Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus type 1 (HIV-1) envelope protein gp41 mediates viral fusion with human host cells. In this study we show that N36, a synthetic peptide derived from the N-terminus of gp41, induced directional migration and calcium mobilization in human monocytes and neutrophils. The activity of N36 on phagocytes was pertussis toxin sensitive, suggesting involvement of a Gi-coupled seven-transmembrane receptor(s). Since high concentrations of the bacterial chemotactic peptide fMet-Leu-Phe (fMLF) partially desensitized the calcium mobilizing activity of N36 in phagocytes, we postulated that N36 might use a low-affinity fMLF receptor. By using cells stably expressing fMLF receptor FPR or FPRL1, we demonstrate that N36 uses FPRL1 as a functional receptor. Our results suggest that HIV-1 gp41 may contain a fragment(s) that activates the innate host immune cells through FPRL1. Since the activation of FPRL1 in monocytes has been shown to heterologously desensitize chemokine receptors, the reduced phagocyte response to chemoattractants seen in AIDS patients may be attributed, at least in part, to heterologous desensitization.
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PMID:N36, a synthetic N-terminal heptad repeat domain of the HIV-1 envelope protein gp41, is an activator of human phagocytes. 1096 42

The alpha chemokine receptor CXCR4 and its only characterized chemokine ligand, stromal cell-derived factor-1 (SDF-1), are postulated to be important in the development of the B-cell arm of the immune system. In addition, CXCR4 is a critical coreceptor in support of viral entry by T-cell line tropic strains (X4) of the Human Immunodeficiency Virus Type 1 (HIV-1), viral variants which predominate in some infected individuals in end stage disease. SDF-1 can block X4-tropic HIV-1 infection of CD4+ target cells in vitro, and allelic variants of the human gene encoding SDF-1 in vivo correlate with delayed disease progression. Therefore, CXCR4 may be an appropriate target for therapeutic intervention in acquired immunodeficiency syndrome (AIDS), and knowledge of the pharmacology of SDF-1 binding to its cognate receptor will be important in the interpretation of these experiments. We report here a Kd derived using a competition binding assay of 4.5 nM for CXCR4 endogenously expressed on peripheral blood monocytes and T-cells. This affinity is similar to that which SDF-1 exhibits when binding to endogenous CXCR4 on an established immortal Jurkat T-cell line as well as recombinant CXCR4 transfected into Chinese Hamster Ovary (CHO) cells. We also demonstrate that the determined affinity of SDF-1 for CXCR4 is reflective of its ability to induce a CXCR4-mediated signal transduction in these different cell types. Furthermore, using Bordetella pertussis toxin, we observe that high affinity binding of SDF-1 to CXCR4 is independent of the G-protein coupled state of the receptor, as uncoupling of G-protein did not lead to the appearance of measurable low affinity SDF-1 binding sites. Moreover, binding affinity and receptor number were unaffected by uncoupling for both recombinant and endogenously expressed CXCR4. Thus, SDF-1 is novel among agonist ligands of G protein-coupled receptors in that it appears to have equal affinity for both the G protein-coupled and uncoupled states of CXCR4.
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PMID:The CXCR4 agonist ligand stromal derived factor-1 maintains high affinity for receptors in both Galpha(i)-coupled and uncoupled states. 1110 27

CD8+ cytolytic T lymphocytes (CTL) are almost certainly an important component of a potentially protective immune response to HIV. To test the ability of pertussis toxin (PT) to deliver an HIV-derived major histocompatibility complex (MHC) class I peptide for CTL stimulation, we constructed a fusion of the gp120 P18-I10 CTL epitope with a genetically detoxified derivative of PT (PT9K/129G) and assayed this fusion for its ability to stimulate a gp120-specific CTL response in vitro and in vivo. Antigen-presenting cells incubated with this fusion protein were lysed by P18-I10-specific CTL in vitro and this activity was shown to be MHC class I restricted. The activity was inhibited by brefeldin A but was not inhibited by proteasome inhibitors, possibly because PT undergoes retrograde intracellular transport through the Golgi apparatus to the endoplasmic reticulum and delivers epitopes directly to nascent class I molecules. Mice immunized intraperitoneally with a single dose of the fusion protein without adjuvant raised a strong gp120-specific CTL response in the spleen. This CTL response was dependent on (1) the dose of fusion administered, (2) the fusion of the epitope with the toxin (since coadministration of peptide and toxin gave no response), and (3) the activity of CD8+ cells. These data demonstrate that this detoxified derivative to PT, which is already a component of a licensed vaccine for humans, could represent a useful vaccine vector molecule for stimulation of HIV-specific CTL responses.
AIDS Res Hum Retroviruses 2001 Jun 10
PMID:Stimulation of HIV gp120-specific cytolytic T lymphocyte responses in vitro and in vivo using a detoxified pertussis toxin vector. 1142 23

