Search PubMed⌕ Search

Biomedical subjects

J R Mead

Publications and source records attributed to J R Mead.

At least 37 records · Page 2Linked to original sources
PubMed1993

Effect of immunomodulators in the hu-PBL-SCID mouse model.

The effects of two immunomodulators were investigated in severe combined immunodeficient mice reconstituted with human peripheral blood lymphocytes (hu-PBL-SCID mice). Both immunomodulators, maleic anhydride divinyl ether (MVE-2) and 4-imino-1,3-diazobicyclo-(3.1.0)-hexan-2- one (imexon), have been previously studied by us in retrovirus-infected mice. To determine the effects of these compounds as they may function in humans, 24 SCID mice were each reconstituted with 20 x 10(6) ficoll-purified lymphocytes from a single donor. Five weeks after reconstitution, the mice received 16 mg/kg/day of MVE-2 intraperitoneally (i.p.) on days 0, 7, and 14 or 110 mg/kg/day of imexon i.p. daily for 14 days. Spleens were removed and splenocytes labeled with monoclonal antibodies for T- and B-cell enumeration as determined by flow cytometry 24 h after final treatment. Imexon-treated mice demonstrated a slight increase in total T cells and T cell subsets compared to control mice. T helper/T suppressor cell ratios in imexon-treated mice were brought to a normal 3:2 ratio compared to placebo-treated mice. Human immunoglobulin levels were markedly increased in imexon-treated mice. MVE-2-treated hu-PBL-SCID mice had significantly reduced numbers of total T cells compared to controls. The T-cell population results using human cells in SCID mice were similar to the effects of these immunomodulators on murine cells in immunologically competent mice.

Adjuvants, Immunologic↗
PubMed1992

Elucidation of mode of retroviral-inhibitory effects of imexon through use of immune competent and severe combined immune deficiency (SCID) mice.

Mice infected with various tumor retroviruses have been used as models for evaluating therapeutic substances for the treatment of some cancers, and more recently, for human immunodeficiency virus (HIV) infection, the causative agent of acquired immune deficiency syndrome (AIDS). Consequently, there is a need to determine the ability of biological response modifiers (BRMs) to specifically reduce virus-infected cells, as compared to their non-specific anti-proliferative effects. To address this need, a BRM, imexon, was evaluated in this study using three strains of mice having different Friend virus (FV)-specific immunological capabilities. The first strain, (B10.A x A/WySn)F1, was genetically capable of producing FV-specific neutralization and cytotoxic antibodies, the second, Balb/c, was not, and the third, SCID mice, lacked functional T and B cell immunity. Imexon treatment reduced virally-induced splenomegaly in all 3 strains; however, the concentration of splenic viral infectious centers (IC) were not affected. Since imexon was efficacious in reducing splenomegaly in SCID mice, the mode of action was concluded to not require functional T or B cell immunity. The observation that imexon did not affect splenic IC titers also suggested that imexon did not specifically eliminate virally infected cells, but may have functioned by other mechanisms. This study also demonstrated the use of various mouse strains as a strategy for delineating the modes of action of BRMs against murine retroviral infections.

Animals↗
PubMed1992

Treatment of murine cytomegalovirus infections in severe combined immunodeficient mice with ganciclovir, (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine, interferon, and bropirimine.

Severe combined immunodeficient (SCID) mice were found to be highly susceptible to murine cytomegalovirus (MCMV) infection. Treatment of infected mice with ganciclovir (12.5, 25, and 50 mg/kg of body weight for 10 days) starting 24 h after virus challenge resulted in delays in death by 2 to 8 days, and no animals survived the infection. (S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) was much more potent, with doses of 1, 3.2, and 10 mg/kg/day (for 10 days) increasing the mean survival time by 15 to 30 days. Twenty-day treatments with HPMPC starting 5 days after virus inoculation increased the mean survival time by 24 to 32 days, with once-weekly (50-mg/kg) treatments being equivalent to daily (10-mg/kg) treatments. Delays in the development of liver, lung, and spleen virus titers in ganciclovir- and HPMPC-treated groups correlated with extensions in the mean survival times relative to the survival times of the placebo controls. The two compounds were approximately equally toxic to uninfected BALB/c mice treated for 10 days, causing 80 to 100% mortality after a dose of 150 mg/kg and 0% mortality after a dose of 75 mg/kg. Thus, the relative therapeutic index of HPMPC was 50-fold greater than that of ganciclovir. Recombinant alpha interferon delta 4 alpha 1/alpha 2 (1 x 10(4) and 5 x 10(4) units per mouse per day) and bropirimine (100 and 300 mg/kg/day) provided no protection from the lethal MCMV infection. The severe combined immunodeficient mouse MCMV infection is an important new model that will permit chemotherapy regimens to be studied over several months.

Animals↗
PubMed1991

Effect of human, recombinant interleukin 2 on Punta Toro virus infections in C57BL/6 mice.

