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Biomedical subjects

M Brogan

Publications and source records attributed to M Brogan.

27 records · Page 2Linked to original sources
PubMed1987

Human mucosal cytotoxic effector cells.

Human intestinal lamina propria mononuclear cells have been shown to mediate mitogen-induced cellular cytotoxicity, antibody-dependent cellular cytotoxicity, and lymphokine activated killer cell function. However, although natural killer cells have been demonstrated in the gut mucosa of rodents, recent reports found little or no spontaneous cytotoxic activity in the lamina propria of the human gut. Using the natural killer cell-related monoclonal antibody NKH-1, which has not previously been applied to studies of mucosal killer cell function, we have shown by immunofluorescence that 2%-3% of enzymatically dispersed lamina propria lymphocytes are NKH-1+. A "panning" technique was then used to enrich for the NKH-1+ cells. Panned cells were consistently greater than or equal to 80% NKH-1+ by indirect immunofluorescence. Unlike their counterparts in the peripheral blood, the mucosal NKH-1+ cells were Leu-11-. Although unseparated lamina propria lymphocytes failed to exhibit natural killer activity against K562 targets in 4-h chromium release assays at effector to target ratios of up to 100:1, the NKH-1+ cells were cytolytically active at ratios of less than 5:1. Mucosal lymphocytes depleted of natural killer cells (NKH-1-) exhibited cytotoxic activity when cultured for 72 h with interleukin-2. The precursors of the lymphokine culture activated phenomenon were NKH-1-, Leu-11-, T4-, T3-, T11+, and T8+. Although lamina propria T3+ cells did not exhibit spontaneous or culture activated cytotoxicity, they were shown to exhibit nonspecific anti-CD3 (anti-T3)-induced T-cell cytotoxicity. In conclusion, functional natural killer and lymphokine activated killer cells are both present in the human gut mucosa and represent distinct populations of cytotoxic cells. In addition, anti-CD3-induced cytotoxicity is a feature of mucosal T cells. These mucosal killer cell subsets differ phenotypically from those previously described in the peripheral blood.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Evidence for involvement of serine proteases in the late stages of the natural killer cell lytic reaction.

An irreversible inhibitor (L-1-tosylamide-2-phenylethyl-chloromethylketone) and substrate (N-acetyl-L-tyrosineethylester) of the neutral serine protease chymotrypsin were evaluated for their effects on the natural killer cell lytic reaction sequence. During direct cell-mediated cytolysis these inhibitors had no effect on natural killer cell binding to target cells but were able to inhibit the "trigger" mechanism which initiates killing. In addition, they inhibited later calcium-dependent events in the lytic reaction and killer cell-independent lysis. These findings suggest that serine proteases may be required during several stages of natural killer cell lysis, including calcium-dependent programming as well as the actual lethal hit.

Calcium↗
PubMed1985

The effect of 6-mercaptopurine on natural killer-cell activities in Crohn's disease.

Crohn's disease patients on long-term 6-mercaptopurine therapy (more than 4 months) were evaluated for activity of peripheral blood natural killer cells. Natural killer-cell cytolytic activity against K-562 tumor-cell targets was examined, as was natural killer-cell suppression of lymphoblastoid B-cell antibody production. In addition, these patients were studied for their ability to generate antitetanus-specific IgG-antibody-producing lymphoblastoid B cells following in vivo booster immunization. Crohn's disease patients on 6-mercaptopurine therapy had significant reductions in peripheral blood natural killer-cell activity against K-562 targets compared to normals, disease controls, and Crohn's disease patients not on 6-mercaptopurine. Natural killer-cell suppression of lymphoblastoid B-cell antibody production was likewise decreased in 6-mercaptopurine-treated patients compared to normal controls. In contrast, the in vivo generated lymphoblastoid B-cell antibody responses of Crohn's disease patients on 6-mercaptopurine therapy were not decreased compared to normal, while Crohn's disease patients not on 6-mercaptopurine therapy had significantly impaired IgG antitetanus antibody responses. These findings suggest that 6-mercaptopurine therapy in Crohn's disease affects several lymphoid subpopulations, resulting in a decreased natural killer-cell cytotoxic activity against K-562 target cells and a decreased natural killer-cell ability to suppress lymphoblastoid B-cell antibody production, as well as an improved humoral immune response following tetanus toxoid booster immunization.

Adult↗
PubMed1985

Defective generation of tetanus-specific antibody-producing B cells after in vivo immunization of Crohn's disease and ulcerative colitis patients.

In vivo booster immunization with tetanus toxoid normally results in the temporal development of circulating populations of B cells that secrete antibody after in vitro culture. In assessing the humoral immunoregulatory status in patients with inflammatory bowel disease, we found that the antibody production by the B cells that spontaneously secrete tetanus-specific immunoglobulin G in vitro, and which occur in the circulation 7 days postimmunization, was highly variable and below normal in the majority of Crohn's disease and ulcerative colitis patients. The decreased in vitro antibody responses correlated with the lack of an increase in the serum antitetanus immunoglobulin G titers, but did not correlate with disease activity, location, or steroid therapy. The majority of patients who did not produce an immunoglobulin G-antitetanus toxoid antibody response similarly failed to produce an immunoglobulin G-antidiphtheria antibody response after immunization. Lymphocytes from the patients who failed to produce normal levels of antitetanus toxoid antibody did, however, proliferate normally when stimulated by tetanus toxoid in vitro. These results suggest there are in vivo humoral immune defects in inflammatory bowel disease.

Adult↗
PubMedDate not supplied

High-resolution 3DFT MR imaging of the endolymphatic duct and soft tissues of the otic capsule.

This study compares the visualization of otic capsule anatomy by thin-section three-dimensional Fourier transformation (3DFT) MR imaging with that by high-resolution CT. The osseous margins of the otic capsule are delineated by high-resolution CT, while MR displays the soft-tissue structures. Routine two-dimensional Fourier transformation (2DFT) spin-echo MR techniques have been limited by slice thickness and signal to noise. Previous longer TE 3DFT gradient-echo MR images of the otic structures have been degraded by magnetic susceptibility effects, which limit spatial resolution and decrease signal to noise. These effects are especially prevalent in the otic capsule, where small soft-tissue structures interface with surrounding air and bone. We developed a high-resolution 3DFT MR technique to image five normal subjects. MR images were compared with high-resolution CT images of the same subjects. Axial, sagittal, and coronal 3DFT gradient-echo MR images with a short TR/TE and 15 degrees flip angle were acquired on a General Electric 1.5-T Signa unit using a 3-in. circular, receive-only surface coil. Axial, sagittal, and coronal 1.5-mm-thick contiguous high-resolution CT bone-algorithm images were obtained also. There was a high correlation between the MR and CT findings. The 3DFT MR images demonstrated significantly higher spatial resolution and soft-tissue detail than the high-resolution CT images did. For example, the endolymphatic duct was seen on twice the number of consecutive sagittal and axial MR slices. Other soft-tissue otic capsule structures routinely seen on the 3DFT MR images included the entire facial nerve, membranous labyrinth including cochlea, and tensor tympani muscle. This study demonstrates a new high-resolution 3DFT MR technique for visualizing the soft-tissue microstructures of the otic capsule and achieves a level of spatial resolution beyond that possible with high-resolution CT.

Adult↗