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Dynamics of the control of body pattern in the development of Xenopus laevis. II. Timing and pattern in the development of single blastomeres (presumptive lateral halves) isolated at the 2-cell stage.

Xenopus embryos have been selected in which the first cleavage plane is tending strongly to correspond with that of bilateral symmetry for the future larval pattern. The two blastomeres produced by this cleavage have been separated and allowed to develop as reciprocal pairs of presumptive lateral-half isolates. The early development and the time course of the gastrulation movements, and the qualitative and quantitative aspects of larval mesodermal patterns, have been studied in relation to synchronously fertilized controls. The result is restoration of bilateral symmetry for developmental potential, and production of a pair of small gastrulae and larvae with qualitatively complete body plans but 50% of control cell numbers each (see Kageura & Yamana, 1983). Most commonly, however, the resulting small patterns deviate from the normal range in their proportions in at least one of two ways. The notochord territory is rarely, if ever, under-represented (i.e. notochords contain at least 50% control cell numbers) but it is frequently over-represented, in some cases approximating that of control whole embryos. Reciprocal pairs of isolates thus tend, on average, to produce more notochordal tissue than they would have if developing normally. Secondly, the balance of cell population sizes assigned to somites up and down the axis is altered so that relatively anterior members of the series are less scaled down than those in trunk and tail regions. The mesodermal plan developed by a lateral-half isolate is thus characteristically intermediate between that of a small, harmonious larva (the proportional presumptive fates of the materials, apart from loss of bilaterality), and that of the mosaically developing presumptive dorsoanterior cell pair from the 4-cell stage, discussed in the previous paper. A minority of the lateral isolates does develop a harmonious and thus well-regulated body plan, however, and the normality or otherwise of the schedules of gastrulation timing in isolates seems a good predictor of their morphogenetic performance in this respect. The results are discussed as informing us about the dynamics of the interactions, prior to gastrular stages, that underlie the normal mesoderm development.

Animals↗

CD16 cross-linking blocks rearrangement of the TCR beta locus and development of alpha beta T cells and induces development of NK cells from thymic progenitors.

Mouse thymocytes normally develop into T lymphocytes, but the embryonic thymus also contains precursor cells capable of developing into NK cells. Here, we describe conditions that induce pro-T cells to develop into NK cells. CD16 is expressed on thymic pro-T cells. We observed that CD16 cross-linking during culture of embryonic thymic organs suppressed rearrangement of the TCR beta locus (but did not inhibit TCR gamma locus rearrangement). Rearrangement of the TCR beta locus is normally required for development to the CD4+CD8+, and this development was also suppressed by CD16 cross-linking. The ability of CD16 cross-linking to block alpha beta T cell development was not attributable to toxic effects, but rather was accompanied by promotion of development into NK cells, identified based on molecular and functional criteria. These results suggest that common lymphoid precursors can respond to environmental signals to commit to the alpha beta T vs NK developmental pathways.

Animals↗

The WHO Collaborative Study of Neoplasia and Steroid Contraceptives: the influence of combined oral contraceptives on risk of neoplasms in developing and developed countries.

A hospital-based case-control study was conducted in eight developing and three developed countries to determine whether use of combined oral contraceptives alters risks of various cancers. An observed trend of increasing risk of invasive cervical cancer with duration of use may not represent a causal relationship and is the subject of further study. Decreased risks of ovarian and endometrial carcinomas in users likely indicate a protective effect of oral contraceptives, the degree of which was similar in developing and developed countries. A small increase in risk of breast cancer in recent and current users was found to be somewhat greater in developing than developed countries. Both causal and non-causal interpretations of this finding have been offered. No associations were found between oral contraceptives and in situ cervical, hepatocellular, cholangio, or gallbladder carcinomas, or uterine sarcomas; but the power of this study to detect alterations in risks of these neoplasms in long-term users was low.

