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Biomedical subjects

J E Merrill

Publications and source records attributed to J E Merrill.

At least 73 records · Page 4Linked to original sources
PubMed1985

Purification and characterization of a human T-lymphocyte-derived glial growth-promoting factor.

Antigen- or lectin-stimulated T lymphocytes and human T-cell leukemia virus (HTLV)-infected cell lines secrete lymphokines that can influence the growth and function of a variety of cell types. We recently demonstrated that supernatants from the HTLV-II-infected Mo-T-cell line stimulate the proliferation of rat brain oligodendrocytes and astrocytes. We have now purified a glial growth-promoting factor (GGPF) from these supernatants. Purification from serum-free conditioned medium was accomplished by sequential concentration, ammonium sulfate precipitation, lentillectin affinity chromatography, gel filtration, and reversed-phase high-performance liquid chromatography. GGPF is assayed by its ability to stimulate DNA synthesis in oligodendrocytes, as measured by [3H]thymidine uptake. The purified GGPF has an apparent Mr of 30,000 when analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis under nonreducing conditions. Under reducing conditions, however, GGPF appears as a single band of Mr 18,000. Both reduced and unreduced forms have biological activity, suggesting that GGPF exists in both a functional monomeric and dimeric form. Purified GGPF appears to be a biochemically and functionally distinct lymphokine.

Animals↗
PubMed1985

Iron fortification of infant foods. A decade of change.

A survey of iron-fortified commercial foods commonly marketed for consumption by infants was conducted in 1972 and again in 1982. Positive changes had occurred in infant formulas and cereals during that decade, in availability of fortifying iron, level of fortification, and label information. Miscellaneous iron-containing products, cookies, and crackers were unreliable sources of dietary iron in both 1972 and 1982. Availability of fortifying iron in regular cereals had improved by 1982, though 10 percent lacked the label information. Fortified infant formulas and cereals contribute iron of high bioavailability to the typical infant diet in amounts equal to the USRDA. Food manufacturers need to continue to apply knowledge gained through research to sustain the lessened but still highly prevalent incidence of anemia in 1-2-year old children.

Biological Availability↗
PubMed1984

Cytotoxic activity of peripheral blood and cerebrospinal fluid lymphocytes from patients with multiple sclerosis and other neurological diseases: analysis at the single cell level of the relationship of cytotoxic effectors and interferon-producing cells.

The production of interferon (IFN alpha) in relationship to NK and ADCC activity of peripheral blood and cerebrospinal lymphocytes was examined at the single cell level in patients with multiple sclerosis (MS) and other neurological diseases (OND) compared with age- and sex-matched controls. IFN-producing cells were assessed by indirect immunofluorescent scoring of cytoplasmic IFN+ cells. Peak production of cytoplasmic IFN alpha in nylon wool-passed ( NWP ) cells occurred between 5 and 17 hr in vitro under the inductive stimulus of MOLT 4, K562, or antibody-coated Chang liver cells. The proportion of K562- and MOLT 4-induced IFN alpha-positive cells in the total lymphocyte and target-binding cell (TBC) population was significantly lower in MS NWP -peripheral blood lymphocytes (PBL) than in OND and normal controls; this was in direct relationship to a decreased percentage of NK cells in MS PBL. In contrast MS cells responded the same as controls (total IFN+ cells) or higher than controls (IFN+-TBC) after IFN alpha induction by antibody-coated Chang, the ADCC target, in parallel with elevated ADCC activity by MS PBL. MS CSF contained a higher proportion of total IFN+ cells but a similar proportion of IFN+-TBC as their homologous NWP PBL population. In OND CSF, both the percentage of total IFN+ and the percentage of IFN+-TBC were higher than in OND blood and higher than their respective MS CSF populations. The relationship of IFN-producing cells in the central nervous system (CNS) to putative cytotoxic cells is discussed.

Cerebrospinal Fluid↗
PubMed1984

Response to and production of interleukin 2 by peripheral blood and cerebrospinal fluid lymphocytes of patients with multiple sclerosis.

