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PubMed2001

Indoor air pollution from biomass combustion and acute respiratory infections in Kenya: an exposure-response study.

BACKGROUND: Acute respiratory infections (ARI) are the leading cause of the global burden of disease and have been causally linked with exposure to pollutants from domestic biomass fuels in less-developed countries. We used longitudinal health data coupled with detailed monitoring of personal exposure from more than 2 years of field measurements in rural Kenya to estimate the exposure-response relation for particulates smaller than 10 mm in diameter (PM(10)) generated from biomass combustion. METHODS: 55 randomly-selected households (including 93 infants and children, 229 individuals between 5 and 49 years of age, and 23 aged 50 or older) in central Kenya were followed up for more than 2 years. Longitudinal data on ARI and acute lower respiratory infections (ALRI) were recorded at weekly clinical examinations. Exposure to PM(10) was monitored by measurement of PM(10) emission concentration and time-activity budgets. FINDINGS: With the best estimate of the exposure-response relation, we found that ARI and ALRI are increasing concave functions of average daily exposure to PM(10), with the rate of increase declining for exposures above about 1000-2000 mg/m(3). After we had included high-intensity exposure episodes, sex was no longer a significant predictor of ARI and ALRI. INTERPRETATION: The benefits of reduced exposure to PM(10) are larger for average exposure less than about 1000-2000 mg/m(3). Our findings have important consequences for international public-health policies, energy and combustion research, and technology transfer efforts that affect more than 2 billion people worldwide.

Acute Disease↗
PubMed1999

Prospects for fetal gene therapy.

Advances in prenatal diagnosis and gene transfer technology have allowed consideration of prenatal gene therapy. A compelling argument can be made for this strategy in treating genetic diseases that are fatal in the prenatal or perinatal period. In other diseases, the fetal environment may offer unique biological advantages that favor a prenatal gene therapy strategy over treatment after birth. Although issues of safety and efficacy must be resolved before clinical application, the development of fetal gene therapy may become a new molecular therapeutic arm in the field of prenatal intervention.

Female↗
PubMed2002

Cytokine regulation of liver development.

Liver development is a sequential array of distinct biological events. Each step of differentiation is regulated by intrinsically programmed mechanisms as well as by extracellular signals. The establishment of cell culture systems that recapitulate each stage of liver development has led to the identification of several extracellular signals that affect hepatocytic differentiation. Furthermore, studies on genetically engineered animals, especially knockout and transgenic mice, have highlighted a number of molecules essential for liver development. By applying primary culture techniques to analyses of mutant mice, it is now possible to link extracellular signals to intracellular pathways that provoke cellular responses of differentiation. Improvement in gene transfer technology utilizing viral vectors has further expanded the molecular analysis of liver development. In this review article, we summarize recent advances and attempt to describe the molecular basis of liver development from beginning to end as a sequential event.

Animals↗
PubMed1997

Testing the HMO competitive strategy: an analysis of its impact on medical resources.

Competitive approaches to health care reform, including managed competition, are hypothesized to reduce health care expenditures and the resources devoted to medical care. Empirical evidence has been limited. The short- and long-run effects of an experiment closely resembling managed competition are analyzed. We examine effects on hospitals, technology diffusion, physicians, and health insurance premiums. The strategy reduces capital in hospitals, has minor effects on physicians and technology, and has only initial effects on average premiums.

Fees and Charges↗
PubMed2002

The pros and cons of human therapeutic cloning in the public debate.

Few issues linked to genetic research have raised as much controversial debate as the use of somatic cell nuclear transfer technology to create embryos specifically for stem cell research. Whereas European countries unanimously agree that reproductive cloning should be prohibited there is no agreement to be found on whether or not research into therapeutic cloning should be permitted. Since the UK took the lead and voted in favour of regulations allowing therapeutic cloning the public debate has intensified on the Continent. This debate reflects the wide spectrum of diverse religious and secular moralities that are prevalent in modern multicultural European democratic societies. Arguments range from putting forward strictly utilitarian views that weight the moral issues involved against the potential benefits that embryonic stem cell research may harbour to considering the embryo as a human being, endowed with human dignity and human rights from the moment of its creation, concluding that its use for research is unethical and should be strictly prohibited. Given the current state of dissension among the various European states, it is difficult to predict whether 'non-harmonisation' will prevail or whether in the long run 'harmonisation' of legislation that will allow stem cell research will evolve in the EU.

