Human immunodeficiency virus disease epidemiology and nosocomial infection.
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Biomedical subjects
Publications and source records attributed to S M Friedman.
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Dendritic cells are a small subset of human blood mononuclear cells that are potent stimulators of several T cell functions. Here we show they are 10-50-fold more potent than monocytes or B cells in inducing T cell responses to a panel of superantigens. Furthermore, dendritic cells can present femtomolar concentrations of superantigen to T cells even at numbers where other antigen-presenting cells (APCs) are inactive. Although dendritic cells express very high levels of the major histocompatibility complex products that are required to present superantigens, it is only necessary to pulse these APCs for 1 hour with picomolar levels of one superantigen, staphylococcal enterotoxin B, to maximally activate T cells. Our results suggest that very small amounts of superantigen will be immunogenic in vivo if presented on dendritic cells.
RATIONALE AND OBJECTIVES: A study was designed to determine whether plain films, used as a screening modality for magnetic resonance imaging (MRI), could reliably detect intraorbital metallic foreign objects. METHODS: In the first experiment, 20 metal particles were placed in five human cadaver orbits. Routine orbital plain film series and computed tomography (CT) were obtained, randomized, and interpreted blinded by three experienced radiologists. RESULTS: The threshold size of particle detection for CT (0.07 mm3) was lower than for plain films (0.12 mm3). Placing metal particles in artificial and true vitreous demonstrated that all particles moved under a magnetic field at 1.5 T. When human globes were exposed to industrial tools (grinder, bandsaw, air hose, etc.), no metal objects penetrated the sclera. CONCLUSIONS: Plain films can be used as a low-cost, low-radiation screening procedure for high-risk patients with occupations involving metal work. CT should be used for patients with a history of eye trauma from other causes.
Recognized posterior ciliary artery occlusion combined with central retinal artery occlusion is relatively uncommon. Clinical and experimental evidence of combined occlusions appear to support a nasal and temporal distribution for the posterior ciliary arteries in most cases. A case involving a patient in whom the posterior ciliary arteries divided superiorly and inferiorly to supply the region of the macula is reported. Some of the more common variations in the distribution of the posterior ciliary arteries are discussed. Clinicians should be aware that the territorial divisions of the choroidal perfusion in the macula may be horizontally based.
From July 1987 to June 1988, 1030 pregnant women with hepatitis B were reported to a New York City surveillance program. Among 832 infants under follow-up, the coverage rates for combined hepatitis B immune globulin and vaccine doses 1, 2, and 3 were 84%, 77%, and 59%, respectively. Infants covered by Medicaid and uninsured Black and Hispanic infants were significantly less likely to be completely vaccinated. An estimated 160 cases of chronic hepatitis B infection were prevented among infants enrolled in the program. Strategies are needed to improve vaccine coverage among hard-to-reach groups.
Microbial superantigens (SA) activate a significant portion of the T cell repertoire based on their dual avidity for MHC class II antigens and T cell receptor (TCR) epitopes common to products of one or several TCR beta chain variable gene families. While SA that induce massive T cell proliferation and cytokine secretion have been implicated in clinical syndromes characterized by shock and generalized immunosuppression, SA activation of a more restricted T cell response may also have significant, perhaps immunostimulatory, effects on the immune system. To investigate this issue, we measured 3H-thymidine incorporation and polyclonal IgM and IgG secretion by normal human peripheral blood mononuclear cells (PBMC) cultured with a panel of microbial SA, including the Staphylococcus aureus-derived SA, SEA, SEB, SEC-1, SEC-2, SEC-3, SEE, TSST-1, and the Mycoplasma arthritidis-derived SA, MAM. The S. aureus-derived SA induce vigorous proliferation by PBMC, while optimal MAM-induced proliferation is significantly lower in magnitude. In all 12 subjects tested, mitogenic concentrations of MAM reproducibly stimulate unselected PBMC to secrete polyclonal IgM and IgG. In contrast, the S. aureus-derived SA induce Ig production only in cultures containing isolated B cell populations and either very low numbers of untreated autologous T cells, larger numbers of X-irradiated autologous T cells, or very low concentrations of the SA. No difference in the activation of helper (CD4) versus suppressor/cytotoxic (CD8) T cells by MAM and the S. aureus-derived SA was noted. Taken together, these data suggest that MAM's capacity to induce B cell differentiation correlates with its induction of a relatively weak proliferative response by unselected human T cells. MAM-like SA, when encountered in vivo, may result in a significant perturbation of the human immune system and potentially contribute to clinical syndromes characterized by immunostimulation and hypergammaglobulinemia.
