Microsurgical renal transplant models in rats: a comparison of four anastomotic techniques.
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Biomedical subjects
Publications and source records attributed to J Chin.
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The short-term forecasting of future AIDS cases has been attempted by statistical extrapolations of the observed curve of reported AIDS cases. In areas where such reporting is very incomplete or has only recently started, extrapolation is not possible and an epidemiologically-based forecasting model has been developed to estimate the annual number of AIDS cases which may have occurred and to project the annual number and distribution of AIDS cases for up to ten years. This model, which relies on the current understanding of the epidemiology and natural history of HIV infections and on the available HIV serologic survey data, is used to provide estimates and short-term projections of AIDS cases for the USA, Europe, Africa and the world. Because of the very long (mean of 8-9 years) incubation period between HIV infection and the development of AIDS, new cases over the next five years will be mostly derived from persons who became infected with HIV in or before 1987. WHO has estimated that 5-10 million persons worldwide were infected with HIV in 1987. Based on the lower estimate of 5 million, the cumulative number of AIDS cases which can be projected for the end of 1991 is over one million, and for the mid-to-late 1990s could reach 2 to 3 million. HIV/AIDS will therefore be an increasing public health problem throughout the world. Health care systems everywhere will have to be strengthened to respond to this large toll of disease and death due to AIDS.
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An analysis of the distribution of HIV-infections in different countries permits to distinguish 3 different patterns. Type 1 occurs in North America, Western Europe, parts of South America, Australia and New Zealand. Type 2 is found in Africa, in sub-Saharan regions and in the Caribbean sea. Type 3 prevails in Eastern Europe, in North Africa, in the Middle East, in Asia, in most of the Pacific and in many parts of Latin America. 138 countries have reported 100.410 AIDS-cases until June 30, 1988. Actually, it can be assumed, that by now approximately 5 million people are infected with HIV, of these about 1.5 million are women. As of mid 1988 over 200.000 persons have clinically manifested AIDS, in addition, 150.000 more cases are expected to occur in the remainder of 1988 and this figure will grow to over a million cases by the early 1990ies. The impact of the AIDS-pandemic on the social and economic structures will grow to very large dimensions in some countries.
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The acquired immunodeficiency syndrome (AIDS) and infection with the human immunodeficiency virus type 1 (HIV-1) constitute a worldwide public health problem. Whereas in Europe and in most of the Americas transmission of HIV-1 has occurred predominantly among homosexual men and intravenous drug abusers, in Africa a distinct epidemiologic pattern has emerged that indicates that HIV-1 infection is mainly heterosexually acquired. Heterosexual transmission appears to be increasing in some parts of Latin America and the Caribbean, and possibly in the United States. In addition to HIV-1, at least one other human retrovirus, namely HIV-2, has been implicated as a cause of AIDS in Africa and Europe. Factors that influence heterosexual transmission of HIV-1 include genital ulcerations, early or late stages of HIV-1 infection in the index case, and possibly oral contraception and immune activation. The rate of perinatal transmission is enhanced when the mother's illness is more advanced. AIDS and HIV-1 infection may have a significant impact not only on public health, but also on the demography and socioeconomic conditions of some developing countries. Programs for the prevention and control of AIDS should be an immediate priority in all countries.
The subcellular location of IL-1 beta was determined using a postsectioning immunoelectron microscopic method on ultrathin frozen sections of human monocytes stimulated with LPS. This methodology permits access of antibody probes to all sectioned intracellular compartments, and their visualization at high resolution. Staining was performed with a rabbit antibody that specifically recognized amino acids 197-215 in the 33-kD IL-1 beta precursor molecule, followed by affinity-purified goat anti-rabbit IgG conjugated to 10 nm colloidal gold particles. Approximately 90% of the IL-1 beta antigens were localized in the ground substance of the cytoplasm at 4 or 20 h after activation, when both intracellular and extracellular accumulation of IL-1 beta was well underway. No significant IL-1 beta staining was observed on the outer cell membrane, nor within the lumens of the endoplasmic reticulum (ER), the Golgi apparatus, or secretory vesicles. In contrast, lysozyme was localized in the ER and dense secretory granules using these methods. Our results suggest that IL-1 beta is not anchored on the plasma membrane, and that its secretion occurs by a novel mechanism that does not use a secretory leader sequence, nor the classical secretory pathway involving the ER and Golgi apparatus.
Infections with the human immunodeficiency virus(es) (HIV) are likely to have a profound impact on the health of those in many parts of Africa over the next several decades. If there are adverse interactions between HIV infections and the endemic tropical diseases the overall impact of the HIV epidemic will be worse than that predicted based on observations on the natural history of HIV infections in developed countries. With the exception of tuberculosis, the evidence for such interactions is presently lacking, but this may be largely due to the dearth of informative studies. In this paper we outline the kinds of epidemiological studies required to investigate such interactions and discuss some of the problems associated with the investigations.
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The activation of T lymphocytes requires their stimulation via clonotypic antigen receptors as well as nonantigen-specific costimulators, the best defined of which is the cytokine interleukin 1 (IL-1). Recent studies have shown that murine CD4+ helper T lymphocytes consist of two nonoverlapping subsets that selectively utilize interleukin 2 (IL-2) or interleukin 4 as their autocrine growth factors and are called Th1 and Th2 cells, respectively. We now show that IL-1 functions as a costimulator for the proliferation of Th2 but not of Th1 clones and only Th2 cells express high-affinity receptors for IL-1. Secretion of autocrine growth-promoting lymphokines by Th1 and Th2 cells occurs after stimulation via the antigen receptor-CD3 complex and is neither dependent on nor affected by IL-1. These findings suggest that the activation of T lymphocytes can be divided into two stages, lymphokine secretion and proliferation, and only proliferation requires costimulators such as IL-1. Moreover, the prevailing view that IL-1 functions as a costimulator by inducing secretion of IL-2 or expression of IL-2 receptors may not be generally applicable, because IL-2-producing Th1 clones do not express receptors for IL-1 and are insensitive to this cytokine.
