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Biomedical subjects

B Joseph

Publications and source records attributed to B Joseph.

At least 37 records · Page 2Linked to original sources

Computer-aided ergonomics: a case study of incorporating ergonomics analyses into workplace design.

One of the primary goals of computer-aided ergonomics is to develop software tools that allow ergonomics information to be accessed at the earliest stages of design. This case study discusses a PC-based software program that allows a designer to quantify a worker's biomechanical risk for injury based on a proposed workplace design. The program couples an established software tool for biomechanical analysis, the Three-Dimensional Static Strength Prediction Program (3DSSPP), with a widely used computer-aided design software package, AutoCAD. The use of this "3DSSPP/AutoCAD interface" in the proactive analysis of an automotive assembly task is described and the results compared with an independent assessment using observations of workers performing the same task. Both studies yield similar conclusions, suggesting that proactive use of software such as the 3DSSPP/AutoCAD interface may be a valid tool in evaluating proposed workplace designs. In this context, issues in the analysis of workplace designs regarding the use of supporting ergonomic tools, assumptions, and posture selection are discussed.

Accidents, Occupational↗

Delayed separation of the capital femoral epiphysis after an ipsilateral transcervical fracture of the femoral neck.

A displaced transcervical fracture of the femoral neck in a three-year-eight-month-old boy was fixed with two screws, which did not cross the growth plate. When he resumed walking five weeks after the injury, a delayed separation of the capital femoral epiphysis occurred. The displaced epiphysis was reduced and fixed with three unthreaded pins. In spite of disruption of the femoral neck at two sites, avascular necrosis of the femoral head did not occur. This was confirmed by two sequential isotope scans. Delayed epiphyseal separation after the femoral neck fracture and the preservation of the vascularity of the epiphysis in this case are both very unusual.

Biomechanical Phenomena↗

Management of congenital pseudarthrosis of the tibia by excision of the pseudarthrosis, onlay grafting, and intramedullary nailing.

Fourteen skeletally immature children with congenital pseudarthrosis of the tibia were treated by excision of the pseudarthrosis, double onlay autogenous cortical bone grafting, and intramedullary nailing. Union was achieved in 12 patients, and no refractures occurred at the site of the original pseudarthrosis. In three patients, a fresh pseudarthrosis developed at a different site; these united after repeat onlay grafting. Five skeletally mature patients were treated by excision of the pseudarthrosis, compression at the site, and limb lengthening by callotasis. Union was achieved in three. Gain in tibial length ranged from 6 to 13 cm, with no significant complications during lengthening. The authors conclude that union can be achieved and refractures prevented in a significant proportion of skeletally immature children with congenital pseudarthrosis of the tibia by excision of the pseudarthrosis, dual onlay bone grafting, and intramedullary nailing. Any residual shortening of the limb can be treated at skeletal maturity.

Adolescent↗

Role of apoptosis in the response of lung carcinomas to anti-cancer treatment.

Resistance of tumor cells to treatment often accounts for the failure of traditional forms of anti-cancer therapy. It is well known that tumors from the same histological group and stage of development are highly heterogeneous in their sensitivity to therapy. Among the factors that can influence tumor sensitivity are DNA repair capacity, distribution of cells throughout the cell cycle, proliferation potential, etc. In many cases, anti-cancer therapy eliminates tumor cells via apoptosis, an active form of cell death characterized by cell shrinkage and the removal of cells in a neat, orderly fashion. However, this process is not always efficient. In the present review, the precise role that apoptosis plays in the response of lung carcinomas to chemotherapy and radiation treatment is discussed.

Animals↗

Agreeableness as obstacle.

The author discusses excessive agreeableness as it appears in the analytic situation, the patient agreeing with all interpretations, accepting all the analyst suggests in such a way as to keep the treatment apparently ongoing and peaceful but actually semi-paralysed. This type of agreeableness is linked with what has been described in the literature under the rubric of compliance. The author aims to show the various ways in which this agreeableness is enacted in the relationship with the analyst, and then to explore further the kind of anxieties that this defensive structure tries to ward off. Material from an adolescent patient is used to describe the slow unravelling of very powerful anxieties about being invaded and taken over by her object, anxieties that lead to her having no life and no mind of her own. It is suggested that such deeply paranoid anxieties may unconsciously be present in other patients of this compliant, 'agreeable' type.