A posterior chamber intraocular lens was transsclerally sutured to the ciliary sulcus with the aid of liquid perfluorophenanthrene (Vitreon). This vitreous substitute facilitates the procedure and reduces the possibility of damage to the retina.
Diabetic retinopathy is a common cause of blindness in the adult population in the United States. Ophthalmologists now have laser and surgical treatment modalities available that can significantly decrease the risk of blindness in the diabetic population. The American Academy of Ophthalmology, through its Diabetes 2000 program, is making a national effort to educate all physicians who care for diabetic patients to recognize the problem and to be aware of the therapies available to prevent blindness.
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While all known microbial superantigens are mitogenic for human peripheral blood lymphocytes (PBL), the functional response induced by Mycoplasma arthritidis-derived superantigen (MAM) is unique in that MAM stimulation of PBL consistently results in T cell-dependent B cell activation characterized by polyclonal IgM and IgG production. These immunostimulatory effects of MAM on the humoral arm of the human immune system warranted a more precise characterization of MAM-reactive human T cells. Using an uncloned MAM reactive human T cell line as immunogen, we have generated a monoclonal antibody (mAb) (termed C1) specific for the T cell receptor V beta gene expressed by the major fraction of MAM-reactive human T cells, V beta 17. In addition, a V beta 17- MAM-reactive T cell population exists, assessed by MAM, induced T cell proliferation and cytotoxic T cell activity. mAb C1 will be useful in characterizing the functional properties of V beta 17+ T cells and their potential role in autoimmune disease.
Microbial superantigens (SA), bound to human B cell surface MHC class II molecules, have been shown to promote direct, "cognate" interaction with SA-reactive autologous Th cells, resulting in polyclonal Ig production. To investigate the potential for microbial SA to support Th cell-dependent, Ag-specific antibody responses, we have extended our studies to the murine system. BALB/c Th cell lines (TCL), specific for either the Mycoplasma arthritis-derived SA or the Staphylococcus aureus-derived toxic shock syndrome toxin-1) were generated. These TCL cells are SA-specific, functionally noncross-reactive, and utilize distinct TCR V beta gene families. Coculture of SA-reactive TCL cells and syngeneic B cells bearing the relevant SA results in B cell proliferation and polyclonal IgM and IgG production. In contrast, Ag-specific (SRBC-specific) antibody-forming cells are only generated in cultures that also contain SRBC. Thus, microbial SA-mediated Th-B cell interactions induce both polyclonal B cell activation and provide selective help for the proliferation and/or differentiation of B cells that have encountered specific Ag. In additional studies, we determined that the in vivo administration of toxic shock syndrome toxin-1 to young, athymic (nude) BALB/c mice results in SA binding to splenic B cells, rendering these B cells effective stimulators of and targets for SA-reactive helper TCL cells. Taken together, these results demonstrate that microbial SA mediate productive Th-B cell interactions analogous to those that occur during allospecific Th-B cell interactions in vitro and GVHD in vivo. These findings are consistent with the hypothesis that microbial SA represent environmental factors that may trigger autoimmune disease in the genetically susceptible host.
We examined two patients with monocular frosted branch angiitis. The patients were young and healthy; they rapidly developed severe visual loss with thick, white sheathing of the retinal veins and responded promptly to systemic corticosteroids. The fluorescein angiograms showed late leakage from the retinal veins, without evidence of stasis or occlusion. Frosted branch angiitis can be either a unilateral or a bilateral condition. We believe the potential for visual loss and the prompt response to systemic corticosteroids make early, accurate diagnosis and institution of therapy desirable.