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In this report the binding of recombinant human interleukins 1 alpha and 1 beta (rIL-1 alpha and rIL-1 beta) to primary cultures of human rheumatoid synovial cells is measured and compared to the concentrations of these mediators required for stimulation of PGE2 production by these same cells. The average concentration of IL-1 alpha required for half-maximal stimulation of PGE2 was 4.6 +/- 1.5 pM (+/- SEM) (n = 6), whereas for IL-1 beta half-maximal stimulation was observed at a concentration of 1.3 +/- 0.24 pM (n = 6). Both direct and competitive binding experiments were performed. In direct binding experiments, IL-1 alpha bound with a Kd of 66 pM (n = 1), while IL-1 beta bound with a Kd of 4 pM (n = 2). In competitive binding experiments, IL-1 alpha inhibited binding of 125I-IL-1 alpha with a Ki of 33-36 pM (n = 2) and binding of 125I-IL-1 beta with a Ki of 51-63 pM (n = 2). IL-1 beta inhibited binding of 125I-IL-1 alpha with a Ki of 2-3 pM (n = 2) and binding of 125I-IL-1 beta with a Ki of 7 pM (n = 2). The binding data were best fit by a model specifying a single class of receptors with homogeneous affinity for either IL-1 alpha or IL-1 beta and with an abundance of 3,000-14,000 sites per cell. Autoradiography showed that the vast majority of the synoviocytes within the cultures possessed IL-1 receptors. Comparison of biological response curves with the binding curves indicates that the observed receptors exhibit sufficiently high affinity to mediate the response of human synoviocytes to low picomolar concentrations of IL-1 alpha and IL-1 beta.
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The two pathways for the biosynthesis of phosphatidylcholine, by way of phosphocholine and by methylation of phosphatidylethanolamine, in wild-type yeast (Saccharomyces cerevisiae) and in the yeast mutant GL7 have been compared. The mutant requires for growth a sterol, unsaturated fatty acids, and methionine. The uptake of labeled choline or labeled methionine and their conversion to phosphatidylcholine were determined in both cell types. The activities of the major enzymes for both pathways were assayed in vitro. We find that the methylation pathway is predominant in both wild-type and mutant cells though the overall activity of the choline pathway is lower in the yeast mutant. The methionine analogue ethionine inhibits the growth of the mutant more strongly than growth of wild-type yeast. Ethionine, while a powerful inhibitor of phosphatidylcholine synthesis by methylation, stimulates the choline pathway in both cell types.
Human immunodeficiency virus (HIV) is one of the most virulent infectious agents ever encountered. This virus, estimated to kill up to a half of those infected, has spread to more than 1 million Americans. There is no safe and effective treatment. Nor is there a vaccine. From our understanding of HIV transmission, further spread of the virus can be stopped by the use of various techniques. The combined use of education-motivation-skill building, serologic screening, and contact tracing/notification could eliminate or substantially reduce transmission. To accomplish this reduction an immense concerted effort by physicians, public health practitioners, business, and community organizations is required to get across the simple prevention messages. Those messages are: Any sexual intercourse (outside of mutually monogamous or HIV antibody-negative relationships) must be protected with a condom. Do not share unsterile needles or syringes. All women who may have been exposed should seek HIV-antibody testing before becoming pregnant and, if positive, avoid pregnancy. Only through a concerted, vigorous, and sustained prevention program that deals frankly with this problem will those individuals at risk be reached and motivated to take personal responsibility to protect themselves. Without such an effort, acquired immunodeficiency syndrome will continue to kill ever-increasing numbers of Americans.
Although complementary DNA (cDNA) encoding human interleukin 1 beta (IL 1 beta) have been cloned in several laboratories, there are as yet no data demonstrating that recombinant IL 1 beta (rIL 1 beta) molecules expressed from such cDNA are faithful, fully active replicas of the native protein secreted by human monocytes. To this purpose, cDNA sequences corresponding to the exact NH2-terminus and amino acid sequence of mature, monocyte-derived human IL 1 beta were placed under control of the inducible trp-lac (TAC) fusion promoter and were expressed in E. coli strain JM105. rIL 1 beta was purified to homogeneity by high pressure liquid chromatography (HPLC). Yields of 10 to 20 mg of rIL 1 beta/liter/10(11) cells were obtained. Purified rIL 1 beta was then compared in a number of biochemical and biologic assays to purified native IL 1 beta. Native and rIL 1 beta co-migrated on SDS-polyacrylamide gels as 17.5 kd polypeptides and reacted with specific polyclonal antisera raised to three synthetic peptides of human IL 1 beta in immunoblot experiments. Amino acid sequence analysis of rIL 1 beta showed that the native amino terminus, an ALA residue, was faithfully maintained. Purified native and rIL 1 beta co-chromatographed on reverse-phase HPLC. Specific biologic activities of rIL 1 beta were indistinguishable from those of the native protein in murine thymocyte and human dermal fibroblast proliferation assays, with half-maximal stimulation occurring at concentrations of 25 pM in the murine thymocyte assay and 2 pM in the human dermal fibroblast assay. Similarly, native and rIL 1 beta competed equally well for high affinity IL 1 receptor binding sites, each exhibiting a Ki of 20 pM on MRC-5 human embryonic lung fibroblasts. These observations indicate that E. coli efficiently expresses large quantities of rIL 1 beta, which emulates exactly the properties of the native protein.