Adolescent↗

The novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalene carboxylic acid can trigger apoptosis through a mitochondrial pathway independent of the nucleus.

The novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphtalene carboxylic acid (AHPN/CD437), a retinoic acid receptor (RAR)gamma activator, has been found to inhibit the growth and to induce apoptosis of a wide variety of malignant cell types including solid tumors and various leukemias. Interestingly, CD437 is able to induce apoptosis in some all-trans-retinoic acid (ATRA)-resistant models. In a number of experimental systems, the early apoptotic stage that precedes nuclear chromatinolysis consists in mitochondrial alterations, including a disruption of the inner mitochondrial transmembrane potential (delta(psi)m) mediated by the mitochondrial permeability transition (MPT). Similarly CD437 causes RPMI 8226, a human myeloma cell line, to undergo a rapid delta(psi)m disruption that precedes other apoptotic alterations such as the generation of reactive oxygen species and DNA fragmentation. The same sequence of events is observed during the CD437-induced apoptosis in L363, a RARgamma-negative human myeloma cell line, as well as RPMI 8226 cytoplasts (anucleate cells). Indeed, RPMI 8226 cells and cytoplasts manifest a similar degree in delta(psi)m loss, phosphatidylserine exposure, and caspase activation in response to CD437, which indicates that nuclear effects cannot account for the apoptogenic potential of CD437. The mitochondrial release of cytochrome c, the activation of caspases as well as nuclear signs of CD437-induced apoptosis are fully prevented by the MPT inhibitory compound cyclosporin A. Purified mitochondria can be directly induced to undergo MPT with CD437 but not with ATRA. In a cell-free in vitro system consisting of exposing mitochondrial supernatants to isolated nuclei, only supernatants from CD437-treated mitochondria provoke chromatin condensation, whereas supernatants from mitochondria treated with ATRA, or with the combination of CD437 and cyclosporin A, remain inactive. In conclusion, these results suggest that the rapid execution of CD437-induced apoptosis is a nucleus-independent (and probably RARgamma-independent) phenomenon involving mitochondria and MPT.

Antineoplastic Agents↗

Differences in expression of pro-caspases in small cell and non-small cell lung carcinoma.

Expression of several molecular determinants of apoptosis was analyzed in 10 untreated small cell (SCLC) and 6 untreated non-small cell (NSCLC) lung carcinoma cell lines. Although SCLC lines were more prone to spontaneous apoptosis compared with NSCLC lines, the former showed higher Bcl-2 expression and a higher Bcl-2/Bax ratio. In order to understand this apparent contradiction, the expression of pro-caspases as well as calpain was analyzed in these cell lines at the protein and mRNA levels. No differences in protein level of pro-caspases-2, -3, -7, and -9 and of calpain were detected between the SCLC and the NSCLC lines, but a striking difference in pro-caspase-8 expression was noted. All 6 NSCLC, but only 2 of the 10 SCLC lines, expressed pro-caspase-8 protein. Further experiments using the RNase protection assay indicated that the lack of pro-caspase-8 expression at the mRNA level was characteristic for SCLC. Using the same experimental approach, we found that SCLC cell lines in addition to pro-caspase-8 were deficient in mRNA expression of pro-caspases-1, -4, and -10, suggesting a different caspase-activating cascade in SCLC compared with NSCLC. This first systematic characterization of pro-caspase expression in lung cancer surprisingly showed that SCLC, which are more prone to undergo spontaneous apoptosis, are deficient in several pro-caspases and have a high Bcl-2/Bax ratio. Thus, the propensity of SCLC cells to undergo apoptosis cannot be explained only by the expression of factors involved in regulation or execution of apoptosis.

Apoptosis↗

Tumor radiosensitivity and apoptosis.

