Search PubMed⌕ Search

Biomedical subjects

B Cohen

Publications and source records attributed to B Cohen.

At least 145 records · Page 8Linked to original sources
PubMed1997

Trends in organ donation.

Presumed consent legislation produces more donors and in particular more organs per donor. In cadaveric donation, the number of elderly donors is increasing, so the quality of organs available is getting poorer. There will be no substantial rise in transplantation unless there is a major breakthrough in the current programs. There will be an increase in the proportion of living (un)related donors and debate about ethics of transplantation. Adverse publicity and debate may affect cadaveric donation and refusal rates.

Australia↗
PubMed1997

A recombinant adenovirus that directs secretion of biologically active kappa-bungarotoxin from mammalian cells.

A novel Cre-lox system was used to construct an adenovirus encoding kappa-bungarotoxin (kappa-Bgt), modified to be secreted by attachment of a bovine prolactin signal sequence at the N-terminus of the toxin. Western blot of medium from HEK-293 cells infected with the virus demonstrated that recombinant kappa-Bgt (R-kappa-Bgt) was secreted. The biological activity of the secreted R-kappa-Bgt was investigated in Xenopus oocytes that expressed neuronal nicotinic acetylcholine receptor (nAChR) subtypes alpha3beta2 and alpha2beta2. The recombinant toxin inhibited the response of alpha3beta2 type AChRs to ACh, but did not inhibit the response of alpha2beta2 type AChRs. These data demonstrated that the recombinant adenovirus directs the secretion of biologically active kappa-Bgt from a mammalian cell line. Because adenovirus can be used to infect post-mitotic cells, recombinant adenoviruses encoding biologically active peptides may be of use as delivery vehicles for in vivo experiments where repeated application of the purified peptide is unfeasible.

Adenoviridae↗
PubMed1997

Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila.

In both vertebrate and invertebrate development, cells are often programmed to adopt fates distinct from their neighbors. Genetic analyses in Drosophila melanogaster have highlighted the importance of cell surface and secreted proteins in these cell fate decisions. Homologues of these proteins have been identified and shown to play similar roles in vertebrate development. Fringe, a novel signalling protein, has been shown to induce wing margin formation in Drosophila. Fringe shares significant sequence homology and predicted secondary structure similarity with bacterial glycosyltransferases. Thus fringe may control wing development by altering glycosylation of cell surface and/or secreted molecules. Recently, two fringe genes were isolated from Xenopus laevis. We report here the cloning and characterization of three murine fringe genes (lunatic fringe, manic fringe and radical fringe). We find in several tissues that fringe expression boundaries coincide with Notch-dependent patterning centres and with Notch-ligand expression boundaries. Ectopic expression of murine manic fringe or radical fringe in Drosophila results in phenotypes that resemble those seen in Notch mutants.

Amino Acid Sequence↗
PubMed1997

Refeeding improves muscle performance without normalization of muscle mass and oxygen consumption in anorexia nervosa patients.

The effect of starvation-related malnutrition on muscle performance and on the energy cost of exercise remains unknown, as does the timing of improvement by refeeding. Indeed, in most diseases that induce malnutrition, muscle dysfunction is worsened by an inflammatory process. Thus, physical performance and the energy cost of exercise were studied in 15 semistarvated malnourished anorexia nervosa (AN) patients during exercise on an ergometric bicycle (3-min steps of 30 W) before and after 8, 30, and 45 d of refeeding. Results were compared with those of 15 normal-weight healthy subjects matched for age, sex, and physical activity. Before refeeding, the workload reached during the exercise was 49% lower in AN patients than in control subjects (P < 0.01). It was correlated with body weight, fat-free mass, and leg muscle circumference (P < 0.002). The performance improved dramatically during refeeding (P < 0.03), reaching normal values after 45 d of refeeding, despite fat-free mass and leg muscle circumference values that were still 20% lower in AN patients than in control subjects (P < 0.01). At this time, the exercise-related VO2 remained unchanged, being approximately 25% lower than that of the control subjects when corrected for muscle mass differences (P < 0.03). In conclusion, in AN patients muscle performance was restored by refeeding long before the patients achieved normal nutritional status. The economic cost of physical activity for these malnourished patients allows them to maintain a relatively high level of physical activity. This relative overactivity has two goals in AN: it reinforces anorexia and contributes to the excess of energy expenditure needed for weight loss.

Adult↗
PubMed1997

Organ shortages: maximising the donor potential.

Of all the problems foreseen in the pioneering days of organ transplantation, a shortage of donor organs, was not even remotely considered as a barrier to progress. Such has been the success of transplantation over the last two decades, organ shortage is now considered the major limitation. This chapter will concentrate on efforts to increase the donor potential. The development of Organ Exchange Organizations is briefly described with special emphasis on their role in organ allocation systems to avoid wastage of this precious resource, procurement transplant coordinators, the organization of organ procurement and the consent process. We look briefly at the influence of the media and end with some considerations on how to maximise the current supply of organs for transplantation.

