydrogen peroxide in activated human neutrophils.

BACKGROUND: As assessed by flow cytometry, the increase in hydrogen peroxide in individual neutrophils from old volunteers was significantly greater than in neutrophils from young volunteers. To explain the discrepancy in previous reports that showed reduced superoxide generation with age and our finding, we measured the kinetics of antioxidative enzymes. METHODS: Neutrophils were obtained from young (ages 21-34) and old (ages over 65) volunteers. The increase in hydrogen peroxide following stimulation with formyl peptide in individual neutrophils was assessed by flow cytometry by using dihydrorhodamine 123. The enzyme kinetics was determined from the best fit curve using Michaelis-Menten equations. RESULTS: Aging was associated with a significant reduction in the Vmax for glutathione peroxidase. The decreased activity was not due to selenium deficiency as the serum and neutrophil concentrations were identical with age. Following activation, a significant increase in the Km was noted in neutrophils from young but not from old volunteers. CONCLUSIONS: These results account for the increased intracellular accumulation of hydrogen peroxide as a function of age in stimulated neutrophils. These results provide evidence in humans of an age-related impairment in antioxidative defense mechanisms that support the free radical theory of aging.

Adult↗
PubMed1998

Predictive sensitivity of human cancer cells in vivo using semipermeable polysulfone fibers.

An in vivo experimental model was developed to predict efficiently and accurately chemosensitivity of human tumors. Human cancer cells either from cultured cell lines or from patients' tumors were injected directly into semipermeable polysulfone fibers subsequently implanted into immunocompetent rats. Results suggest utility of this novel model system for predicting tumor sensitivity to a wide range of anticancer agents and for potentially guiding the treatment of cancer patients in the clinical setting.

Animals↗
PubMed1998

Preadmission psychosocial screening of older orthopedic surgery patients: evaluation of a Social Work Service.

A preadmission social work intervention was evaluated for impact on length of hospital stay (LOS) and patient satisfaction. Psychosocial issues related to function and post-discharge needs were assessed at an exploratory level. A modified post-test only control group design was used. Study group patients were screened before hospitalization and offered services on admission. Control group patients received standard care. Study group patients were significantly more satisfied with services but impact on length of stay was not demonstrated with one possible exception. Post-operative complications were significantly related to longer LOS; however, unlike control group patients, study group patients with complications did not have significantly longer LOS. Women and those limited in preadmission physical function were most likely to report insufficient help after discharge. A more intensive preadmission intervention is recommended to improve impact on LOS and informal support system involvement, while future outcome studies would clarify the nature of service gaps and high risk groups.

Aged↗
PubMed1998

Interdependence between cytokines and cell adhesion molecules to induce interleukin-6 production by stromal cells in myeloma.

Bone marrow (BM) environment is thought to support the growth of myeloma cells and thus to play an important role in the pathogenesis of multiple myeloma (MM). Because interleukin-6 (IL-6) is an essential growth factor in MM, we have examined the effects of two myeloma cell lines (U266 and ARH-77) on the IL-6 production by BM stromal cells in a co-culture system. These cell lines strongly stimulate the IL-6 production and IL-6 triggering was partially dependent on physical contact between lines and stroma. The percentages of cell adhesion to stromal layers were 39% and 25% respectively for ARH77 and U266 cell lines. Inhibition studies with blocking monoclonal antibodies showed the importance of CD49d/CD106 and CD11a/CD54 interactions in the stimulation of IL-6 production by stromal cells. However, cell-to-cell contact was not an absolute requirement for IL-6 production. Cytokines, of which TNF-alpha and IL-1beta produced by MM or accessory cells, were also able to stimulate IL-6 production by fibroblasts and show additive effects. In adhesion assays, TNF-alpha and IL-1beta were able to increase the adhesion of MM cells to stromal cells. CD54 was upregulated by IL-1beta, TNF-alpha or a contact with MM cells while CD106 expression was not, suggesting only a functional change of this molecule. However, the role of monoclonal antibodies, directed against these factors, confirmed the role of TNF-alpha in the IL-6 production by stromal cells, while any IL-1beta intervention was not shown in our co-culture system. IL-6 favoured and maintained adhesion of MM cells to stromal cells spontaneously since its reintroduction in the favoured co-culture system restored their decreased adhesion observed on a glutaraldehyde fixed stromal layer. Overall our data suggest a functional overlap between cytokines and adhesion molecules for the paracrine IL-6 production.

