Interaction of relativistic H- ions with thin foils.
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Journal Article↗
Biomedical subjects
S Cohen
Publications and source records attributed to S Cohen.
Morning or evening bright light treatment of winter depression? The significance of hypersomnia.
In a randomized crossover design 19 patients with winter depression were treated with 7 days of bright morning light (6:00 to 8:00 AM) and 7 days of evening light (7:00 to 9:00 PM). Bright light in the morning reduced the Hamilton Depression Rating Scale score from 22.3 to 5.5; bright light in the evening decreased the Hamilton score from 21.0 to 12.2. Improvement in the depression as measured by the Hamilton Depression Rating scores was greater with morning light compared with evening lights. Hypersomnia was associated (p less than 0.05) with a superior response to morning light.
Adult↗
Bilateral corneal immune ring opacity in Behçet's syndrome.
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Adolescent↗
Initiation of lymphocyte DNA synthesis.
The initiation of DNA replication in T lymphocytes appears to be regulated by two distinct activities: one associated with proliferation which mediates initiation, and another associated with quiescence which blocks initiation. Activated lymphocytes and proliferating lymphoid cell lines produce an activity, termed ADR, which can initiate DNA replication in isolated, quiescent nuclei. ADR is heat-labile, has protease activity or interacts closely with a protease, and is distinct from the DNA polymerases. ADR activity is absent in quiescent lymphocytes and appears in mitogen-stimulated lymphocytes after IL-2 binding. The generation of active ADR appears to be mediated by phosphorylation of a precursor which is present in resting cells. Nuclei from mitogen-unresponsive lymphocytes fail to initiate DNA replication in response to ADR, of potential importance in the age-related decline of immunity. Quiescent lymphocytes lack ADR and synthesize an ADR-inhibitory activity. The ADR inhibitor is a heat-stable protein which suppresses the initiation of DNA synthesis, but is ineffective at suppressing elongation once DNA strand replication has begun. Nuclei from several neoplastic cell lines fail to respond to the ADR inhibitor, which may play a role in the continuous proliferation of these cells. At least one of these neoplastic cell lines produces both ADR and an inhibitory factor. These findings suggest that the regulation of proliferation is dependent on the balance between activating and inhibitory pathways.
Aged↗
Studies on the role of protein kinases in the TNF-mediated enhancement of murine tumor cell-endothelial cell interactions.
We have previously demonstrated that the exposure of mouse microvascular endothelium (MME) to tumor necrosis factor-alpha (TNF) led to the increased binding of mouse mastocytoma cells (P815) to endothelial monolayers (Bereta et al., in press). In the current study we examined the possible involvement of protein kinases in TNF signal transduction in the endothelial cells. PKA does not appear to play a role in the potentiation of binding by TNF. We found that the TNF-generated signal is inhibited by H-7 and sangivamycin, but not by staurosporine. TNF did not cause translocation of PKC to the cell membrane and its effect could not be completely mimicked by PMA nor by PMA in the presence of calcium-raising agents. Thus, we concluded that the "classical" PKC pathway is not completely responsible for TNF signalling in this system. We also found that staurosporine itself strongly enhanced adhesion of tumor cells to endothelium, utilizing a mechanism distinct from that of TNF. Although the data provide evidence for the role of kinases in the effect of TNF on binding of tumor cells to MME, this role appears to be a complex one.
Adenylyl Cyclases↗
Partial molal volumes and solubilities of physostigmine in isopropanol:isopropyl myristate solvents in relation to skin penetrability.
Partial molal volumes (Vi infinity) of physostigmine, ranging from 232.9 to 239.8 cm3.mol-1, and its mole fraction solubilities (Xi), ranging from 0.051 to 0.009, were determined at 25 degrees C in solutions of isopropanol (IPA), isopropyl myristate (IPM), and their mixtures. An inverse relation was found between Vi infinity and Xi. At solubility----0, Vi infinity----240.6 (by extrapolation). The experimentally derived liquid molal volume in the standard state, Vi degrees (231.1), of physostigmine was lower than its lowest Vi infinity (value 232.9) in the series tested. Virtual cohesion parameters (lambda i) and excess free energies (delta EGi) of physostigmine in the various solutions were estimated from the partial molal volumes, assuming regular solution behavior. For each solution, the free energy (-RT In Xi) of the drug was estimated from its solubility. An increase in the virtual cohesion parameter and a decrease in the excess free energy and the free energy was found with an increase in volume fraction of IPA in the mixed solvent. The increase in lambda i over the invariant cohesion parameter, delta i (10.2), reflects a compensation effect needed to maintain the geometric mean assumption of Regular Solution Theory. Deviation from the theoretically expected linearity between -RT In Xi and delta EGi of physostigmine is ascribed to the existence of solvated molecules distinct from unsolvated molecules of physostigmine. The highest permeability coefficient of the delivery of physostigmine through excised human skin from IPA:IPM mixtures was seen from the mixture exhibiting the highest solvation effect, giving additional evidence that physostigmine penetrates through the skin, possibly in combination with IPA.