In an effort to further characterize the defective proliferative response of T lymphocytes to mitogens in multiple sclerosis (MS) patients, we examined the response to and production of interleukin 2 (IL 2) by both peripheral blood lymphocytes (PBL) and cerebrospinal fluid mononuclear cells. We also examined the proportion of cells bearing receptors for IL 2 and transferrin. Chronic progressive MS patients have an abnormally low response to exogenous IL 2 as compared to controls. Whereas acute relapse patients' PBL demonstrated a normal IL 2 response during an exacerbation, they showed reduced responsiveness during remission. These abnormalities could not be explained by different dose or kinetic response optima to PHA or IL 2, nor could they be explained by depressed numbers of IL 2 or transferrin receptor-bearing lymphocytes. Production of IL 2 by PBL was also abnormal in MS patients. Chronic progressive patients produced elevated levels of IL 2, whereas acute relapse patients undergoing an exacerbation produced diminished levels of IL 2. During remission, these levels returned to that of controls'. The effect of 1200 rad x-irradiation or nylon wool removal of adherent cells was a significantly greater augmentation of IL 2 production in MS patients than in other neurologic disease or normal controls. Cerebrospinal fluid lymphocytes from MS patients had normal proportions of IL 2 receptor-bearing cells, but were deficient in their IL 2 response and production as compared to autochthonous or control PBL. The inability of some MS patients' lymphocytes to clonally expand in response to IL 2 might contribute to the pathogenicity of the disease.

Cell Separation↗
PubMed1983

Natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) activities can be differentiated by their different sensitivities to interferon and prostaglandin E1.

Though purported to be identical cells (or in identical populations of cells), the natural killer (NK) cell mediating spontaneous natural cytotoxicity and the killer (K) cell mediating antibody-dependent cellular cytotoxicity (ADCC) may not be totally identical, at least in susceptibility to regulation by the immunomodulators prostaglandin E1 (PGE1) and interferon (IFN). We demonstrate here that NK cells are always enhanced by IFN, while K cells are inhibited from binding targets, resulting in fewer effectors at optimal concentrations of antibody. Only at 10- to 100-fold suboptimal concentrations of antibody is ADCC activity enhanced. As measured by magnitude of inhibition and dose-response titration, ADCC activity is less sensitive to the effects of PGE1 than is NK activity in the 51Cr release assay and single-cell assay. After overnight incubation with or without PGE1, whatever sensitivity ADCC activity had to PGE1 is lost. However, NK cells incubated in the presence of PGE1 overnight are still sensitive to inhibition. Indomethacin boosts NK activity without having any effect on ADCC activity. Finally, NK activity is substantially reduced by overnight incubation of cells at room temperature, which has no effect on K cells.

Alprostadil↗
PubMed1983

Regulation of natural killer cell cytotoxicity by prostaglandin E in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Part 1. Association between amount of prostaglandin produced, natural killer, and endogenous interferon.

MS patients' peripheral blood mononuclear cells (MNC) spontaneously produced more prostaglandin E1&2 (PGE) in vitro than did OND or normal control MNC correlating with lower levels of NK activity and endogenous interferon (IFN) production while there were no differences between OND and normal controls. MS neat CSF contained significantly higher levels of measurable PGE with concomitantly lower NK activity and % IFN-positive cells than was seen in OND CSF. The PGE producing cells were depleted in the nylon wool-passed (NWP) and enriched in the nylon wool-adherent (NWAd) populations in direct correlation with depletion and enrichment of esterase-positive monocyte/macrophages, respectively, suggesting that at least some of the PGE-producing cells were adherent monocyte/macrophages. At 24 and 48 h after stimulation with PHA, MS unfractionated MNC produced significantly more PGE than OND and normal MNC; at 24 and 72 h, MS NWAd cells produced significantly more PGE than normals and ONDs. MS and ONDs produced the same amount of PGE at 48 h in the stimulated NWAd fraction.

