Lymphocyte Blastogenesis In Response Research Articles

The effects of a single injection of dexamethasone-21-isonicotinate on the lymphocyte functions of dairy cows at two weeks post partum.

Dexamethasone is a potent therapeutic for treatment of the fatty liver syndrome or primary ketosis in post partum dairy cows. Reservations exist, however, among practitioners with respect to the risk of immunosuppression induced by corticosteroids. The aim of this study was to investigate the effect of a single injection of dexamethasone-21-isonicotinate on distinct immune functions of postpartum dairy cows because only scarce information is available on the effects of corticosteroid preparations when administered at a dosage and frequency for treatment of the fatty liver syndrome or primary ketosis. Sixteen Swedish red-pied dairy cows, between days 9 and 15 post partum, were allotted to either a control group (n = 8) or a treatment group (n = 8). The cows in the treatment group received a single intramuscular injection of a dexamethasone-21-isonicotinate suspension at a dosage of 0.02 mg/kg i.m. at the start of the experiment. White blood cell counts and selected lymphocyte functions (lymphocyte proliferation, expression of lymphocyte markers and the b2 and a4 chain of adhesion molecules belonging to the integrin family) and some parameters of the energy metabolism (glucose, insulin) were determined before the administration of corticosteroids (day 0) and subsequently at days 2, 4, 7 and 9 of the experiment. Changes in glucose and insulin were within the target range for treatment of the fatty liver syndrome or primary ketosis. Significant (P < 0.05) increases in the number of circulating white blood cells were observed in treated cows on the second day following treatment which was exclusively caused by an increase in the number of circulating neutrophils. Lymphocyte blastogenesis in response to ConA and the percentages of lymphocytes positive for CD2, CD4, CD8, CD49d and CD18 as well as the intensity of CD49d expression did not differ between the treatment and control groups. There was, however, a significant reduction (P < 0.01) in the intensity of CD18 expression on lymphocytes in the treated animals on the fourth day after treatment. In conclusion, a single administration of dexamethasone-21-isonicotinate in a dosage of 0.02 mg/kg i.m. at two weeks post partum in healthy cows had a significant but highly transient effect on CD18 expression on lymphocytes and the number of peripheral blood neutrophils, but did not affect lymphocyte blastogenesis or lymphocyte subpopulation patterns in peripheral blood.

Oxidized lipid depresses canine growth, immune function, and bone formation

Dietary oxidized lipids can increase oxidative stress and potentially contribute to a variety of disease syndromes. This research describes the first use of a canine model to assess the effects of dietary oxidized lipids on growth, antioxidant status, and some immune functions. Three groups of eight, two-month old coon-hound puppies were pair fed diets for 16 weeks. The control diet contained <50 ppm aldehydes, and two additional diets contained thermally oxidized lipids targeted to contain 100 ppm aldehydes (medium-oxidation) and 500 ppm aldehydes (high-oxidation). Dogs fed the high-oxidation diet weighed less than those from the medium-oxidation (P < 0.05) and control groups (P < 0.001) at the end of the study. Oxidized lipids reduced serum vitamin E levels, total body fat content, and bone appositional rate. At different time points of the study, peripheral blood neutrophils and monocytes from dogs fed the HO diet had reduced oxidative burst capacity and produced less superoxide and hydrogen peroxide when stimulated with phorbol esters compared to the control group. Lymphocyte blastogenesis in response to concanavalin A was suppressed by dietary oxidized lipid. This study indicates that dietary oxidized lipids negatively affect the growth, antioxidant status, and some immune functions of dogs. Importantly, some effects are evident at 100 ppm aldehydes in the diet, which is a moderate level of oxidation. The rapid growth and weight gain of the dog during the first 6 months of life may also provide a better model for assessing the risks of dietary oxidized lipid in children and adolescents than previously used rodent models.