Breast Neoplasms↗

The burden of pneumococcal disease among adults in developed and developing countries: what is and is not known.

The burden of pneumococcal disease among adults in developed countries is neither widely known nor appreciated. The incidence of pneumococcal pneumonia is uncertain because a precise diagnosis cannot be obtained for most patients. Population-based data on invasive pneumococcal disease (e.g., bacteraemia and meningitis) suggest an annual incidence in all developed countries of > or =15-20 cases per 100,000 persons of all ages and > or =50 cases per 100,000 elderly adults (> or =65 years). In developing countries there are no population-based data on the burden of pneumococcal disease among adults. Studies of high risk groups, hospital-based studies, vaccine efficacy trials, extrapolations from surveillance of "native populations" in developed countries, and demographic studies in developing regions all suggest a high burden of disease. The broad variation in these estimates, however, indicates that better studies are needed. Increased use of pneumococcal vaccines among adults in all countries will depend on better scientific and public understanding of the burden of pneumococcal disease. In developing countries, intensive community-based studies of the impact of pneumococcal disease, or, alternatively, a "vaccine probe" approach, in which a population is vaccinated and the reduction in pneumonia is compared with that in a control population, could give more accurate estimates of the burden of disease and of the potential effectiveness of pneumococcal vaccination among adults.

Adult↗

Diarrhea in developed and developing countries: magnitude, special settings, and etiologies.

Diarrheal diseases are major causes of morbidity, with attack rates ranging from two to 12 or more illnesses per person per year in developed and developing countries. In addition, diarrheal illnesses account for an estimated 12,600 deaths each day in children in Asia, Africa, and Latin America. The causes of diarrhea include a wide array of viruses, bacteria, and parasites, many of which have been recognized only in the last decade or two. While enterotoxigenic Escherichia coli and rotaviruses predominate in developing areas, Norwalk-like viruses, Campylobacter jejuni, and cytotoxigenic Clostridium difficile are seen with increasing frequency in developed areas; and Shigella, Salmonella, Cryptosporidium species, and Giardia lamblia are found throughout the world. The rational management of infectious diarrhea requires the highly selective use of laboratory tests for these varied etiologic agents, depending on the clinical and epidemiologic setting. The purpose of this review is to provide an overview of the magnitude, special settings, and etiologies of diarrhea endemic to developed and developing countries. This information permits a practical approach to the diagnosis and management of common diarrheal illnesses in different settings.

Acquired Immunodeficiency Syndrome↗

Safe drinking water production in rural areas: a comparison between developed and less developed countries.

At the fundamental level, there are remarkable parallels between developed and less developed countries in problems of providing safe drinking water in rural areas, but of course, they differ greatly in degree and in the opportunities for resolution. Small water supplies frequently encounter difficulty accessing sufficient quantities of drinking water for all domestic uses. If the water must be treated for safety reasons, then treatment facilities and trained operating personnel and finances are always in short supply. Ideally, each solution should be sustainable within its own cultural, political and economic context, and preferably with local personnel and financial resources. Otherwise, the water supply will be continuously dependent on outside resources and thus will not be able to control its destiny, and its future will be questionable. The history of success in this regard has been inconsistent, particularly in less developed but also in some developed countries. The traditional and ideal solution in developing countries has been central water treatment and a piped distribution network, however, results have had a mixed history primarily due to high initial costs and operation and maintenance, inadequate access to training, management and finance sufficient to support a fairly complex system for the long term. These complete systems are also slow to be implemented so waterborne disease continues in the interim. Thus, non-traditional, creative, cost-effective practical solutions that can be more rapidly implemented are needed. Some of these options could involve: small package central treatment coupled with non piped distribution, e.g. community supplied bottled water; decentralized treatment for the home using basic filtration and/or disinfection; higher levels of technology to deal with chemical contaminants e.g. natural fluoride or arsenic. These technological options coupled with training, technical support and other essential elements like community commitment provide opportunities that should be explored both for rural small communities and in rapidly growing periurban areas in developing countries.