1-Propanol↗
Recombinant human acetylcholinesterase is secreted from transiently transfected 293 cells as a soluble globular enzyme.
1. Coding sequences for the human acetylcholinesterase (HuAChE; EC 3.1.1.7) hydrophilic subunit were subcloned in an expression plasmid vector under the control of cytomegalovirus IE gene enhancer-promoter. The human embryonic kidney cell line 293, transiently transfected with this vector, expressed catalytically active acetylcholinesterase. 2. The recombinant gene product exhibits biochemical traits similar to native "true" acetylcholinesterase as manifested by characteristic substrate inhibition, a Km of 117 microM toward acetylthiocholine, and a high sensitivity to the specific acetylcholinesterase inhibitor BW284C51. 3. The transiently transfected 293 cells (100 mm dish) produce in 24 hr active enzyme capable of hydrolyzing 1500 nmol acetylthiocholine per min. Eighty percent of the enzymatic activity appears in the cell growth medium as soluble acetylcholinesterase; most of the cell associated activity is confined to the cytosolic fraction requiring neither detergent nor high salt for its solubilization. 4. The active secreted recombinant enzyme appears in the monomeric, dimeric, and tetrameric globular hydrophilic molecular forms. 5. In conclusion, the catalytic subunit expressed from the hydrophilic AChE cDNA species has the inherent potential to be secreted in the soluble globular form and to generate polymorphism through self-association.
Acetylcholinesterase↗
Control of DNA replication in a transformed lymphoid cell line: coexistence of activator and inhibitor activities.
Proliferating lymphocytes contain an intracellular factor, ADR (activator of DNA replication), which can initiate DNA synthesis in isolated quiescent nuclei. Resting lymphocytes lack ADR activity and contain an intracellular inhibitory factor that suppresses DNA synthesis in normal but not transformed nuclei. In this study we describe a MOLT-4 subline that produces both the activator and inhibitory activities which can be separated by ammonium sulfate fractionation. The inhibitor is heat stable and inhibits ADR-mediated DNA replication in a dose-dependent manner. It does not inhibit DNA polymerase alpha activity. The inhibitor must be present at the initiation of DNA replication to be effective, as it loses most of its effectiveness if it is added after replication has begun. The presence of inhibitory activity in proliferating MOLT-4 cells, taken with the previous observation that inhibitor derived from normal resting cells does not affect DNA synthesis by MOLT-4 nuclei, suggests that failure of a down-regulating signal may play an important role in proliferative disorder.
DNA Replication↗
Effect of inflammatory cytokines on the adherence of tumor cells to endothelium in a murine model.
We have demonstrated that pretreatment of mouse brain microvascular endothelial cells (MBE) with tumor necrosis factor-alpha (TNF), IL-1, or LPS augmented the binding of P815 mastocytoma cells in vitro. The effect of these agents was dose and time dependent. PMA was able to mimic the influence of these factors to a limited degree. The effect of TNF on endothelium was accompanied by the appearance of changes in the expression of proteins isolated from endothelial cell membranes. The adherence of tumor cells to endothelium was not inhibited by RGD-containing peptides but could be decreased by preincubation of endothelium with high concentrations of FCS. Our data suggest that cytokines regulate the synthesis of endothelial adhesion proteins which may be involved in tumor cell adherence leading to metastasis. These results raise the possibility that cytokines may exert paradoxical effects in vivo, i.e., a cytotoxic effect that reduces tumor mass accompanied by a metastasis-enhancing effect that actually promotes dissemination of the remaining tumor cells. Definition of the molecular events involved in tumor cell-endothelial cell interactions may lead to strategies for minimizing the latter effect in therapeutic settings.
Amino Acid Sequence↗
A comparison of foreign body and hypersensitivity granuloma formation in the mouse: kinetic development, anergy, angiotensin converting enzyme levels, and response to captopril therapy.
