Biomedical subjects

K L White

Publications and source records attributed to K L White.

At least 127 records · Page 7Linked to original sources

PubMed1991

The medical school's mission and the population's health.

A conference organized by the Royal Society of Medicine Foundation was attended by 37 participants from Canada, the United Kingdom, the United States, and Australia. The discussants reviewed eight precirculated papers and concluded that society's concerns about the provision, availability, and costs of health care warranted re-examination of the assumptions and priorities of medical education. To reorient medical education to the actual and perceived health care needs of the population, specific recommendations were developed in five areas that integrate the patient, physician, and population perspectives on medical education: the medical school's goals and objectives, faculty development, undergraduate and postgraduate education, educational resources, and health intelligence. The participants also devised implementation strategies.

Australia↗

PubMed1991

Suppression of the in vitro humoral immune response of mouse splenocytes by 7,12-dimethylbenz[a]anthracene metabolites and inhibition of immunosuppression by alpha-naphthoflavone.

Exposure to 7,12-dimethylbenz[a]anthracene (DMBA) has been demonstrated by numerous investigators to result in suppression of both humoral and cell-mediated immune responses of mice and cultured splenocytes. The mechanism(s) of this DMBA-induced immunosuppression, however, is not well characterized. PAHs must be converted to reactive metabolites via cytochrome P450-dependent monooxygenase systems to exert their carcinogenic and mutagenic effects. Thus, we have hypothesized that immunosuppression seen upon exposure to DMBA may also be mediated by its reactive metabolites. The objective of this study was to determine if DMBA metabolites can suppress the in vitro, T-dependent humoral immune response to sheep red blood cells. Compounds were evaluated in the in vitro plaque-forming cell (PFC) response at concentrations of 10(-9) to 10(-5) M. DMBA and benzo[a]pyrene (B[a]P) were also evaluated for their ability to suppress the in vitro PFC response. Addition of either of these PAHs to splenocyte cultures produced a concentration-dependent suppression of the PFC response, in which B[a]P was found to be 17.5-fold more potent than DMBA. These results are in contrast to those found in vivo, where DMBA has been shown to be more potent than B[a]P at suppressing humoral immunity. The 3,4-diol metabolite of DMBA produced a concentration-dependent suppression (10(-8) to 10(-5) M) of the in vitro PFC response and was found to be 65-fold more potent than the parent compound DMBA. In contrast, the 5,6-diol metabolite of DMBA had no effect on the PFC response or cell viability. Both the 3-OH-DMBA and 7-hydroxymethyl-12-methyl-benz[a]anthracene (7-OHMe-12-Me-BA) metabolites were found to be immunosuppressive at concentrations of 10(-6)M. Furthermore, suppression by 7-OHMe-12-Me-BA was observed at concentrations as low as 10(-8) M. Immunosuppression by the 7-Me-12-OHMe-BA and the di-OHMe-BA metabolites was only observed at high (10(-5) M) concentrations. The cytochrome P450 inhibitor, alpha-naphthoflavone (ANF), was utilized to determine if cytochrome P450-mediated metabolism is involved in DMBA-induced suppression of the in vitro PFC response. ANF (10(-5) M) reversed the DMBA-induced immunosuppression seen at 10(-5) M and attenuated the immunosuppression at 3 x 10(-5) and 10(-4) M. The results of these studies demonstrate that several metabolites of DMBA which can be generated by the cytochrome P450-dependent monooxygenase systems are immunosuppressive in the in vitro PFC response assay. Furthermore, the cytochrome P450 inhibitor, ANF, was able to reverse DMBA-induced immunosuppression.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

Effects of PCB (Aroclor 1254) on non-specific immune parameters in rhesus (Macaca mulatta) monkeys.

