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PubMed1981

The deterioration of the food situation in the Third World and the capitalist system.

Hunger and malnutrition are today associated with the capitalist system. The evidence points to a further deterioration of the food situation in the Third World in the foreseeable future, as a result of massive capital and technology transfers from the rich capitalist countries to the underdeveloped agricultures operated by trans-national concerns or private investors, with the active support of development assistance agencies such as the World Bank. Contrary to the superficial predictions of the World Bank, for example, poverty is bound to increase and the purchasing power of the masses must decline. Particular attention must be paid to the supply of staple foods and the proletariat. This is threatened by a variety of factors, attributable to the operation of the capitalist system. Among them are the senseless waste of Third World resources caused by the foreign investors' insatiable thirst for the quick repatriation of super-profits and the increasing orientation of Third World agricultures toward high-value or export crops (which are usually the same), an orientation which is imposed upon them by the industrial countries' agricultural development strategies. Even self-sufficiency programs for more staple foods, such as the ill-reputed Green Revolution, predictably cannot be of long duration.

Agriculture↗
PubMed2003

PDX-1 protein containing its own antennapedia-like protein transduction domain can transduce pancreatic duct and islet cells.

The pancreatic and duodenal homeobox factor-1 (PDX-1), also known as IDX-1/STF-1/IPF1, a homeodomain-containing transcription factor, plays a central role in regulating pancreatic development and insulin gene transcription. Furthermore, even in adults, PDX-1 is associated with islet neogenesis and differentiation of insulin-producing cells from progenitor cells. Here, we report for the first time that PDX-1 protein can permeate cells due to an Antennapedia-like protein transduction domain sequence in its structure and that transduced PDX-1 functions similarly to endogenous PDX-1; it binds to the insulin promoter and activates its expression. PDX-1 protein can also permeate into isolated pancreatic islets, which leads to stimulation of insulin gene expression. Moreover, PDX-1 protein transduced into cultures of pancreatic ducts, thought to be islet progenitor cells, induces insulin gene expression. These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription and for facilitating differentiation of ductal progenitor cells into insulin-producing cells without requiring gene transfer technology.

Amino Acid Sequence↗
PubMed2005

BETA2/NeuroD protein can be transduced into cells due to an arginine- and lysine-rich sequence.

BETA2/NeuroD, a basic helix-loop-helix transcription factor, is a key regulator of pancreatic islet morphogenesis and insulin gene transcription. Here we report for the first time that the BETA2/NeuroD protein can permeate several cells, including pancreatic islets, due to an arginine- and lysine-rich protein transduction domain sequence in its structure. The BETA2/NeuroD protein was transduced in a dose-dependent manner up to 1 micromol/l. Transduced BETA2/NeuroD functions similarly to endogenous BETA2/NeuroD: it binds to the insulin promoter and activates its expression. We also investigated the mechanism of BETA2/NeuroD protein transduction. The BETA2/NeuroD protein penetrated cells by macropinocytosis and was released from endosomes homogeneously in cytoplasm and nuclei. These data suggest that BETA2/NeuroD protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription without requiring gene transfer technology.

Amino Acid Sequence↗
PubMed2006

Managing the effect of TRIPS on availability of priority vaccines.

The stated purpose of intellectual property protection is to stimulate innovation. The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) requires all Members of the World Trade Organization (WTO) to enact national laws conferring minimum standards of intellectual property protection by certain deadlines. Critics of the Agreement fear that such action is inconsistent with ensuring access to medicines in the developing world. A WHO convened meeting on intellectual property rights and vaccines in developing countries, on which this paper is based, found no evidence that TRIPS has stimulated innovation in developing market vaccine development (where markets are weak) or that protection of intellectual property rights has had a negative effect on access to vaccines. However, access to future vaccines in the developing world could be threatened by compliance with TRIPS. The management of such threats requires adherence of all countries to the Doha Declaration on TRIPS, and the protections guaranteed by the Agreement itself, vigilance on TRIPS-plus elements of free trade agreements, developing frameworks for licensing and technology transfer, and promoting innovative vaccine development in developing countries. The role of international organizations in defining best practices, dissemination of information, and monitoring TRIPS impact will be crucial to ensuring optimal access to priority new vaccines for the developing world.

Developing Countries↗
PubMed2002

Work improvement and occupational safety and health management systems: common features and research needs.