With approximately 50% of all cancer patients receiving radiation therapy at some point in their treatment, increasing the sensitivity of tumor cells to the lethal effects of irradiation has the potential to significantly improve the rate of recovery from many malignancies. The major biological determinant of radiotherapy failure is tumor radioresistance. It is well known that tumors from the same histological group and stage of development are extremely heterogeneous in their sensitivity to radiotherapy. There are many factors which could affect tumor radiosensitivity. One cellular mechanism common to various therapeutic regiments, including radiation, is killing tumor cells via apoptosis. However, this killing is not always efficient. In this review the link between tumor sensitivity to radiation treatment and the capacity of tumor cells to be killed by apoptotic mechanisms will be discussed.

Animals↗

p21(waf1) mRNA contains a conserved element in its 3'-untranslated region that is bound by the Elav-like mRNA-stabilizing proteins.

The Elav-like proteins are specific mRNA-binding proteins that regulate mRNA stability. The neuronal members of this family (HuD, HuC, and Hel-N1) are required for neuronal differentiation. In this report, using purified HuD protein we have localized a high affinity HuD binding site to a 42-nucleotide region within a U-rich tract in the 3'-untranslated region p21(waf1) mRNA. The binding of HuD to this site is readily displaced by an RNA oligonucleotide encoding the HuD binding site of c-fos. The sequence of this binding site is well conserved in human, mouse, and rat p21(waf1) mRNA. p21(waf1) is an inhibitor of cyclin-dependent kinases and proliferating cell nuclear antigen and induces cell cycle arrest at G1/S, a requisite early step in cell differentiation. The identification of an Elav-like protein binding site in the 3'-untranslated region of p21(waf1) provides a novel link between the induction of differentiation, mRNA stability, and the termination of the cell cycle.

Animals↗

Evidence for the involvement of both retinoic acid receptor- and retinoic X receptor-dependent signaling pathways in the induction of tissue transglutaminase and apoptosis in the human myeloma cell line RPMI 8226.

In this study, we show that both all-trans-retinoic acid (atRA) and 9-cis-retinoic acid (9-cis-RA) are potent inducers of tissue transglutaminase (TGase II), an enzyme involved in apoptosis, at the level of both enzyme activity and mRNA in the human myeloma cell line RPMI 8226. RPMI 8226 cells were shown to express mRNAs for all the retinoid receptors subtypes, ie, RARalpha, RARbeta, RARgamma, RXRalpha, RXRbeta, and RXRgamma. To identify which of these receptors are involved in regulating TGase II expression, several receptor-selective synthetic retinoids were used. Neither CD367, a very potent retinoid that selectively binds and activates receptors of the RAR family, nor CD2425, an RXR-selective agonist, induced TGase II when used alone. However, combination of CD367 and CD2425 resulted in nearly full induction of the enzyme. Moreover, when used in combination with atRA, CD367 partially inhibited the atRA-dependent induction of TGase II, whereas CD2425 enhanced it. The effects of Am 580, CD417, and CD437, three synthetic retinoids selective for the RARs subtypes RARalpha, RARbeta, and RARgamma, respectively, were also investigated. None of these compounds was able to induce TGase II when used alone; however, the combination of each of them with CD2425 resulted in strong induction of the enzyme activity, reaching 30% to 50% of the values obtained in the presence of retinoic acid and suggesting functional redundancy between the RAR subtypes. Finally, treatment with atRA or the combination of CD367 and CD2425, but not with CD367 or CD2425 alone, was also shown to trigger apoptosis in RPMI 8226 cells, with prominent accumulation of TGase II immunoreactivity in apoptotic cells. Taken together these data suggest that the induction of TGase II expression and apoptosis in the RPMI 8226 myeloma cell line required ligand-dependent activation of both the RAR and RXR receptors.

Apoptosis↗

Treatment of internal rotation gait due to gluteus medius and minimus overactivity in cerebral palsy: anatomical rationale of a new surgical procedure and preliminary results in twelve hips.

Spastic overactivity of the anterior fibers of the gluteus medius and minimus can result in an internal rotation gait associated with excessive hip and pelvic rotation. The currently advocated operation for this problem can result in weakness of hip abduction. The anatomical features of the gluteal muscles suggest that this gait abnormality can be corrected by selectively reducing the internal rotator function of the anterior fibers of the glutei without disturbing the abductor fibers. Such an operative procedure was devised and performed on 12 hips. The gait improved in all hips without any demonstrable weakness of the hip abductor power.

