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Biomedical subjects

D G Colley

Publications and source records attributed to D G Colley.

At least 127 records · Page 7Linked to original sources
PubMed1983

Immune responses during human schistosomiasis mansoni. IX. T-lymphocyte subset analysis by monoclonal antibodies in hepatosplenic disease.

T lymphocyte immunoregulatory subsets (T4+ and T8+ cells) have been analysed in eight cases of hepatosplenic schistosomiasis mansoni, and compared to parallel analyses of seven intestinal Schistosoma mansoni-infected patients and four uninfected control subjects. The mean T4+:T8+ ratio in hepatosplenic cases was markedly less than observed in other groups (0.94 vs 1.86 vs 2.22, respectively). Proliferative responses stimulated by a soluble adult worm extract correlated directly with the observed T4:T8 ratios. Normal levels of E rosette-positive and surface immunoglobulin-bearing lymphoid cells were observed in intestinal patients, while hepatosplenic patients demonstrated normal B lymphocyte proportions but highly erratic E rosette-positive percentages. Curiously, in hepatosplenic patients the percentage of E rosette-positive cells often did not correlate with the proportion of T3+ cells.

Antibodies, Monoclonal↗
PubMed1983

Work in progress: radionuclide imaging of indium-111-labeled eosinophils in mice.

Eosinophils isolated from peritoneal exudates were labeled with indium-111-oxine and injected intravenously into sensitized mice. They became localized at sites of inflammation produced by intradermal injections of schistosomal antigen or Toxocara canis larvae, whereas labeled neutrophils did not. Intense uptake of eosinophils by normal spleen, liver, and bone marrow was noted, with tracer distribution effectively complete by 5 hours after injection. Indium-111-eosinophil studies appear to be quite sensitive to parasitic inflammatory reactions; in contrast, nonspecific inflammation such as that induced by turpentine causes localization of eosinophils, but to a lesser extent. This technique may be useful in the study of parasitic and allergic disease.

Animals↗
PubMed1983

Differences in adult Schistosoma mansoni worm burden requirements for the establishment of resistance to reinfection in inbred mice. II. C57BL/KsJ, SWR/J, SJL/J, BALB/cAnN, DBA/2N, A/J, B10.A(3R), and B10.A(5R) mice.

Eight strains of mice (C57BL/KsJ, SWR/J, SJL/J, BALB/cAnN, DBA/2N, A/J, B10.A(3R), and B10.A(5R) were studied in regard to the development of resistance to secondary challenge with Schistosoma mansoni following a primary infection. Also analyzed were the number of eggs recoverable from the livers of these strains after primary infection and the size of the hepatic, schistosome egg-focused granulomas newly formed at various times after infection. As previously observed by us and others, most often the degree of resistance conferred by an acute primary infection is related to the number of adult worms harbored due to the initial infection. The mean levels of protection observed in the different strains were seen to cover a spectrum from moderate to strong resistance, rather than demonstrating high or low resistance strains. There was no observable effect of the major histocompatibility complex on this resistance state. The number of eggs recoverable from the livers of the various strains was calculated on a total liver, per female worm basis, and was seen to be less in C57BL/KsJ, SWR/J and SJL/J mice. Granulomatous reactivity also varied considerably in a strain-dependent manner. These data are compared with previously reported strain differences in S. mansoni infections. Although some similarities are observed between laboratories certain strain-related discrepancies also exist and are discussed.

Animals↗
PubMed1983

Immune responses during human schistosomiasis mansoni. X. Production and standardization of an antigen-induced mitogenic activity by peripheral blood mononuclear cells from treated, but not active cases of schistosomiasis.

