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Biomedical subjects

M M Fanning

Publications and source records attributed to M M Fanning.

33 records · Page 2Linked to original sources
PubMed1986

The relationship between 2-5A synthetase levels and persistent lymphadenopathy in homosexual men with antibodies to HTLV-III.

This study compared clinical and laboratory parameters in 37 individuals with serologic evidence of exposure to human T-cell lymphotropic virus type 3 (HTLV-III) and generalized lymphadenopathy. Basal levels of the interferon-induced enzyme, 2-5A synthetase were also measured and compared with the clinical parameters. A significant linear relationship (p less than .05) was demonstrated between the logarithm of the basal synthetase level and both the number and size of palpable nodes in the posterior cervical triangles of the men studied. No other lymph node chains demonstrated such a relationship. In addition, men with more than 3 palpable nodes (the median number) in the posterior triangles had lower mean levels of lymphocytes, reduced mean mitogen responses to PWM, PHA, and ConA, elevated mean levels of IgG, IgA, and IgM, and were more frequently anergic on skin testing. These findings suggest the need for further longitudinal study of the possibility that extent of lymphadenopathy and level of 2-5A synthetase might serve as useful parameters to monitor disease activity.

2',5'-Oligoadenylate Synthetase↗
PubMed1985

Brugia malayi: clearance of microfilaremia induced by diethylcarbamazine independently of antibody.

The microfilaricidal effect of diethylcarbamazine was studied in the murine model of Brugia malayi microfilaremia. CFI mice with circulating microfilariae were treated with either diethylcarbamazine (6 mg kg-1 day-1) for 10 days or with normal saline. Although antibodies against crude microfilarial antigen were detected in both groups at the time of completion of therapy, the chemically induced microfilarial clearance occurred prior to the development of these antibodies. In addition, the passive transfer of antibody just prior to chemical treatment did not enhance diethylcarbamizine-induced microfilarial clearance. In vitro studies confirmed previous observations that diethylcarbamazine enhanced antibody-dependent neutrophil adherence. Microfilarial clearance was found to be due to trapping and lysis in the liver on pathologic examination. These studies demonstrate that diethylcarbamazine leads to microfilarial clearance in the liver by mechanisms that are not dependent on host antibody.

Animals↗
PubMed1985

Elevated levels of interferon-induced 2'-5' oligoadenylate synthetase in generalized persistent lymphadenopathy and the acquired immunodeficiency syndrome.

The levels of the 2'-5' oligoadenylate enzyme synthetase in extracts of peripheral blood mononuclear cells from individuals with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) were measured and compared with synthetase levels in peripheral blood mononuclear cells (PBMs) from healthy heterosexual and homosexual controls. The mean basal synthetase level in heterosexual and homosexual controls was 14 +/- 13 and 12 +/- 9 pmol per hr/10(5) PBMs, respectively. Thirteen individuals with AIDS had a mean basal level of 129 +/- 75 pmol. Serial levels were persistently elevated in six of these individuals over a one- to 10-month period. Twelve of the 13 individuals had antibodies to human T cell lymphotrophic virus-III/lymphadenopathy-associated virus (HTLV-III/LAV). Thirty-three individuals with ARC had a mean basal synthetase level of 68 +/- 84 pmol. Thirty-two of the 33 had antibodies to HTLV-III/LAV. Eleven (33%) have had consistently normal synthetase levels (less than 2 SD above the mean for the homosexual controls, i.e., 30 pmol) over a three- to nine-month follow-up period. Fourteen (42%) had persistently elevated levels over the same period; four (29%) of these developed AIDS during the follow-up period. Eight have had fluctuating levels but have remained clinically well. These studies suggest that persistently elevated synthetase levels in individuals with ARC and antibodies to HTLV-III/LAV indicate progressive virus-induced disease activity. Elevated synthetase levels may be an important prognostic indicator of increased risk of progression to AIDS.

2',5'-Oligoadenylate Synthetase↗
PubMed1985

Further studies on genetic variation of hepatosplenic disease and modulation in murine schistosomiasis mansoni.

The influence of genetic factors on the modulation of hepatosplenomegaly, portal venous pressure and granuloma size in chronic murine schistosomiasis mansoni was studied. Experiments with congenic mice confirmed previous observations that after 8 weeks of infection these disease manifestations are influenced by non-H-2 genes. During chronic infection (20 weeks compared to 8 weeks of infection), hepatosplenomegaly was minimally altered. Portal venous pressure was found to increase in 129/J and BALB/cJ mice, did not change in C57BL/6J and DBA/2J and decreased in CBA/CaJ mice. Simultaneous measurements of granuloma size delineated two groups: decrease of greater than 40%--C57BL/6J, DBA/2J and CBA/CaJ strains and decrease of less than or equal to 20%--129/J, BALB/cJ and C3H/HeJ mice. There was no consistent correlation between the magnitude or direction of alterations in portal pressure and granuloma size among the various strains studied. Furthermore, these alterations were independent of changes in parasite burden (adult worms or hepatic eggs). This amelioration of disease (modulation) was found to be influenced by a small number of non-H-2 genes.