The effects of low level, chronic polychlorinated biphenyl--Aroclor 1254--(PCB) exposure were investigated on non-specific immune parameters in female rhesus (Macaca mulatta) monkeys. Five groups of monkeys were orally administered with PCB at concentrations of 0, 5, 20, 40 or 80 micrograms/kg bw/day. Immunotoxicity testing was initiated after 55 months of exposure. The serum hemolytic complement activity in all PCB treated groups was significantly higher (P less than 0.05) than that in the control group. A statistically significant dose-related increase in natural killer cell activity was evident at the 75:1 effector to target cell ratio. Similarly, a statistically significant dose-related increase was noted for thymosin alpha-1 levels but not for thymosin beta-4 levels. Statistically significant increased interferon levels were noted in the 20 and 80 micrograms/kg groups compared with the control group while the levels in the 40 micrograms/kg group were decreased significantly compared with the control group. The production of tumor necrosis factor by monocytes in the PCB treated groups was not different to that in the control group. The results indicated that long term exposure to PCB modulate several non-specific immune parameters.

Animals↗

PubMed1991

Effects of CI-949, a novel antiallergy compound, on host resistance in mice.

The effect of CI-949, a novel inhibitor of allergic mediator release, on immune function was assessed with holistic mouse models of immunocompetence. Resistance to the bacterial pathogens Listeria monocytogenes and Streptococcus pneumoniae and the B16F10 melanoma cell line was used to evaluate the potential of CI-949 to affect immune function. CI-949 treatment of female B6C3F1 mice increased pulmonary tumor burden at 100 mg/kg/day in the B16F10 melanoma model, with a no effect level of at least 50 mg/kg/day. A correlation was seen between decreased clearance of the B16F10 cells and increased tumor burden. However, CI-949 produced this effect only at the maximum tolerated dose. No effect of the drug was seen in the S. pneumoniae model. Host resistance to L. monocytogenes was increased after CI-949 administration, with the no adverse effect level in this model being at least equivalent to the top dose of 100 mg/kg/day. Therefore, the immune system does not appear to be adversely affected or to be a specific target for CI-949 even at an overtly toxic dose.

Animals↗

PubMed1991

Kleptomania: a report of 20 cases.

OBJECTIVE: The authors' objective was to provide phenomenologic, family history, and treatment response data on a group of rigorously diagnosed patients with kleptomania. METHOD: Twenty consecutive inpatients and outpatients met DSM-III-R criteria for current kleptomania or a past history of kleptomania. These patients were given structured diagnostic interviews, and their family histories of psychiatric disorders were assessed blindly. The patients' responses to psychosocial and biological treatments were also assessed. RESULTS: All of the kleptomanic patients had lifetime diagnoses of major mood disorders, 16 had lifetime diagnoses of anxiety disorders, and 12 had lifetime diagnoses of eating disorders. A high morbid risk of major mood disorders (0.31) was found in their first-degree relatives. Ten of 18 patients receiving thymoleptic medications reported reduction or remission of their stealing behavior. CONCLUSIONS: Kleptomania may be related to major mood disorder and perhaps may represent another form of "affective spectrum disorder."

Adult↗

PubMed1991

Suppression of sheep and goat lymphocyte proliferation by sheep, goat, and sheep x goat hybrid trophoblast tissue cultures.

Immunosuppressive activity of conditioned medium from cultured ovine, caprine, and hybrid trophoblast tissue was examined. Conceptuses were obtained from naturally mated donor ewes and does at d 20 of gestation and trophoblast tissue was cultured for 24 h in medium supplemented with 15% calf serum and 1% antibiotic/antimycotic. Conditioned medium was added to pokeweed mitogen-stimulated sheep and goat lymphocyte cultures. Quantification of [3H]thymidine uptake by cells was used to measure lymphocyte proliferation. Ovine, caprine, and hybrid conditioned medium effectively suppressed sheep and goat lymphocyte proliferation (P less than .01). There were no differences (P greater than .05) between the immunosuppressive activity of the three tissue types on either sheep or goat lymphocytes. For all treatment groups, sheep lymphocytes were suppressed more than goat lymphocytes (P less than .05). These results indicate that, at d 20 of gestation, sheep x goat hybrid trophoblast tissue is capable of suppressing pokeweed mitogen-stimulated lymphocyte proliferation.