Humans↗
PubMed1983

Regulation of natural killer cell cytotoxicity by prostaglandin E in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis and other neurological diseases. Part 2. Effect of exogenous PGE1 on spontaneous and interferon-induced natural killer.

Compared to normal and other neurological disease (OND) controls, multiple sclerosis (MS) pre nylon wool (pre NW) and nylon wool passed (NWP)-peripheral blood cells' natural killer (NK) activity was more sensitive to prostaglandin E (PGE1); it was suppressed to a greater degree and at lower concentrations of PGE1. At the single cell level this was reflected by lower numbers of target-binding cells (TBCs) and fewer killers among the TBCs. ONDs and normal controls were equally sensitive to PGE1. Though PGE-producing cells were depleted in the NWP population of normal and control ONDs, MS patients still had indomethacin-sensitive NK suppressors in the NWP population; these apparently did not suppress at the single cell effector level but at the level of recycling. MS and OND cerebrospinal fluid (CSF) cells' NK activity could not be 'enhanced' by indomethacin. Depression of interferon (IFN)-induced NK by PGE1 was greater in MS than in OND or normal controls perhaps through its effect on IFN-induced recycling. All subjects' cells maintained sensitivity to PGE1 after overnight incubation in the presence of PGE-producing cells (pre NW) or exogenous PGE1. In sharp contrast to normal and OND controls, MS NWP cells were still inhibited by PGE1 even after overnight incubation in the absence of PGE1.

Alprostadil↗
PubMed1982

Cytotoxic activity of peripheral blood and cerebrospinal fluid lymphocytes from patients with multiple sclerosis and other neurological diseases. Analysis at the single cell level using morphological and surface marker phenotype criteria.

The large granular lymphocyte (LGL) has been identified in normal individuals' MNC population as the NK-K cell (Ault and Weiner 1978; Timonen et al. 1981); it bears the OKM1 surface antigen (Breard et al. 1981; Fast et al. 1981) and while negative for T cell antigens OKT4 and OKT8, is a low avidity E-rosette forming cell. However, in a unfractionated nylon wool passed peripheral blood lymphocyte (NWP PBL) population, we show that not more than 50% of KN activity in normal or OND control NWP PBL and 30% NK activity in MS NWP PBL can be attributed to this cell. Nevertheless, 100% of control K cell activity and 50% of MS K cell activity can be mediated by an LGL. MS patients have normal proportions of LGLs in their NWP PBL. The proportion of LGLs in CSF of MS and OND patients is too low to account for the number of CSF K cells. While in control NWP PBLs, the LGLs are OKM1+ and mediate NK and ADCC, in MS the LGL NK effectors are probably different from LGL-K cell effectors. In MS both populations include effector cells with cell surface antigens. Thus, the OKM1+ LGL characteristics may not be used in analysis of NK and K cells in multiple sclerosis.

Acute Disease↗
PubMed1981

Distribution of IgG and IgM receptors on human peripheral natural killer cells measured on the level of the single effector cell.

Using an agarose single-cell cytotoxicity assay simultaneously with the antibody-coated ox erythrocyte assay for detecting Fc receptor (FcR)-positive cells, the number of natural killer (NK) cells in fresh human peripheral blood which bear FcR for IgG or IgM have been determined. Of the target binding blood which bear FcR for IgG or IgM have been determined. Of the target binding cells (TBC) which form conjugates with NK-sensitive target cell lines Molt 4, 1301 and Hd-Mar, 55% had FcR for IgG and 24% had FcR for IgM. In the active NK cell population, which amounts to about 6% in nylon wool column-passed peripheral lymphocytes, cells with FcR for IgG account for 60% and cells with FcR for IgM for 17% of the total killing. Even though there is an increase in the number of FcR-IgM-positive cells from fresh peripheral blood after overnight incubation at 37 degrees C, no increase was found in FcR-IgM-positive NK cells. The reasons why FcR for IgM have not been described earlier on human NK cells are discussed, as well as the functional implications of these and their probable expression on other types of cytotoxic effector cells.

