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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We assessed the number of Langerhans cells (LC) before and after bone marrow transplantation (BMT) in 27 patients in order to study the fate and behavior of these dendritic antigen-presenting cells following allogeneic BMT. LC were identified using monoclonal antibody OKT6 on skin biopsies performed on days - 10, 0, 11, 25, 39, 120, and 365. In a control group composed of 15 healthy adults aged 20-37 yr, the mean number of LC (+/- SEM) was 25.6 +/- 1.17/0.1 sq mm of epidermal surface. Our study shows that pretransplant, the number of LC in patients with aplastic anemia or leukemia was lower than that of controls. The finding of low numbers of LC in patients with untreated aplastic anemia is suggestive of a medullary origin of LC in man. Moreover, during the early posttransplant period, nearly all patients present a severe deficit in LC. This deficit may delay the maturation of their immune system. The number of LC reaches nearly normal levels 4-12 mo after BMT. Finally, we have noted a significant impairment of LC reconstitution in patients with acute graft-versus-host disease (GVHD), providing evidence that this defect may be an important mechanism involved in acute GVHD-related immunodeficiency.
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PMID:Study of Langerhans cells after allogeneic bone marrow transplantation. 636 51

Ocular microangiopathic syndrome including retinal and conjunctival abnormalities is frequently found in patients with human immunodeficiency virus type 1 (HIV-1) disease. Kaposi's sarcoma (KS) is the most frequent neoplasia found in patients with HIV-1 disease. We have recently reported a significant association between conjunctival microvasculopathy and KS in 117 patients with HIV-1 disease. The objective of the present study was to determine whether this association is existent when matched patients with and without KS are compared. A total of 22 matched pairs were obtained under consideration of the absolute CD4+ lymphocyte count, Walter Reed (WR) classification, gender, and serum levels of beta-2-microglobulin and neopterin. Conjunctival microangiopathy was determined for each eye by a standardized rating scale ranging from 0 to 5, allowing a reliable and valid quantification of conjunctival blood-flow sludging. The mean value obtained for conjunctival sludge was 1.8 (SEM, 0.4) for patients without KS and 3.2 (SEM, 0.3) for patients with KS, demonstrating a clinically and statistically significant difference between the two groups (Student's t = 3.0; P = 0.003). This difference was higher when patients with a CD4+ lymphocyte count exceeding 200/microliters were regarded. Similar factors or mechanisms may contribute to HIV-related conjunctival microvasculopathy and KS.
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PMID:Human immunodeficiency virus-related microvasculopathy and Kaposi's sarcoma: a case-control study. 749 37

This report presents results concerning the potential role of negative regulators in hematopoietic suppression observed in human immunodeficiency virus (HIV)-infected long-term cultures (LTC) of human bone marrow cells. Confluent stromal cell layers established from human bone marrow cells were exposed to HIV-1ADA, a monocytotropic strain of HIV-1. A progressive increase in the concentration of HIV-1 p24 antigen in cultures exposed to HIV-1ADA demonstrated that there was a productive infection. Cells from both noninfected and HIV-infected stromal cell layers produced factors that stimulated the proliferation of colony-forming units for granulocytes and macrophages (CFU-GM) from non-infected CD34+ cells. In contrast, when noninfected CD34+ cells were directly cocultured on intact stromal cell layers fewer CFU-GM and burst-forming units for erythroid cells (BFU-E) were detected in HIV-infected LTC than in noninfected LTC. One week after the addition of CD34+ cells, the number of CFU-GM in HIV-infected LTC in six of nine experiments was reduced compared to noninfected control LTC. In those six experiments, the number of CFU-GM was only 53 +/- 5% (SEM) of the number in noninfected LTC. The number of BFU-E in HIV-1-infected LTC was only 46 +/- 5% of the number in noninfected LTC (n = 5). There were fewer BFU-E in HIV-1-infected LTC, whether or not there was a reduced number of CFU-GM. Neutralizing antibody to tumor necrosis factor alpha (TNF-alpha) had no effect on the number of BFU-E in HIV-infected LTC. The number of BFU-E, however, was 2.1 +/- 0.2-fold greater (n = 3) in HIV-infected LTC incubated with neutralizing antibody to interferon-alpha. In HIV-infected LTC with decreased numbers of CFU-GM, the number of CFU-GM was approximately 2-fold greater after incubation of HIV-infected LTC with anti-interleukin-4 (IL-4). The effect of anti-TNF-alpha was variable, and anti-transforming growth factor-beta had no effect on the number of CFU-GM in HIV-infected LTC. After 2 weeks, the number of CFU-GM in HIV-infected LTC incubated with anti-IL-4 and anti-TNF-alpha was 2- to 4-fold greater than in untreated HIV-infected LTC. Antibody treatment did not promote an increase in the number of CFU-GM in noninfected LTC or in LTC in which CFU-GM numbers were not reduced after HIV infection.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Negative regulators may mediate some of the inhibitory effects of HIV-1 infected stromal cell layers on erythropoiesis and myelopoiesis in human bone marrow long term cultures. 754 Jun 43