Humoral and cellular immune responses of piglets after castration at different ages

In this study, growth of piglets and their humoral and cellular immune responses were used to evaluate the effect of castration at different ages. Piglets (n = 84) from 14 litters were assigned to one of the six treatments: castration or sham-castration at 3, 10 or 17 d of age. An injection of bovine serum albumin (BSA) was given on the day of castration and a second one 14 d later. Blood samples were taken at different times to evaluate the antibody levels against BSA and lymphocyte blastogenesis responses to concanavalin A (Con A), phytohaemagglutinin (PHA) and pokeweed mitogen (PWM). The age of piglets at the first immunization significantly influenced (P &lt; 0.0001) the ability to raise antibodies to the injected antigen. Three-day-old piglets developed weaker antibody response than those immunized at 10 or 17 d of age. Ten- and 17-d-old castrated piglets tended to develop weaker secondary antibody responses than sham-castrated piglets, while those castrated and sham-castrated at 3 d of age did not differ in their antibody response (interaction castration × age; P &lt; 0.08). The fluctuation in lymphocyte blastogenesis response between days 21 and 35 was numerically greater in castrated than in shamcastrated piglets. Ratios between days 35 and 21 of PWM proliferative indexes were significantly higher (P &lt; 0.05) in piglets castrated at 10 or 17 d of age than in sham-castrated piglets. The results indicate that castration of piglets at 10 d of age or older impairs antibody response to BSA and modulates piglet lymphocyte responses to mitogens. Castration at 3 d of age had no marked effect on antibody response and lymphocyte proliferation. Thus castration appears to be less disruptive to immune response if performed at three days of age compared to 10 d of age or older. Key words: Castration, stress, antibody formation, lymphocytes, pigs

Effect of estradiol and exercise on lymphocyte proliferation responses in female mice

Many North American women are encouraged to take estrogen replacement therapy and to begin (or continue) physical activity during the postmenopausal years. This study investigated the effect of estradiol exposure and physical exercise on lymphocyte proliferation responses to T and B cell mitogens in female mice. Sixty C57BL/6 mice were randomized to hormone and exercise treatment conditions: hormone treatment consisted of estradiol in vivo (71.4 μg estradiol per day for 21 days) or placebo pellet following bilateral ovariectomy, or surgical sham (mice were not ovariectomized). Exercise consisted of a single forced treadmill run (26 m/min, 6° slope, 90 min) or a sedentary control condition. Outcomes were thymic and splenic lymphocyte proliferation responses to the mitogens concanavalin A (ConA, 1.0 and 5.0 μg/mL concentrations) and lipopolysaccharide (LPS, 0.5, 1.0, and 2.0 μg/mL concentrations). In the thymus, there was a significant reduction of proliferation to ConA in the Ovx + E2 animals relative to the other conditions at both concentrations of mitogen. At 1.0 μg/mL concentration, there was a significant interaction of hormone and exercise treatments. Sham (control) mice given exercise had a higher proliferation response relative to sedentary counterparts, whereas E2 mice did not differ in proliferation responses, irrespective of exercise condition. In the spleen, exposure to high concentrations of estradiol was associated with reduced proliferation responses to both mitogens; there were, however, no main or interaction effects of exercise. These results suggest that high levels of estradiol exposure following ovariectomy in mice significantly reduces lymphocyte blastogenesis responses, and that thymic immunomodulation after acute exercise is masked by the hormonal effect.

HEALTH OF TREE SWALLOWS (TACHYCINETA BICOLOR) NESTING IN PESTICIDE-SPRAYED APPLE ORCHARDS IN ONTARIO, CANADA. I. IMMUNOLOGICAL PARAMETERS

