Post-treatment Serum Samples Research Articles

Circulating Bioactive and Immunoreactive Recombinant Human Follicle-Stimulating Hormone (Org 32489) After Administration to Gonadotropin-Deficient Subjects

Objective: To study the bioactivity of recombinant and urinary human FSH after single IM injection into gonadotropin-deficient subjects. Design: Serum FSH levels were measured by immature rat granulosa cell bioassay and immunofluorometric assay. The isohormone distributions of injected FSH materials were analyzed by chromatofocusing. Serum samples were collected before, and 6, 24, and 72 hours after 300 IU of recombinant or urinary FSH. Volunteers: Fifteen gonadotropin-deficient subjects (8 women and 7 men) received recombinant FSH and 8 of them (4 women and 4 men) received an equal dose of urinary FSH. Result(s): No significant differences were apparent between the bioactive FSH levels after recombinant and urinary FSH treatments (n = 8). The immunoreactive FSH levels at 72 hours after urinary FSH were significantly higher than after recombinant FSH injection with values (median and range) of 3.80 (2.76 to 5.75) IU/L (IRP 78/549) and 3.10 (1.78 to 4.95) IU/L, respectively. There were no significant changes in the bioactive to immunoreactive ratios of FSH within time and between sexes after either recombinant FSH (n = 15) or urinary FSH (n = 8). However, the bioactive to immunoreactive ratio of the FSH material injected and of the post-treatment serum samples were both higher after recombinant FSH than after urinary FSH injection. Chromatofocusing revealed that injected recombinant FSH contained more activity in the basic fractions than urinary FSH. Conclusion(s): Recombinant human FSH maintains its biological activity when injected into gonadotropin-deficient subjects. The bioactive to immunoreactive ratio of recombinant FSH was higher than that of urinary FSH indicating that recombinant FSH contains relatively more basic isohormones, and this finding was strengthened by chromatofocusing.

Serum antibody responses against human papillomavirus in relation to tumor characteristics, response to treatment, and survival in carcinoma of the uterine cervix.

To investigate whether the serum antibody responses to human papillomavirus (HPV) in cervical carcinoma were related to the clinical and histopathological features of the tumors and how the antibody responses were affected by treatment, pretreatment serum samples from 66 patients with carcinoma of the cervix were studied for the presence of IgA or IgG responses against six defined HPV epitopes. Posttreatment serum samples were drawn from the same patients 2-24 months after initiation of treatment. There was no significant correlation between pretreatment level of any of the investigated antibodies and clinical stage or differentiation of tumor. For the IgA responses to the epitopes 245:16 and 245:18 in the E2 protein there was a significant correlation between an increased pretreatment antibody level and a shortened survival. A high pretreatment value of IgA against 245:16 was also associated with the absence of any complete response after therapy. The antibody levels declined dramatically after therapy for most of the antigens studied. However, this decline was seen both among the 53 patients with complete remission and among the 13 patients with remaining or progressive disease. Thus, the investigated serological responses were not useful as tumor markers, since patients with progressive, late-stage disease may fail to mount an antibody response to these proteins. However, pretreatment levels of the serological responses to the HPV epitopes 245:16 and 245:18 were associated with prognosis in cervical cancer.

Circulating bioactive and immunoreactive recombinant human follicle stimulating hormone (Org 32489) after administration to gonadotropin-deficient subjects

To study the bioactivity of recombinant and urinary human FSH after single IM injection into gonadotropin-deficient subjects. Serum FSH levels were measured by immature rat granulosa cell bioassay and immuno-fluorometric assay. The isohormone distributions of injected FSH materials were analyzed by chromatofocusing. Serum samples were collected before, and 6, 24, and 72 hours after 300 IU of recombinant or urinary FSH. Fifteen gonadotropin-deficient subjects (8 women and 7 men) received recombinant FSH and 8 of them (4 women and 4 men) received an equal dose of urinary FSH. No significant differences were apparent between the bioactive FSH levels after recombinant and urinary FSH treatments (n = 8). The immunoreactive FSH levels at 72 hours after urinary FSH were significantly higher than after recombinant FSH injection with values (median and range) of 3.80 (2.76 to 5.75) IU/L (IRP 78/549) and 3.10 (1.78 to 4.95) IU/L, respectively. There were no significant changes in the bioactive to immunoreactive ratios of FSH within time and between sexes after either recombinant FSH (n = 15) or urinary FSH (n = 8). However, the bioactive to immunoreactive ratio of the FSH material injected and of the post-treatment serum samples were both higher after recombinant FSH than after urinary FSH injection. Chromatofocusing revealed that injected recombinant FSH contained more activity in the basic fractions than urinary FSH. Recombinant human FSH maintains its biological activity when injected into gonadotropin-deficient subjects. The bioactive to immunoreactive ratio of recombinant FSH was higher than that of urinary FSH indicating that recombinant FSH contains relatively more basic isohormones, and this finding was strengthened by chromatofocusing.