Pulmonary granuloma size, anergy, serum and lung angiotensin converting enzyme (ACE) levels, and responsiveness to captopril therapy were measured in both pulmonary hypersensitivity granuloma (HSG) and foreign body granuloma (FBG) murine models. The kinetic development of the granuloma was similar in both models, peaking at 3 days and resolving by 14 days. The granuloma size of the FBG model was significantly larger than the HSG model at 1 and 3 days. The FBG model further differed from the HSG model in that anergy was observed at 3 days and lung ACE levels were increased at 1, 7, and 14 days. In the HSG model anergy was not observed and lung ACE levels were significantly elevated only at 1 and 7 days. Furthermore, the HSG model was shown to be responsive to captopril therapy whereas the FBG model was not. This study shows that two murine pulmonary granuloma models, although displaying similar growth and resolution kinetics, differ in terms of granuloma size, anergy, lung ACE activity, and responsiveness to captopril therapy, suggesting that the mechanism(s) involved in the inflammatory response of the two models may be different.
Animals↗
Mental health, stress, and poor health behaviors in two community samples.
BACKGROUND: The relationships of obesity, smoking, drinking, and lack of exercise to mental health and stress were evaluated in separate community samples of men and women. RESULTS: Among men, the only significant positive relationship was between history of depression and smoking. Among women, four psychosocial factors were associated with smoking: history of depression, increased marital conflict, greater number of undesirable life events, and full-time employment. Depression and marital conflict were also associated with higher drinking levels, and full-time employment was associated with lack of exercise. History of emotional disorders was not found to exacerbate the effects of stress on poor health behaviors. However, some combinations of stress were detrimental. Among men, the joint effect of high job demands and low decision latitude was significantly associated with a greater likelihood of smoking. Among women, the interaction of full-time employment and greater marital conflict was associated with increased alcohol use. CONCLUSION: These results emphasize the importance of considering gender-specific risk factors in the design of intervention programs.
Alcohol Drinking↗
Drosophila headlines.
Recent genetic and molecular data from Drosophila support the long-standing observations of morphology in suggesting that segmentation of the insect embryo proceeds in two phases. Organization of the cephalic segments uses a mechanism distinct from the familiar bierarchical cascade of segmentation genes that subdivides the trunk of the embryo.
Animals↗
Delineation of protective epitopes on the E2-envelope glycoprotein of Semliki Forest virus.
Two short linear peptides, 17 and 14 amino acids long, on the Semliki Forest virus (SFV) E2-envelope polypeptide are shown to be involved in the protection of mice against lethal challenge with SFV. Peptides corresponding to these two regions, designated H and L, were selected for study on the basis of our model for prediction of protective epitopes on E2 polypeptide of alphaviruses. These peptides were produced in Escherichia coli as recombinant proteins fused to the amino terminus of beta-galactosidase. Both the H epitope (amino acid positions 227-243 on E2) and L epitope (amino acid positions 297-310) are recognized by antibodies raised against SFV, and both trigger antibodies that interact with native SFV-E2. Vaccination of mice with the H-beta-galactosidase polypeptide confers 64-87% protection against a lethal viral challenge (250 LD50), and immunization with L-beta-galactosidase leads to 23-66% protection of challenged mice. The efficacy of the L-based synthetic vaccine could be improved further (up to 100% protection) by presentation of this epitope as a dimer fused to beta-galactosidase. These results provide evidence that the algorithm and the methodology proposed by us previously are effective tools for identification of linear protective epitopes on E2-envelope of SFV.
Amino Acid Sequence↗
Alterations in specific antibody production due to rank and social instability.
Separate studies examined the influence of the social environment of male cynomolgus macaques on primary and secondary antibody responses to immunization with tetanus toxoid. All animals showed evidence of both primary and secondary anti-tetanus antibody response. In the first study, subordinate animals had a greater primary antibody response to tetanus toxoid, while a single social reorganization (acute stressor) did not influence the response. In the second study, social rank was not associated with the secondary antibody response but repeated social reorganizations (chronic stressor) resulted in a greater level of specific antibody production in comparison to nonreorganized controls. These effects could not be accounted for on the basis of nonspecific differences in total serum IgG or serum albumin.
Animals↗
[A survey on recovery rooms of French university hospitals and Ile de France hospitals].