Peripheral blood mononuclear cells (PBMN) from patients with active schistosomiasis mansoni are generally induced to proliferate upon exposure to a soluble worm antigenic preparation (SWAP). In contrast, only 25% of such patients responded to SWAP exposure by the production of detectable levels of a mitogenic factor (MF) activity capable of stimulating proliferation of resting cultures of allogeneic PBMN. When former schistosomal patients (chemotherapeutically cured 10 to 40 yr previously) were tested for these two responses to SWAP, all manifested blastogenesis; 80% also responded by the production of MF activity. Only 9% of control subjects with no history of schistosomiasis produced MF activity when exposed to SWAP. The production and assay of MF activity by former schistosomiasis patients was standardized. Reliable, optimal production was achieved by using 6 X 10(6) PBMN in 2-ml cultures upon exposure to 15 micrograms protein SWAP/ml. The cells were incubated for 20 hr in the presence or absence of SWAP, at which time they were washed and recultured in fresh medium for at least 28 more hours. Subject to subject variability occurred in the optimal time of detection of MF activity in culture supernatant fluids, but detection was assured between 24 and 48 hr after the wash. The assay system for MF detection required a 5 to 7-day culture. The consistent production of MF activity by former schistosomal patients emphasized the longevity of immunologic memory to SWAP, and may indicate a post-treatment decline of immunoregulatory mechanisms that are operative in patients with active schistosome infections.

Antigens↗
PubMed1983

Arachidonic acid metabolism in the murine eosinophil. III. Effect of nonsteroid anti-inflammatory drugs on lymphokine-directed eosinophil migration in vivo.

In vitro studies of murine eosinophils indicated that lymphokine-stimulated metabolism of arachidonic acid by a lipoxygenase pathway was required for a migration response. In this study we tested the effects of drugs that affect arachidonic acid metabolism on lymphokine-dependent eosinophil accumulation in vivo by the use of 111In-labeled eosinophils. Indomethacin at different dosages either stimulated (1 mg/kg) or partially inhibited (5 to 25 mg/kg) eosinophil accumulation. Aspirin had no significant effects in doses up to 50 mg/kg. BW755C, a drug that inhibits both cyclooxygenase and lipoxygenase, dramatically inhibited eosinophil accumulation at 25 to 125 mg/kg. Pretreatment in vitro of 111In-labeled eosinophils with some drugs known to inhibit lipoxygenase reduced their subsequent accumulation at a lymphokine-injected site in vivo, but the high concentrations required for inhibition suggested that the effects of the drugs were at least partially reversible. Pretreatment with indomethacin did not inhibit the ability of 111In-labeled eosinophils to accumulate at the site of lymphokine injection in vivo. It may be anticipated from these results that drugs inhibiting lipoxygenase will have critical effects on manifestations of immunologic reactions that recruit eosinophils.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1983

Murine eosinophils labeled with indium-111 oxine: localization to delayed hypersensitivity reactions against a schistosomal antigen and to lymphokine in vivo.

We have evaluated a method for quantitation of eosinophil migration to stimuli in vivo. Upon transfusion into normal syngeneic mice, 111In-labeled eosinophils had an intravascular half-life of 9.5 hr and distributed predominantly into spleen, bone marrow, and liver. In either Schistosoma mansoni-infected mice or recipients of lymphoid cells from infected mice, intradermal (ear pinna) injection of the schistosomal egg antigenic preparation (SEA) elicited time-dependent accumulation of 111In-labeled eosinophils detectable by either gamma scintillation counting of tissue samples or by nuclear medicine external imaging. Intradermal administration of a lymphokine fraction (containing eosinophil stimulation promoter activity) similarly caused accumulation of 111In-labeled eosinophils. Both reactions depended on the concentration of stimulus (SEA or lymphokine). 111In-labeled neutrophils or macrophages or 125I-albumin did not preferentially accumulate at the reactions examined to the extent found with 111In-labeled eosinophils, indicating that localization of label depends on an active process and is due to eosinophils rather than a contaminating cell type. The method was used to estimate how long eosinotactic lymphokine remained at dermal sites: 60% of initial activity was present 12 hr after injection. The model is discussed with regard to the role of lymphokines in hypersensitivity reactions with eosinophil involvement, such as the granulomatous response to S. mansoni eggs.

Animals↗
PubMed1983

Natural killer cell activity during murine Schistosomiasis mansoni.