Animals↗

PubMed1991

Responses of cortisol and prolactin to sexual excitement and stress in stallions and geldings.

Sexual stimulation induces rapid secretion of cortisol and prolactin (PRL) in stallions. Experiment 1 was designated to determine whether stallions associated location and(or) procedure with previous sexual stimulation in that location. After a control period on d 1, four stallions were exposed to an estrous mare for 5 min on d 2. On d 3, 4, 5, and 6, the same procedure was followed with no mare present. Concentrations of PRL and cortisol increased (P less than .05) after mare exposure on d 2 but did not vary (P greater than .05) on d 1, 3, 4, 5, or 6. In Exp. 2, six stallions were used to determine the short-term effects of 1) sexual stimulation, 2) acute physical exercise, 3) restraint via a twitch (twitching), 4) epinephrine administration, and 5) no stimulation on plasma concentrations of PRL and cortisol. Stallions received one treatment per day separated by 2 d of no treatment. Concentrations of cortisol increased (P less than .05) within 10 min after sexual stimulation, exercise, twitching, and epinephrine administration but not during control bleedings. Concentrations of PRL increased (P less than .05) immediately after sexual stimulation, exercise, and twitching but not after epinephrine administration or during control bleeding. In Exp. 3, the same five treatments were administered to six geldings. Concentrations of cortisol increased (P less than .05) after epinephrine administration, exercise, and twitching but not after sexual stimulation or during control bleedings. Concentrations of PRL increased (P less than .05) after exercise and sexual stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effects of CI-949, a novel antiallergy agent, on immune function of male Fischer 344 rats.

CI-949 is an orally effective inhibitor of allergic mediator release as measured with in vitro and animal models. To assess the effects of CI-949 on immune function, male Fischer 344 rats were evaluated for splenic T- and B-lymphocyte populations, antibody-forming cell response to sheep red blood cells (sRBC), concanavalin A- and pokeweed mitogen-induced lymphocyte proliferation, Natural Killer cell activity and reticuloendothelial system clearance of sRBC. CI-949 was administered by gavage to rats at 25, 50 and 100 mg/kg/day for 14 consecutive days. A vehicle control and two positive controls (cyclosporine A and cyclophosphamide) were run concurrently. CI-949 at 100 mg/kg/day decreased body weight gain and was lethal to 5 of 40 rats. The deaths occurred between days 5 and 12 of study. This overtly toxic dose did not alter splenic cellularity or change the percentages of T- and B-lymphocyte subpopulations. Additionally, CI-949 did not inhibit lymphocyte proliferation or hinder clearance of sRBC by the reticuloendothelial system. Antibody-forming cell response after immunization showed a dose-related increase in the number of immunoglobulin M secreting cells. Based on the results of these assays, the immune system does not appear to be adversely affected by CI-949 even at high doses.

Animals↗

PubMed1990

Effect of microinjection and two types of electrical stimuli on bovine sperm-hamster egg penetration.

These experiments were designed to test the effects of an electrofusion and an electroporation pulse on bovine sperm-hamster egg development. In experiment 1, single motile sperm were injected into the perivitelline space of each egg. A 4,500 V/cm, 30 microseconds fusion pulse (FP) was applied while sperm-egg membrane contact was maintained. It was observed that single motile sperm were rendered immotile immediately after FP application whereas nonpulsed single motile sperm remained motile for up to 36 h postinjection. In addition, both motile and sonicated spermatozoa were injected directly into the ooplasm prior to receiving an FP to determine whether the FP was detrimental to sperm viability. In experiment 2, to induce the acrosome reaction, an 1,150 V/cm electroporation pulse was applied to washed bovine sperm suspended in TALP medium containing 5 mM Ca2+. Treated and nontreated sperm were coincubated with zona-free hamster ova, and sperm-pentrating ability was measured. Results from experiment 1 indicate that FP failed to induce sperm-egg fusion (0/69). FP did not, however, inhibit decondensation or pronuclear formation of sperm injected into hamster egg ooplasm. Single motile sperm injected into the ooplasm resulted in development of both pulsed (19/28) and nonpulsed (21/28) groups. Sonicated tail-free sperm heads injected into the ooplasm resulted in no detectable difference between treated (18/30) and nontreated (19/30) groups. In experiment 2, treatment of sperm with electroporation pulse +5 mM Ca2+ increased zona-free hamster ova penetration scores over nontreated sperm within bulls (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗

PubMed1990

Formation and characterization of vesicles from day-10 horse conceptuses.