Remission of leukemia and loss of feline leukemia virus in cats injected with Staphylococcus protein A: association with increased circulating interferon and complement-dependent cytotoxic antibody.

We have injected purified Staphylococcus aureus protein A intraperitoneally into leukemic cats infected with feline leukemia virus, into cats persistently infected with feline leukemia virus but without hematologic or cytologic abnormalities, and into healthy cats without feline leukemia virus infection. Pre- and post-treatment serum samples were evaluated sequentially for interferon activity and for complement-dependent cytotoxic antibody. Our results indicate that serum interferon increased dramatically (less than 3 to 324 units/ml) during treatment only in cats that responded to staphylococcal protein A therapy. Increase of interferon preceded or was closely associated with increasing levels of cytotoxic antibody, loss of viremia, and correction of cytological and hematological abnormalities of three leukemic cats. The cytotoxic antibody was shown to be specific for envelope glycoprotein gp70 of the feline leukemia virus. One persistently feline leukemia virus-infected cat without leukemia that became nonviremic also developed high levels of interferon and specific cytotoxic antibody. By contrast, interferon levels of cats not responding to treatment had levels of less than 3 to 27 units/ml. Normal healthy cats injected with staphylococcal protein A showed moderate transient increases of interferon but no detectable cytotoxic antibodies to FL-74 cells. These data suggest that interferon and cytotoxic antibody may play important, possibly complementary roles in inducing remission of leukemia and loss of viremia in cats treated with staphylococcal protein A.

Effects of naloxone and an enkephalin analog on serum prolactin, cortisol, and gonadotropins in the chimpanzee.

To assess a possible regulatory influence of opioids upon anterior pituitary function in the chimpanzee, we evaluated the effects of the specific opiate receptor antagonist naloxone and the agonistic enkephalin analog [D-Ala2, MePhe4,Met(o)-ol]enkephalin (FK 33-824; Sandoz) on serum levels of PRL, cortisol, FSH, and LH. Under ketamine anesthesia, the following were administered by iv injection during the early follicular phase of successive menstrual cycles in nine female chimpanzees: naloxone (10 mg; n = 7) or saline vehicle (n = 7) randomly assigned in the first two cycles, FK 33-824 0.25 mg (n = 3) in the third cycle, FK 33-824 0.50 mg (n = 4) in the fourth cycle, and FK 33-824 (0.50 mg) immediately preceded by naloxone (10 mg; n = 4) in the last cycle. Five pretreatment and 12 posttreatment serum samples were obtained at 10- to 15-min intervals for subsequent RIA. Naloxone caused a significant reduction in PRL levels from a pretreatment mean of 29.3 ng/ml to a mean of 11.1 ng/ml at 180 min. Values from 60-180 min were significantly below the saline control group at comparable times. A dose-related increment in PRL levels was seen after FK 33-824 administration, with mean peak values at 30 min of 61.0 and 92.3 ng/ml after the low and high doses, respectively. Naloxone pretreatment markedly attenuated the response to high dose FK 33-824. Cortisol levels rose in all groups throughout the study period, a presumed effect of the ketamine anesthesia. Compared to the saline group, no effects of FK 33-824 were observed. Naloxone, given alone or with FK 33-824, had a small, but significant, stimulatory effect on cortisol from 60-120 min posttreatment compared to the control group. Naloxone caused a significant increment in LH levels from a pretreatment mean of 11.7 micrograms/dl to a peak of 19.1 micrograms/dl at 30 min and in FSH level from 33.2 micrograms/dl before therapy to 40.0 micrograms/dl at 45 min. There was no influence of FK 33-824 on gonadotropin levels, although the high dose did blunt the response to naloxone. Taken together, these effects suggest that opiate agonists and endogenous opioid pathways may modulate anterior pituitary function in the chimpanzee, as in man.

Rapid decrease of precipitating and reaginic antibodies in Dirofilaria immitis-infected dogs which develop severe adverse reactions following treatment with diethylcarbamazine.

Dirofilaria immitis-infected dogs were treated with diethylcarbamazine. Measurement of the level of IgG precipitating antibody was carried out by counterimmunoelectrophoresis and that of IgE by passive cutaneous anaphylaxis in pre-treatment and post-treatment serum samples. In dogs showing severe to moderate adverse reactions to the drug there were pronounced decreases of both antibodies to a "metabolic" antigen prepared from the medium in which adult female worms had been incubated. These antibody levels did not decline in non-reacting dogs. Precipitating antibody levels to somatic antigens extracted from adult worms and microfilariae remained unaltered in both reactive and non-reactive animals.