Cyclosporine-induced autologous graft versus host disease: assessment of cytolytic effector mechanisms and the V beta T-cell receptor repertoire.
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Antigens, CD↗
Biomedical subjects
L Morris
Publications and source records attributed to L Morris.
Comparative study of safety and efficacy of IUD insertions by physicians and nursing personnel in Brazil.
To assess whether trained nursing personnel could provide IUD services as safely and effectively as physicians in Brazil, an experimental study was conducted at the main clinic of the Center for Research on Integrated Maternal and Child Care in Rio de Janeiro. From November 1984 through April 1986, a total of 1,711 women who requested IUD insertion at the clinic were randomly assigned to have a Copper-T 200 IUD inserted by one of the clinic's 11 physicians or 13 nurses. All of the physicians and nursing staff members who provided these services had taken the Center's standard clinical family planning training course. Of 860 insertions attempted by the physicians and nurses, 1.3% and 3.3%, respectively, were unsuccessful. Statistically, this difference was very significant (P < 0.01). Also, mainly because the cervix was small and undilated, nulliparous women had a relatively high insertion failure rate of 8.0%, as compared to 1.5% for primiparas and 1.0% for multiparas. The overall rate of complications at insertion was 1.8%, these complications including diaphoresis, vomiting, syncope, cervical laceration, and one case of perforation of the uterus; no significant difference was found between the complication rates for insertions performed by physicians as compared to nurses. However, 9.0% of the study subjects reported severe pain during IUD insertion, with significantly higher percentages reporting pain if the IUD was inserted by a physician, or if the subject was nulliparous, had preinsertion symptoms, or had a history of pelvic inflammatory disease (PID) or sexually transmitted disease (STD). It was also found that the nurses had a dramatically high insertion failure rate (11.6%) with nulliparous subjects, while the physicians' failure rate with such subjects was a significantly lower 3.4%. No significant difference was found in the groups served by nurses and physicians with regard to postinsertion complaints or termination of use within 12 months of insertion. These findings suggest that future training, besides preparing nursing personnel in IUD insertion, should emphasize preparation in taking the client's medical history and diagnosing existing medical symptoms that could be associated with IUD insertion complications. In addition, if a nulliparous woman requests an insertion, it should be performed by a physician or more experienced nursing staff member with close medical supervision. Because of high rates of reported pain at insertion, such women, as well as those with medical symptoms associated IUD insertion complications and those with a history of PID or STD, should be considered candidates for extra care and counseling.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Gene for familial psoriasis susceptibility mapped to the distal end of human chromosome 17q.
A gene involved in psoriasis susceptibility was localized to the distal region of human chromosome 17q as a result of a genome-wide linkage analysis with polymorphic microsatellites and eight multiply affected psoriasis kindreds. In the family which showed the strongest evidence for linkage, the recombination fraction between a psoriasis susceptibility locus and D17S784 was 0.04 with a maximum two-point lod score of 5.33. There was also evidence for genetic heterogeneity and although none of the linked families showed any association with HLA-Cw6, two unlinked families showed weak levels of association. This study demonstrates that in some families, psoriasis susceptibility is due to variation at a single major genetic locus other than the human lymphocyte antigen locus.
Alleles↗
DNA distortion and nucleation of local DNA unwinding within sigma-54 (sigma N) holoenzyme closed promoter complexes.
The sigma N (sigma 54) RNA polymerase holoenzyme has the distinctive property of binding to promoters to form a closed promoter complex, which only isomerizes to the open complex when acted upon by an enhancer binding activator protein. We probed promoter complexes that form between sigma N and its holoenzyme with the conformationally sensitive footprinting reagents ortho-copper phenanthroline, potassium permanganate, and diethylpyrocarbonate. Results from these experiments indicate that the contacts sigma N makes at the -12 promoter element are necessary to promote a local DNA distortion immediately adjacent to this promoter element when the holoenzyme but not sigma N alone binds promoter DNA. Complexes in which this local distortion is not detected are not activatable, and the altered DNA conformation is diminished in the activated complex. We propose that a barrier to open complex formation in the sigma N holoenzyme closed complex is at some step or steps after the initial nucleation of DNA strand separation, which is detected as an altered DNA conformation stably maintained within the closed complex. Thus the activator protein may promote a conformational change in the sigma N holoenzyme to allow propagation of the altered DNA conformation, probably local unwinding, which we propose is necessary for formation of the melted DNA state, characteristic of the open promoter complex.