Adolescent↗

mRNA expression of HNF-4 isoforms and of HNF-1alpha/HNF-1beta variants and differentiation of human cell lines that mimic highly specialized phenotypes of intestinal epithelium.

The mRNA expression of HNF-4 isoforms and the ratio of HNF-1alpha/HNF-1beta variants in cell lines representing highly specialized phenotypes of human intestinal epithelium were studied by RT-PCR. A strong rise in expression of HNF-4 isoforms alpha2, alpha4 and gamma correlates with commitment into highly differentiated enterocyte-like phenotype of Caco-2 cells which best mimic enterocytes, whereas only isoform alpha4 expression is high in the less differentiated HT-29 G- cells. These increased expressions are not encountered in the highly differentiated mucous-secreting HT-29 MTX cells. Differentiation into highly specialized enterocyte-like Caco-2 cells and mucous-secreting HT-29 MTX cells is accompanied by a moderate rise in HNF-1 without change in the ratio of its variants. Our data corroborate those of Spath et al. (Mol. Cell. Biol., 1997, 17, 1913) in hepatoma cells and suggest that HNF-4 isoforms alpha2, alpha4 and gamma play a major role in the differentiation of enterocytes.

Base Sequence↗

Transfer of social attributions in stimulus equivalence classes by preschool children.

The transfer of social attributions within stimulus-equivalence classes comprised of photographs of children was examined. Five children (mean age: 4 yr., 2 mo.) were taught conditional discriminations sufficient for the emergence of two 3-member equivalence classes (A1-B1-C1 and A2-B2-C2). Social attributions were established by using two photographs to identify fictional children who could facilitate (B1) or prevent (B2) the participant's reinforcement on a computer game. Transfer of attribution was assessed by asking the participants questions regarding predicted social behaviors by children in all six photographs. One set of questions pertained explicitly to the response-options of the computer game; a second set referred to other prosocial and antisocial behaviors. Three children chose photographs in response to questions consistent with their experience with members B1 and B2 of the shared equivalence class when the questions pertained to the computer game. One subject also selected photographs in response to questions about predicted prosocial and antisocial behavior which reflected her experience with the B1 and B2 photographs.

Association Learning↗

Food- and nonfood-related differential outcomes in equivalence learning by adults with Prader-Willi syndrome.

Adults with Prader-Willi syndrome learned the conditional relations necessary for the formation of two equivalence classes under four conditions: (a) nondifferential, nonedible outcomes; (b) nondifferential, edible outcomes; (c) differential, nonedible outcomes; and (d) differential, edible outcomes. Tests for transitive relations revealed superior performance when the two differential outcomes procedures, in which a distinct reinforcer was associated with each stimulus set, were used during teaching. Performance on test trials following nondifferential outcomes training was better when edible outcomes were used during teaching for 4 of the 5 participants. An enhancement of performance on the derived relations separated by two or three nodal stimuli was seen when a differential outcomes procedure was used to teach the baseline conditional relations.

Adult↗

Rhinovirus inhibits antigen-specific T cell proliferation through an intercellular adhesion molecule-1-dependent mechanism.

To determine whether binding of human rhinovirus (HRV) to intracellular adhesion molecule-1 might disrupt airway immune processes, effects of a major HRV group, HRV-16, on T cell proliferation and cytotoxicity were defined. HRV (1-10 TCID50/cell) significantly inhibited T cell proliferation induced by antigen but not proliferation secondary to mitogens, interleukin-2, or an irradiated allogeneic T cell line. Noninfectious (UV-irradiated) HRV had similar effects. Inhibition of T cell proliferation was dependent on HRV binding to intercellular adhesion molecule-1 on monocytes, indicating that the virus interferes with lymphocyte activation indirectly through effects on antigen-presenting cells. In addition, HRV inhibited T cell cytotoxic responses but not NK cell activity. If these effects also occur in vivo, the resulting disturbance in local airway immunity could increase the chances of successful viral replication, and might also be a factor in the pathogenesis of secondary viral or bacterial respiratory tract infections.

Antigen Presentation↗