The effect of human recombinant interleukin-2 (rIL-2) on Punta Toro virus (PTV) infection was investigated in C57BL/6 mice. Immunologic and viral parameters were assessed after mice were treated i.p. with rIL-2 for 5 days. Treatment of mice with 25000 and 12500 units/mouse of rIL-2 resulted in significant inhibition of the disease as indicated by increases in survival of mice as well as decreases in liver and serum virus titers. Serum glutamic oxalic acid and pyruvic acid transaminase levels were also lowered indicating reduced liver damage. Murine IL-2 production returned to normal or above-normal levels in rIL-2 treated mice. Natural killer cell activity was also moderately stimulated by rIL-2 treatment. Significant amounts of interferon were not detected in the sera of treated mice. Weight gain and survival rates were similar for both toxicity and normal controls indicating that rIL-2 treatments had no toxic effect.

Animals↗
PubMed1991

Chronic Cryptosporidium parvum infections in congenitally immunodeficient SCID and nude mice.

Severe combined immune deficient (SCID) and athymic National Institutes of Health (NIH)-III (bg/nu/xid) mice were evaluated for susceptibility to Cryptosporidium parvum infections as neonates and as adults after challenge with inocula of 5 x 10(4) and 1 x 10(6) oocysts/mouse, respectively. SCID and NIH-III nude mice developed chronic infections that persisted over 12 weeks. Cryptosporidial organisms were observed in the small and large intestines of all mice. Colonization of the gallbladder and hepatobiliary duct epithelium occurred in a majority of the NIH-III nude mice and a smaller number of the SCID mice. Severe infections in both mouse strains were associated with clinical deterioration followed by death. Signs in these mice included dehydration, icterus, and emaciation. Deaths apparently resulted from hepatic dysfunction. Control mice experienced transient infections with no clinical signs. Immunodeficient mice should prove useful in studies of disease pathogenesis and in evaluating potential anticryptosporidial agents.

Animals↗
PubMed1990

Effects of ozone, chlorine dioxide, chlorine, and monochloramine on Cryptosporidium parvum oocyst viability.

Purified Cryptosporidium parvum oocysts were exposed to ozone, chlorine dioxide, chlorine, and monochloramine. Excystation and mouse infectivity were comparatively evaluated to assess oocyst viability. Ozone and chlorine dioxide more effectively inactivated oocysts than chlorine and monochloramine did. Greater than 90% inactivation as measured by infectivity was achieved by treating oocysts with 1 ppm of ozone (1 mg/liter) for 5 min. Exposure to 1.3 ppm of chlorine dioxide yielded 90% inactivation after 1 h, while 80 ppm of chlorine and 80 ppm of monochloramine required approximately 90 min for 90% inactivation. The data indicate that C. parvum oocysts are 30 times more resistant to ozone and 14 times more resistant to chlorine dioxide than Giardia cysts exposed to these disinfectants under the same conditions. With the possible exception of ozone, the use of disinfectants alone should not be expected to inactivate C. parvum oocysts in drinking water.

Animals↗
PubMed1990

Identification of isolate-specific sporozoite proteins of Cryptosporidium parvum by two-dimensional gel electrophoresis.

Five isolates of Cryptosporidium parvum collected from human, horse, and calf sources were compared for differences in sporozoite protein patterns by using two-dimensional gel electrophoresis. Silver-stained two-dimensional gels contained over 300 protein spots from detergent-solubilized sporozoites. A distinguishing 106-kilodalton peptide that shifted in isoelectric point was detected in four of the five isolates. Computerized two-dimensional gel analysis was performed to obtain objective quantitation of the pI shift. Three of these four isolates could be differentiated from one other by the pI shift in this peptide. The fifth isolate was distinguished by the absence of the 106-kilodalton peptide and the presence of a 40-kilodalton peptide that was not observed in any other isolate.

Alabama↗
PubMed1990

Endemic Cryptosporidium and Giardia lamblia infections in a Thai orphanage.

We conducted a point prevalence survey for enteric protozoa in 205 institutionalized orphans 1-61 months of age in Bangkok, Thailand. Cryptosporidium was identified in 17 children (8%), Giardia lamblia in 42 (20%), and 3 children (1%) had both parasites. At the time of diagnosis, diarrheal symptoms were present in a minority of subjects: 36% of children with Cryptosporidium alone, 10% with G. lamblia alone, and in 20% of those with neither parasite. Although chronic nutritional status (height/age) was similar in all groups, acute nutritional status (weight/height) was lower only in children with Cryptosporidium (Z score = -1.39 +/- 0.13) compared with children with G. lamblia (mean Z score +/- SEM = -0.56 +/- 0.26) or neither parasite (Z score = -0.78 +/- 0.13; P = 0.05). Detectable levels of Cryptosporidium-specific IgG antibodies by ELISA were identified in 15 of 16 Thai children with Cryptosporidium and in 17 of 19 Thai children without Cryptosporidium (mean OD +/- SEM = 1.27 +/- 0.18 vs. 1.06 +/- 0.13, respectively), but in only 1 of 18 sera from toddlers in day-care centers in Denver, CO (OD = 0.128 +/- 0.03). Although neither infection with Cryptosporidium nor G. lamblia was consistently associated with acute diarrheal symptoms, Cryptosporidium was more often associated with depressed acute nutritional status than G. lamblia. The high prevalence of specific antibodies to Cryptosporidium in Thai orphans suggests an association between high rates of exposure with asymptomatic excretion of the parasites.