The cytokines interleukin-12 (IL-12) and IL-4 play important roles in the development of Th1-like (type-1) and Th2-like (type-2) T-cell responses, respectively, and there is evidence that type-1/type-2 T helper imbalances are important in the pathogenesis of human immunodeficiency virus (HIV) disease. With this background, we examined the effects of these cytokines on HIV replication. Neither stimulated HIV replication in fresh peripheral blood mononuclear cells (PBMC). However, in prestimulated PBMC, IL-12, and to a greater extent, IL-4 as well as IL-2, induced production of HIV p24 antigen over 7 days of culture (no cytokine 3,900 x/divided by 1.31 [GM x/divided by SEM] pg/mL; IL-12, 34,300 x/divided by 1.39 pg/mL; IL-4, 283,000 x/divided by 1.14 pg/mL; and IL-2, 328,000 x/divided by 1.31 pg/mL). Neither IL-12- nor IL-4-induced HIV replication was attributable to induction of IL-1, IL-2, tumor necrosis factor (TNF)-alpha, or TNF-beta. Both IL-12- and IL-4-induced HIV replication was associated with selective loss of the CD4+ subset in stimulated cultures. IL-4 stimulated HIV replication in monocyte/macrophages, while IL-12 had little or no effect in these cells. Finally, HIV replication stimulated by IL-12 or IL-4 was inhibited by dideoxynucleosides. Thus, IL-12 and IL-4 enhance HIV replication and HIV-induced cell death in prestimulated PBMC. Through killing of the CD4+ T cells stimulated by these cytokines, this may result in inappropriate type-1/type-2 responses in HIV-infected patients and contribute to their Th1 immunodeficiency.
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PMID:Effects of the Th1 and Th2 stimulatory cytokines interleukin-12 and interleukin-4 on human immunodeficiency virus replication. 771 82

An antisense oligodeoxynucleotide phosphorothioate, namely gene expression modulator 91 (GEM 91), has been demonstrated to have significant anti-human immunodeficiency virus activity in various tissue culture models. The present study was undertaken to determine the pharmacokinetics and tissue distribution of GEM 91 in rats following i.v. bolus administration of 35S-radiolabeled GEM 91. Plasma disappearance curves for GEM 91-derived radioactivity could be described by the sum of two exponentials, with half-lives (mean +/- SEM) of 0.95 (+/- 0.07) and 47.57 (+/- 14.48) hr. Urinary excretion represented the major pathway of elimination of GEM 91, with 26.67 +/- 6.46% (mean +/- SD) of the administered dose excreted within 24 hr and 58.12 +/- 4.36% over 240 hr after GEM 91 administration. Fecal excretion was a minor pathway of elimination of GEM 91 with 1.4 +/- 0.62% (mean +/- SD) of the administered dose excreted over 24 hr and 8.54 +/- 0.64% over 240 hr. A wide tissue distribution of GEM 91 was observed. During the initial 30 min, the highest levels of tissue radioactivity were found in the kidney, liver, spleen, lungs, and heart. Radioactivity was retained over longer time periods in the kidneys, liver, heart, and intestine. Analyses of the extracted radioactivities from plasma, kidney, and liver by gel electrophoresis showed the presence of both intact GEM 91 and degradative products with smaller molecular weights. Radioactivity in urine was found to be degradative metabolites of GEM 91. Based on the experimental data, pharmacokinetic parameters for GEM 91 in each tissue and biological fluids were calculated using computer-based two-compartmental i.v. bolus or absorption models. This study is important not only in providing the basis for future studies of GEM 91 in humans, but also in understanding the pharmacology and toxicology of antisense oligodeoxynucleotide phosphorothioates, in general.
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PMID:Pharmacokinetics and tissue distribution in rats of an oligodeoxynucleotide phosphorothioate (GEM 91) developed as a therapeutic agent for human immunodeficiency virus type-1. 774 65