The degree of pesticide exposure and its effects on the immune system and its development were determined in 16-d-old tree swallow (Tachycineta bicolor) chicks from 4 sprayed apple orchards and three nonsprayed sites in southern Ontario, Canada, during 1994-1995. Persistent contaminant residues were measured in tree swallow eggs and in each chick hepatic ethoxyresorufin O -deethylase (EROD) activity; body, immune organ,and liver masses; lymphocyte blastogenesis response; respiratory burst and phagocytic responses; hematological evaluation; and histological development of thymus, bursa of fabricius, and spleen were determined. Chemicals sprayed on apple orchards were mainly ethylene bisdithiocarbamate and myclobutanil fungicides and organophosphorus, carbamate, and synthetic pyrethroid insecticides. During the period between oviposition of the first egg in each nest to d 16 after hatching, individual nests in orchards were exposed to between 4 and 11 individual chemical applications and up to 3 mixtures of pesticide sprays. Concentrations of pesticides, polychlorinated biphenyls ( PCBs), and lead and arsenic residues in tree swallow eggs and liver were low and not variable among sites except p,p '-DDE, which was as high as 2.29 mug/g wet weight in eggs. EROD activity was not different among sites. Organochlorine and trace metal residues and EROD activity were not correlated with any immune parameter. In sprayed birds, we found a significantly increased blastogenic response to pokeweed mitogen (12.5 mug/ ml). However, nests were initiated over a period of several weeks and we also found changes in other tree swallow immune parameters that were related to the date of chick collection. Hematological parameters, bursal and thymic masses, phagocytic response, and thymic development were all correlated with the day the chicks were 16 d of age. After accounting for the collection date of birds from each nest, we found cell proliferation in the cortex and delayed thymic involution correlated positively with increasing spray exposure. We also found that birds in sprayed orchards were slightly anemic compared to birds from nonsprayed sites, and there were smaller bursal masses and an increase in relative heterophil concentrations in the sprayed orchard birds. The local inflammation may have been caused by trematode parasite infections, although pesticide exposure also correlated positively with these parameters. This is the first study of the immunology and effects of current pesticide exposures in wild passerines; therefore it is difficult to predict the longterm consequences of the apparent stimulated immune systems in sprayed birds. However, some environmental contaminants that overtly stimulate the immune system in mammals have induced hypersensitivity and/or autoimmunity. Therefore we speculate that these effects are possible in tree swallows.

Delayed tuberculin reactivity in persons of Indochinese origin: implications for preventive therapy.

To 1) study a variant delayed reaction to tuberculin testing as a way to enhance screening for tuberculosis among high-risk persons and 2) correlate the delayed reaction with lymphocyte blastogenesis. Cross-sectional study. 2 public health department clinics in North Carolina. 121 adults who had recently emigrated from Vietnam to North Carolina and who were ethnic Vietnamese and ethnic Dega, a minority population group from the central highlands region of Vietnam. Medical history, physical examination, laboratory evaluation, and standard purified protein derivative (PPD) testing (Mantoux method). Skin test results were read at 72 hours and again at 6 days. Variant reactivity was defined as induration of less than 10 mm at 72 hours that, when reassessed at 6 days, had increased in size to 10 mm or greater. Persons with negative (n=54) and variant (n=32) PPD results also had booster testing at 10 to 12 weeks. Serum samples were obtained from 57 participants for lymphocyte blastogenesis studies. 26% of participants had variant tuberculin reactivity. Variant reactivity was strongly associated with booster positivity: Sixty-five percent of persons with variant PPD results had booster positivity compared with 16% of persons with negative PPD results (P<0.001). The lymphocyte blastogenesis response of persons with variant PPD results was between the response of persons with negative PPD results and that of persons with positive PPD results. Variant reactivity in this high-risk group was a predictor of booster positivity. Together with the blastogenic response pattern, this association strongly suggests that variant reactivity has a high positive predictive value for tuberculous infection. Clinicians should incorporate these findings into their approach for choosing candidates for preventive therapy.

Humoral antibody and lymphocyte blastogenesis responses in BALE/c, C3H/HeJ and AKR/N mice following Ehrlichia risticii infection

Three strains of mice, two susceptible to Ehrlichia risticii induced disease ( balb/c and C3H/HeJ) and one resistant ( akr/n), were evaluated for the development of Immoral and cell mediated immune responses following infection with E risticii. The production of serum antibody was determined by indirect fluorescent antibody testing of sera from mice of each strain challenged with one of three different dose levels of E risticii. Antibody was assayed on days 7, 9, 12, 15 and 20 after inoculation. Cell mediated immune responses were evaluated by measuring the blastogenesis response of spleen cells from E risticii infected mice 28 days after inoculation. All three strains of mice at the high challenge level responded with the production of antibody by day 9 after inoculation. Overall, the antibody response occurred earlier and was of greater magnitude in the susceptible balb/c and C3H/HeJ strains. A marked blastogenesis response occurred in splenocytes from E risticii infected mice of all three strains upon re-exposure to ehrlichial antigen. The findings of this study indicate that susceptibility to E risticii induced disease was not the result of deficient or delayed humoral immune responses and that E risticii infection induced the development of strong cell mediated immunity.