Bacterial Proteins↗
Unintended pregnancy and sex education in Chile: a behavioural model.
This study analysed factors associated with unintended pregnancy among adolescent and young adult women in Santiago, Chile. Three variations of a behavioural model were developed. Logistic regression showed that the effect of sex education on unintended pregnancy works through the use of contraception. Other significant effects were found for variables reflecting socioeconomic status and a woman's acceptance of her sexuality. The results also suggested that labelling affects measurement of 'unintended' pregnancy.
Adolescent↗
Ricin-resistant mutants of Leishmania major which express modified lipophosphoglycan remain infective for mice.
Glycosylation variants of the virulent Leishmania major clone V121 were generated by mutagenesis with N-methyl-N-nitroso-N-nitroguanidine and selected using the galactose-specific lectin Ricinus communis II (RCA II). Three mutants, 4B9, 1D1 and 1C12, which failed to bind RCA II, were found to have an altered expression of lipophosphoglycan (LPG), a molecule implicated in the attachment to host macrophages and survival within the phagolysosome. There were differences in the antigenicity, molecular weight and localization of LPG from mutant parasites as compared to V121. Expression of gp63, a surface molecule also implicated in attachment to macrophages, was unaltered. All 3 mutants caused disease when injected into genetically susceptible BALB/c mice but lesions developed at a much slower rate than those caused by the virulent V121 clone. This slow rate of lesion development did not correlate with promastigotes' ability to invade macrophages in vitro. Karyotype analysis showed that there was a reduction in the size of chromosome band number 2 in all 3 mutants. The differences in LPG and chromosome band 2 were retained by mutant clones following passage through mice, suggesting that these phenotypes are stable. Although the mutant parasites were infective and caused lesions, the changed structure of the LPG appeared to influence the virulence of the parasites.
Agglutination↗
Intravenous injection of irradiated Leishmania major into susceptible BALB/c mice: immunization or protective tolerance.
It is well established that BALB/c mice can be protected from fatal infection with Leishmania major by prophylactic intravenous (i.v.) immunization with irradiated parasites. Protection is critically dependent on the route of injection with i.v. injection being protective and subcutaneous injection not protective. We used this BALB/c-L. major model system to investigate this phenomenon. We analyzed quantitatively the parasite-specific, CD4+ T cell mediated immune responses by limiting dilution. Subcutaneous vaccination resulted in priming of CD4+ precursor T cells, whereas i.v. vaccination was ineffectual. Moreover, i.v. injection prevented the increase in the number of specific precursor cells induced by infection of normal mice during the first weeks post-challenge with virulent parasites. We show here that this was not due to the elimination of the virulent challenge parasites as a result of immunity nor to inefficient antigen presentation of the irradiated organisms after i.v. injection. The data presented here suggest that i.v. injection results in tolerization rather than immunization. Tolerization as a mechanism of host protection is consistent with earlier observations that transient immunosuppression results in cure of L. major infection in BALB/c mice. Transfer of antigen presenting cells (APC) isolated from spleens of mice injected previously with irradiated parasites mimicked to some extent the effect of i.v. immunization with irradiated parasites. The possible involvement of these APC in decreasing the parasite-specific T cell response is discussed.
Animals↗
Sexual behavior of young adults in Latin America.
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Adolescent↗
Dysspondyloenchondromatosis in the newborn. Report of four cases.
Dysspondyloenchondromatosis is a rare form of generalised enchondromatosis with hypoplastic/dysplastic changes in the lower thoracic and upper lumbar spine. The disease presents at birth as neonatal dwarfism and is characterised later in life by marked shortening of stature, unequal length of the extremities and early development of kyphoscoliosis. We report four newborn babies--three boys and a girl--with dysspondyloenchondromatosis, who had skeletal survey performed shortly after birth. The condition can be established in the newborn, as the radiographic examination (skeletal survey) shows diagnostic radiographic findings.
Child↗
Surveillance for pregnancy and birth rates among teenagers, by state--United States, 1980 and 1990.