Cloning, Organism↗
PubMed1997

Regulating biotechnology: a rational-political model of policy development.

While technology assessment is seen as a mechanism for achieving effective and efficient use of health care resources, it has not as yet made the impact on policy decisions that its potential would suggest. Considerable barriers have been encountered in translating assessment results into policy concerning the adoption and use of technologies, with 'political' factors often being decisive. This paper places technology assessment in the content of the policy process to clarify both (a) how conflicting interests and organizational features can often hinder the selection of optimal policies, and (b) the potential roles technology assessment could nonetheless play. The resulting framework is termed the 'rational-political' model of policy development. The paper uses the example of policy making about the regulation of biotechnology, drawing on information from a survey of decision-makers (n = 561) involved in issues concerning the development, approval, and payment for pharmaceutical products.

Biotechnology↗
PubMed2000

Developmental regulation of eukaryotic gene loci: which cis-regulatory information is required?

It is becoming increasingly accepted that gene loci comprise an extensive cis-regulatory system that encodes different layers of regulatory information, all of which are necessary to achieve and maintain tissue-specific gene expression in ontogeny. To gain a detailed understanding of developmental processes, it is clearly necessary to unravel the molecular basis behind the different regulatory processes that control gene expression. This information is also of utmost importance for any practical application that uses gene transfer technology.

Animals↗
PubMed2003

Global infertility and the globalization of new reproductive technologies: illustrations from Egypt.

Infertility is a problem of global proportions, affecting on average 8-12 percent of couples worldwide. In some societies, however-particularly those in the "infertility belt" of sub-Saharan Africa-as many as one-third of all couples are unable to conceive. Factors causing high rates of tubal infertility in parts of the developing world include sexually transmitted, postpartum, and postabortion infections; however, male infertility, which is rarely acknowledged, contributes to more than half of all cases. Unfortunately, the new reproductive technologies (NRTs) such as in vitro fertilization (IVF), which are prohibitively expensive and difficult to implement in many parts of the developing world, represent the only solution to most cases of tubal and male infertility. Not surprisingly, these technologies are rapidly globalizing to pronatalist developing societies, where children are highly desired, parenthood is culturally mandatory, and childlessness socially unacceptable. Using Egypt as an illustrative case study, this paper examines five of the major forces fueling the global demand for NRTs; these include demographic and epidemiological factors, the fertility-infertility dialectic, problems in health care seeking, gendered suffering, and adoption restrictions. Following this overview, a detailed examination of the implications of the rapid global spread of NRTs to the developing world will be offered. By focusing on Egypt, where nearly 40 IVF centers are in operation, this article will demonstrate the considerable constraints on the practice and utilization of NRTs in a developing country on the "receiving end" of global reproductive technology transfer. The article concludes by stressing the need for primary prevention of infections leading to infertility, thereby reducing global reliance on NRTs.

Anthropology, Cultural↗
PubMed2002

Transient detection of beta-galactosidase activity in hematopoietic cells, following reinjection of retrovirally marked autologous blood progenitors in patients with breast or ovarian cancer receiving high-dose chemotherapy.

