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Biomedical subjects

L Cohen

Publications and source records attributed to L Cohen.

At least 271 records · Page 15Linked to original sources

NF-kappa B activity in T cells stably expressing the Tax protein of human T cell lymphotropic virus type I.

The effect of constitutive Tax expression on the interaction of NF-kappa B with its recognition sequence and on NF-kappa B-dependent gene expression was examined in T lymphoid Jurkat cell lines (19D and 9J) stably transformed with a Tax expression vector. Tax expressing T cell lines contained a constitutive level of NF-kappa B binding activity, detectable by mobility shift assay and uv cross-linking using a palindromic NF-kappa B probe homologous to the interferon beta PRDII site. In Jurkat and NC2.10 induction with phorbol esters resulted in the appearance of new DNA binding proteins of 85, 75, and 54 kDa, whereas in Tax expressing cells the 85-kDa protein and a 92-kDa DNA binding protein were constitutively induced. Expression of Tax protein in 19D and 9J resulted in transcription of the endogenous NF-kappa B-dependent granulocyte-macrophage colony stimulating factor gene and increased basal level expression of transfected NF-kappa B-regulated promoters. Nonetheless transcription of both the endogenous and the transfected gene was inducible by PMA treatment. Tax expression in Jurkat T cells may alter the stoichiometry of NF-kappa B DNA binding proteins and thus change the expression of NF-kappa B-regulated promoters.

Cell Line↗

Interleukin-3 enhances cytokine production by LPS-stimulated macrophages.

In addition to its hematopoietic activities, interleukin-3 (IL-3) can modulate macrophage functions. We have studied the production of interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor (TNF) by mouse peritoneal macrophages triggered by lipopolysaccharide (LPS) in the presence or absence of IL-3. Interleukin-3 at the concentration used (i.e., 100 U/ml) did not induce the production of any cytokines, whereas it enhanced significantly the secretion of IL-1, IL-6 and TNF by LPS-stimulated macrophages. The synergistic activity of IL-3 was observed over a wide range of Escherichia coli or Salmonella enteritidis LPS concentrations. No additive effect was noticed between IL-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF), another factor able to enhance LPS-induced IL-1 production. Thus, IL-3 can potentiate the inflammatory response induced by endotoxin from Gram-negative bacteria through a potentiation of cytokine production.

Animals↗

Lectin soybean agglutinin: measurements in colonic epithelial cells of human subjects following supplemental dietary calcium.

A biomarker of cell differentiation was analyzed in normal and abnormal colonic epithelial cells. Soybean agglutinin (SBA) lectin which binds to specific carbohydrate residues was studied in normal human colonic epithelial cells, in epithelial cells in transitional colonic mucosa adjacent to carcinomas, and in colonic carcinomas. Findings revealed that increased SBA binding occurred maximally in normal, well-differentiated colonic epithelial cells, and least in colonic carcinomas. Further quantitation of SBA lectin binding also was carried out before and after supplemental dietary calcium. Findings revealed that in subjects whose colonic crypt biopsies had normal SBA lectin binding before calcium supplementation, SBA remained unchanged after calcium supplementation. However, in subjects whose biopsies initially had reduced SBA binding, the SBA increased after calcium and became more characteristic of that observed in normal colonic epithelium. In subjects receiving calcium for less than 3 months, the increased SBA was not statistically significant; but when subjects received calcium for durations of 3 months or longer SBA lectin binding was significantly increased, changing towards that observed in normal mucosa containing greater numbers of well-differentiated colonic epithelial cells.

Adenocarcinoma↗

Issues in the early termination of the aspirin component of the Physicians' Health Study. Data Monitoring Board of the Physicians' Health Study.

The Physicians' Health Study is a randomized, double-blind, placebo-controlled prevention trial of 22,071 US physicians, using a factorial design to evaluate the role of aspirin in the prevention of cardiovascular mortality and beta carotene in the reduction of cancer incidence. After approximately 5 years of follow-up, the aspirin component was terminated, 3 years ahead of schedule. Several factors were considered in the decision to terminate, including a cardiovascular mortality rate markedly lower than expected in both aspirin and placebo subjects, precluding the evaluation of the primary aspirin hypothesis, and a highly significant (P < .00001) and impressive (44%) reduction in the risk of first myocardial infarction in the aspirin group. Issues in the decision to terminate are described in this report.

Adult↗

Implementation of a patient fall prevention program.