PROBLEM/CONDITION: In the United States in 1990, there were an estimated 1 million pregnancies and 521,826 births among women ages 15-19 years. Rates of teenage pregnancy and birth rates by state in 1990 exceeded those in most developed countries. An estimated 95% of teenage pregnancies are unintended (i.e., they occur sooner than desired or are not wanted at any time). REPORTING PERIOD COVERED: This report summarizes and reviews surveillance data for pregnancies, abortions, and births among women ages 15-19, 15-17, and 18-19 years reported by CDC for 1980 and 1990. DESCRIPTION OF SYSTEM: Data for births and abortions were reported to state health departments and other health agencies and sent to CDC. The data from each state included the total number of births and abortions by age and race/ethnicity. RESULTS: Data in this report indicate that pregnancy rates by state among U.S. teenagers ages 15-19 years have changed little since 1980. Moreover, many states have reported increases in birth rates that are probably related to concurrent decreases in abortion rates. Pregnancy rates range from 25 to 75 per 1,000 for 15- to 17-year-olds and from 92 to 165 per 1,000 for 18- to 19-year-olds. INTERPRETATION: States with low rates of teenage pregnancy or birth may have developed and used prevention strategies directed at the needs of both younger and older teenagers; these programs may serve as models for other states where birth rates have remained high or have increased since 1980. ACTIONS TAKEN: CDC will continue to conduct surveillance of and analyze data for pregnancies, abortions, and births among teenagers to monitor progress toward national goals and to assist in targeting program efforts for reducing teenage pregnancy.
Abortion, Legal↗
Characterization of T-cell clones generated from skin of patients with psoriasis.
BACKGROUND: The infiltrating cells in psoriasis include a subpopulation of autoreactive T cells. OBJECTIVE: The aim of this study was to further characterize skin-infiltrating T lymphocytes in patients with psoriasis. METHODS: Forty-five T-cell clones were generated from skin biopsy specimens from two patients. RESULTS: Phenotypic studies on 25 of 45 clones revealed that 19 (76%) of the clones were CD4+, 5 (20%) were CD8+, and 1 (4%) clone was CD4- and CD8-. Twenty-three clones were stained for identification of T-cell receptors. Twenty-two clones expressed alpha/beta T-cell receptors and one clone (CD4-/CD8-) expressed no T-cell receptor. Nineteen clones (42%) were autoreactive with no restriction to class I or class II HLA antigens. By contrast, proliferation of two of the seven clones was inhibited by class I monoclonal antibody, whereas proliferation of four of seven clones was inhibited by class II monoclonal antibody. CONCLUSION: These data suggest that skin-infiltrating lymphocytes in patients with psoriasis may recognize HLA-associated molecules, perhaps the peptide of the HLA groove. The recognition of the peptide is presumably inhibited when monoclonal antibody is bound to the HLA molecule.
CD4 Antigens↗
The fertility decline in developing countries.
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Adult↗
Resistance of BALB/c mice to Leishmania major infection is associated with a decrease in the precursor frequency of antigen-specific CD4+ cells secreting interleukin-4.
BALB/c mice are highly susceptible to infection with the protozoan parasite Leishmania major and develop a chronic fatal disease. They can, however, be manipulated to resist disease and this has been shown to correlate with increased expression of IFN-gamma mRNA and the absence of IL-4 mRNA in the draining lymph nodes and spleens of these animals. Here we show that anti-IL-4 or anti-CD4 treatment of BALB/c mice resulted in a reduction in the size of the lesion and in the number of parasites in the draining lymph nodes compared with untreated mice. The precursor frequency of CD4+ T cells proliferating in response to Leishmania antigens in vitro in the treated animals was not significantly different from untreated animals. Analysis of the lymphokines secreted by the clonal progeny of these cells showed that the precursor frequency of IL-4 secreting clones was at least 10-fold lower in animals treated with either mAb. However, there was no reciprocal increase in the precursor frequencies of IFN-gamma secreting clones. Comparisons of the total number of precursors of specific CD4+ cells secreting IFN-gamma showed that anti-CD4-treated animals, which are resistant to disease, had considerably fewer for the first 6 weeks than untreated mice with chronic disease. Protection of BALB/c mice was therefore associated with a reduction in the numbers of precursors of cells secreting IL-4 without a concomitant increase in the number of precursors of IFN-gamma secreting cells.
Animals↗
Interleukin-4 but not gamma interferon production correlates with the severity of murine cutaneous leishmaniasis.