Animals↗
PubMed1989

Effects of immune colostrum and orally administered antisporozoite monoclonal antibodies on the outcome of Cryptosporidium parvum infections in neonatal mice.

A neonatal BALB/c mouse model of cryptosporidiosis was used to examine the potential passive transfer of immunity via immune colostrum and oral treatment with anticryptosporidial monoclonal antibodies. Neonates suckled by dams that recovered from Cryptosporidium parvum infections were equally susceptible to infection as their control counterparts suckled by naive dams. Parasite loads among the control and immune colostrum-fed mice were indistinguishable. Neonates receiving orally administered antisporozoite monoclonal antibodies were equally susceptible to infections compared with the control and immune colostrum-fed mice. Parasite loads among the mice receiving daily oral treatment with monoclonal antibody mixtures exhibited significantly lower parasite loads compared with the control mice (P less than 0.05).

Administration, Oral↗
PubMed1988

Antigens of Cryptosporidium sporozoites recognized by immune sera of infected animals and humans.

The humoral response of humans, calves, and horses to Cryptosporidium sporozoite antigens was evaluated using a western blot technique. Sera from calves, humans, and horses were obtained at various times following the detection of infection. Sera were reacted with detergent-solubilized, sodium dodecyl sulfate polyacrylamide gel-electrophoresed (SDS-PAGE) sporozoite antigens. The number of antigens recognized by immune sera from humans and animals increased with time postinfection. A 20-kDa antigen appears to be a major sporozoite surface determinant labeled via membrane protein biotinylation and recognized by mouse monoclonal antibodies using indirect immunofluorescence and western blotting. Detectable recognition of the 20-kDa band occurred in 3-wk postinfection (PI) sera from all species tested. Reactivity to the 20-kDa band diminished significantly in sera 5 mo PI or longer from infected humans with no known recurrence of cryptosporidial diarrhea. In contrast, 12-mo PI sera from an individual constantly exposed to oocysts under working conditions was as strongly reactive as the 3-wk convalescent sera. Serum reactivity to the 20-kDa antigen appears to be a good indicator of exposure to Cryptosporidium.

Animals↗
PubMed1988

Field inversion gel electrophoretic separation of Cryptosporidium spp. chromosome-sized DNA.

Chromosomal DNA from 5 isolates of Cryptosporidium parvum and 1 of C. baileyi were compared by field-inversion gel electrophoresis (FIGE). FIGE analyses of parasite DNA prepared from purified sporozoites versus intact oocysts showed no observable differences. Chromosomal DNA migration patterns of the 5 C. parvum isolates were indistinguishable, whereas similar but distinct differences were evident between C. baileyi and the isolates of C. parvum. Oocyst-reactive monoclonal antibodies differentiated oocysts of C. parvum from those of C. baileyi but were unable to distinguish oocysts of 1 isolate of C. parvum from another.

Animals↗
PubMedDate not supplied

Mucosal cytokine and antigen-specific responses to Cryptosporidium parvum in IL-12p40 KO mice.

Studies of cellular immune responses to Cryptosporidium parvum have been limited in part by lack of suitable animal models. IL-12p40(-/-)mice are susceptible to initial infection with C. parvum but recover within 2 weeks, rendering the animals resistant to reinfection. Because the host responses that determine duration and severity of primary infection are not yet understood, we studied the cellular immune response to primary infection with C. parvum in IL-12p40(-/-)mice and also explored possible mechanisms for this response. Female IL-12p40(-/-)mice were inoculated with 10,000 oocysts. Uninfected age-matched mice served as controls. At different time intervals following exposure to oocysts, mice were sacrificed and their intestine, spleen, and mesenteric lymph node tissues were harvested. Cellular immune responses to C. parvum were characterized. Infection of IL-12p40(-/-)mice induced changes in the gene expression of the cytokines IFN-gamma, IL-4, IL-15, IL-18, TNF-alpha and TGF-beta during primary infection. There was also a significant increase in total numbers of lymphocytes and CD19/CD62L-expressing cells in mesenteric lymph nodes. These MLN cells exhibited increased antigen-specific proliferation and cytokine production (IL-6 and IFN-gamma) levels when stimulated in vitro. These observations delineate the cellular immune responses during acute C. parvum infection of the IL-12p40(-/-)mouse model.

Animals↗
PubMedDate not supplied

Characterization of an alpha-tubulin gene of Cryptosporidium parvum.

A gene encoding an alpha-tubulin of Cryptosporidium parvum was isolated and characterized. It had no introns, and encoded a 441-amino acid protein whose predicted ORF represented a typical alpha-tubulin protein with a MW of 50.5 kDa. This tubulin had an amino acid sequence similarity with Apicomplexa Plasmodium falciparum and Toxoplasma gondii higher than 88% and shared a number of conserved motifs.

Animals↗