This study reports the results of a survey of post-anaesthesia recovery rooms (PARR) in French public University Hospitals (UH), and in those of the "Ile de France" (IdFH) area. The study, carried out between the 2nd and 8th of April 1990, aimed to identify the place where patients recovered from anaesthesia, and the personnel and monitoring equipment available in these places. 90% of 55 departments of anaesthesia and intensive care in University Hospitals and 94% of 34 departments in "Ile de France" Hospitals responded. A total number of 20,567 patients was collected, with 10,027 from University Hospitals. Of the latter, 31.4% recovered in the operating room or in the anaesthetic room itself; 7.5% were directly transferred to an intensive care unit (ICU), and 61.1% (10,397) were admitted to a PARR. However, 2,460 of those admitted to such a PARR were in fact admitted to a PARR without any permanent nursing staff. Overall, 45.8% of the patients were not admitted to a PARR where adequate care by nurses was available. Of the 3,540 patients anaesthetized in "Ile de France" Hospitals, 3.1% were transferred to an ICU, 25% were not admitted to a PARR, and the remaining 71.7% were. However, 35% of those admitted to a PARR were admitted to a PARR without any permanent nursing staff. Therefore 50.1% of patients anaesthetized in the "Ile de France" Hospitals did not benefit from adequate post-anaesthetic supervision. In 82% of the patients anaesthetized in University Hospitals, the lowest rates of admission to a PARR were found in patients undergoing gastrointestinal endoscopy (GIE), and ENT, ophthalmological or stomatological surgical procedures. After anaesthesia for GIE, 69% of patients recovered at the anaesthetic post and 12% were admitted to a PARR without any permanent nursing staff. In ENT-Ophthalmology-Stomatology, Gynaecology and Obstetrics, and Radiology departments, 56%, 69% and 69% of patients, respectively, recovered in the anaesthetic room or in a PARR without any permanent staff, or, for the Radiology and Obstetrics departments, sent straight back to their room. Similar results were obtained with the patients in the "Ile de France" Hospitals. Nurses were not always present in 37% and 24% of PARR in University and "Ile de France" Hospitals respectively. In the PARR, there were three ECG monitors for 4 beds, and one pulse oximeter for seven beds. It seems therefore that, despite several ministerial recommendations, not all anaesthetized patients are admitted to a recovery room after their anaesthetic.
Academic Medical Centers↗
Controlled delivery systems for proteins based on poly(lactic/glycolic acid) microspheres.
This paper describes an investigation of the use of poly(lactic/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled horseradish peroxidase, were prepared by a modified solvent evaporation method using a double emulsion. The microspheres were spherical with diameters of 55-95 microns and encapsulated more than 90% of the protein. The preparation method was gentle and maintained enzyme activity and protein solubility. Stability studies showed that the encapsulation of an enzyme inside PLGA microspheres can protect them from activity loss. When not placed inside PLGA microspheres, (fluorescein isothiocyanate)-labeled horseradish peroxidase lost 80% of its activity in solution at 37 degrees C in a few days, whereas inside the PLGA microspheres it retained more than 55% of its activity after 21 days of incubation at 37 degrees C. In vitro release studies revealed that different release profiles (i.e., near-constant or biphasic) and release rates can be achieved by simply modifying factors in the preparation procedure such as mixing rate and volume of inner water and organic phases. Degradation studies by scanning electron microscopy and gel-permeation chromatography suggested that the mechanism responsible for protein release is mainly through matrix erosion.
Biological Availability↗
Stress and infectious disease in humans.
This article reviews research on the role of stress in infectious disease as measured either by illness behaviors (symptoms and use of health services) or by verified pathology. Substantial evidence was found for an association between stress and increased illness behavior, and less convincing but provocative evidence was found for a similar association between stress and infectious pathology. Introverts, isolates, and persons lacking social skills may also be at increased risk for both illness behaviors and pathology. Psychobiological models of how stress could influence the onset and progression of infectious disease and a psychological model of how stress could influence illness behaviors are proposed.
Communicable Diseases↗
A novel synthetic method for hybridoma cell encapsulation.
We report here what we believe is the first example of the encapsulation of hybridoma cells within a synthetic polymer by a simple gelation with dissolved cations in water, and at room temperature. Two lines of hybridoma cells were encapsulated within calcium cross-linked polyphosphazene gel microbeads without affecting their viability or their capability to produce antibodies. Interaction of these gel beads with the positively-charged polyelectrolyte, poly(L-lysine), of 102-kD molecular weight, produced a semipermeable membrane that was capable of retaining the cell-secreted antibodies inside the beads. Cell density increased 3.5-fold within 13 days concomitant with a 6.4-fold increase in antibody production. These synthetic membranes have the potential to aid in protein recovery schemes.
Antibodies, Monoclonal↗