Developed Countries↗

Developing and maintaining of hemophilia programs in developing countries.

There are elements key to the success of developing and maintaining hemophilia programs in developing countries. Health care providers who are dedicated champions of hemophilia care are essential. Their training through the WFH International Hemophilia Training Centers brings them in contact with modern comprehensive care as well as establishes collegial linkages with treaters in developed centers. Affordable, safe, viral free coagulation products are essential for an effective hemophilia program. Developing essential for an effective hemophilia program. Developing countries may have to use intermediate purity products because of economic considerations, but technologies must be used which reduce the risk of viral contamination. Successful programs also result from linking to hemophilia programs with national health care initiatives. Hemophilia health care must be recognized as a priority within the developing country's health care system.

Developing Countries↗

Telemedicine and developing countries. A report of study group 2 of the ITU Development Sector.

While there are significant potential advantages and benefits from telemedicine, the evidence of its cost-effectiveness and sustainability is meagre. This is because much of the telemedicine activity so far has been in the form of pilot projects of demonstrations in universities and hospitals with subsidized funding from government or other sources. The number of self-sustaining, commercial applications of telemedicine is still very small. Telemedicine undoubtedly yields cost savings in certain circumstances, but often the savings and benefits accrue to those who do not have to pay for the service. Thus, few service providers have found a way to recover their costs (and make a profit) from those to whom they provide their service. Even fewer countries have actually budgeted for the provision of telemedicine as a service widely available to their citizens. Nevertheless, with the rapidly declining cost in hardware and telecommunications, the level of interest and the corresponding activity in telemedicine is rising rapidly. Most of the telemedicine experience to date has been in the industrialized world. It is apparent that the first requirement of developing countries is for more information about telemedicine, what it is, and how it might be able to help solve some of the shortages in medical and health care. Given the potential of telemedicine to facilitate the provision of medical information and health care in rural areas, it seems useful for developing countries to undertake pilot projects in order to evaluate its potential and cost-benefits. The results of such pilot projects could be part of the development of a national health for all policy which takes telemedicine into account. In view of the other priorities of developing countries, especially those of the least developed countries, financing telemedicine activity is likely to remain a challenge for some time to come. Funding from external donor agencies may well be necessary, but local commitment and participation in pilot projects is essential if the project is to have a chance of success. As telemedicine requires a multidisciplinary approach, the active participation of telecommunication operators must be assured. Despite some false starts in the deployment of telemedicine as a continuing service to the general population--as opposed to a few well-to-do clients--telemedicine has great potential to improve access to health care and to contain costs in developing countries.

Computer Communication Networks↗

Development of catecholaminergic neurons in the pond snail, Lymnaea stagnalis: I. Embryonic development of dopamine-containing neurons and dopamine-dependent behaviors.

The embryonic development of the catecholaminergic system of the pond snail, Lymnaea stagnalis, was investigated by using chromatographic and histochemical methods. High performance liquid chromatography suggested that dopamine was the only catecholamine present in significant concentrations throughout the embryonic development of Lymnaea. Dopamine first became detectable at about embryonic stage (E) 15 (15% of embryonic development) and then increased in amount during early development to reach about 120-140 fmol per animal by around E40. Dopamine content remained stable during mid-embryogenesis (E40-65), increased slowing for the next couple of days, and then increased rapidly to culminate at about 400 fmol per animal by hatching. The detection of aldehyde- and glyoxylate-induced fluorescence and of tyrosine hydroxylaselike immunoreactivity indicated that the first catecholaminergic cells appeared in the late trochophore or early veliger stage of embryonic development (E32-35). The paired perikarya of these transient apical catecholaminergic (TAC) neurons were located beneath the apical plate, remained outside of the central ganglia during embryogenesis, and no longer contained detectable catecholamines close to hatching. TAC neurons bore cilia on the ends of short processes that penetrated the overlying epithelium; their long processes branched repeatedly under the ciliated apical plate. Several smaller catecholaminergic cells first appeared in the anterior margin of the foot at a stage when the embryos began to metamorphose from the veliger form (E55). Similar bipolar cells later appeared in the tentacle and lips. The axons of all of these small peripheral cells projected centrally and terminated within the neuropil of different central ganglia. Central catecholaminergic neurons, including RPeD1, differentiated only after metamorphosis was complete (E75). Development of locomotor, respiratory, and feeding behaviors correlated with maturation of catecholaminergic neurons, as indicated by histology and chromatography.