OBJECTIVE: The aim of this report is to demonstrate the feasibility and safety of genetically modifying autologous human blood CD34(+) cells in vitro, with a retroviral vector that encodes a marker gene. The fate of genetically modified cells and their progeny was followed in vivo, after reinfusion in patients treated with high-dose chemotherapy for poor-prognosis breast or ovarian carcinomas. PATIENTS AND METHODS: Six patients received genetically modified autologous peripheral blood progenitors, together with unmanipulated aphereses, following high-dose chemotherapy. CD34(+) cells were immunoselected from aphereses, and retrovirally transduced by coculture with the retroviral vector producing cell line, to express a nuclear localized version of E. coli beta-galactosidase, encoded by a defective Moloney-murine leukemia virus-derived retroviral vector. Cells were reinfused to the patients after myeloablation, without prior ex vivo selection. RESULTS: Five out of six patients showed the transient presence of low numbers of beta-galactosidase(+) cells, as detected with an immunocytochemical assay, in the peripheral blood, during the first month following infusion. One patient had beta-galactosidase(+) clonogenic progenitors in her marrow at two months after transplantation, including HPP-CFC; intriguingly, this patient had the lowest percentage of X-gal(+) cells in her graft. Patients experienced side effects that are often observed after high-dose chemotherapy. CONCLUSIONS: Feasibility and safety of genetic modification of human hematopoietic stem and progenitor cells are demonstrated by this study. Ex vivo or in vivo selection is not mandatory, even in clinical situations where transduced cells have no survival advantage over wild-type cells; however, significant improvements in gene transfer technology are needed to achieve potentially useful levels of expression in such clinical situations.

Aged↗
PubMed1998

Parentage assessment of an IVF calf from Bubalus bubalis by DNA fingerprinting.

We used two synthetic oligodeoxyribonucleotide probes, OAT18 and OMS1 comprising (TGG)6 and (GGTA)4 repeat motifs, respectively, in combination with HinfI enzyme for DNA fingerprinting of a calf born from embryo transfer technology, its surrogate mother (SM) and the sperm donor (bull). Of the two polymorphic probes, OAT18 was found to be more informative for correctly establishing the parentage status of the in-vitro fertilized (IVF) calf and demonstrated the genetic relationship of the SM with the bull. Two types of cluster analysis, SAHN clustering and neighbour joining tree, performed with similarity indices of these individuals produced by OAT18 probe were found to be different. Using the SAHN cluster method, SM was found to be genetically closer to the bull than to IVF calf, whereas using the neighbour joining method, IVF was closer to bull than SM. A similar result was obtained by SAHN clustering with OMS1 probe. The relevance of this approach for parentage control in the context of animal biotechnology is described.

Animals↗
PubMed1997

Factors associated with variation in the superovulatory response of cattle.

Kafi, M., McGowan, M.R., 1997. Factors associated with variation in the superovulatory response of cattle. Anim. Reprod. Sci. Variability in the superovulatory response of cattle is still one of the major limiting factors in extensive usage of embryo transfer technology. A variety of approaches including recent attempts to eliminate the suppressive effect of the dominant follicle have been used to reduce the unpredictability of the superovulatory response of cattle. The development of techniques such as transrectal ultrasonography, have enabled a re-evaluation of ovarian dynamics during superovulation of cattle. In addition, advances in reproductive hormone assays have increased knowledge of the mechanisms controlling follicular development, ovulation and corpus luteum function. This review focuses on the current understanding of factors affecting the superovulatory response of cattle. Also, abnormalities of ovulation and endocrine disorders that may occur during superovulation are reviewed.

Animals↗
PubMed1997

Critical care in India.

India is a vast democracy of nearly one billion people. Before the British rule ended in 1947, the life span of an Indian was a mere 21 years. Within a short span of 50 years, it increased to an impressive 63 years, largely due to public health measures initiated by the government. This created a pool of more than 300 million middle class Indians who could afford the benefits of modern and specialized care when needed. Critical care medicine, as practiced in the West, is still confined to large Metropolitan areas. A large pool of expatriate Indian physicians from all over the world are helping bridge the resource gap between the West and India by transfer of technology and providing appropriate training to physicians and paramedical personnel. This article describes the history and current status of development of critical care medicine in India.

Critical Care↗
PubMed1997

Use of transgenic plants to study antioxidant defenses.

The abundance of O2 and the highly energetic electron transfer reactions associated with thylakoid membranes make chloroplasts a major source of reactive oxygen intermediates (ROI) in photosynthetic tissues of plants. Attempts to reduce oxidative damage in chloroplasts have included the manipulation of ROI-scavenging enzymes by gene transfer technology. Much of this work has focused on chloroplast-localized superoxide dismutase (SOD), both chloroplast-targeted and cytosolic ascorbate peroxidase (APX) and glutathione reductase (GR). Increased activity of SOD in chloroplasts of transgenic tobacco plants generally leads to increased protection from membrane damage caused by exposure to methyl viologen (MV). In addition, overexpression of chloroplastic Cu/Zn SOD can lead to increased protection from photooxidative damage caused by high light intensity and low temperatures. Transgenic tobacco plants that overexpress APX either in the cytosol or chloroplastic compartments also show reduced damage following either MV exposure or photooxidative treatment and transgenic plants that express increased levels of GR have elevated pools of ascorbate and GSH. Though still preliminary, these results clearly indicate that alterations in the expression of enzymes involved in ROI-scavenging can have significant metabolic effects and provide the hope that this strategy can be used to develop crop plants with increased stress tolerance.