The dissemination of T cell hybridomas to multiple nonhematopoietic tissues is blocked by pertussis toxin, suggesting the involvement of a chemokine. To study whether this chemokine is SDF-1, we employed a strategy proposed previously for gene therapy of AIDS, whereby the SDF-1 receptor CXCR4 (also a coreceptor for HIV) is retained in the endoplasmic reticulum (ER) and fails to reach the cell surface. We transfected SDF-1, carrying an ER retention sequence, into a T cell hybridoma. This altered chemokine is retained in the ER, where it binds CXCR4 and prevents the latter protein from reaching the surface. These cells failed to migrate toward SDF-1 or to invade fibroblast monolayers, although they could still migrate toward thymus and activation-regulated chemokine (TARC) and invade TARC-treated monolayers. Furthermore, the ability of the transfected cells to disseminate to multiple organs upon intravenous injection into mice was abolished. This dissemination reflects the in vivo migration patterns of activated and memory T cells into nonhematopoietic tissues, which is thus likely to depend on CXCR4. Attempts to block CXCR4 function as a therapy for AIDS may affect this migration with consequences for T cell function. Our results also suggest a decisive role for CXCR4 in the dissemination of hematopoietic malignancies expressing this receptor.
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PMID:Retention of CXCR4 in the endoplasmic reticulum blocks dissemination of a T cell hybridoma. 1145 80

In the first half of the 20th century, improved living conditions, preventive measures, vaccines and antibiotics led to a marked reduction in morbidity and mortality from infectious diseases. It was predicted that the conquest of all infectious diseases was imminent. However, 50 years later, in 1999, they were still the major cause of disease worldwide, and caused nearly one third of all deaths (a total of 55.9 million). The eradication of smallpox in the 1970s and the approaching eradication of poliomyelitis represent major achievements. The prevalence of measles, pertussis and tetanus neonatorum is also markedly reduced, but still 1.5 million children in developing countries die each year because of lack of vaccines. Malaria and tuberculosis are re-emerging. Tuberculosis and HIV/AIDS are the diseases with known aetiology that cause most deaths, altogether 5 million each year. Respiratory and gastrointestinal infections cause 6.5 million deaths annually. Infections in the immunocompromised host have become a "trade mark" of today's advanced medicine. Almost every year, new diseases related to new micro-organisms are described; over the last 30 years, approximately 40 new diseases/micro-organisms have been diagnosed. Among the best known are HIV/AIDS, peptic ulcer caused by Helicobacter pylori, Legionnaires' disease, borreliosis (Lyme disease), hepatitis C, gastroenteritis caused by rotavirus, and Ebola haemorrhagic fever. Antimicrobial resistance development of micro-organisms has become one of the major health problems worldwide; a number of preventive measures are being introduced.
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PMID:[Microorganisms strike back--infectious diseases during the last 50 years]. 1180 14

The World Health Organization EPIMODEL computer program has projected that in 1993, there will be 41,023 cumulative cases of AIDS and 642,897 cumulative HIV infections among Nigerian adults. 1.2% of pregnant Nigerian women are reported to be HIV seropositive, 20-30% of whom can be expected to transmit HIV to their offspring. There are therefore many cases of pediatric HIV infection and AIDS in Nigeria. Infants and children can also be infected with HIV through the receipt of HIV-contaminated blood or blood products during transfusion, the use of unsterilized syringes and needles, and the use of contaminated instruments by traditional healers for circumcision, scarification, and tattoos. Vertical transmission, however, is the mode through which pediatric AIDS is most commonly spread. Preventive measures should therefore be directed toward promoting HIV risk reduction behaviors. Diagnosing AIDS and securing the laboratory confirmation of HIV infection are problematic in poor tropical countries like Nigeria. HIV-infected infants of unimpaired immunological status should be immunized with measles, injectable diphtheria/tetanus/pertussis, and inactivated polio virus vaccines. However, measles vaccine must not be given to an already immunocompromised patient. Likewise, BCG vaccination and oral live poliovaccine should not be given to HIV-infected children.
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PMID:Paediatric AIDS in Nigeria. 1229 67