The risk factors and clinical and laboratory parameters in Pneumocystis carinii pneumonia in patients with Wegener's granulomatosis have not been well characterized. We undertook a retrospective chart review of all patients with a diagnosis of Wegener's granulomatosis and P. carinii pneumonia who were followed at the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. The chart review focused on clinical, laboratory, and roentgenologic evidence of P. carinii pneumonia. Eleven cases of P. carinii pneumonia were diagnosed in some 180 patients with Wegener's granulomatosis, for an overall incidence of approximately 6%. All patients developed P. carinii pneumonia either during the initial course of treatment or during therapy for recurrent Wegener's granulomatosis. All patients were receiving daily glucocorticoids and a second immunosuppressive therapy. Lymphocytopenia was noted in all patients, with a mean +/- SEM total lymphocyte count of 303 +/- 69 cells/microL. All patients tested (10 of 11) were seronegative for human immunodeficiency virus (HIV) infection. Eight presented with worsening chest roentgenograms compared with baseline, whereas three presented with normal chest roentgenograms. We conclude that P. carinii is a common opportunistic pathogen in patients with Wegener's granulomatosis receiving immunosuppressive therapy. Therapeutic immunosuppression (daily glucocorticoids and immunosuppressive agents) and the resultant lymphocytopenia, as well as the lymphocyte and monocyte functional abnormalities caused by glucocorticoids, may be the most likely factors predisposing to P. carinii pneumonia in patients with Wegener's granulomatosis. Based on our data, all patients with Wegener's granulomatosis should be given chemoprophylaxis against P. carinii while they are receiving daily glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pneumocystis carinii pneumonia: a major complication of immunosuppressive therapy in patients with Wegener's granulomatosis. 852 Jul 98

The immune dysfunction in human immunodeficiency virus (HIV) infection is complex and cannot be explained solely on the basis of numerical depletion of T lymphocytes. Inappropriate, uncontrolled activation of the immune system may be involved. In a test of this hypothesis, five HIV-infected children were prospectively treated with prednisone and selected immunologic and virologic indices were analyzed. Subjects had marked T lymphopenia (CD4+ T lymphocytes < 500 cells/ml) and antigenemia (serum p24 antigen > 30 pg/ml) and were free of opportunistic infections. There was a significant drop in serum p24 antigen concentrations from baseline (60.2 +/- 10.1% SEM; P < 0.005) 4 weeks after initiation of prednisone, which returned to baseline concentrations as the prednisone was tapered. Concomitant with this decrease, there was decreased expression of cell surface activation markers (HLA-DR, CD25 (interleukin 2 receptor) and CD26 (Ta-1)) in peripheral T lymphocytes. There was no significant change in either T lymphocyte subset numbers or mitogen and antigen-specific lymphoproliferation. A regulatory dysfunction of the immune system, allowing inappropriate activation of T lymphocytes, may be involved in the pathogenesis of HIV disease, and further studies involving selective immunosuppression in HIV disease are warranted.
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PMID:Immunologic and virologic effects of glucocorticoids on human immunodeficiency virus infection in children: a preliminary study. 790 39

Alveolar macrophages (AMs) harvested from 32 HIV-infected patients with respiratory problems (opportunistic pulmonary infections, n = 12; other lung disease, n = 20) and 13 healthy controls were stained with a panel of 15 monoclonal antibodies directed against surface antigens implicated in cell function. Antigen expression was quantified by flow cytometry and expressed as relative linear median fluorescence intensity (RLMFI). On AMs of patients, as compared with controls, there was a significant enhancement of HLA DP (12.1 +/- 1.5 vs 6.5 +/- 0.9, p = 0.01, M +/- SEM, RLMFI units), CD11b (3.4 +/- 0.5 vs 1.7 +/- 0.4, p = 0.014), CD11c (8.9 +/- 1.0 vs 4.8 +/- 0.8, p = 0.0046), CD14 (2.1 +/- 0.3 vs 1.0 +/- 0.2, p = 0.0009), and CD33 (1.7 +/- 0.1 vs 1.0 +/- 0.2, p = 0.0093). No significant differences could be established for HLA-DR (36.9 +/- 5.8 vs 30.9 +/- 7.5, NS), HLA-DQ (3.4 +/- 0.3 vs 3.1 +/- 0.6, NS), CD54 (1.9 +/- 0.3 vs 1.2 +/- 0.1, NS), CD13 (2.5 +/- 0.6 vs 1.5 +/- 0.3, NS), CD36 (1.4 +/- 0.2 vs 0.9 +/- 0.3, NS), CD71 (10.3 +/- 1.9 vs 8.9 +/- 1.8, NS), CD25 (0.8 +/- 0.0 vs 0.9 +/- 0.1, NS), 27E10 (1.1 +/- 0.1 vs 0.8 +/- 0.3, NS), RM3/1 (1.9 +/- 0.4 vs 1.5 +/- 0.4, NS), and CD4 (1.5 +/- 0.3 vs 1.0 +/- 0.0, NS). The expression of CD14 and CD11b, but not of HLA class II antigens and CD71, was increased in the smaller cell population compared with the larger, thus suggesting monocyte recruitment. The increased expression of HLA-DP, CD11c, CD14, and CD33 on the patients' AMs was independent of smoking habits. The degree of immunodeficiency as indicated by the absolute peripheral CD4 count, the character of HIV-related pulmonary disease, and the prophylactic use of pentamidine or zidovudine did not significantly modify the antigen expression pattern. It is concluded that HIV infection may lead, most probably indirectly, to enhanced expression of surface antigens by local upregulation and/or recruitment of monocytes from the peripheral circulation. The functional significance of enhanced marker expression requires further clarification.
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PMID:Expression of surface markers on alveolar macrophages from symptomatic patients with HIV infection as detected by flow cytometry. 818 14

