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At least 1,063 records · Page 59Linked to original sources
PubMed2001

ClpX-mediated remodeling of mu transpososomes: selective unfolding of subunits destabilizes the entire complex.

E. coli ClpX, a member of the Clp/Hsp100 family of ATPases, remodels multicomponent complexes and facilitates ATP-dependent degradation. Here, we analyze the mechanism by which ClpX destabilizes the exceedingly stable Mu transpososome, a natural substrate for remodeling rather than degradation. We find that ClpX has the capacity to globally unfold transposase monomers, the building blocks of the transpososome. A biochemical probe for protein unfolding reveals that ClpX also unfolds MuA subunits during remodeling reactions, but that not all subunits have their structure extensively modified. In fact, direct recognition and unfolding of a single transposase subunit are sufficient for ClpX to destabilize the entire transpososome. Thus, the ability of ClpX to unfold proteins is sufficient to explain its role in both complex destabilization and ATP-dependent proteolysis.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1993

Fluxionate Lewis acidity of the Zn2+ ion in carboxypeptidase A.

Competitive inhibition constants Ki for a series of phenol-ring-substituted derivatives of alpha-(2-hydroxyphenyl)benzenepropanoic acid have been ascertained by observing their influence on the catalytic hydrolysis of a peptide substrate by the zinc enzyme carboxypeptidase A. The pH-dependence of Ki shows that binding is maximal between two pKa values: one is that of the phenol group of the inhibitor, and the other uniformly has a value of 6, the pKa of a Zn(2+)-bound water molecule on the enzyme in the absence of substrate or inhibitor. This is the dependence expected if phenolate binds to the Zn2+ displacing its bound H2O/HO-. A log-log plot of the dissociation constants for the productive forms of inhibitor plus enzyme versus the acid dissociation constants of the phenolic residues in the inhibitors yields a straight line with a slope of +0.76. This number indicates that the active-site metal ion has special capacity for dispersing negative charge, such as builds up on the oxygen atom of a carboxamide group undergoing nucleophilic addition.

Binding Sites↗
PubMed1999

Age-dependent altered proportions in subpopulations of tonsillar lymphocytes.

Age-related changes in functional subsets of lymphocytes may influence the potential to build up immune responses. In particular, the capacity of tonsillar lymphocytes to counter infections may be altered during ageing. In order to address this question we investigated the proportional distribution of several subsets of tonsillar T and B cells with regard to ageing. Tonsils were derived from 119 patients between 2 and 65 years of age. Lymphocyte subsets were monitored by three-colour fluorescence of relevant CD markers in flow cytometry. As a general tendency the percentage of CD3+ T cells steadily increased whereas that of CD19+ B cells decreased at the same time. No significant differences were observed between lymphocytes of patients with and without inflammatory history of the tonsils. The percentage of CD8+ T cells declined whereas that of CD4+ T cells increased during the same time span. CD45RA+ T cells increased during the first two decades of life and gradually decreased thereafter. In contrast, CD45RO+ T cells showed an opposite trend. No differences were seen in the population of CD3-/CD56+ natural killer (NK) cells. The mature B cell marker CD40 showed no significant changes during ageing. However, CD38+ B cells, representing B cells of late maturation stages, dramatically declined up to the age of 65. In a similar manner the CD5+ subpopulation of B cells decreased during ageing. Substantial changes in major tonsillar T and B cell populations as shown in this study may have an impact on the ageing process of the immune system.

Adolescent↗
PubMed2004

The role of U.S. public hospitals in urban health.

