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B D Meade

Publications and source records attributed to B D Meade.

26 records · Page 2Linked to original sources
PubMed1990

Characterization of the protective capacity and immunogenicity of the 69-kD outer membrane protein of Bordetella pertussis.

Immunization with the 69-kD outer membrane protein (OMP) of Bordetella pertussis protected neonatal mice against lethal respiratory challenge with B. pertussis 18323. Active immunization elicited a serum IgG anti-69-kD OMP response at the time of challenge, with IgG anti-69-kD OMP antibodies detected in bronchoalveolar lavage fluid after challenge. Intravenous administration of BPE8, a monoclonal IgG1 anti-69-kD OMP, also protected young mice against B. pertussis challenge. Intravenously injected BPE8 was detected in the lungs of mice at the time of aerosol challenge, suggesting that the presence of specific antibody in the lungs may mediate protection. Thus the 69-kD OMP of B. pertussis is a protective antigen in mice that elicits specific serum antibody that can transude to the lung. The 69-kD OMP was detected in a preparation of a Takeda acellular vaccine by immunoblot analysis and a serum antibody response to the 69-kD OMP was observed in 18-mo-old children boosted with this preparation of Japanese acellular vaccine. Our results demonstrate that the B. pertussis 69-kD OMP is a protective antigen in animals, is immunogenic in humans, and is present in a preparation of acellular pertussis vaccine that is widely used in Japan. These findings indicate that the 69-kD OMP should be seriously considered as a candidate for inclusion in new formulations of antigenically defined acellular pertussis vaccines.

Animals↗
PubMed1985

Pertussis toxin inhibition of chemotaxis and the ADP-ribosylation of a membrane protein in a human-mouse hybrid cell line.

When WBC264-9C cells are preincubated with pertussis toxin, chemotaxis is inhibited and ADP-ribosylation of a membrane protein with a subunit Mr 41,000 is observed. Both the inhibition of chemotaxis and the ADP-ribosylation by pertussis toxin display a similar time lag, temperature dependence, and pertussis toxin-concentration dependence. Although the inhibition of chemotaxis and the ADP-ribosylation of the membrane protein are qualitatively correlated, nearly complete inhibition of chemotaxis occurs when there is only partial ADP-ribosylation of the membrane protein. Pertussis toxin-catalyzed ADP-ribosylation of the Mr 41,000 protein in WBC264-9C membranes is stimulated by GDP, GTP, and to a lesser extent by GMP; the nonhydrolyzable GTP analog guanosine 5'-[beta, gamma-imido]triphosphate has no effect. WBC264-9C membranes have a high-affinity GTPase activity, which is partially inhibited in membranes from pertussis toxin-treated cells. Neither GTPase activity nor adenylate cyclase activity in membranes from WBC264-9C cells is affected by fMet-Leu-Phe, an attractant for these cells. Our results suggest that a guanine nucleotide binding protein may be involved in chemotaxis, but they do not indicate an involvement of adenylate cyclase.

Adenosine Diphosphate Ribose↗
PubMed1985

Altered mononuclear phagocyte function in mice treated with the lymphocytosis promoting factor of Bordetella pertussis.

Lymphocytosis promoting factor (LPF) is a protein toxin which may have a role in the pathogenesis of pertussis. Previous results from our laboratory demonstrated that LPF inhibited random migration and chemotaxis of resident peritoneal macrophages, but had little or no effect on macrophage viability, adherence, superoxide anion release, or Fc-mediated phagocytosis. The current experiments have examined mononuclear phagocyte function in mice treated with LPF. Intravenous injection of mice with 200 ng LPF induced a prolonged monocytosis which peaked with a five-fold increase on the fifth day after injection. LPF (200 ng) also inhibited the increase in peritoneal macrophages induced by the intraperitoneal injection of either thioglycolate broth, phytohemagglutinin, or paraffin oil. The LPF-induced monocytosis on the fifth day after injections was not altered by the intraperitoneal injection of thioglycolate broth. LPF doses sufficient to induce leukocytosis (greater than or equal to 25 ng) significantly inhibited the increase in peritoneal macrophages induced by an inflammatory agent. These observed in vitro and in vivo effects of LPF were lost when LPF was subjected to treatments that eliminated its leukocytosis-promoting activity. The results indicate that coincident with an LPF-induced monocytosis is a reduction in the number of macrophages at a site of inflammation. An in vivo inhibition of mononuclear phagocyte migration would explain both of these effects of LPF, and is consistent with the in vitro inhibition of macrophage migration. The results suggest that a possible role for LPF in pathogenesis is the inhibition of macrophage migration to the site of Bordetella pertussis infection.

Animals↗
PubMed1984

In vitro inhibition of murine macrophage migration by Bordetella pertussis lymphocytosis-promoting factor.