Natural killer cell (NK) activity of spleen cells from CBA/J and C57BL/6 mice infected with Schistosoma mansoni was assayed using 51Cr-labeled YAC-1 cells as target cells. No significant difference in NK activity was detected between infected and age-matched control spleen cells from 1 to 4 wk after infection. The NK-mediated cytotoxic abilities of both infected and age-matched control mice fell in parallel, as expected, on an age-related basis. However, on a cell-to-cell basis the splenic NK activity of mice infected from 8 to 18 wk was significantly less than that of age-matched control mice. Meanwhile, because of the splenomegaly associated with patent infection, the total number of nucleated splenocytes in chronically infected mice increased to fourfold that of age-matched control mice. Therefore, the total available NK activity per spleen was increased by chronic infection. The NK activities of spleen cells from age-matched control mice and those infected for 18 wk could be augmented by in vivo administration of polyinosinic-polycytidylic acid, indicating the continued responsiveness of NK cells from chronically infected mice to activation. Spleen cell NK activity in age-matched control and infected C57BL/6 mice exhibited a pattern similar to that of CBA/J mice.

Animals↗
PubMed1983

Immune responses during human Schistosomiasis mansoni. VIII. Differential in vitro cellular responsiveness to adult worm and schistosomular tegumental preparations.

The proliferative responses of peripheral blood mononuclear cells from patients with Schistosoma mansoni infections were studied in response to heterogeneous schistosomal antigenic preparations derived from whole adult worms, cercariae or schistosomula, and soluble tegumental preparations from adult worms or schistosomula. The use of these preparations was standardized with a Brazilian patient population, and comparisons were made between previously used and newly, variously prepared antigenic preparations. Responses of cells from these intestinal/ambulatory patients were generally strong to whole adult worm antigens and low to moderate to whole cercarial or schistosomular materials. Although most patients responded well to whole worm extracts, they were not stimulated by the soluble adult tegumental preparation. In contrast, the responses to the soluble schistosomular tegumental material were vigorous. These responses were usually much higher than to whole schistosomula-derived materials. Thus it appears, using these particular preparations, that human schistosomal patient lymphocytes recognize and are stimulated by schistosomular tegumental antigens but they do not demonstrate good reactivity when exposed to an adult worm tegumental preparation.

Antigens↗
PubMed1982

Primary in vitro sensitization to heterogeneous soluble antigens of Schistosoma mansoni adult worms.

Primary in vitro sensitization of normal mouse spleen cells was accomplished using a saline soluble heterogeneous antigenic preparation from the whole adult worms (SWAP) of Schistosoma mansoni. A SWAP-specific rosette-forming cell (RFC) assay, using antigen on sheep erythrocytes, was used to detect sensitization due to S. mansoni infection and primary in vitro SWAP exposure. The latter exposure was facilitated by SWAP adsorption to the culture vessel via poly-L-lysine. RFC expression was maximal on day 3 of culture. It was antigen-specific in regard to unexposed controls, SWAP and human gamma globulin, and as controlled by RFC detected by parallel treated (control) erythrocytes. The RFC assay was best read between 90 and 180 min after initiation of rosette formation. Assay erythrocytes gave reproducible results for at least 3 weeks after preparation.

Animals↗
PubMed1982

Immune responses and immunoregulation in relation to human schistosomiasis in Egypt. I. Effect of treatment on in vitro cellular responsiveness.

Cell mediated immune reactivity of chronic schistosomiasis patients was tested in vitro by peripheral blood mononuclear cell (PBMN) responses against phytohemagglutinin P (PHA), Candida albicans extract, soluble schistosomal antigenic preparations derived from eggs (SEA), adult worms (SWAP) and cercariae (CAP), before and after treatment of the patients with parziquantel. The patient population was from villages in the Qalyub province, Egypt, that are endemic for Schistosoma mansoni and S. haematobium. Patients were studied immediately before, and at 1, 3, 6, and 9 months after chemotherapy. Egg counts were done on stool and urine specimens taken simultaneously with blood samples. There was a significant increase in PBMN responses to SWAP and CAP but not to SEA, PHA or C. albicans in 27 patients (age 8-65) 1 month after treatment. Eleven patients treated 1.5 years previously did not show such elevated responses 1 month after re-treatment. Three months after treatment higher mean responses were observed to SWAP, CAP, SEA, and PHA, but not to C. albicans in 24 patients (age 6-26). Significant increases in PBMN responses to SWAP and CAP, but not to SEA, PHA or C. albicans were obtained at 6 months after treatment in 12 patients (age 6-30). By 9 months after treatment in a group of 11 patients (age 8-25) SWAP and CAP responses were still elevated as were SEA and C. albicans induced reactivities. The PBMN responses of 10 patients were followed longitudinally at pretreatment, 3-, 6-, and 9-month post-treatment times. In general, elevated responses were maintained throughout this period to the schistosomal preparations. Unrelated responses occasionally fluctuated but were not consistently altered over time.