Antioxidants↗
PubMed2001

[French pediatric oncology: analysis of the present situation and future prospects].

In France, the cure rate of paediatric malignancies is presently above 70%. The main contributing factors of the major improvement in the management of paediatric malignancies in recent years have been the development of a multicentric national and international clinical research, and the setting up of a network of multidisciplinary teams covering the whole country and working with technology transfer laboratories. The French group of study of cancers and leukemias in childhood works on the structuring of the French paediatric oncology on the three following themes: 1) the definition of the criteria required to be recognised as a reference centre in paediatric oncology; 2) the training of the future paediatricians specialised in haematology and oncology; and 3) the modalities of development and financial support of the clinical research. This paper mainly concerns the first point. Based on a national questionnaire survey, the measures needed to improve the organisation of the paediatric hyperspecialties are presented.

Child↗
PubMed1999

A view from the genome: spatial control of transcription in sea urchin development.

The process of embryogenesis depends on differential regulation of genes in the spatial components defined by the embryonic cells (blastomeres). Developmental regulation is mediated by complex, hardwired genomic control systems consisting of clusters of multiple target sites at which specific interactions with regionally presented transcription factors occur. In the age of genomics and gene-transfer technology, the sea urchin embryo provides unique opportunities for experimental analysis of these processes. Research on gene regulation in sea urchin embryos in the past year has seen remarkable progress in two large areas: in understanding functional cis-regulatory architecture; and in understanding the mechanism by which the axial coordinates of the egg are transduced into a molecular system for differential gene activation.

Animals↗
PubMed1996

Structure and dynamics of oligosaccharides: NMR and modeling studies.

Recent advances in the conformational analysis of oligosaccharides have focused on protein-bound oligosaccharides, glycopeptides, and glycoproteins, as well as on the conformational dynamics about glycosidic linkages. Significant progress has been made possible by dramatic improvements in NMR techniques and advances in computational chemistry and technology. Transferred nuclear Overhauser effects have been used to infer the conformations of carbohydrate ligands bound to protein receptors such as antibodies, lectins and enzymes. The increased use of combined NMR spectroscopic and computational protocols has resulted in insights into the dynamics of glycan chains.

Animals↗
PubMed2001

Definitions of human fertilization and preimplantation growth revisited.

Assisted reproductive techniques and the science of embryology have advanced rapidly over the last decades. The fact that social and moral objectives vary from country to country has resulted in differences not only in legislation, but also in the definition of embryological terms. Among the latest additions to the field has been nuclear transfer technology, which has led to concerns about the possibilities of human cloning. These facts call for a review of gametogenesis and early embryogenesis. The aim of the present paper is to initiate a discussion on terminology with a view to reaching a consensus. As a starting point definitions are proposed for the most important terms.

Journal Article↗
PubMed1995

The distribution of "big ticket" medical technologies in OECD countries. Organization for Economic Cooperation and Development.

Five "big ticket" medical technologies (BTTs) in 1990 were compared in the 24 OECD countries in relation to population, the number of physicians, gross domestic product (GDP), and health care expenditures (HCE). Wide variations were observed between and within countries for all measures. Regression analysis revealed that HCE explains part of the variation in the distribution of computed tomography scanners (excluding Japan), magnetic resonance imaging units, and radiation therapy units (R2 between 0.40 and 0.69), but not extracorporeal shock wave lithotripters. To a lesser extent, GDP was also found to correlate with the distribution of these technologies, but no correlation was found with number of physicians. Other factors affecting the diffusion of these technologies are proposed for study.

Developed Countries↗