Lymphocytosis promoting factor (LPF) of Bordetella pertussis is a protein toxin which may have a role in the pathogenesis of pertussis. Since macrophages have an important role in the control of respiratory infections, the in vitro effects of LPF on macrophages from C3H/HeN and C3H/HeJ mice and on a murine macrophage-like cell line, RAW264, were examined. LPF inhibited random migration of resident peritoneal macrophages as well as the chemotaxis of peritoneal macrophages and the cell line. Fifty percent inhibition of chemotaxis occurred at 0.2 to 0.3 ng of LPF per ml for the macrophages and at 1 to 2 ng of LPF per ml for the cell line. When LPF was either heated at 80 degrees C for 5 min or premixed with specific antibodies, it failed to inhibit migration. At 20 ng/ml, LPF inhibited chemotaxis by more than 80% and also decreased Fc-mediated phagocytosis by 25 to 35%. At this dose, LPF was not a chemoattractant for murine macrophages and did not reduce macrophage viability, adherence, or opsonized zymosan-stimulated superoxide release. When LPF-treated macrophages were added to tissue culture dishes and then examined microscopically after 4 h, the LPF-treated cells adhered but failed to spread and elongate as well as control macrophages. These data indicate that LPF specifically inhibits macrophage migration in vitro and suggest that a possible role for LPF in pathogenesis is to inhibit migration of macrophages to the site of B. pertussis infection.

Animals↗
PubMed1984

Lymphocytosis-promoting factor of Bordetella pertussis alters mononuclear phagocyte circulation and response to inflammation.

Previous results from our laboratory demonstrated that purified lymphocytosis-promoting factor (LPF), a protein toxin from Bordetella pertussis, inhibited the migration of murine macrophages in vitro. The current study examined the in vivo effects of LPF on mononuclear phagocyte circulation and response to an inflammatory stimulus. Intravenous injection of mice with 200 ng of LPF produced a prolonged monocytosis which peaked with a fivefold increase on day 5 after injection. LPF (200 ng) also inhibited by more than 75% the increase in peritoneal inflammatory macrophages induced by intraperitoneal injection of thioglycolate broth, phytohemagglutinin, or paraffin oil. The inhibition was significant when thioglycolate was given 1 h or 2 or 4 days after LPF but not when thioglycolate was given 2 or 4 days before LPF. The LPF-induced monocytosis on day 5 after injections was not altered by the intraperitoneal injection of thioglycolate broth. The leukocytosis-promoting and macrophage-inhibiting properties of LPF were the same in N:NIH(S) and C3H/HeJ mice. Treatments of LPF that reduced the leukocytosis-promoting effect of LPF also reduced the ability of LPF to inhibit the macrophage response. LPF doses sufficient to induce leukocytosis (greater than or equal to 25 ng) significantly inhibited the thioglycolate-induced increase in peritoneal macrophages. The results indicate that coincident with an LPF-induced monocytosis is a reduction in the number of mononuclear phagocytes at a site of inflammation. An in vivo inhibition of mononuclear phagocyte migration would explain both effects of LPF and is consistent with the in vitro inhibition of macrophage migration by LPF.

Animals↗
PubMed1976

The Sézary syndrome: a malignant proliferation of helper T cells.

The Sézary syndrome is a frequently lethal disease characterized by circulating malignant cells of thymus-derived (T)-cell origin. The capacity of circulating malignant lymphocytes from patients with this syndrome to synthesize immunoglobulins and to function as helper or suppressor cells regulating immunoglobulin synthesis by bone marrow-derived (B) lymphocytes was determined. Peripheral blood lymphocytes from normal individuals had geometric mean immunoglobulin synthetic rates of 4,910 ng for IgM, 1,270 ng for IgA, and 1,625 ng for IgG per 2 X 10(6) cells in culture with pokeweed mitogen for 7 days. Purified normal B cells had geometric mean synthetic rates of 198 ng for IgM, 145 ng for IgA, and 102 ng for IgG. Leukemic cells from patients with the Sézary syndrome produced essentially no immunoglobulins. Adding normal T cells to normal B cells restored their immunoglobin producing capacity. Leukemic cells from four of five patients tested had a similar capacity to help immunoglobulin synthesis by purified normal B cells. Additionally, Sézary cells from one patient studied induced a nearly 10-fold increase in IgA synthesis by lymphocytes from a child with ataxia telangiectasia and selective IgA deficiency. Furthermore, these Sézary cells induced more than a 500-fold increase in IgG and IgA synthesis by lymphocytes from a child with Nezelof's syndrome. When Sézary cells were added to normal unfractionated lymphocytes, they did not suppress immunoglobulin biosynthesis. In addition, unlike the situation observed when large numbers of normal T cells were added to purified B cells, there was no depression of immunoglobulin synthesis at very high malignant T-cell to B-cell ratios. These data support the view that Sézary T cells do not express suppressor cell activity. The results presented in this paper suggest that neoplastic lymphocytes from the majority of patients with the Sézary syndrome originate from a subset of T cells programmed exclusively for helper-like interactions with B cells in their production of immunoglobulin molecules.

Adult↗
PubMedDate not supplied

Comparison of Tensilon and antivenom for the treatment of cobra-bite paralysis.

We prospectively compared the ability of anti-venom and edrophonium (Tensilon) to improve paralytic symptoms in 8 patients envenomed by the Philippine cobra (Naja naja philippinensis). Twenty, 50 or 100 ml of Philippine cobra antivenom were administered in a double-blind fashion by constant intravenous infusion over 30 min. Even the largest dose of antivenom failed to produce marked improvement within 2 h, though enzyme-linked immunosorbent assays and neutralization tests demonstrated that it possessed high titres of anti-neurotoxin antibodies. Tensilon given at 2 h was significantly more effective than antivenom at increasing the duration of upward gaze (78 +/- 28 vs 43 +/- 26 sec, P less than 0.001), and either completely reversed or markedly decreased paralysis in every patient. The Tensilon test should be given to all patients with paralytic envenoming by cobras, and anticholinesterases administered to those with a positive response.

Adolescent↗