There is a growing trend in re-orientating occupational health research towards risk management. Such a trend is accelerated by the increasing attention to occupational safety and health management systems. The trend, also seen in many Asian countries, is offering new opportunities for strengthening primary prevention. Useful examples are provided from recent work improvement projects dealing with technology transfer, small workplaces and rural areas. Common features of both these work improvement projects and accepted occupational risk management principles are reviewed based on recent experiences in Asian countries. Such features seem highly relevant in examining the occupational health research strategies. These experiences clearly show that locally adjusted procedures for risk assessment and control must be developed. There are new research needs concerning (a) the effective ways to encourage voluntary control at the workplace; (b) practical methods for local risk assessment; and (c) the types of participatory steps leading to continual improvements in the varying local context. Criteria of action-oriented research that can contribute to more effective risk control in different settings are discussed. Six relevant criteria may be mentioned: (a) adaptive risk management; (b) work/risk relationships; (c) action-oriented risk assessment; (d) use of collective expertise; (e) participation of local people; and (f) mutual learning. It appears crucial to stimulate research into the practical risk control procedures adjusted to the local situation.

Asia↗
PubMed1999

What are the livestock industries doing, and what do they need from us?

Livestock industries are facing global competition and revolutionary changes. While facing this global competition, the similarities of many animal meat products require that they compete on a cost-of-production basis. Additional issues include the environmental impact of animal agriculture, the role of animal products in human nutrition, food safety and quality, biotechnology, animal welfare, and market access. Progressive producers are becoming more aware of the needs of their customers and are striving to improve product quality. Checkoff funds are used to finance promotion, research, and consumer information programs and are increasingly used to finance producer education. Industrialization trends in the livestock industries are changing the needs of constituencies, delivery mechanisms, and relationships with the people involved. Characteristics of closed operations include high production cost, outdated technology, smaller size, older operators, and lack of management focus. Successful operations tend to be growing in capacity, are system-oriented, maintain high throughput, keep accurate records, use outside consultants, and control production costs. Modern livestock production has lowered the cost of production by integrating new production and management technologies. In order for producers to be successful in the future, access to technology, capital, and timely information will be critical. Animal scientists have many common objectives with livestock industries. Their work in research, teaching, and extension is critical for continued progress. However, people in the industries sometimes have the perception that academic arrogance, discipline myopia, uncoordinated research, slow technology transfer, increasing research costs, and counter-productive tenure systems prevent animal scientists from being as relevant and responsive as they could be. Support from the industries is essential as animal scientists and academic departments seek political and funding support. This support can be attained by including integrated systems research, improving communication skills, achieving more efficient research budgets, rapidly publishing results, reducing the cost of information distribution, developing flexible research agendas, retraining scientists, acquiring modern methods, and emphasizing critical thinking, communication, and teamwork when teaching.

Animal Husbandry↗
PubMed1997

Network Therapy for addiction: assessment of the clinical outcome of training.

Mental health practitioners in the office setting are often seen as deficient in addiction treatment skills. Relevant training in often quite limited, and trainees are generally not introduced in an effective office-based modality. We studied the feasibility of teaching beginning therapists how to apply Network Therapy, a cognitive-behavioral approach to achieving abstinence and preventing relapse that augments individual therapy with support from family and friends. The therapists were 19 psychiatric residents without experience in substance abuse treatment or outpatient therapy, and the patients were 24 cocaine-dependent patients who received a 24-week course of Network treatment. The patients remained in treatment for an average of 15.4 weeks. Seventy-nine percent of their observed weekly urine toxicologies were negative for cocaine, and 42% of patients produced clean urines in the 3 weeks immediately before termination. The overall outcome compares favorably with that reported in studies on cocaine treatment where experienced therapists were employed. Our results suggest that naive mental health trainees can be taught to apply Network Therapy for effective substance abuse management. This is particularly relevant to technology transfer for general mental health trainees, who are often thought to be perceived to be refractory to learning about the outpatient management of addiction.

Adult↗
PubMed1993

Problems in scale-up of biotechnology production processes.

The unique nature of biotechnology processes adds to the complexity and difficulty of scale-up. Successful scale-up means a shortened cycle to full-scale production, competitive advantage, and cost savings. The many pitfalls as well as actual and potential scale-up problems are reviewed. Emphasis is placed on covering all areas of concern in planning, executing, and documenting key studies. Needs in technology transfer are discussed and regulatory requirements are incorporated into scale-up needs. A review of the recent literature is coupled with actual case studies; problem avoidance is stressed. Problems in asepsis, in construction, and in validation are discussed and potential solutions given. Organizational problems are noted. Finally, checklists are given for project planning, for a safety audit, and for timely attainment of successful scale-up. Eighty-two references are included.

Asepsis↗
PubMed1984

Gene expression in the brain and the control of blood pressure.

Identification of genes involved in initiation or maintenance of hypertension is complicated by the possibility that blood pressure may not be directly regulated. However, a promising avenue of investigation would be to look for biochemical abnormalities associated with hypertension in a genetically defined strain of rats, and to analyze the structural and functional features of the genes which subserve the relevant biochemical pathways. Recent major advances in recombinant DNA and gene transfer technology should facilitate such studies. Within 10 years the important genetic markers of hypertension in man should be defined at a molecular level.