The esterified plasma fatty acid profile is altered in early HIV‐1 infection

Previous studies have shown that alterations in micronutrient utilization occur in patients with Acquired Immune Deficiency Syndrome. In this study, total plasma fatty acid composition was measured in 36 homosexual men infected with the Human Immunodeficiency Virus 1 (HIV-1) and in 17 HIV-1 seronegative homosexual men in order to evaluate differences associated with early HIV-1 infection. Immunologic assessment included CD4 cell number count and lymphocyte blastogenesis in response to the mitogens phytohemagglutinin (PHA) and pokeweed (PWM). The mean total amount of omega 6 polyunsaturated fatty acids (18:2 and 20:4) was significantly lower in the HIV-1 seropositive subjects (38 +/- 8.1% SD) as compared to HIV-1 seronegative subjects (43 +/- 4.2%; P = 0.0027). This was also reflected in a higher level of total saturated fatty acids (16:0 and 18:0) in HIV-1 seropositive subjects (30 +/- 2.2% vs. 26 +/- 2.8%; P = 0.0001). The ratio of linoleic to arachidonic acid (18:2 to 20:4) was higher in the HIV-1 seropositive group (6.76 +/- 4.88) compared to the HIV-1 seronegative group (4.86 +/- 1.37; P = 0.0213). The response to PHA in seropositive subjects correlated inversely with total plasma omega 6 fatty acids (r = -0.36; P = 0.027), and directly with the 18:2 to 20:4 ratio (r = 0.33; P = 0.046). CD4 cell counts and the response to PWM did not correlate with plasma fatty acid levels in HIV-1 seropositive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Partial Adenosine Deaminase Deficiency in an Immunodeficient Child

ABSTRACT We report a child with partial adenosine deaminase (ADA) deficiency who in infancy had clinical features suggestive of the hyperimmunoglobulinemia E syndrome (HIE), including recurrent staphylococcal cutaneous abscesses and pneumonia, atopic dermatitis, and sinusitis associated with lymphopenia, eosinophilia, and an elevated IgE of 16,400 IU/ml. No ADA activity was found in his erythrocytes, and 15% of normal activity was found in his lymphocytes. Immunologic evaluation showed no evidence of delayed hypersensitivity, normal in vitro lymphocyte blastogenesis response to mitogen, decreased helper/suppressor T cell ratios, and decreased IgG2 levels with elevated total IgG, IgM, and IgA. He had low isohemagglutinin titers, no antibody response to tetanus toxoid, and a nonprotective level of antibodies to Haemophilus influenzae type b and pneumococcus at the age of 68 months. Because of the family's religious faith, immunologic treatment with blood products was not permitted. After 3 years of age, the...

A canine febrile disorder associated with elevated interleukin-6

Familial Mediterranean Fever (FMF) is a human disorder characterized by recurrent fever of unknown origin (RFUO), renal amyloidosis, and evidence of peritonitis, pleuritis, and/or synovitis. This report suggests that Chinese Shar-pei (CSP) dogs suffer from a similar syndrome. CSP dogs with RFUO ( n = 15) showed greater levels of IL-6 in serum than normal controls, hypergammaglobulinemia, and normal or supranormal in vitro lymphocyte blastogenesis in response to mitogen stimulation, when compared to healthy afebrile dogs. In patients 2 years old or older, RFUO was associated with renal failure, renal amyloidosis, and swollen joints. An epidemiological survey of privately owned dogs indicated a RFUO prevalence of 23% in CSP dogs ( n = 132) and 1% in dogs of all breeds ( n = 98). Increased levels of circulating cytokines, such as IL-6, have been shown to influence such processes as the febrile response, antibody production, and the synthesis of amyloid precursors. We propose that CSP dogs with RFUO, renal amyloidosis, and joint inflammation may serve as an animal model of FMF and that the clinical syndrome is associated with elevated levels of circulating IL-6.