Animals↗

EDTA stimulates cleavage stage bovine embryo development in culture but inhibits blastocyst development and differentiation.

Culture of bovine zygotes in medium SOFaa supplemented with 100 microM EDTA significantly increased cleavage rates during the first 72 hr of development compared to development in SOFaa. However, continued culture in the presence of EDTA for a further 72 hr (total of 6 days of culture) resulted in significantly reduced development to the morulae/blastocyst and blastocyst stages compared to culture without EDTA. Highest rates of development to the morulae/blastocyst stage (56.5%) and to the blastocyst stage (43.2%) were achieved when zygotes were cultured for 72 hr with EDTA before transfer to medium SOFaa without EDTA. Resultant blastocysts also had significantly increased blastocyst cell number and ICM cell number compared to those cultured without EDTA in the first 72 hr. EDTA was shown to inhibit glycolytic activity of the cleavage stage embryo, thereby preventing the premature stimulation of glycolysis and enhancing development. However, EDTA should not be used for the later stage embryo as the inhibition of glycolysis reduces energy production at the blastocyst stage and significantly inhibits inner cell mass development.

Animals↗

Clonal analysis of corn plant development. I. The development of the tassel and the ear shoot.

The development of the tassel and the ear shoot has been investigated in corn (Zea mays L.). X irradiation of dry kernels and seedlings heterozygous for anthocyanin markers or for factors altering tassel and ear morphology results in the formation of clones (sectors) from cells of the apical meristem. Most tassels develop from 4 +/- 1 cells of the mature embryo. The expression of ramosa-1, tunicate, tassel seed-6, and vestigial is cell autonomous in the tassel. These genes act late in development and modify the developmental fate or decision of an individual clone and not of the whole group of cells producing a tassel. The ear shoot develops from lineages of one to three cells derived each from the L-I (outmost cell layer) and L-II (second cell layer) of the apical meristem. Typically the clones start in the ear shoot (in the husks and possibly in the cob), extend upward in an internode, continue along the margin of the leaf sheath or leaf blade at the node above, and terminate in this or the next higher leaf. The separation of lineages for ear shoot and internode occurs in the period around 13 days after sowing. The analysis of clonal boundaries shows that a small number of embryonic cells become isolated in their developmental capacity. This commitment process appears to be analogous to the process of compartmentation in the imaginal disks of fruit flies. The extent of proliferation of individual cells within a group of highly flexible and any particular clone does not generate a specific part of a tassel or an ear shoot. There must be cellular communication between various clones so that the overall size and morphology of an organ remain normal and more or less fixed. Thus the process of development in plants is also highly regulative in nature and shares many features in common with development in fruit flies.

Anthocyanins↗

Blastomere development after embryo biopsy: a new model to predict embryo development and to select for transfer.