Animals↗
PubMed1992

Recommendations for improving drug treatment.

Recognizing that drug use is both chronic and relapsing once an individual is addicted, and that treatment is effective in reducing drug use/misuse, improving drug misuse treatment is examined and research as well as practice recommendations are presented. Drug misuse treatment is now recognized in the United States to meet the expanding drug use problem and for reducing the spread of HIV. With that background, the current status of drug misuse treatment is reviewed, clinical issues are emphasized, and policy issues are noted. Recommendations include the need for uniform funding, linkage with community agencies, technology transfer, training, and expanding research and evaluation efforts.

HIV Infections↗
PubMed2003

Control and prevention of emerging zoonoses.

Emerging and re-emerging zoonoses are zoonotic diseases caused by either totally new or partially new agents or by microorganisms previously known but now occurring in places or in species where the disease was previously unknown. Zoonotic diseases account for the majority of all emerging infectious diseases. Several factors have led to the emergence of these infections, including human demographics, the industrialization of food production, globalization, international travel and commerce, land use, microbial adaptation, and changes and breakdown in public health measures. Several zoonotic agents are also potential agents that could be used as biological weapons. The recent use of anthrax spores in tainted mall in the US underlines our need for preparedness against bioterrorism. Prevention and control of these emerging zoonotic diseases is based on recognition, investigation, and collaboration, the development of advanced diagnosis and surveillance tools, the use of applied epidemiology and molecular biology methods, as well as education, information, communication, and technology transfer.

Animals↗
PubMed2003

Impacts of dairy diagnostic teams on herd performance.

This study evaluated impacts of educational diagnostic teams of consultants used to transfer technology to dairy farms. Herd management performance changes were measured by comparing Dairy Herd Improvement data from 38 project farms to data from herds that were geographical contemporaries. The value of focused goals for effecting change was also assessed. Interviews provided producers' perception of project outcomes and insight on organization and conduct of dairy diagnostic teams. Changes observed in project herds were small compared with controls with tendencies for increased herd size and improved milk production per cow. Focused goals had greater impacts on increasing herd size, milk per cow, first lactation peak milk, reducing age at first calving, and percentages of cows with subclinical mastitis. Time, money, facility limitations, labor, and alternative priorities were the most cited constraints to implementing changes. Satisfaction scores of producers were significantly related to the degree that team recommendations were followed. Improved attitudes, quality of life, and financial well-being were benefits listed by a majority of producers from participation in the project. If similar projects were to be offered, 83% said they would participate again, and 69% indicated they would pay at least some of the costs. Project farms served as demonstration farms for 1930 other producers in their respective locales, resulting in a multiplier effect of original advice given by consultant teams. Suggestions by farmer participants for improvements in dairy diagnostic teams included needs for at least some unbiased team members, more frequent meetings, more follow-up on recommendations, and consistency of recommendations with family goals.

Aging↗
PubMedDate not supplied

Cancer statistics 2001: quo vadis or whither goest thou?

In his first Guest Editorial for CA as newly elected President of the American Cancer Society, Dr. Dileep Bal moves beyond the encouraging trends reported in the annual cancer statistics article to target areas for future efforts and improvement. Noting that resources and the public health activities of local, regional, and national medical communities should focus on cancer prevention, screening and early detection/treatment, technology transfer, and research, Dr. Bal emphasizes the feasibility of the 2015 goals set by the ACS: A 25% reduction in cancer incidence and a 50% reduction in mortality from cancer.

Humans↗
PubMed2005

PDX-1 protein is internalized by lipid raft-dependent macropinocytosis.

PDX-1 plays a central role in regulating insulin gene transcription and differentiation of insulin-producing cells. It was previously reported that, due to its own Antennapedia-like protein transduction domain (PTD), exogenous PDX-1 protein can permeate cells and induces insulin gene expression in pancreatic ducts, thought to be islet progenitor cells. These data suggest that PDX-1 protein transduction could be a safe and valuable strategy for facilitating differentiation of progenitor cells into insulin-producing cells without requiring gene transfer technology. Here it is shown that after an initial ionic cell-surface interaction, PDX-1 proteins are rapidly internalized by lipid raft-dependent macropinocytosis. HeLa cells were treated with both FITC-conjugated PDX-1 PTD and FM 4-64, a general fluorescent marker of endocytosis. A punctate cytoplasmic distribution of PDX-1 PTD, which colocalized with FM 4-64, was observed in treated cells. Because expression of dominant-negative dynamin-1 did not block PDX-1 PTD uptake, PDX-1 protein transduction is independent on phagocytosis and clathrin- or caveolar-mediated endocytosis. Cells were pretreated with amiloride, a specific inhibitor of the Na+/H+ exchange required for macropinocytosis, or cytochalasin D, an F-actin elongation inhibitor. Treatment of cells with both macropinosome inhibitors resulted in the reduction in PDX-1 PTD transduction into vesicles, suggesting that PDX-1 PTD-mediated cellular entry occurs by lipid raft-mediated macropinocytosis. Taken together, these observations provide the mechanism of PDX-1 protein transduction and suggest that the protein transduction system could work for experimental and therapeutic strategies.