Falls among hospitalized patients are common occurrences and can have detrimental effects on patient outcomes. Identifying high-risk patients and taking measures to prevent patient falls have been successful. The purpose of this project was to decrease the fall rate in adult neuroscience patients. This was accomplished through implementation of a patient fall prevention program. Patients were assessed for risk factors associated with patient falls. Risk factors were identified through the use of the patient's history, nursing data base and patient classification system. Patients with identified risk factors were placed on fall precautions which included interventions specifically designed to prevent patient falls. This project resulted in a decrease in the number of patient falls and increased staff awareness of the risk factors associated with falls among adult neuroscience patients.

Accidental Falls↗

Similarity between Cytokinin and Blue Light Inhibition of Cucumber Hypocotyl Elongation.

The cytokinin benzyladenine inhibited endogenous hypocotyl elongation in intact etiolated seedlings of cucumber (Cucumis sativus L.). In hypocotyl segments, the inhibitory effect of benzyladenine on growth was clearly detectable in the presence of indoleacetic acid. Fusicoccin-induced elongation was unaffected by the presence of cytokinin. The effect of cytokinin on elongation of the segments was determined by measuring changes in fresh weight, a linear function of extension growth. The effect of benzyladenine on hypocotyl growth was at least as large in segments prepared from red-light-grown seedlings as in those from seedlings grown in total darkness. A comparison was made between the inhibitory effects of cytokinin and blue light. The use of the calcium chelator ethyleneglycol-bis(beta-aminoethyl ether)-N, N'-tetraacetic acid indicated that calcium ions are required for manifestation of benzyladenine-induced inhibition.

Journal Article↗

Bronchial provocation determined by breath sounds compared with lung function.

Bronchial provocation testing with methacholine was undertaken in 15 children aged 5 to 8 years with obstructive lung disease, mostly asthma (13/15). The methacholine was inhaled during two minutes of tidal breathing in increasing concentrations. After each inhalation, lung function was measured and clinical signs recorded independently by two observers unaware of each other's results. The logarithm of the concentration of methacholine which caused wheezing over the trachea correlated closely with the logarithm of the concentration of methacholine causing a 20% fall in the forced expiratory volume in one second (FEV1) but was 52% greater on average. At the end of the test there was a mean (SD) fall in FEV1 of 33.3 (7.4)% and a fall in oxygen saturation of 5.2 (3.1)%. Bronchial provocation testing by listening for wheeze over the trachea is a safe technique, which correlates with objective measures of lung function in young children.

Bronchi↗

Normal venous anatomy of the brain: demonstration with gadopentetate dimeglumine in enhanced 3-D MR angiography.

This investigation evaluates whether gadopentetate dimeglumine enhancement of three-dimensional (3-D) acquisition MR angiography can generate clinically useful images of the normal venous anatomy of the brain. 3-D MR angiography of normal cerebral arterial anatomy has made rapid progress, although demonstration of detailed venous anatomy with similar techniques has been much less revealing. To overcome the limitation of slow venous flow, IV gadopentetate dimeglumine contrast enhancement was used to alter the relaxation times of blood, thus augmenting the venous signal. Several groups of patients were evaluated: we studied eight patients both with and without contrast enhancement, 20 patients and volunteers with multiple techniques to determine optimal technical parameters, and seven patients in whom enhanced MR studies were compared with standard selective biplane cut-film arterial angiograms. Only the large dural sinuses (such as the transverse sinus) could be seen on unenhanced studies owing to the saturation of slowly flowing venous spins. With contrast enhancement, many of the important small and large cerebral venous structures were routinely seen with reasonable scanning times (7 min). The venous anatomy was well seen for approximately one-half hour after injection and correlated well with angiograms. There are several important limitations to this technique, including a limited field of view, variable visibility of specific veins owing to technical and physiologic factors, confusion of enhancing non-flow-related structures, and lack of detailed physiologic information. Single excitation 3-D MR angiograms are insensitive in the evaluation of cerebral venous structures. Enhancement with gadopentetate dimeglumine affords rapid scanning and excellent visualization of the pertinent venous anatomy. The best image quality was obtained with a sequence of 50/7/30 degrees (TR/TE/flip angle).

Adolescent↗

[Illusion of visual tilt: a case].