Public hospitals in the United States play a key role in urban health. In many metropolitan communities, public hospitals maintain the health care safety net. Most urban public hospitals have evolved to not only provide care for the indigent but also to serve their communities in other ways, including serving as major providers for tertiary services such as trauma and those that support homeland security; serving as the foundation for primary care services; continuing to train a significant number of physician, nurses, and other medical personnel; and providing laboratories for clinical medical research. Federal budget cuts such as those in the Balanced Budget Act of 1997, recent state budget deficits, competition for Medicaid Managed Care, and the growth in the number of uninsured have led to a decline in revenues among urban public hospitals. To be better stewards of scarce resources, public hospitals have moved to reduce inpatient demand by adopting prevention strategies that are aimed at addressing the determinants of health, the complex interactions among social and economic factors, the physical environment, and individual behavior. These factors contribute to health status and offer opportunities to intervene and improve community health. Urban public hospitals, to be successful in the next stage of their evolution, need to learn to manage the "in-betweens"--partnering with governmental and nongovernmental entities to identify and work together on common health and safety issues. If public hospitals engage the community successfully, building trust and establishing new capability and capacity, urban public hospitals will survive, evolve, and continue their tradition of service.

Cities↗
PubMed1982

The effect of deoxycoformycin and deoxyadenosine on deoxyribonucleotide concentrations in leukaemic cells.

Intracellular deoxynucleoside triphosphate pools of normal bone marrow, thymocytes and cells from patients with ALL and AML were measured after 2 h incubation with deoxycoformycin (dCF) 10(-5) M and deoxyadenosine (AdR) 10(-4) M in vitro and after another 30 min incubation in the absence of dCF and AdR ('chase' experiment). Incubation with dCF and AdR resulted in a significant rise of dATP concentrations in all groups (the highest rises occurring in the leukaemic groups particularly in AML and Thy-ALL). The concentrations of the other three deoxyribonucleoside triphosphates fell in all groups. The dATP level fell during the 'chase' period but in Thy-ALL and thymocytes this fall was insignificant and slower than in the other groups. This suggests that not only intracellular build-up of dATP but also the capacity of the cell to degrade dATP is important for in vivo cytotoxicity of dCF treatment. These results help to explain the differences in response to dCF of the different leukaemias.

Bone Marrow↗
PubMed2004

Community capacity for environmental health promotion: determinants and implications for practice.

The human response to an environmental hazard can either reduce or exacerbate its impact on health. This article reviews determinants of community-level responses to environmental health hazards. The aim is to identify factors that can enhance a community's capacity to protect itself and to suggest public health strategies that can increase such capacity. Four case histories of community environmental health action are presented to test a theoretical model for understanding the determinants of community capacity to promote environmental health. Specific actions public health professionals can take to strengthen community capacity include increasing access to accurate science, building strong relationships between communities and local health departments, and supporting political reforms that level the playing field for communities that seek to challenge corporate or government practices.

Community Health Planning↗
PubMed2004

The 21st century: the age of family medicine research?

Family medicine has matured as an academic and scientific discipline with its own core concepts, knowledge, skills, and research domains. It has acquired much expertise in studying common illnesses; the integration of medical, psychological, social, and behavioral sciences; patient-centered care; and health services delivery. Many health care challenges in the 21st century will place a great demand on primary care, which can serve its purpose only if it is of high quality and evidence based. Family medicine research can contribute to many areas of primary care, ranging from the early diagnosis to equitable health care. Stakeholders, such as the World Health Organization, governments, and funding agencies, are becoming more supportive to family medicine research because they recognize its key importance in improving the quality of primary care and bridging the gap between biomedical research and clinical practice. Family medicine can play a leading role in shifting the paradigm of medical research from the laboratory to the person. The 21st century should be a golden age of family medicine research because the time is right for the discipline, the health care environment is most suitable, and stakeholders are supportive. Family medicine must prepare for it by building up its research track record and capacity.

Biomedical Research↗
PubMed1988

Public Law 100-202, Joint Resolution making further continuing appropriations for the fiscal year 1988, and for other purposes, 22 December 1987.