Impaired T-cell priming and proliferation in cats infected with feline immunodeficiency virus

Cats naturally infected with feline immunodeficiency virus (FIV) are particularly susceptible to infection with opportunistic pathogens, suggesting that these animals are unable to develop an effective immune response against the pathogen. Previous studies have used CD4+:CD8+ lymphocyte ratios and mitogen blastogenesis to identify immunological abnormalities in FIV-infected cats. However, these studies provide limited information for understanding the nature of the cellular dysfunction in FIV-infected cats, particularly defects in antigen-specific immune responses. To investigate whether cats infected with FIV are less able to mount an immune response to previously unencountered antigens, we compared the development of antigen-specific cellular immunity at the stage of T-cell priming in uninfected and FIV-infected cats. The general immune status of cats was assessed by peripheral blood CD4+:CD8+ lymphocyte ratios (flow cytometry), and by lymphocyte blastogenesis response to T- and B-cell mitogens. In addition, we describe the development of an autologous culture system to measure specific priming of naive feline T-cells to soluble antigen in vitro. This assay was used to compare T-cell priming in uninfected cats and cats which had been infected with FIV for 6-27 months. As in HIV infection, CD4+:CD8+ lymphocyte ratios in FIV-infected cats were found to be inverted, due to a reduction in the percentage of CD4+ cells. In addition, lymphocyte blastogenesis to both T- and B-cell mitogens was significantly impaired in FIV-infected cats. Priming to keyhole limpet haemocyanin (KLH) elicited a late proliferative response resulting from the expansion of CD4+ (T-helper cells). T-cell growth factor secretion correlated with cell proliferation. Restimulation of cells with fresh antigen-presenting cells and antigen showed that antigen-specific T-cell priming had occurred in the initial culture. When primary proliferation responses in FIV-infected cats were examined, it was observed that naive CD4+ T-cells from FIV-infected cats were significantly impaired (P less than 0.001) in their ability to be primed to KLH when compared with uninfected controls. Impaired priming of naive CD4+ T-helper cells to antigen in FIV-infected cats may explain the increased susceptibility of these animals to infection by opportunistic pathogens. The poor ability of human patients with AIDS to develop humoral immunity following vaccination may also be caused by such a defect in T-cell priming.

The effect of cyclosporin a on the development of Eimeria in non-specific hosts

The role of T lymphocytes on the development of turkey coccidia in chickens was investigated to further document the involvement of immune mechanisms in the reactions of non-specific hosts to infections with species of Eimeria. All chickens treated with the T cell-specific immunosuppressive drug, cyclosporin A (CsA), 1, 2 or 3 days before or for 3 consecutive days immediately before inoculation with sporulated oocysts of Eimeria from the turkey, shed oocysts in their feces 7–12 days after inoculation. Those chickens treated with CsA after inoculation produced no oocysts although in one experiment a small number of oocysts were discharged by birds injected with CsA 1 day after inoculation. High serum levels of CsA were maintained in the CsA-treated chickens for at least 24 h post-inoculation with the oocysts. Immunosuppressive activity of the drug was determined by measuring lymphocyte blastogenesis in response to concanavalin A. These results demonstrate that the suppression of T lymphocyte activity in a non-specific host early during an infection with a heterologous species of Eimeria permits the complete intracellular development of the parasite. Our findings are suggestive of a role for T lymphocytes in preventing the development of Eimeria in non-specific hosts possibly via a lymphokine-mediated mechanism.

In vitro evaluation on contact sensitivity from DNCB and DNBS using lymphocyte blastogenesis response test.

To assess the contact allergic potential of sensitizers, an in vitro predictive model was developed. First of all, guinea pigs were sensitized by 1-chloro-2-4,dinitrobenzene (DNCB), and lymph node cells from sensitized and control guinea pigs were cultured in the presence of DNCB, 2,4-dinitrobenzene sulfonic acid sodium salt (DNBS), DNCB plus epidermal cell (DNCB + EC), DNBS + EC and epidermal cell modified hapten (dinitrophenyl-EC, DNP-EC) at 3 x 10(5), 5 x 10(5) and 8 x 10(5) cells/well, respectively. Lymphocyte blastogenesis responses were assessed by uptake of 5H-thymidine. The results indicated that lymphocytes from sensitized guinea pigs responded to the foregoing antigens in vitro to a greater degree than those from control guinea pigs and the blastogenesis response by DNBS was the highest among the challenges of DNBS, DNCB, DNCB + EC, DNBS + EC and DNP-EC. When the number of lymphocytes was sufficient, the blastogenesis response of lymphocytes could be in vitro challenged successfully not only by DNBS, DNCB + EC, DNBS + EC and DNP-EC, but also DNCB alone. There was a cross sensitivity between DNCB and DNBS for in vivo and in vitro challenges. Moreover, significant relationships were observed between lymphocyte blastogenesis response and doses of DNBS used in vitro assay at 5 x 10(5) and 8 x 10(5) cells/well. The results indicate that this assay is an useful in vitro predictive model of contact sensitivity and cross sensitivity of sensitizers.