Biological Transport↗
PubMed2006

Gene therapy of liver cancer.

The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/pro-drug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition, gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy. These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reached clinical phases. We present a review on the basis and the actual status of gene therapy approaches applied to liver cancer.

Angiogenesis Inhibitors↗
PubMed2001

Murine IL-10 gene transfer inhibits established collagen-induced arthritis and reduces adenovirus-mediated inflammatory responses in mouse liver.

The effects of homologous IL-10 administration during an established autoimmune disease are controversial, given its reported immunostimulatory and immunosuppressive properties. Studies of collagen-induced arthritis have shown efficacy with repeated administrations of IL-10; however, when the EBV IL-10 homologue was administered via adenovirus gene transfer technology the results were equivocal. Therefore, the present study was undertaken to elucidate the effects of prolonged homologous IL-10 administration via adenovirus-mediated gene delivery on the progression of established arthritis. Collagen type II (CII)-immunized mice received i.v. injections of 10(7) or 10(8) PFU of an E1-deleted adenoviral vector containing the murine IL-10 gene (AdIL-10), after arthritis onset. Mice were monitored for 3 wk for disease progression, and gene transduction was assessed by quantification of serum mIL-10. CII-specific cell-mediated and humoral immune responses were analyzed by lymph node cell proliferation, cytokine production, and anti-CII Ab responses. Furthermore, because adenoviral vectors have been reported to induce organ dysfunction due to cell-mediated immune responses to the viral Ags, we have also evaluated delayed-type hypersensitivity responses and reactive hepatitis to the systemically delivered adenovirus and whether the IL-10 produced could influence those responses. Sustained suppression of autoimmune arthritis and elevated serum levels of IL-10 were achieved in our study. AdIL-10 treatment reduced cell-mediated immune reactivity, but did not affect humoral responses. Furthermore, IL-10 was able to reduce, but not totally abrogate, adenovirus-induced hepatic inflammation. These findings provide further insights into the diverse interplay of immune processes involved in autoimmune inflammation and the mechanism of cytokine immunotherapy.

Adenoviruses, Human↗
PubMed1999

Phases of alcohol problem prevention research.

We build on precedents from other health research to present a phases model of research for alcohol problem prevention that accommodates the special characteristics of this research. We propose a five-level model, in which research moves along a series of relevant continua: from basic to more and more applied research; from descriptive hypothesis-generating pilot studies to full-fledged, methodologically sophisticated, hypothesis-testing studies; from smaller to larger samples for testing; from greater to lesser control of experimental conditions; from more artificial "laboratory" environments to real-world geographically defined communities; from testing the effects of single prevention strategies to more complex studies of multiple strategies integrated into intervention systems; and from research-driven outcome studies to "demonstration" projects that evaluate the capacity of various types of communities to implement prevention programs based on prior evaluations. The five phases of research are: (1) foundational research to define and determine the prevalence of specific alcohol-involved problems, establish causal factors and processes that yield the specific problems or increase the risk of a problem, and provide the foundations for the development of effective prevention interventions; (2) developmental (preliminary effectiveness) studies to develop and test the likely effectiveness, safety, and costs of new interventions or to assess the effectiveness, safety, and costs of an existing intervention; (3) efficacy studies to determine the effects, safety, and costs of an intervention under optimal conditions of implementation (or availability or enforcement) and acceptance (or adoption at the community, organizational, or group level; or participation, compliance, or adherence at the individual level); (4) effectiveness studies of the real-world effectiveness of preventive interventions with purposeful or natural variation in implementation and acceptance; and (5) demonstration studies of the effects of interventions when widely disseminated. The proposed phases model for alcohol problem prevention research presented herein differs in significant ways from the models established by other National Institutes of Health agencies. Greater emphasis is placed on natural experiments, on methods development along the whole research continuum, on collapsing or combining research phases when appropriate, on recognizing the critical importance of behavioral parameters early as well as late in the research sequence, and on extending the research continuum to embrace diffusion and dissemination (i.e., technology transfer) studies. We also include examples of phased research in existing alcohol studies and a discussion of relevant issues, including cost, special populations, methods, and dissemination. If systematically followed, this model has the potential to contribute to wider testing and dissemination of prevention interventions of known effectiveness.

Alcohol Drinking↗