The objectives of this research were 1) to determine if cellular vesicles could be formed from Day-10 horse conceptuses similar to trophoblastic vesicles reported for other domestic species and 2) to characterize various aspects of their development in vitro and their ability to withstand the freeze-thaw process. Twenty-five conceptuses were recovered from lighthorse mares on Day 10 after ovulation. After two washes in 0.05% trypsin, each conceptus was placed in 0.25% trypsin until the capsule thinned. Mechanical dispersion with a glass pipette resulted in a combination of individual cells and cell clumps. When cultured in vitro, all preparations exhibited both partially and completely formed vesicles within 24 h. Cellular monolayers also developed within the first 24 h of culture and were predominant by 96 h. Within 13 to 20 d, all monolayers developed dense areas of cells that eventually released from the cell matrix and aggregated to form vesicles. Progesterone and total estrogen concentrations in media samples were lower (P < 0.05) for conceptuses that had required long trypsinization periods for dispersion. Pregnant mare serum gonadotropin was not detectable in any samples. Vesicles cultured in nontreated tissue culture flasks.doubled in size within 24 h but did not increase further by 48 h. Of 234 vesicles frozen after 48 h of culture, the postthaw viability, as measured by the ability to return to prefreeze characteristics, was 34, 21 and 11% after 24, 96 and 168 h in culture, respectively. We conclude that vesicles can be formed by enzymatic dispersion of Day-10 horse conceptuses. However, monolayers were the predominant result of both the initial dispersions and the long-term culture of vesicles. Vesicles showed a limited ability to grow in vitro.

Journal Article↗

PubMed1990

Effects of naphthalene and naphthalene metabolites on the in vitro humoral immune response.

Naphthalene-induced pulmonary and renal toxicity and polycyclic aromatic hydrocarbon-induced carcinogenesis are known to be mediated by their reactive metabolites. Subchronic exposure (90 d) of mice to naphthalene does not alter humoral and cellular-mediated immune responses, whereas polycyclic aromatic hydrocarbons, such as benzo[a]pyrene and 7,12-dimethylbenzanthracene, are known to be immunosuppressive. To understand these differences, the antibody-forming cell (AFC) responses of splenocyte cultures exposed to naphthalene (2, 20, and 200 microM) were evaluated. At these concentrations, the antibody-forming cell response to sheep red blood cells (RBC) was not affected. To determine if reactive metabolites of naphthalene were immunosuppressive, splenocytes were exposed to naphthalene metabolites by direct addition or through the use of a metabolic activation system. The addition of 1-naphthol (70 and 200 microM) and 1,4-naphthoquinone (2, 7, and 20 microM) resulted in a decreased antibody-forming cell response. Suppression of AFC responses was also obtained by culturing splenocytes with liver S9 and naphthalene. Since splenic metabolism of naphthalene to nonimmunosuppressive metabolites may account for the absence of immunotoxicity, the types of naphthalene metabolites generated by splenic microsomes were determined. It was observed that splenic microsomes were unable to generate any detectable naphthalene metabolites, whereas liver microsomes were able to generate both 1,2-naphthalene diol and 1-naphthol. Thus, the absence of an immunosuppressive effect by naphthalene exposure may be related to the inability of splenocytes to metabolize naphthalene. Moreover, the concentration of naphthalene metabolites generated within the liver that may diffuse to the spleen may be inadequate to produce immunotoxicity.

Animals↗

PubMed1990

Suppression of lymphocyte proliferation by a greater than 30,000 molecular weight factor in horse conceptus-conditioned medium.