Adolescent↗
PubMed1982

Arachidonic acid metabolism of the murine eosinophil. II. Involvement of the lipoxygenase pathway in the response to the lymphokine eosinophil stimulation promoter.

Eosinophil stimulation promoter (ESP) is a murine lymphokine that enhances the migration of eosinophils. Exogenous arachidonic acid between 0.5 and 2 micrograms/ml potentiated the activity of ESP on murine eosinophil migration, whereas such concentrations did not affect migration in the absence of ESP. Among the lipoxygenase products identified from an enriched population of murine eosinophils, leukotriene B4 (optimal activity at 100 ng/ml) and 12-HETE (optimal activity at 2 micrograms/ml) stimulated migration of these cells. Another lipoxygenase product from these cells 15-HETE inhibited ESP-induced migration; between 5 and 10 micrograms/ml 15-HETE decreased by one-half both stimulated migration and 12-HETE biosynthesis. Structurally diverse drugs at concentrations that inhibited HETE biosynthesis inhibited ESP-induced migration. The concentrations that decreased migration activity by one-half were 5 microM NDGA, 10 microM ETYA, and 150 microM BW755C. Aspirin and indomethacin at concentrations reported to inhibit prostaglandin biosynthesis did not substantially inhibit ESP activity, but concentrations of indomethacin above 20 microM caused concentration-dependent inhibition of migration. The selective lipoxygenases inhibitor 134,7,10,13-eicosatetraynoic acid was more potent than ETYA in inhibition of ESP-induced migration, and the selective cyclooxygenase inhibitor 6,9,12-octadecatriynoic acid did not effect inhibition. These results are consistent with the hypothesis that stimulation of eosinophils by the lymphokine ESP involves the generation of lipoxygenase products from arachidonic acid, which positively and negatively regulate the migratory activities of these cells.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1982

Serologic responses to Schistosoma japonicum: evaluation of total and parasite-specific immunoglobulins during the course of murine infection.

Mice with a primary infection of Schistosoma japonicum develop high levels of both total immunoglobulins and parasitic-specific antibodies, beginning about 1.5 wk after the onset of oviposition in the host. Radial immunodiffusion demonstrated an 18-fold, fivefold, and threefold increase in the levels of IgG1, IgM, and IgA, respectively, during the course of infection. Schistosoma japonicum-specific antibodies, as measured by an enzyme-linked immunoabsorbent assay, appeared and increased at about the same time as total immunoglobulins, and were predominantly of the IgG1 and IgM classes. The specific/ELISA response to a purified antigen from S. japonicum SEA was distinct from the total specific response to crude SEA. Hemagglutinating antibodies increased at 5 wk PI and remained at high levels for the duration of infection. Specific, circulating IgE measured by PCA appeared 6 wk PI, reaching a peak at 9 wk, and persisted at moderate levels throughout the infection period.

Animals↗
PubMed1981

Comparison of whole blood cultures and peripheral blood mononuclear cell cultures for evaluation of lymphocyte reactivity during chronic schistosomiasis.

Lymphocyte blastogenesis during chronic schistosomiasis has been evaluated previously by either whole blood or peripheral blood mononuclear cell (PBMN) culture techniques. These two methods were compared in the present study. Blastogenesis to the mitogen phytohaemagglutinin was greater in the whole blood cultures at the time assayed. Substantial antigen-induced lymphocyte transformation was elicited in both culture systems using cells from uninfected patients. However, patients' responses to schistosome-derived antigenic preparations as determined by whole blood culture were greatly reduced compared with PBMN cultures. In view of the known immunoregulatory activities associated with sera and cells from infected patients the whole blood technique may better reflect in vivo lymphocyte reactivity. The PBMN cultures are better suited to examine the immunoregulatory activities which may develop during this chronic infection.

Cells, Cultured↗