This US Act provides the following with respect to universal access to child immunization: "The Congress calls upon the President to direct the Agency for International Development, working through the Centers for Disease Control and other appropriate Federal agencies, to work in a global effort to provide enhanced support towards achieving the goal of universal access to childhood immunization by 1990 by 1) assisting in the delivery, distribution, and use of vaccines, including a) the building of locally sustainable systems and technical capacities in developing countries to reach, by the appropriate age, not less than 80% of their annually projected target population with the full schedule of required immunizations and b) the development of a sufficient network of indigenous professionals and institutions with responsibility for developing, monitoring, and assessing immunization program and continually adapting strategies to reach the goal of preventing immunizable diseases and 2) performing, supporting, and encouraging research and development activities, in both the public and the private sector, that will be targeted at developing new vaccines and at modifying and improving existing vaccines to make them more appropriate for use in developing countries. In support of this global effort, the President should appeal to the people of the US and the US private sector to support public and private efforts to provide the resources necessary to achieve universal access to childhood immunization by 1990." The Act also does the following with respect to various forms of bilateral assistance: 1) prohibits the use of funds for an organization or program that supports coercive abortion or involuntary sterilization; 2) prohibits the use of funds for the performance of abortion as a method of family planning (FP); 3) provides that in awarding grants for natural FP under section 104 of the Foreign Assistance Act no applicant shall be discriminated against because of such applicant's religious or conscientious commitment to offer only natural FP. In addition, the Act stipulates that with respect to appropriations for the Department of Health and Human Services no funds will be used to perform abortions except where the life of the mother would be endangered if the fetus were carried to term.

Abortion, Induced↗
PubMed2002

Darwinian psychiatry and the concept of mental disorder.

In this paper, we discuss the concept of mental disorder from the perspective of Darwinian psychiatry. Using this perspective does not resolve all of the quandaries which philosophers of medicine face when trying to provide a general definition of disease. However, it does take an important step toward clarifying why current methods of psychiatric diagnosis are criticizable and how clinicians can improve the identification of true mental disorders. According to Darwinian psychiatry, the validity of the conventional criteria of psychiatric morbidity is dependent on their association with functional impairment. Suffering, statistical deviance, and physical lesion are frequent correlates of mental disorders but, in absence of dysfunctional consequences, none of these criteria is sufficient for considering a psychological or behavioral condition as a psychiatric disorder. The Darwinian concept of mental disorder builds from two basic ideas: (1) the capacity to achieve biological goals is the best single attribute that characterizes mental health; and (2), the assessment of functional capacities cannot be properly made without consideration of the environment in which the individual lives. These two ideas reflect a concept of mental disorder that is both functional and ecological. A correct application of evolutionary knowledge should not necessarily lead to the conclusion that therapeutic intervention should be limited to conditions that jeopardize biological adaptation. Because one of the basic aims of medicine is to alleviate human suffering, an understanding of the evolutionary foundations of the concept of mental disorder should translate into more effective ways for promoting individual and social well-being, not into the search for natural laws determining what is therapeutically right or wrong.

Biological Evolution↗
PubMed1990

Wound healing and the aged patient.

The aged patient is more susceptible to wound healing problems because of the interactions of body systems, environmental stresses, and disease with an aging process that takes place over many years. The multifactorial nature of wound healing in the elderly makes it difficult to determine whether observed healing problems are attributable to results of aging or other factors. Healing is affected by multiple factors in addition to patient age, which itself is not a dependable indicator of physiologic health. Some of these factors are disease, nutrition, perfusion, skin quality, environment, and individual responses to life events. It is particularly difficult for the aged patient to sustain the motivation to participate in care required during the healing process when cascading problems are allowed to build on the decreasing functions and reserve capacities of aging body systems and deplete available energy levels. Assessment of each individual is required because of the wide variety of aging changes and healing responses seen in aged patients. Compared with a younger adult, the aged patient generally heals well, following the same healing process but at a slower rate. Wound healing for the aged can be optimized through techniques of energy conservation, correction of existing problems, and management of risks related to aging and the individual patient. Healing problems are usually the result of decreases in systemic and local perfusion, decreases in the ability to ward off infection, and fragility of aging skin. The aged patient requires the same care as younger patients. It is more critical that this care be meticulously delivered with particular attention to care of intact skin, effects of chronic disease and medications, motivation, social habits, and discharge planning. Nurses can promote improved healing through the care they provide and by studying the progression of healing in aged patients.