A 21-year-old man experienced sudden and intense rotational vertigo. A moment later, he was amazed to see the whole visual world rotate clockwise progressively by about 160 degrees. On the following day, the visual tilt was only 30 degrees, and it soon receded completely, while headache appeared. CT scan, magnetic resonance imaging, vertebral arteriography, and cerebrospinal fluid analysis were normal, and the aetiology could not be ascertained. Illusions of visual tilt are an unusual consequence of disorders affecting the vestibular system. The locus of the impairment is usually in the brainstem, particularly in association with Wallenberg's syndrome. However, the peripheral vestibular pathways or the vestibular projections into the cerebral cortex may occasionally be involved. In the latter case, the visual tilt is part of a vestibular epileptic seizure.

Adult↗

A developmentally regulated octamer-binding activity in embryonal carcinoma cells which represses beta-interferon expression.

We have previously described ECIF-1, a DNA-binding factor present in nuclear extracts of murine embryonal carcinoma cells which specifically recognizes a region within the human beta-interferon promoter. We show that the promoter region located between -112 and -93 is sufficient for this binding activity, which is not due to binding of interferon-regulatory factor 1 or 2. By mutational analysis of the ECIF-1 site, it was determined that the central nucleotides which are critical for binding contain an octameric motif: ATTTACAT. The binding activity of ECIF-1 with its cognate site within the beta-interferon promoter decreases upon differentiation concurrently with the onset of interferon inducibility. Furthermore, by using an in vitro transcription assay with deleted promoter elements of the beta-interferon gene, we show that undifferentiated P19 nuclear extracts contain a repressing activity which depends on the presence of the ECIF-1 site. This repression is not observed using nuclear extracts from differentiated P19 cells. Comparison of the binding activity of this octamer site with others previously shown to be active in embryonal carcinoma cells reveals similarities and differences in the spectrum of proteins binding there.

Animals↗

Stimulation of interferon beta gene transcription in vitro by purified NF-kappa B and a novel TH protein.

The human interferon beta (IFN-beta) regulatory element consists of multiple enhanson domains which are targets for transcription factors involved in inducible expression of the promoter. To further characterize the protein-DNA interactions mediating IFN-beta induction, positive regulatory domain (PRD) II binding proteins were purified from phorbol ester induced Jurkat T-cells and from IFN primed, cycloheximide/polyinosinic-polycytidylic acid treated HeLa S3 cells. From HeLa cells, two major proteins of 52 and 45 kilodaltons (kD) copurified with DNA binding activity, whereas from T-cells, four proteins--a major protein of 52 kD and three minor proteins of 82, 67, and 43-47 kD--were purified. Also, an induction specific DNA binding protein was purified from HeLa cells that interacted with the (AAGTGA)4 tetrahexamer sequence and the PRDI domain. This protein is immunologically distinct from IRF-1/ISGF2. Uninduced or Sendai virus induced HeLa extracts were used to examine transcription in vitro using a series of IFN beta promoter deletions. Deletions upstream of the PRDII element increased transcription in the uninduced extract, indicating predominantly negative regulation of the promoter. A 2-4-fold increase in IFN-beta promoter transcription was observed in Sendai virus induced extracts, and deletion of PRDI and PRDII elements decreased this induced level of transcription. When purified PRDII and tetrahexamer binding proteins were added to the induced extract, a 4-fold increase in transcription was observed. These experiments demonstrate that it is possible to modulate IFN-beta transcription in vitro but indicate that additional proteins may be required to fully activate IFN-beta transcription.

Amino Acid Sequence↗

Cytomegalovirus endomyocarditis in a transplanted heart. A case report with in situ hybridization.

A 64-year-old man underwent cardiac transplantation for long-standing severe dilated cardiomyopathy. Postoperative complications included primary cytomegalovirus (CMV) infection with several episodes of moderate acute rejection and severe pneumonia. Six months after transplantation, an endomyocardial biopsy specimen revealed focal necrotizing myocarditis with intranuclear inclusions consistent with CMV. The patient subsequently developed fulminant pneumonia and died 7 months after transplantation. Postmortem examination revealed that the cause of death was acute necrotizing bronchopneumonia due to Staphylococcus aureus, with underlying CMV pneumonitis. The transplanted heart had left ventricular hypertrophy with multiple organizing myocardial infarcts, moderate coronary atherosclerosis, and organizing thrombi of the left atrium. Characteristic inclusions of CMV were identified, predominantly within endothelial cells, in the left coronary artery, left ventricular endocardium, and myocardium. With in situ hybridization, the presence of CMV was verified in the inclusions, as well as in many fibroblasts without inclusions. In situ hybridization is warranted in myocardial biopsy specimens when suspicious inclusions or infiltrates are present, to confirm CMV infection, so that appropriate therapy can be initiated.

Biopsy↗