Antibodies↗
PubMed1998

The bone marrow stromal environment is a major factor in myeloma cell resistance to dexamethasone.

Dexamethasone (Dex), which is often used for the treatment of multiple myeloma, produces rapid reductions in tumor mass and improvement in disease symptoms; however, it is not curative, and drug-resistant cells eventually emerge. To elucidate this apparent paradox, we tested the effect of the bone marrow environment on myeloma cell response to this drug. To determine whether bone marrow stroma provides sufficient amounts of interleukin (IL)-6 to protect myeloma cells against the effects of Dex, we compared the production of IL-6 by marrow stromal cells from four myeloma patients before, during, and after exposure to 10(-7) M Dex, and found that even in the presence of this drug, stromal cells continued to produce IL-6, albeit in reduced concentrations. We tested the ability of stromal cells to protect myeloma cells, purified from the bone marrow of seven patients by cell sorting on the basis of CD38 and CD45 expression, and two light-scatter parameters, from Dex-induced apoptosis. In contrast to mature CD38+CD45- cells, which were not protected, coculture with stroma very effectively protected immature CD38+CD45+ myeloma cells from Dex. These data may explain the palliative efficacy of Dex treatment and provide a rationale for combining IL-6 antagonists with Dex to overcome the IL-6-mediated resistance of immature tumor cells.

Antigen-Antibody Reactions↗
PubMed1997

Murine macrophage mannose receptor promoter is regulated by the transcription factors PU.1 and SP1.

The mannose receptor (MR) is a transmembrane protein that functions primarily as a phagocytic receptor for a wide range of microorganisms. Its expression appears to be restricted to tissue macrophages and Langerhans cells. To gain an understanding of the regulation of the gene, we have isolated the 5' flanking sequence of the murine MR gene and have analyzed a 536-bp sequence upstream of the ATG start site for transcriptional activity. This sequence lacks a TATA box but contains an initiator (Inr) consensus element overlapping the single transcriptional start site. Transcription factor binding sites contained within this sequence include PU.1, Sp1, ETS, GATA, and MYB motifs. Serial 100-bp deletions of this promoter fragment fused to a luciferase reporter gene showed various patterns of activity when transfected into different cell types. In myeloid cells, sequence elements upstream of bp -300 appeared to have a silencing effect on promoter activity. Of the four potential PU.1 binding sites contained within the fragment, one site (at -164) bound the PU.1 factor most strongly, whereas the adjacent PU.1 site (at -177 bp) bound PU.1 to a lesser degree. Mutations of these sites decreased transcriptional activity but did not abolish it. However, promoter activity was abrogated when both the -164 bp PU.1 site and the adjacent -177 bp PU.1 site were mutated. In addition, mutation of the Sp1 site also significantly reduced promoter activity. Cotransfection studies in Drosophila Schneider cells indicated that PU.1 and Sp1 may function synergistically in transactivating the murine MR. This study indicates that MR gene expression is regulated in part by the interaction between the ubiquitously expressed factor Sp1 and the lymphoid/myeloid factor PU.1 and provides a basis for studying the regulation of this gene.

Animals↗
PubMed1997

Myeloma stem cell phenotype. Implications for treatment.

The phenotypic heterogeneity of myeloma cells in fact delineates a differentiation process that appears to be an integral part of the disease process. Immature myeloma cells interact with their microenvironment differently than do the more mature cells. As a result of this interaction, the immature cells display different responses to chemotherapy than do the mature cells. Addressing this issue by tailoring treatment to target immature as well as mature myeloma cells may change dramatically the outcome of treatment. The ability to define the myeloma clone by molecular genetic techniques has markedly increased the ability to detect clonal cells. This technique provides a most sensitive tool for monitoring elimination of tumor cells; however, the role of the early clonal B cells identified through the use of ASO-PCR in the disease process needs to be clarified. Currently, a great deal of effort is directed towards development of treatment protocol that will eliminate all clonal cells, and a method of purging clonal cells from harvested mobilized peripheral stem cells. Understanding the biologic significance of early clonal B cells in myeloma will allow for a more rational approach to curative treatment.

Animals↗