Aged↗
PubMed2005

Health care workers' ability and willingness to report to duty during catastrophic disasters.

Catastrophic disasters create surge capacity needs for health care systems. This is especially true in the urban setting because the high population density and reliance on complex urban infrastructures (e.g., mass transit systems and high rise buildings) could adversely affect the ability to meet surge capacity needs. To better understand responsiveness in this setting, we conducted a survey of health care workers (HCWs) (N =6,428) from 47 health care facilities in New York City and the surrounding metropolitan region to determine their ability and willingness to report to work during various catastrophic events. A range of facility types and sizes were represented in the sample. Results indicate that HCWs were most able to report to work for a mass casualty incident (MCI) (83%), environmental disaster (81%), and chemical event (71%) and least able to report during a smallpox epidemic (69%), radiological event (64%), sudden acute respiratory distress syndrome (SARS) outbreak (64%), or severe snow storm (49%). In terms of willingness, HCWs were most willing to report during a snow storm (80%), MCI (86%), and environmental disaster (84%) and least willing during a SARS outbreak (48%), radiological event (57%), smallpox epidemic (61%), and chemical event (68%). Barriers to ability included transportation problems, child care, eldercare, and pet care obligations. Barriers to willingness included fear and concern for family and self and personal health problems. The findings were consistent for all types of facilities. Importantly, many of the barriers identified are amenable to interventions.

Adolescent↗
PubMed1997

Are boys better than girls at building a tower or a bridge at 2 years of age?

This study was designed to look at the differences in visuospatial abilities between boys and girls before they can speak fluently. At the mandatory two year follow up visit, children were given the opportunity to build a tower and a bridge. In children whose birth weight was > or = 2500 g, the capacity for erecting a tower was the same in both sexes, but for building a bridge striking differences were noted according to their sex. Among the 376 children of this category, 41 out of 199 boys (21%) were able to build a bridge in comparison with 15 out of 177 girls (8%). This difference is highly significant. In children whose birth weight was < or = 2500 g, no differences were noted either for building a tower or a bridge. By showing that boys outnumber girls among the most skilled toddlers in spatial abilities, this work confirmed the action of a male related factor on cerebral lateralisation.

Aptitude Tests↗
PubMed1990

[Respiratory symptoms and ventilatory capacity in pig-farm workers].

A group of 59 swine farmers was studied to assess the prevalence of acute and chronic respiratory symptoms and ventilatory capacity changes. Among men there was a significantly higher prevalence of almost all chronic respiratory symptoms compared to the control workers. For female workers there was a significantly higher prevalence of chronic cough, dyspnea and chest tightness than in control workers. There was a high prevalence of acute symptoms during work shift among the swine confinement workers. Significant acute reductions were recorded for all ventilatory capacity tests being largest for FEF25 indicating obstructive changes mostly in smaller airways. All significantly lower ventilatory capacity data in male and FVC and FEV1 in women were found in comparison to predicted normal values. The results obtained indicate that exposure in swine confinement buildings may cause the development of respiratory symptoms and ventilatory capacity abnormalities.

Adult↗
PubMed2000

Simulation to estimate the capacity of a stroke unit.

Preceding the implementation of a Stroke Unit (SU), data have been collected and used for building a simulation model of patient flow. This model was subsequently used to estimate the optimal capacity of the SU to be implemented. Because stroke patients require acute hospital care, this implies a highly variable number of immediate admissions. This variability complicates optimizing the capacity. In order to support decisions with regard to staffing (i.e. capacity) of the SU, different scenarios are simulated and compared to provide insight in the trade-off between regular understaffing and a low bed occupancy rate. In 1996 the Department of Neurology of the Academic Medical Center in the Netherlands implemented its SU to improve the quality of care for stroke patients. Data collected in the years 1997 and 1998 that the SU has been operational were evaluated and confirm the predictions made from simulating different scenarios. We conclude that simulation models provide a powerful tool for supporting decision making with regard to resource planning at the departmental level in our hospital.

Computer Simulation↗