Animals↗
PubMed1981

Influence of IgG and IgM receptor triggering on human natural killer cell cytotoxicity measured on the level of the single effector cell.

By using an agarose single cell cytotoxicity assay, in combination with rosetting with IgG- or IgM-coated ox red blood cells for detection of Fc receptors for IgG (Fc gamma R) or IgM (Fc muR), it was found that 60% of natural killer (NK) cells are Fc gamma R+ and 17% FcmuR+. This system was further used to investigate the consequence of FcmuR and FC gamma R triggering on NK killing as measured on the single effector cell level. It was found that stimulation of the Fc gamma R, but not the FCmuR, resulted in substantial NK inhibition. In order for NK cells to be inhibited by IgG-coated ox red blood cells, they must first be exposed to the IgG-containing complex prior to conjugation with the target. While exposure of the Fc gamma R to immune complexes can block up to 57% of NK activity, the particulate immune complexes do not interfere with binding of effector cells to targets. Modulation of Fc gamma R by capping at 37 degrees C does not interfere with the NK inhibition for up to 3 h, though after 20 h, when Fc gamma R+ cells are almost completely modulated, NK activity has fully returned. Although to a lesser extent, the soluble immune complex human transferrin-anti-transferrin also reduces NK cell activity when activating effector cell FC gamma R prior to target cell binding. Also, pretreatment of target cells with high concentrations of specific antibody toward membrane antigens can block NK activity while not inhibiting target cell binding as evidenced by anti-IgM IgG binding to Daudi cells. The regulatory influence of the Fc gamma R on the NK system is discussed in terms of other functions associated with this receptor and in terms of its possible biological significance.

Animals↗
PubMed1980

A T lymphocyte subpopulation in multiple sclerosis patients bearing Fc receptors for both IgG and IgM1.

Abnormally low proportions of total T lymphocytes were found in peripheral blood lymphocytes (PBL) of patients with multiple sclerosis (MS) accompanied by high proportions of T lymphocytes with Fc receptors (FcR) for IgG (T gamma cells). Seventy-five percent of the MS patients had greater than 40% T gamma in the T lymphocyte-enriched population. In 6 out of 16 cases, T mu were also elevated. This elevation, however, did not seem to correlated with disease stage. By mixed rosetting and direct observation with an indirect immunofluorescence test, 30 to 50% of the T gamma cells in MS PBL were also shown to bear FcR for IgM. This population bearing FcR for IgG and IgM, designated T gamma mu, was usually found to be 10% or less of the T gamma population in normal controls. The significance of this T gamma mu population for the MS disease process requires further evaluation.

Adult↗
PubMed1980

Identification of three FcR-positive T cell subsets (T gamma, T mu and T gamma mu) in the cerebrospinal fluid of multiple sclerosis patients.

Proportions of T cells and T cell subsets, as identified by their Fc receptors (FcR) for IgM and IgG (Tmu and T gamma), were determined in the peripheral blood lymphocyte (PBL) and cerebrospinal fluid (CSF) lymphocyte populations in patients with multiple sclerosis (MS). On average, MS patients had 79% total T cells (62% of which were T gamma, 66% Tmu) in CSF lymphocytes compared to 66% total T cells (30% T gamma, 63% Tmu) in PBL. Normal age- and sex-matched controls PBL had 74% total T cells (20% T gamma, 54% Tmu). By direct observation using an indirect immunofluorescence assay, 41% of the CSF T gamma cells in MS patients bore receptors for IgM; these cells were designated T gamma mu and, according to the double-marker analysis, did not seem to correlate with disease stage. In MS PBL, 20% of T gamma cells were T gamma mu compared to 9% in the control PBL T gamma population. Thus, MS patients had a higher proportion of total T cells, T gamma cells and T gamma mu cells in their CSF than in their peripheral blood and than those populations found in normal control blood. The significance of this T gamma mu population for the continuing disease state in MS is discussed.

Adult↗