One of the most important and unsolved problems in in-vitro fertilization is to decide which embryos are more suitable to implant and therefore should be transferred. We analysed the in-vitro development of isolated biopsied blastomeres and compared it to the development of the original embryo, in order to find a relationship that could show the embryo's potential future development and so increase implantation rates. A total of 66 normally fertilized human embryos were biopsied at the 6- to 10-cell stages. At day 6, blastomeres were counted by nuclear labelling. A total of 33 embryos (50%) reached the blastocyst stage. Of the isolated blastomeres, 63% divided and 53% cavitated over 3 days in culture. Of the blastomeres taken from embryos that developed to the blastocyst stage, 88% divided, 79% cavitated, 76% divided and cavitated and 9% neither divided nor cavitated. In those from arrested embryos, 39% divided (P < 0.001), 21% cavitated (P < 0.001), 15% divided and cavitated (P < 0.001) and 55% neither divided nor cavitated (P < 0.001). Blastomeres biopsied from embryos that reached the blastocyst stage showed a significantly higher proportion of division and cavitation than those originated from arrested embryos. Culture of the isolated blastomeres can demonstrate those embryos more likely to develop to the blastocyst stage and that are probably more suitable to implant. Cryopreserving biopsed embryos and culturing blastomeres would increase implantation rates. Embryos can then be selected according to the blastomere development and thawed for transfer in a future cycle.

Biopsy↗

Development of a culture medium (BECM-3) for porcine embryos: effects of bovine serum albumin and fetal bovine serum on embryo development.

Media are available that can deliver modest porcine embryonic development from a single-cell zygote to the blastocyst stage. However, few embryos develop to hatched blastocysts by Day 7 in vitro, indicating deficiencies in media that inhibit early embryonic development. A defined culture medium, Beltsville Embryo Culture Medium (BECM-3), was developed to support porcine zygote development to the blastocyst stage. When fetal bovine serum was added by late Day 5 (late morula/early blastocyst stage), 80% of total embryos cultured from Day 2 developed into hatched blastocysts by Day 8. There was also a significant increase in the mean cell number of blastocysts and hatched blastocysts when culture was performed in BECM-3-based media in the absence of BSA fraction V. These studies provide a chemically defined foundation for elucidating key developmental components of preimplantation pig embryos.

Animals↗

Transfer of regulatory toxicology from developed to developing countries.

Over the past two decades, industrialized nations have addressed and attempted to solve the problems of chemical risk through the development of laws, government and private organizations, and specialized manpower. Developing nations are now recognizing that the presence of toxicants in the environment, foods, consumer products, and the workplace can seriously affect human health, the ecology, international relations, and economic activities such as trade and tourism. The design and implementation of regulatory programs in developing countries is hampered by lack of government and public concern, pressure of more urgent needs, vested interests of industry, and lack of adequately trained professionals. These factors have allowed developed nations to sell abroad drugs, pesticides, and other chemicals considered too hazardous for use in their own countries. Conversely, products from developing nations must comply with rigorous standards for acceptance by developed nations. Some of these problems would be lessened by agreement on international chemical control guidelines. Multilateral availability of complete information about chemicals is essential. The coordination of this effort should be in the hands of international organizations and reinforced by bilateral agreements between countries. Appropriate public education and economic incentives at the national level would help in enforcing regulatory toxicology.

Developing Countries↗

The relative contribution of prematurity and fetal growth retardation to low birth weight in developing and developed societies.

The relative proportions of prematurity (less than or equal to 2,500 gm less than 37 weeks' gestation) and intrauterine growth retardation-low birth weight (IUGR-LBW) (less than or equal to 2,500 gm, greater than or equal 37 weeks' gestation) among total LBW infants were studied in 11 regions in the developed world and 25 developing areas where known gestational ages and birth weights were reported. In developing countries a straight correlation was observed between total LBW incidence and IUGR-LBW incidence rates (r = 0.95; b = 0.98; p less than 0.001); in contrast, prematurity was not significantly associated with total LBW incidence. Data from the developed population showed results exactly opposite to those described for developing areas. Therefore, when the incidence of LBW is higher than 10%, it is almost exclusively due to the increase in IUGR-LBW infants, while prematurity remains almost unchanged (5% to 7%). When LBW incidence is less than 10% (mean=6%), preterm infants represent the major component of LBW. Environmental factors susceptible to changing socioeconomic conditions may be responsible for the observed differences.

Birth Weight↗