In this experiment we have identified and partially characterized the immunosuppressive activity of preimplantation horse conceptus-conditioned medium (HCCM). Horse conceptuses were nonsurgically flushed from mares at Days 9-10 (n = 6), 15-16 (n = 3), and 25-26 (n = 3). After incubating the conceptuses for 24 h in RPMI-1640 supplemented with 15% fetal calf serum (FCS) and 1% penicillin/streptomycin, HCCM was obtained from cultures and tested for immunosuppressive activity in lymphocyte proliferation assays. Peripheral blood lymphocytes obtained from randomly selected mares were stimulated with mitogens (pokeweed mitogen [PWM], concanavalin A [Con A], and phytohemagglutinin [PHA]) in cultures supplemented with 0%, 25%, or 50% HCCM. HCCM from all cultures suppressed lymphocyte proliferation induced by all three mitogens (p less than 0.001). After being subjected to various treatments (heating, freeze-thawing, and nitrocellulose filtration), HCCM maintained its full biological suppressor activity. Amicon microconcentrators with 10,000 and 30,000 molecular weight (MW) exclusion filter membranes were used to fractionate HCCM by molecular weight. The suppressor factor was found to be in the greater than 30,000 MW fraction. HCCM was further tested interspecifically on donkey and goat lymphocytes stimulated with PWM. HCCM did suppress proliferation of interspecific lymphocytes (p less than 0.01); however, the suppressive capacity of HCCM in caprine lymphocyte cultures was less (p less than 0.05) than that observed in equine cultures. These data support the hypothesis that the horse conceptus produces an immunoregulatory factor. This factor is extremely stabile and appears to exhibit some degree of species-specificity. The production and immunosuppressive effectiveness of such a factor may play an important role in maintaining the fetal allograft throughout gestation.

Animals↗

PubMed1990

Incorporation and expression of a neo gene after transfer to caprine hematopoietic cells using a modified retrovirus.

The ability of the N2 retrovirus to introduce the selectable neo gene into (transform) caprine hematopoietic cells (CHC) was evaluated. Helper-free amphotropic retrovirus producing cells (RPC) were plated at approximately 1.0 x 10(5) cells per 25 cm2 tissue culture flask, cultured to 80% confluence and irradiated (1,500 rads) prior to CHC incubation. The CHC collected from three donor goats were washed and cultured for 24 h in either the RPC or control flasks. Cells were cultured in Dulbecco's Modified Eagles Medium containing 10% fetal calf serum (FCS) (DMEM) and 4 micrograms polybrene/ml. After 48 h of culture in fresh DMEM, cells were recovered and suspended in Iscove's DMEM supplemented with .3% gar, 12% FCS and 400 micrograms geneticin/ml (G418; neomycin) and transferred to 35-mm petri dishes (7.5 x 10(5) cells) for selection of G418 resistant cells. After 17 d of culture, plates were evaluated for total number of colony forming units (CFU, greater than 10 cells). Total number of CFU was greater (P less than .01) in treatment samples (means = 175, SEM = 70) than in control cultures (mean = 0, SEM = 0). The N2 retrovirus appears to be an effective vector for the transformation of CHC and may provide a means to introduce gene(s) into cells of domestic animals.

Animals↗

PubMed1990

Isobolographic characterization of drug interactions incorporating biological variability.

Isobolograms have been widely used to characterize the nature of the interaction between combinations of drugs or chemicals. Some authors have applied this technique without accounting for the variability in the data or without adjusting for multiple comparisons to the line of additivity. This paper develops a graphical procedure which takes into account the variability of the data and which maintains favorable statistical properties. The isobolographic procedure utilized is illustrated by using three classical pharmacological drug combinations in female ICR mice. An additive relationship is illustrated with the loss of righting reflex after combinations of doses of sodium hexobarbital with itself. An antagonistic relationship is illustrated with the protection by mecamylamine of nicotine-induced lethality. A synergistic relationship is illustrated with the loss of righting reflex after combinations of ethanol and chloral hydrate. The procedure's statistical properties (level of significance and power) were determined using a simulation study. The isobolographic procedures developed here are applicable for quantal, continuous and count data. These procedures are applicable for identifying beneficial drug combinations, or conversely, identifying hazards resulting from exposure to multiple toxicants.