Ethics, Medical↗
PubMed1997

Contribution of vestibular commissural pathways to spatial orientation of the angular vestibuloocular reflex.

During nystagmus induced by the angular vestibuloocular reflex (aVOR), the axis of eye velocity tends to align with the direction of gravito-inertial acceleration (GIA), a process we term "spatial orientation of the aVOR." We studied spatial orientation of the aVOR in rhesus and cynomolgus monkeys before and after midline section of the rostral medulla abolished all oculomotor functions related to velocity storage, leaving the direct optokinetic and vestibular pathways intact. Optokinetic afternystagmus and the bias component of off-vertical-axis rotation were lost, and the aVOR time constant was reduced to a value commensurate with the time constants of primary semicircular canal afferents. Spatial orientation of the aVOR, induced either during optokinetic or vestibular stimulation, was also lost. Vertical and roll aVOR time constants could no longer be lengthened in side-down or supine/prone positions, and static and dynamic tilts of the GIA no longer produced cross-coupling from the yaw to pitch and yaw to roll axes. Consequently, the induced nystagmus remained entirely in head coordinates after the lesion, regardless of the direction of the resultant GIA vector. Gains of the aVOR and of optokinetic nystagmus to steps of velocity were unaffected or slightly increased. These results are consistent with a model in which the direct aVOR pathways are organized in semicircular canal coordinates and spatial orientation is restricted to the indirect (velocity storage) pathways.

Animals↗
PubMed1997

Prospective study of patients' refusal of antipsychotic medication under a physician discretion review procedure.

OBJECTIVE: The authors examined the refusal of antipsychotic medications and associated outcomes prospectively in a group of 348 psychiatric patients admitted to three acute inpatient units in a state-operated mental health facility in Virginia where psychiatrists have the discretionary power to administer treatment over patients' objections. METHODS: Newly admitted patients were administered both a questionnaire to ascertain their attitudes toward admission and the Brief Psychiatric Rating Scale (BPRS). Patients who refused antipsychotic medication were identified, and data were collected on the length of refusal and whether the refusal episode was terminated voluntarily or involuntarily. A group of patients compliant with antipsychotic medication was selected for comparison on outcome measures, including the rate of seclusion and restraint and length of hospitalization. RESULTS: Patients who refused treatment were found to have significantly higher BPRS scores than were patients who complied with antipsychotic treatment and more negative attitudes toward hospitalization and past, present, and future treatment. Refusal episodes were brief, on average 2.8 days, and all patients, who refused treatment were treated. When compared with the compliant patients, patients who refused treatment were more likely to be assaultive, were more likely to require seclusion and restraint, and had longer hospitalizations. CONCLUSIONS: Psychiatrists exercised their discretion to promptly treat all patients who refused treatment. Nonetheless, these patients suffered more morbidity than compliant patients. This study suggests that the negative sequelae of in-hospital treatment refusal cannot be eliminated by rapid treatment. The policy implications are discussed.

Adult↗
PubMed1997

Organ transplantation and European Community law: the case of non-residents.

OBJECTIVES: The role of the European Union in influencing health care policies in member states is of increasing importance. The Eurotransplant Foundation is an organization which provides donor organs to the most suitable transplant recipients. It covers a region of five countries (Austria, Belgium, Germany, Luxembourg, The Netherlands). As there is a severe shortage of donor organs within its region, registration of so-called non-resident patients on the waiting lists aggravates this shortage. Could European Community law, especially rules on competition, limit Eurotransplant's freedom to introduce a restrictive policy on non-residents? If so, could participating transplant centres or patients initiate legal action against Eurotransplant to stop the execution of such a policy? METHODS: Quantitative descriptive data on organ donation and use by the Eurotransplant Foundation during 1994 and 1995, by residents and non-residents. Analysis on basis of economic and legal framework. RESULTS: Solidarity between potential donors and potential recipients is organized in a different manner in an organization such as Eurotransplant as compared to a national organization under national law. National regulations may introduce a restrictive policy for the acceptance of non-resident patients. Eurotransplant--as a matter of its own policy--has to consider international solidarity. The scope of the non-resident issue is dealt with, and it is explained why it is considered to be a problem. On the basis of a discussion of the economic and the legal framework for a non-resident policy, an answer to the question is suggested. CONCLUSION: It might be possible for Eurotransplant to introduce a restrictive policy on the admission of non-residents without violating the European Community Treaty.

Emigration and Immigration↗
PubMed1997

Changing patterns in organ donation in Eurotransplant, 1990-1994.