We have attempted herein to demonstrate how microbial superantigens could promote an abnormal form of "cognate" T helper-B cell interaction, analogous to that which may occur during GVH disease, leading to B cell activation and systemic autoimmunity. In vitro studies performed at our laboratory and others have demonstrated that resting human B cells bind microbial superantigens and present them to superantigen-reactive autologous T helper cells, resulting in T cell activation and polyclonal IgM and IgG production by the superantigen-bearing B cells. In vitro studies of microbial superantigen-mediated murine T helper-B cell interactions demonstrate preferential help for B cells that have encountered specific antigen. Both in humans and in mice, the cellular interactions involved and the B cell responses induced are highly analogous to those mediated by allospecific T helper-B cell interaction. Finally, the results of studies carried out on T cell-deficient (nude) mice suggest that microbial superantigens may trigger similar T helper cell-dependent polyclonal IgM and IgG responses in vivo. These mice will be studied over time and tested for the development of autoantibodies characteristic of SLE and of autoimmune organ system damage, the occurrence of which are predicted by our model.
We have recently shown that changes in blood sodium concentration within the limited range of +/- 15 mmol/l induce changes in blood pressure which are directly related to intracellular sodium concentration and inversely related to the transmembrane sodium gradient. It followed from this that the blood pressure response to an incremental change in blood sodium concentration induced by an intraperitoneal salt load should be a function of the rate of accumulation of cell sodium. This was tested in rats treated with deoxycorticosterone acetate (DOCA)-saline for 3 days since at this time cell permeability to sodium is known to be increased. The rise of cell sodium when blood sodium concentration, measured 30 min after loading, ranged from 140-160 mmol/l, was significantly increased in treated animals (0.14 versus 0.21 mmol/kg dry weight for each 1 mmol/l rise in extracellular sodium concentration) and the rise in blood pressure was correspondingly greater (0.81 versus 1.43 mmHg for a 1 mmol/l rise in extracellular sodium concentration). The increased accumulation of cell sodium was not accompanied by a similar increase in water, so that the rise in intracellular sodium concentration was also exaggerated. Prior uninephrectomy slowed the excretion of the salt load sufficiently to exaggerate the rise of blood sodium concentration in response to a given load. The osmotic effects of intraperitoneal high sodium or high sucrose were both equally reduced, indicating that the increased permeability induced by DOCA is not specific for sodium but affects non-electrolytes as well; thus, it probably involves the phospholipid matrix.
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A 28-year-old man with unilateral Coats' disease and cystoid macular edema secondary to juxtafoveolar telangiectasis underwent successful juxtafoveolar argon green laser photocoagulation therapy with resolution of the edema and improvement in metamorphopsia and visual acuity. Despite this success, the effect of laser therapy in these patients remains uncertain. It should be considered only after detailed discussion with the patient about the possibility of posttreatment paracentral scotomata and the alternative of a reasonable period of observation for possible spontaneous resolution of the edema.
Experimentally induced murine graft-vs.-host disease may be characterized by hypergammaglobulinemia, autoantibody formation, and immune complex-mediated organ system damage that mimics SLE. These autoimmune phenomena are mediated by abnormal Th-B cell cooperation, across MHC disparities, in which donor-derived allospecific Th cells recognize and interact with MHC class II antigens on the surface of recipient B cells. Microbial toxins, termed superantigens, which bind to MHC class II molecules and activate selected T cells based on TCR variable gene usage, may induce a similar form of Th-B cell interaction. In the present study, we generated and characterized human Th cell lines reactive with the Mycoplasma arthritidis superantigen (MAM). The essential observation is that resting human B cells bind MAM and present it to superantigen-reactive autologous or allogeneic Th cells, resulting in both Th cell activation and a consequent polyclonal Ig response by the superantigen-bearing B cells.
A 34-year-old man in good general health became bilaterally totally blind by an unusual retinochoroidal degenerative disease 3 years after the initial onset of visual symptoms. The advanced stages of the retinochoroidal disease were associated with bilateral progressive iris necrosis and severe ocular pain. The constellation of findings and course of this disease represent a clinical entity that has not been previously described in the literature.