Animals↗
PubMed1984

AIDS in a patient with hemophilia receiving mainly cryoprecipitate.

A 25-year-old man with hemophilia who had been treated primarily with cryoprecipitate presented with epigastric pain and loose, melenic stools. He had a long history of malaise and intermittent upper respiratory tract infection with fever. The patient was shown to have disseminated histoplasmosis and refractory herpes simplex. Immunologic studies demonstrated a markedly decreased ratio of helper to suppressor T cells, lymphopenia, cutaneous anergy and a slightly elevated serum IgA level. These findings met the criteria for the diagnosis of acquired immune deficiency syndrome. In addition, antibodies to human T-cell leukemia virus were detectable in the serum.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Genetic-linked variation in susceptibility of mice to Schistosomiasis mansoni.

Genetic dependence of susceptibility to primary infection with Schistosoma mansoni was studied in inbred strains of mice. Eight weeks after the subcutaneous injection of 30 cercariae, C3H/HeJ (H-2k), DBA/1J (H-2q) and BALB/cJ (H-2d) had the highest number of adult worms per animal (8.0-9.8); DBA/2J (H-2d) and 129/J (H-2b) had an intermediate number (6.2-6.4); C57BL/6J (H-2b), BUB/BnJ (H-2q) and CBA/CaJ (H-2k) had the lowest number (3.4-4.0). Studies in congenic mice further suggested that genes within the major histocompatibility complex do not have a major influence on determining the ability of schistosomes to develop into mature adult worms. Results of experiments in which adult worm loads in the F1 generation of C57BL/6J X BALB/cJ were compared with F1 X C57BL/6J and F1 X BALB/cJ backcrosses are consistent with homozygosity for a polygenic phenomenon controlling susceptibility to primary S. mansoni infection. Strain associated differences in parasite development appeared to be related to host defense processes directed against maturing adult worms.

Animals↗
PubMed1983

Genetic association of murine susceptibility to Brugia malayi microfilaraemia.

The influence of host genetics on susceptibility of mice to Brugia malayi microfilariae and its possible mechanism were studied. There was a strain-association for duration and peak level of microfilaraemia: CBA/CaJ, C3H/HeJ, DBA/1J, AuSs/J and A.S.w/Sn had a short duration (3-5 days) and low parasitemia (19-26 parasites/100 microliters blood) compared to C57Br/cdJ, AKR/J, C57BL/6J, 129/J, BALB/cJ, DBA/2J, B10.D2/NSn, B10.D2/OSn and SJL/J (duration of 58-73 days, peak parasitaemia of 58-74 parasites/100 microliters blood). Relative resistance to microfilariae was not related to the H-2 complex as determined in studies of congenic C3H.B10 (H-2b) and B10.H-2k mice and their background strains. This trait was inherited in a dominant fashion and involved a single or small number of genes. Serum anti-microfilarial antibodies reached highest levels in strains with a long duration compared to those with a short duration of parasitaemia (geometric mean titres of 1:13450 vs 1:284). The distribution of 51Cr-labelled microfilariae among the livers, spleens, lungs and kidneys of a resistant (CBA/CaJ) and a susceptible (C57BL/6J) strain was similar. Transfer of immune lymphoid cells or sera between histocompatible (H-2k) resistant CBA/CaJ mice and susceptible C57Br/cdJ animals did not alter the duration of microfilaraemia.

Animals↗
PubMed1983

Non-specific suppression of antigen-induced lymphocyte blastogenesis in Onchocerca volvulus infection in man.

Lymphocyte blastogenic responses to O. volvulus antigen (Oncho Ag), SKSD, and the mitogen PHA were tested in three groups of persons: light to moderately infected persons (INF); previously exposed but uninfected persons (EXP) and normal controls (NC). The exposed group showed significant responsiveness to Oncho Ag (delta ct/min = 6,002 +/- 1,375), while the infected (delta ct/min = 943 +/- 418) and normal control (delta ct/min = 428 +/- 418) groups did not. The mean blastogenic response to SKSD were EXP, 8,644 +/- 5,249; NC 6,039 +/- 2,880; INF, 2,619 +/- 1,012. The reduced reactivity in the INF group to Oncho Ag showed a significant correlation with reactivity to SKSD (P less than 0.05). To elucidate the mechanism of hyporesponsiveness in the infected group rigorous adherent cell depletion, by adherence to plastic followed by a nylon wool column, was utilized. When 20% plastic adherent cells were added back to the T cells prepared in this fashion, the mean blastogenic response to SKSD was significantly augmented (P less than 0.01). In contrast, the responsiveness to Oncho Ag was not significantly altered. The addition of indomethacin (1 microgram/ml) or autologous plasma had no significant effect on reactivity to either SKSD or Oncho Ag. There were no significant differences in the mean reactivity of the three groups to PHA-M (delta ct/min EXP 78,514 +/- 12,564; INF 62,393 +/- 14,447; NC 61,423 +/- 4,465). These results suggest that O. volvulus infection is associated with decreased lymphocyte reactivity to both parasite related and unrelated antigens, and imply that the mechanism for the two types of hyporesponsiveness may be distinct. While a weakly adherent suppressor cell may account for non-specific hyporesponsiveness, the mechanism of parasite specific decreased reactivity remains unknown.