For murine cutaneous leishmaniasis, data to date suggest a correlation between the presence of gamma interferon (IFN-gamma) and resistance in C57BL/6 mice and the presence of interleukin-4 (IL-4) and disease in BALB/c mice. In this study, 13 inbred strains of mice covering the range of susceptibility to disease were infected with Leishmania major to determine whether the subsequent expression of IFN-gamma or IL-4 is a reliable indicator of cure or progressive disease. The presence of IL-4 and IFN-gamma mRNAs in the draining lymph nodes was examined 9 weeks after infection, when differences in disease severity became obvious. There were large differences in the levels of IL-4 mRNA among the different strains, whereas IFN-gamma mRNA was detected at similar levels in all strains. The levels of IL-4 mRNA correlated with lesion score, with susceptible and intermediate strains containing up to 100-fold more than any of the resistant strains. Differences in the levels of IFN-gamma mRNA were within only a fourfold range, with significant overlap among susceptible, intermediate, and resistant strains. Similarly, the levels of IFN-gamma secreted in vitro by lymph node cells from infected mice in response to L. major antigens were within a 10-fold range for most strains, and there was no correlation with lesion score. Analysis of Leishmania-specific antibody levels revealed a correlation between immunoglobulin G1 (IgG1) titers and lesion score, consistent with the role of IL-4 as a switch factor for IgG1. In contrast, there was no correlation between IgG2a titers and lesion score, supporting the notion that IFN-gamma synthesis (which promotes IgG2a production) is not correlated with disease state. These data suggest that along the spectrum of murine cutaneous leishmaniasis, IL-4 is a reliable indicator of disease, but IFN-gamma is not prognostic for resistance.
Animals↗
The ultimate system.
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Decision Making, Organizational↗
Health care fraud: a primer on the schemes and the tools to fight health care fraud.
As the national debate over health care reform moves forward, one issue with which policy makers must grapple is the percentage of health care dollars lost to fraud and abuse. The General Accounting Office estimates that as much as ten percent of total health care dollars are lost to the inappropriate, and in some cases criminal, practices of health care providers. This article discusses the characteristics of the health care industry that make it particularly susceptible to abuse and then reviews the efforts by the Office of Inspector General, Department of Health and Human Services, to deter and punish those who defraud the federal health care programs.
Adult↗
Measuring adolescent sexual behaviors and related health outcomes.
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Adolescent↗
Changes in the precursor frequencies of IL-4 and IFN-gamma secreting CD4+ cells correlate with resolution of lesions in murine cutaneous leishmaniasis.
Limiting dilution analysis was used to estimate the frequency of clonogenic Ag-specific CD4+ T lymphocytes in draining lymph nodes of mice over the course of infection with Leishmania major, and to measure the production of IL-2, IL-3, IL-4, IFN-gamma, and TNF by the resultant clones. Infection of both genetically susceptible BALB/c ("non-healer") and resistant C57BL/6 ("healer") mice resulted in at least a fourfold increase in the frequency (to about 0.3%) and at least a 10-fold increase in the total number of lymph node CD4+ cells that formed clones when cultured with L. major Ag in vitro. At 1 wk after infection, the majority of clones from BALB/c mice secreted IL-4 (precursor frequency 0.15%) and fewer secreted IFN-gamma (0.05%); this pattern remained constant for at least 8 wk after infection. In C57BL/6 mice, however, a high precursor frequency of IL-4-secreting clones was measured in the first 1 to 2 wk when the mice had lesions, but resolution of infection was associated with a decrease in the frequency of IL-4-secreting clones (from 0.13% at 2 wk to 0.03% at 4 wk) and an increase in the frequency of IFN-gamma-secreting clones (from 0.08% to 0.22%). At all stages of infection, most clones from either mouse strain secreted IL-3 and very few secreted TNF. Analysis of PCR-amplified cDNA from draining lymph nodes of infected mice also revealed that IL-4 and IFN-gamma mRNA were expressed in both mouse strains early in infection. IL-4 mRNA was the major species at 2 and 6 wk after infection in BALB/c mice, but declined relative to IFN-gamma mRNA over this time in C57BL/6 lymph nodes. Precursor frequency estimates of lymphokine-secreting CD4+ cells in draining lymph nodes therefore correlated with lymphokine expression patterns in vivo. Analysis of a panel of individual short term clones derived from mice 1 wk after infection revealed marked heterogeneity in lymphokine production patterns. In BALB/c mice, 49% secreted IL-4 without IFN-gamma, 18% secreted IFN-gamma without IL-4, and 14% secreted both IL-4 and IFN-gamma. Similarly in C57BL/6 mice, 39% secreted IL-4, 20% secreted IFN-gamma, and 17% secreted both lymphokines. Many of the clones also produced IL-3 and/or IL-2. Together the data suggest that both IL-4 and IFN-gamma are synthesized early in infection of susceptible and resistant mice as assessed by mRNA and precursor frequency analyses.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