Animals↗

PubMed1989

Benzo(a)pyrene metabolism by murine spleen microsomes.

The immunosuppressive actions of benzo(a)pyrene have been proposed to be mediated by reactive metabolites rather than the parent compound. Reactive metabolites which suppress splenic humoral immune responses are thought to be generated within the spleen rather than in distant tissues. Although the spleen has been shown to be capable of metabolizing benzo(a)pyrene, the relative amounts and types of metabolites generated have not been determined. In this study, high-pressure liquid chromatography was used to separate benzo(a)pyrene metabolites generated by splenic microsomes. The major metabolites generated by the splenic microsomal preparations of untreated female B6C3F1 mice were found to be the 9,10- and 7,8-dihydrodiols and 9-, 7-, and 3-hydroxy benzo(a)pyrene. The 1,3-, 3,6-, and 6,12-diones and 4,5-dihydrodiol constituted only a small fraction of the metabolites generated. The generation of all metabolites were inhibited by alpha-naphthoflavone and antiserum to NADPH-cytochrome P-450 reductase, whereas SKF 525-A had only a minimal effect. Dihydrodiol production was completely inhibited by the epoxide hydrolase inhibitor, trichloropropylene oxide. Benzo(a)pyrene pretreatment of mice produced a dramatic increase in the amount of metabolites formed; however, the pattern of metabolites remained similar to that generated by splenic microsomes of untreated mice. The role of prostaglandin synthetase in generating these metabolites was also examined. The addition of arachidonic acid in place of NADPH resulted in the formation of only quinones. Dihydrodiols and phenols were undetectable. The results of this study indicate that splenocytes may be capable of generating the 7,8-dihydrodiol, the precursor to the highly reactive 7,8-dihydrodiol-9,10-epoxide. Furthermore, the addition of the 7,8-dihydrodiol-9,10-epoxide to splenocyte cultures resulted in a decreased in vitro antibody forming cell response to sheep red blood cells. Thus, benzo(a)pyrene-induced immunosuppression may be mediated by the dihydrodiol-epoxide generated within the spleen. Since benzo(a)pyrene exposure was found to increase its own metabolism, immunosuppression produced by the administration of benzo(a)pyrene over several days may be the result of an increased production of immunosuppressive metabolites. The pattern of metabolites generated and the effects of the two types of cytochrome P-450 inhibitors suggests that the major isozyme of cytochrome P-450 that mediates the metabolism of benzo(a)pyrene within the spleen of untreated mice may be similar to the isozyme induced in the liver upon pretreatment with polycyclic aromatic hydrocarbons.

Animals↗

PubMed1989

A comparison of three nucleoside analogs with anti-retroviral activity on immune and hematopoietic functions in mice: in vitro toxicity to precursor cells and microstromal environment.

A number of 2'3'-dideoxynucleosides have been reported to markedly inhibit the in vitro growth of HIV, the causative agent of acquired immunodeficiency syndrome (AIDS). Clinical trials have shown that the continued therapeutic use of these nucleoside derivatives can be associated with adverse side effects. Since these side effects include myelotoxicity, as occurs in many patients treated with zidovudine (AZT; 3'-azido'3-deoxythymidine), and AIDS patients already represent an immunologically compromised population, we examined the immunological effects of three nucleoside inhibitors, including zidovudine, 2'3'-dideoxycytidine, and 2'3'-dideoxyadenosine (DDA) in a mouse model. Additional studies were conducted to further determine and characterize the potential toxic effects associated with these drugs on the hematopoietic system. Of the three dideoxynucleosides examined, only DDA altered immune functions following a 30-day subchronic exposure in mice. This was evidenced by a marked suppression of the antibody plaque-forming cell response and a slight alteration in macrophage function. None of the nucleoside derivatives affected bone marrow function following in vivo exposure, although AZT produced a mild macrocytic anemia in vivo and was myelotoxic when added in vitro to bone marrow cell cultures. In vitro studies indicated that AZT was capable of affecting both proliferating stem cells as well as the stromal cell microenvironment, both of which play a role in hematopoiesis. These data indicate that, although the mice may not develop the identical toxicities associated with nucleoside therapy in humans, certain adverse immunological and hematological effects were readily discerned which could have relevance to humans.