Adolescent↗
PubMed1981

Immunopathology of murine infection with Schistosoma mansoni: relationship of genetic background to hepatosplenic disease and modulation.

The influence of genetic factors on the manifestations of disease associated with infection with Schistosoma mansoni (portal hypertension, liver granulomas, hepatosplenomegaly) and their modulation were studied in inbred strains of mice. Three groups were identified according to the degree of portal hypertension: high (portal venous pressure, 19.1 cm H2O: DBA/1J), intermediate (8.9-13.4 cm H2O; BALB/cJ, DBA/2J, CBA/CaJ, C3H/HeJ, and BUB/BnJ), and low responders (6.1 cm H2O; C57BL/6J). Granuloma size, organomegaly, and portal venous pressure were strain dependent and not H-2 dependent and were determined by more than one gene. Studies of schistosomiasis in the F1 generation of high and low responders indicated that more than one gene is involved. Modulation of portal venous pressure between eight and 20 weeks of infection occurred in C57BL/6J but not in BALB/cJ mice and was transferable with immune lymphoid cells. These data indicate that disease associated with infection with S. mansoni and its modulation in mice are influenced by the genetic (non-H-2) background of the host and dependent in part on cell-mediated immunity.

Animals↗
PubMed1981

Role of cell-generated hydrogen peroxide in granulocyte-mediated killing of schistosomula of Schistosoma mansoni in vitro.

Human as well as murine granulocytes have been shown to kill the larval stages of helminth parasites; the mechanism of this cell-mediated cytotoxicity is, however, poorly understood. The present study was designed to assess the role of peroxidative processes in killing of schistosomula of Schistosoma mansoni by human granulocytes in vitro. The rate of H(2)O(2) production by human neutrophils, eosinophils, and basophils was measured upon incubation with schistosomula alone or in the presence of specific antibody or complement. Opsonized parasites (antibody and/or complement) increased the rate of H(2)O(2) production by neutrophils, eosinophils, and basophils by respective percentages of 500, 500, and 371. The rate of H(2)O(2) release was directly related to the number of granulocytes and to the proportion of cells attached to the surface of the schistosomula. Increased hydrogen peroxide release occurred by 10 min of incubation and was demonstrable up to 16 h after addition of leukocytes to schistosomula. The primary source of this oxygen product was found to be the granulocytes adherent to the schistosomula and not those that remained unattached. Hydrogen peroxide production by neutrophils and eosinophils was quantitatively similar (schistosomula coated with antibody plus complement stimulated 5 x 10(6) neutrophils and eosinophils to release H(2)O(2) at respective rates of 0.35 and 0.40 nmol/min). Granulocyte-mediated parasite killing correlated with rate of H(2)O(2) generation; both processes were inhibited by catalase. To define further the role of oxidative metabolites, neutrophils and eosinophils of two subjects with chronic granulomatous disease were used; marked reduction of granulocyte-mediated parasite mortality was observed. Peroxidase was required for H(2)O(2)-mediated killing. Addition of the peroxidase inhibitors azide (1 mM), cyanide (1 mM), or aminotriazole (1 cM) to neutrophilschistosomula mixtures significantly reduced parasite cytotoxicity (P < 0.01); similar reduction was observed when eosinophils were used (P < 0.01). Fixation of halide (iodide) to trichloroacetic acid-precipitable protein (2.4-6.0 nmol/h per 10(7) neutrophils) was demonstrated in the presence of granulocytes, opsonins, and parasites; this process was completely inhibited by 1 mM azide. These data indicate that contact between the surfaces of human granulocytes and schistosomula results in release of cellular hydrogen peroxide and iodination. The generation of H(2)O(2) and its interaction with peroxidase appear to be crucial in effecting in vitro granulocyte-mediated parasite cytotoxicity.

Animals↗
PubMedDate not supplied

Sexual behaviour changes in a cohort of male sexual contacts of men with HIV disease: a three-year overview.

We describe the sexual behaviour reported by 240 seronegative and seropositive homosexual men over a 3-year period. Sexual partners of men with HIV disease were recruited into a prospective study between July 1984 and July 1985 and were monitored every 3 months thereafter. Data on sexual activities were collected through interviewer-administered questionnaires. The cohort experienced a reduction in both the number of sexual partners and the volume of sexual activity. Reductions in the number of partners were early and dramatic. Changes in sexual activities were gradual and consistent in trend. The greatest reduction occurred in high risk activities (receptive and insertive anal intercourse). After 3 years of follow-up, only 10% of the men continue to be exposed to semen through unprotected receptive anal intercourse and 18% through unprotected receptive oral-genital sex. The proportion of men engaging in oral-genital contact and masturbation remained stable over the 3 years. Once informed of their serostatus, both seropositive and seronegative men reduced their high risk behaviour. The decline in rates of STDs and seroconversion confirmed that this cohort had indeed reduced their high risk behaviour.

Cohort Studies↗