Tumor necrosis factor alpha (TNF-alpha), a cytokine produced during the host defense against infection, is associated with fevers, weakness, and progressive weight loss. Thalidomide inhibits the synthesis of TNF-alpha both in vitro and in vivo and may have clinical usefulness. We therefore initiated a pilot study of thalidomide treatment in patients with human immunodeficiency virus type 1 (HIV-1)-associated wasting with or without concomitant infection with tuberculosis. Thirty-nine patients were randomly allocated to treatment with either thalidomide or placebo in a double-blind manner for 21 days. Thirty-two patients completed the study. In patients with concomitant HIV-1 and tuberculosis infections, thalidomide therapy was associated with a reduction in both plasma TNF-alpha levels and HIV-1 levels. No significant reduction in either TNF-alpha or HIV- 1 levels was observed in patients with HIV-1 infection only. During the study period, patients receiving thalidomide treatment (n=16) showed a significant weight gain (mean +/- SEM: 6.5 +/- 1.2%; p<0.02) relative to placebo-treated patients (n=16). Patients with simultaneous HIV-1 and tuberculosis infections experienced a higher mean weight gain during thalidomide treatment than the group of patients with HIV-1 infection only. The results of this pilot study suggest that thalidomide may have a clinical role in enhancing weight gain and possibly reducing TNF-alpha and HIV-1 levels in patients with HIV-1 and concomitant mycobacterial infections.
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PMID:The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection. 860 61

Photosensitivity disorders have been reported in human immunodeficiency virus (HIV)-infected patients, often as the initial manifestation of the disease. The objective of this study was to evaluate whether the HIV-infected population demonstrates increased sensitivity to ultraviolet B (UVB) radiation. Minimal erythema dose values to UVB (MED-B) of 57 consecutive HIV-infected patients were compared to those of a control group of 57 consecutive patients with skin diseases, who were otherwise healthy and had no risk factors for HIV infection. MED-B determinations were performed in all individuals prior to the initiation of phototherapy for treatment of skin disease. None of the patients had a history of photosensitivity. Furthermore, the mean levels of the highest UVB doses received by each group during the treatment courses were compared. The mean age of the HIV-infected cohort was 43 years (range 26-61 years). The mean MED-B for this group was 82.8 +/- 3.8 (SEM) mJ/cm2. The mean age of the control group was 45 years (range 24-77 years), and their mean MED-B was 81.0 +/- 3.8 (SEM) mJ/cm2. After 12 weeks of treatment, one HIV-infected patient developed photosensitivity associated with a decreased MED-B value. The mean level of the highest UVB doses received by the HIV-infected group [427.5 +/- 67.2 (SEM) mJ/cm2] was lower than that received by the control group [640.8 +/- 65.9 (SEM) mJ/cm2], since HIV-infected patients received fewer treatments (mean: 34.7 treatments per patient) than the patients in the control group (mean: 65.6 treatments per patient). These data indicate that the HIV-infected patient population, without history of photosensitivity, does not show increased sensitivity to UVB light as determined by MED-B values.
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PMID:Skin response to ultraviolet B light in patients infected with human immunodeficiency virus. 873 12


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