This supplement to The Family Planning Manager explains the meaning and importance to reproductive health of commonly used national- and local-level evaluation indicators. The first section of the publication contains a table of sample reproductive health indicators for national- and local-level use in the reproductive health areas of family planning (FP), maternal health, infant health, infant nutrition, adolescent health, and reproductive tract infection (RTI), sexually transmitted disease (STD), and HIV infection services. A description is provided of the context for the use of each of the indicators. Information is also provided on how the data generated by the local-level indicators can be used to assess and improve program performance. The second section of the publication explains how each major national-level indicator is calculated (contraceptive prevalence rate; age-specific fertility rates; total fertility rate; percentage approving of FP; percentage desiring a child within 2 years; percentage of unmet need for FP; maternal mortality ratio; maternal morbidity ratios by cause; percentage of women attended prenatally at least once by trained personnel; percentage of infants fully immunized with diphtheria, pertussis, and tetanus vaccine; infant mortality rate; percentage of low birth weight infants; median length of birth intervals; percentage of infants severely underweight; percentage of adolescents who have begun childbearing; female secondary or primary school enrollment percentage; STD prevalence rates; HIV/AIDS prevalence rate; non-sexually transmitted RTI prevalence rates) and explains that local-level indicators can be calculated in the same way with the substitution of local-level population figures.
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PMID:Guide to national and local reproductive health indicators. 1229 32

This document presents an interview with Dr. Anthony Fauci on the development of a new generation of vaccines to prevent and possibly eradicate a legion of deadly diseases ranging from tuberculosis to AIDS. Infections that have caused major devastations in the world today include tuberculosis, malaria, schistosomiasis, filariasis, pneumococcal pneumonia, influenza, AIDS, and Ebola. Agencies should be making sure that the basic research base in microbiology, immunology, antimicrobials, and vaccinology is at the very highest level. The integration of research efforts between countries depends on collaboration between the investigators of home countries with foreign investigators. Among new developments in vaccinology are an acellular pertussis vaccine for pertussis/whooping cough (an extremely contagious disease that causes death), DNA immunization (a new technique applicable to all types of diseases), and transgenic plants for immunization against hepatitis, pertussis, and polio. As of now, AIDS in Western countries has declined, while in Africa and Asia its spread has accelerated. Combination therapy for AIDS has had a profound impact on the level of the virus in the body; however, the treatment is still vague. The good news with regard to AIDS is that education is having an impact; this is exemplified by the situation in Thailand, where the government together with nongovernmental organizations and the military has begun a crash education campaign regarding prostitutes and the use of condoms. Progress is being made in the search for better vaccine candidates. AIDS-like epidemics involving new diseases are bound to emerge at some future point, though, given the long-term historical trend.
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PMID:New drugs, new vaccines, new diseases. An interview with Dr. Anthony Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID). 1234 52

We investigated 18 AIDS hearts (5 with and 13 without cardiomyopathy) by using immunocytochemistry and computerized image analysis regarding the roles of HIV-1 proteins and tumor necrosis factor ligands in HIV cardiomyopathy (HIVCM). HIVCM and cardiomyocyte apoptosis were significantly related to each other and to the expression by inflammatory cells of gp120 and tumor necrosis factor-alpha. In HIVCM heart, active caspase 9, a component of the mitochondrion-controlled apoptotic pathway, and the elements of the death receptor-mediated pathway, tumor necrosis factor-alpha and Fas ligand, were expressed strongly on macrophages and weakly on cardiomyocytes. HIVCM showed significantly greater macrophage infiltration and cardiomyocyte apoptosis rate compared with non-HIVCM. HIV-1 entered cultured neonatal rat ventricular myocytes by macropinocytosis but did not replicate. HIV-1- or gp120-induced apoptosis of rat myocytes through a mitochondrion-controlled pathway, which was inhibited by heparin, AOP-RANTES, or pertussis toxin, suggesting that cardiomyocyte apoptosis is induced by signaling through chemokine receptors. In conclusion, in patients with HIVCM, cardiomyocytes die through both mitochondrion- and death receptor-controlled apoptotic pathways.
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PMID:Cardiomyocytes undergo apoptosis in human immunodeficiency virus cardiomyopathy through mitochondrion- and death receptor-controlled pathways. 1237 43

In 2001 surveillance system of infectious diseases in Poland remained unchanged. New cases of infectious diseases were recorded in 103 positions including intoxications. Tuberculosis and sexually transmitted infections were registered in separate systems. Influenza was the most frequently reported infectious disease with 576,449 cases, 63.9% less then in the previous year. The next most numerous were foodborne infections, which were reported in 24,393 cases, including 19,788 cases of infections caused by Salmonella sp. An increase in incidence was observed in the following diseases: viral hepatitis type A, rubella, measles and pertussis. Also the number of recorded cases of Lyme boreliosis and tickborne encephalitis were higher then in 2000. Incidence of AIDS remained within the range recorded during the last few years. In 2001 further drop in incidence of viral hepatitis type B was observed reaching the level of 6.2 per 100,000. It was the result of implemented comprehensive program of prophylactic measures, which brought incidence of this disease from the highest in Europe down to the level close to European average. Infectious diseases contributed to 0.75% of deaths. The most frequent cause of death among infectious diseases was tuberculosis and its sequels (1,061 cases). 13 cases of death due to tuberculosis occurred in people below 30 years of age.
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PMID:[Infectious diseases in Poland in 2001]. 1292 4


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