Cellular immune responses in pigs fed a vitamin E- and selenium-deficient diet.

The effects of dietary restriction of vitamin E (Vit E) and selenium (Se) on lymphocyte proliferation, natural killer (NK) cell activity, antibody-dependent cell-mediated cytotoxicity (ADCC), and on burst respiratory response of stimulated granulocytes as measured by chemiluminescence (CL) were studied in pigs. Six male weanling pigs were maintained for 25 d on a torula yeast-based diet containing no measurable amount of alpha-tocopherol and less than .02 mg of Se per kilogram of feed. Six others received the same basal diet supplemented with 33 IU of DL-alpha-tocopheryl acetate and .2 mg of Se per kilogram of feed. All pigs were inoculated with Salmonella typhisuis on d 21 of the feeding period and killed on d 25. Tests to measure cellular immune functions were performed on cells isolated from blood samples taken on d 21 and 25. After 21 d of feeding, lymphocyte blastogenesis responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen in pigs fed the Vit E- and Se-deficient diet were normal compared with the response in pigs fed the supplemented diet. Moreover, the cytotoxic activity of NK cells, the ADCC response, and the CL response of granulocytes were not affected. After 25 d, a marked suppression of lymphocyte response to mitogens occurred in pigs fed the Vit E- and Se-deficient diet when the cells were cultured in the presence of autologous serum. When fetal bovine serum replaced autologous serum in the cultures, no suppression was observed. No effect on NK activity and ADCC was observed, whereas the CL peak response of granulocytes tended to be higher in pigs fed the deficient diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of immunological responses in rabbits experimentally infected with bovine leukemia virus

Ten 2- to 4-month-old rabbits were inoculated subcutaneously with bovine leukemia virus (BLV)-infected bovine or sheep cells. By 6 weeks after inoculation all ten rabbits had converted to BLV antibody-positive, and BLV or BLV antigen was detected in lymphocytes from most of the rabbits tested, although there were few antigen-producing cells. Three rabbits showed continuous respiratory symptoms after infection and one died with pneumonia. Humoral immune responses against mouse serum were significantly suppressed in BLV-infected rabbits compared with non-infected control rabbits. The lymphocyte blastogenesis response was also suppressed in BLV-infected rabbits. At the time of necropsy, six rabbits showed pulmonary lesions; however, none of the BLV-infected rabbits had tumors during an observation period of over 1 year.

Effect of different separation protocols between mares and foals on plasma cortisol and cell-mediated immune response

The objective was to compare effects of weaning in pairs or singly on physiological indicators of stress (plasma cortisol [F] and lymphocyte proliferation response to mitogens expressed as a stimulation index [S.I.] in mares and foals. Twenty pairs of Standardbred mares and foals were assigned to treatment groups as follows: non-weaned (control), n=6; weaned singly (WS), n=6; weaned pairs (WP), n=8. Blood sampling to determine cortisol was performed via jugular venipuncture prior to weaning and at 4, 8, 16, 24, 32, 40 and 48h post-weaning. Blood samples for lymphocyte blastogenesis in response to Concanavalin A (Con A) or Phytohemagglutinin (PHA) were taken prior to, 4 and 28h post-weaning. There was a trend toward increased F concentrations post-weaning in both mares and foals. WS and WP foals displayed increased F concentrations for up to 40 hours post-weaning when compared to control foals (48.8, 59.0, 22.1 ng/ml, respectively). Weaned mares displayed elevated F concentrations compared to controls for up to 24 hours post-weaning (65.9 and 40.5 ng/ml, respectively). There was less (p<0.05) lymphocyte proliferation in weaned mares compared to controls in response to stimulation by both Con A and PHA. There was also lower (P<0.05) lymphocyte proliferation response to mitogens in WP foals compared to control foals and WS foals. There was no difference (p>0.05) between WS or control foals. While weaning caused an increase in plasma F concentration, there was no difference in that increase due to the effect of separation protocol. Lymphocyte proliferation in response to mitogen was lessened in weaned mares and WP foals. The traditional management practice of paired weaning appears to be more stressful than weaning singly, perhaps through aggressive behavior by a dominant partner.

Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma.

Fifty patients with locally advanced or metastatic renal cell carcinoma were treated with coumarin (1,2-benzopyrone) at 100 mg orally daily starting on day 1 and cimetidine 300 mg orally four times a day starting on day 15. When disease progressed, coumarin was escalated to 100 mg orally four times a day. Three patients (6%; 95% confidence interval [Cl], 2% to 17%) achieved a partial response, one of those after dose escalation. In addition, one patient had a minor response, then progressing disease, and again had a minor response after dose escalation. All four responders had nonassessable primary tumors (three had had prior nephrectomy and one a renal angioinfarction). The only major toxicity was renal (37 patients had minor to moderate elevations in serum creatinine level). Immunologic studies (hypersensitivity skin testing, lymphocyte blastogenesis response, number of lymphocytes, T lymphocytes, T helper and T suppressor subsets, and T helper: suppressor ratio), performed before and after therapy, showed a relative lymphopenia and decreased hypersensitivity skin-testing results at baseline, and a general decline over time in the number of T cells and T helper and T suppressor subsets. There was no enhancement in any of the immunologic parameters tested. The response rate was 6%, lower than previously reported; a general immunodeficiency was noted at baseline, and the lymphopenia worsened with progressing disease, unaffected by therapy.

Effect of acute stressors on endocrinological and immunological functions in lambs.

Lambs were used to evaluate the effect of acute heat stress (HS) or restraint and isolation stress (RIS) on endocrinological and immunological functions. In Exp. 1, lambs were exposed to HS (35 degrees C) and control lambs (CN) were exposed to 21 degrees C for 24 h in two replicates (n = 8 lambs total per treatment). Samples of serum were obtained at frequent intervals for evaluation of cortisol; whole blood was obtained for total and differential leukocyte numbers and lymphocyte blastogenic function. The time-trends for cortisol between HS and CN lambs were different following treatment (P less than .005), but neither leukocyte numbers nor lymphocyte blastogenesis in response to mitogens were affected by acute exposure to the elevated ambient temperature. In Exp. 2, lambs (n = 6 per treatment) were given a 6-h RIS treatment and control lambs remained in their home stanchions (CON). Plasma and serum were obtained frequently during treatment and continued until 24 h after the onset of treatment. Plasma was evaluated for adrenocorticotropic hormone (ACTH) and serum was assayed for cortisol. Samples of whole blood also were obtained before and at 6, 12 and 24 h after the onset of treatment for determination of total and differential leukocyte numbers and lymphocyte blastogenic responses to mitogens. Both ACTH and cortisol were elevated in response to RIS; the profiles of these hormones over the 24-h bleeding period differed for RIS and CON lambs (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro immunologic features of weimaraner dogs with neutrophil abnormalities and recurrent infections

In vitro evaluation of cellular and humoral immunity in Weimaraner dogs with recurrent infections and abnormal neutrophil function revealed significantly lower serum immunoglobulin (Ig) G and M concentrations than control dogs. Lymphocyte blastogenesis in response to three different mitogens, interleukin-1 and -2 production, natural killer (NK) cell activity, and in vitro IgG and IgM production were similar to those of control dogs.

An immunologic profile of young adults with head and neck cancer

Numerous reports have suggested, although never demonstrated, a suppressed immune defense mechanism as a contributing factor in the development of head and neck cancer in the young adult. Twenty-four previously untreated adults less than or equal to 40 years of age with squamous cell carcinoma were examined for lymphocyte function (natural killer cell activity and in vitro lymphocyte blastogenesis response to mitogens), total lymphocyte number and percentage of lymphocyte subsets, and humoral immune status (circulating IgA, IgG, and IgM). As compared with 33 healthy young adults, no significant immunologic deficit could be identified. On the contrary, the young adult cancer population had significantly increased lymphocyte numbers (P less than 0.05) and serum IgA, IgG, and IgM levels (P less than 0.001, respectively). These young cancer patients cannot be considered to be immunosuppressed. Alternative biologic mechanisms must be defined to account for the increasing incidence of head and neck cancer over the last decade among young adults in the United States.