Organ transplantation has become the treatment of choice for patients with end-stage organ failure and has led to progressive increases in the size of waiting lists over the past decade. Unfortunately, from 1990 to 1994, the number of organ donors remained stable while the number of organs transplanted from these donors increased by only 10%. In view of the severity of the current organ shortage, elderly individuals are increasingly being accepted as organ donors. The graft survival rate with kidneys from donors older than 55 years is 5% lower than that with kidneys from younger donors at 1 years and 9% lower at 3 years post-transplantation. Graft survival is also significantly lower with organs from donors who die from cerebrovascular accidents than it is with organs from donors whose cause of death is cerebral trauma. The number of patients waiting for a nonrenal donor organ has increased rapidly in the past 5 years, and an increasing number of donor kidneys are now being provided by multiorgan donors. The favorable graft survival rate with multiorgan donor kidneys, which is significantly better than that obtained with single organ donor kidneys, confirms their suitability for renal transplantation.

Adult↗
PubMed1996

Modulation of insulin activities by leptin.

Leptin mediates its effects on food intake through the hypothalamic form of its receptor OB-R. Variants of OB-R are found in other tissues, but their function is unknown. Here, an OB-R variant was found in human hepatic cells. Exposure of these cells to leptin, at concentrations comparable with those present in obese individuals, caused attenuation of several insulin-induced activities, including tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), association of the adapter molecule growth factor receptor-bound protein 2 with IRS-1, and down-regulation of gluconeogenesis. In contrast, leptin increased the activity of IRS-1-associated phosphatidylinositol 3-kinase. These in vitro studies raise the possibility that leptin modulates insulin activities in obese individuals.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation.

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.

Cohort Studies↗
PubMed1996

Efferent pathways of the nucleus of the optic tract in monkey and their role in eye movements.

To clarify the role of the pretectal nucleus of the optic tract (NOT) in ocular following, we traced NOT efferents with tritiated leucine in the monkey and identified the cell groups they targeted. Strong local projections from the NOT were demonstrated to the superior colliculus and the dorsal terminal nucleus bilaterally and to the contralateral NOT. The contralateral oculomotor complex, including motoneurons (C-group) and subdivisions of the Edinger-Westphal complex, including motoneurons (C-group) and subdivisions of the Edinger-Westphal complex, also received inputs. NOT efferents terminated in all accessory optic nuclei (AON) ipsilaterally; contralateral AON projections arose from the pretectal olivary nucleus embedded in the NOT. Descending pathways contacted precerebellar nuclei: the dorsolateral and dorsomedial pontine nuclei, the nucleus reticularis tegmenti pontis, and the inferior olive. Direct projections from NOT to the ipsilateral nucleus prepositus hypoglossi (ppH) appeared to be weak, but retrograde tracer injections into rostral ppH verified this projection; furthermore, the injections demonstrated that AON efferents also enter this area. Efferents from the NOT also targeted ascending reticular networks from the pedunculopontine tegmental nucleus and the locus coeruleus. Rostrally, NOT projections included the magnocellular layers of the lateral geniculate nucleus (lgn); the pregeniculate, peripeduncular, and thalamic reticular nuclei; and the pulvinar, the zona incerta, the mesencephalic reticular formation, the intralaminar thalamic nuclei, and the hypothalamus. The NOT could generate optokinetic nystagmus through projections to the AON, the ppH, and the precerebellar nuclei. However, NOT also projects to structures controlling saccades, ocular pursuit, the near response, lgn motion sensitivity, visual attention, vigilance, and gain modification of the vestibulo-ocular reflex. Any hypothesis on the function of NOT must take into account its connectivity to all of these visuomotor structures.

Afferent Pathways↗
PubMed1996

Modeling the organization of the linear and angular vestibulo-ocular reflexes.

A one-dimensional mathematical model of the compensatory linear vestibuloocular reflex (lVOR) was developed. The model was based on the concept that to effect oculomotor compensation, linear head acceleration sensed by the otoliths must be integrated twice to form the angular position-related signal required by the motoneurons. This contradicts the postulate that linear acceleration is differentiated to generate "jerk," which is then used to drive the compensatory lVOR. The transfer characteristics of different otolith afferent classes were modeled by a transfer function with a common modal structure and different degrees of compensation. Both the time and frequency domain behavior of regular and irregular otolith afferents were simulated. The outputs of the various afferent classes were superposed by a linear filter to generate the velocity command which drives the oculomotor velocity-position integrator. The model was used to simulate the dominant gain and phase characteristics of the compensatory lVOR in monkey and the dynamic characteristics of the compensatory human lVOR response for brief periods of linear acceleration on a sled. The model was then combined with the velocity storage-based model of the angular vestibulo-ocular reflex (aVOR) to simulate the eye velocity response to centrifugation in monkey and man. The model suggests that the orientation response that modifies the time constants of the velocity storage integrator is the dominant aspect of the response to linear acceleration in monkey. Human responses, on the other hand, are dominated by an effect of the beating field, which modifies the eye velocity command to the oculomotor system.

Afferent Pathways↗