Acquired Immunodeficiency Syndrome↗

PubMed1989

Immunotoxicity of the semiconductor gallium arsenide in female B6C3F1 mice.

The effects of gallium arsenide (GaAs) exposure on immunocompetence of B6C3F1 female mice were investigated. GaAs was administered as a single intratracheal instillation at doses of 50, 100, and 200 mg/kg. Fourteen days after exposure, various cellular and humoral immune parameters were assessed. GaAs exposure increased spleen cellularity in a dose-dependent manner. However, the percentages of Thy 1.2 positive and Ig positive cells were decreased and that of F4/80 positive cells was increased dose dependently. The IgM and IgG antibody-forming cell response of the spleen to the T-dependent antigen sheep erythrocytes was reduced by 66 and 48%, respectively, at 200 mg/kg. Levels of the serum complement protein, C3, were increased by as much as 16% with no significant change in CH50 levels. The mitogenic response of splenic T cells to Con A and PHA was unaffected by GaAs, but that of B cells to LPS was increased by 52%. The delayed hypersensitivity response to keyhole limpet hemocyanin and mixed lymphocyte response were significantly reduced in a dose-dependent manner by GaAs exposure. Natural killer cell activity against the YAC-1 mouse lymphoma was enhanced in treated mice. Analysis of peritoneal exudate cells (PEC) revealed a dose-dependent decrease in number and a shift in the composition of PECs. The percentage of PEC monocytes increased from 53% of the population to 81%, while the lymphocytes decreased from 46 to 20%. The adherent PEC population demonstrated decreased phagocytosis of covaspheres and increased phagocytosis of chicken erythrocytes (CRBC). GaAs exposure had no effect on host resistance to Plasmodium yoelii or Streptococcus pneumoniae, but dose dependently increased resistance of the mouse to Listeria monocytogenes. Treated mice demonstrated a significantly decreased resistance to the B16F10 melanoma with a sevenfold increase in tumor burden at 200 mg/kg. GaAs affects both humoral and cellular immune parameters in mice and impairs the ability of the immune system to protect against B16F10 tumor challenge.

Animals↗

PubMed1989

Early embryonic development in vitro by coculture with oviductal epithelial cells in pigs.

This experiment was designed to evaluate the ability of three different somatic cell cultures to promote development of early cleavage stage pig embryos. A total of 245 2-cell, 4-cell, 8-cell, and 16-cell pig embryos were cocultured for 5 days with porcine oviductal epithelial cells (POEC), porcine fetal fibroblast monolayer (PEF), a combined POEC and PEF coculture system (PEF-POEC), or Dulbecco's Modified Eagle Medium alone (DMEM). Embryos were collected at slaughter from the reproductive tracts of superovulated prepubertal gilts. Embryos were recovered, evaluated, and randomly placed in one of the four treatment groups. POEC were recovered from oviductal flushes, washed, and placed in 24-well plates. PEF were obtained from 30-day to 60-day fetuses and established in culture. Finally, PEF-POEC consisted of a confluent monolayer of PEF in the bottom of 24-well plates also containing a Costar semipermeable membrane chamber with POEC in it. Embryos were evaluated every 24 h to determine stage of development. More (p less than 0.05) embryos developed to blastocysts in POEC (70% and 54%, respectively) and PEF-POEC (67% and 61%, respectively), than in either DMEM (16% and 2%, respectively) or PEF (27% and 23%, respectively). However, development of embryos did not differ (p less than 0.05) for POEC and PEF-POEC. These data indicate the presence of a primary culture of POEC promotes in vitro development of early cleavage stage pig embryos.

Animals↗