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PubMed1990

Depressed in vitro T cell responses concomitant with augmented interleukin-2 responses by lymphocytes from cancer patients following in vivo treatment with interleukin-2.

Peripheral blood lymphocytes obtained from cancer patients receiving interleukin-2 (IL-2) on two separate clinical protocols were evaluated for their in vitro responses to IL-2, alloantigens, and PHA. IL-2 in vivo induced enhanced in vitro proliferative responses to IL-2 and diminished in vitro proliferative responses to phytohemagglutinin (PHA) and alloantigens. Alloinduced cytotoxic T cell responses were also depressed following in vivo IL-2. We examined the kinetics of the in vitro proliferative response to PHA and IL-2 and found that while the response of lymphocytes primed in vivo with IL-2 to PHA was depressed at all times during the 2 week in vitro exposure, the response to IL-2 peaked earlier and higher than did the response to IL-2 by lymphocytes obtained prior to IL-2 therapy. These contrasting effects on antigen-induced T cell responses vs. IL-2 induced nonspecific proliferative and cytotoxic responses suggest the importance of dose and timing of IL-2 administration when used to enhance antigen-specific T cell responses or as an immune enhancing agent combined with vaccines.

Cell Division↗
PubMed1986

Differential helper and effector responses of Lyt-2+ T cells to H-2Kb mutant (Kbm) determinants and the appearance of thymic influence on anti-Kbm CTL responsiveness.

The goal of this study was to assess and compare the allorecognition requirements for eliciting Lyt-2+ helper and effector functions from primary T cell populations. By using interleukin 2 (IL 2) secretion as a measure of T helper (Th) function, and cytolytic T lymphocyte (CTL) generation as a measure of effector function, this study compared the responses of Lyt-2+ T cells from wild-type B6 mice against a series of H-2Kb mutant determinants. Although all Kbm determinants stimulated B6 Lyt-2+ T cells to become cytolytic effector cells, the various Kbm determinants differed dramatically in their ability to stimulate Lyt-2+ T cells to function as IL 2-secreting helper cells. For example, in contrast to Kbm1 determinants that stimulated both helper and effector functions, Kbm6 determinants only stimulated B6 Lyt-2+ T cells to become cytolytic and failed to stimulate them to secrete IL 2. The distinct functional responses of Lyt-2+ T cells to Kbm6 determinants was documented by precursor frequency determinations, and was not due to an inability of the Kbm6 molecule to stimulate Lyt-2+ Th cells to secrete IL 2. Rather, it was the specific recognition and response of Lyt-2+ T cells to novel mutant epitopes on the Kbm6 molecule that was defective, such that anti-Kbm6 Lyt-2+ T cells only functioned as CTL effectors and did not function as IL 2-secreting Th cells. The failure of Lyt-2+ anti-Kbm6 T cells to function as IL 2-secreting Th cells was a characteristic of all Lyt-2+ T cell populations examined in which the response to novel mutant epitopes could be distinguished from the response to other epitopes expressed on the Kbm6 molecule. The absence of significant numbers of anti-Kbm6 Th cells in Lyt-2+ T cell populations was examined for its functional consequences on anti-Kbm6 CTL responsiveness. It was found that primary anti-Kbm6 CTL responses could be readily generated in vitro, but unlike responses to most class I alloantigens that can be mediated by Lyt-2+ Th cells, anti-Kbm6 CTL responses were strictly dependent upon self-Ia-restricted L3T4+ Th cells. Because the restriction specificity of L3T4+ Th cells is determined by the thymus, in which their precursors had differentiated, anti-Kbm6 CTL responsiveness, unlike responsiveness to most class I alloantigens, was significantly influenced by the Ia phenotype of the thymus in which the responder cells had differentiated.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Separation of the immune response genes for LDH-B and MOPC-173. II. Description of an immune response defect in B10.ASR7.

By using the intra-I region recombinant mouse strain B10.ASR7 (H-2as3), the immune response (Ir) genes for LDH-B and MOPC-173 were genetically and serologically separated, as assayed by T cell proliferation. Previous work demonstrated that H-2s and H-2b strains respond to LDH-B and MOPC-173 whereas H-2a and H-2k strains failed to respond due to haplotype-specific suppression of I-Ak molecule-activated T helper cells by I-Ek molecule-activated T suppressor cells. In the experiments reported here, B10.ASR7 mice, which lack I-Ek expression, mounted a significant T cell proliferative response to LDH-B but not to MOPC-173. Separation of the Ia determinants used in restricting these two antigen responses was further confirmed when pretreatment of B10.S(9R) (A beta sA alpha sE beta sE alpha k) macrophages with A.TL anti-B10.HTT serum (anti-As beta Es beta Js) adsorbed with B10.ASR7 spleen cells blocked the MOPC-173 response but not the LDH-B response. Unadsorbed serum blocked both antigen responses. The B10.ASR7 E beta allele was determined to be s due to the ability of (A.TL X B10.ASR7)F1 hybrids to mount a T cell proliferative response to the terpolymer GLPhe. Monoclonal antibody blocking of the B10.ASR7 T cell proliferative response to LDH-B demonstrated that the Ia.2 and Ia.17, and not the Ia.15 epitopes are spatially related to the Ia epitopes involved in the restriction of the B10.ASR7 LDH-B T cell proliferative response. In addition, B10.ASR7 helper T cells generated in response to LDH-B were suppressed in a haplotype-specific manner by I-Ek molecule-restricted suppressor T cells in that (A.TL X B10.ASR7)F1 hybrids failed to respond to LDH-B. This nonresponsiveness was eliminated by treatment with monoclonal antibodies directed against the I-Ek molecule. These results suggest the possibility that the immune response defect in B10.ASR7 could be related to the site of recombination.

Alleles↗
PubMed1994

Endogenous nitric oxide modulates vasopressor responses, but not depressor responses, to spinal sympathetic nerve stimulation in pithed rats.

The effects of N omega-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide (NO) synthase (1,5, and 10 mg/kg) on vasopressor and depressor responses to segmental sympathetic nerve stimulation were studied in the pithed rat preparation. Vasopressor responses were evoked by stimulation of the spinal sympathetic outflow at T6-T8 (30 V, 0.05 ms at 5 Hz with 10 pulses). This pressor response was biphasic: An initial transient response (to nerve stimulation) was followed by a later prolonged response (to adrenal catecholamine release). L-NAME 1, 5, and 10 mg/kg increased mean arterial blood pressure (MAP); this effect was maximal at 1 mg/kg L-NAME, but had no effect on heart rate (HR). L-NAME 1, 5, and 10 mg/kg potentiated both phases of the pressor response; the effect was maximal at 10 mg/kg. Vasodepressor responses were evoked by stimulation of the spinal sympathetic outflow at S2-L6 (30 V, 0.05 ms at 5 Hz with 10 pulses). L-NAME 1, 5, and 10 mg/kg did not inhibit these depressor responses. We conclude that inhibition of the synthesis of endogenous NO causes a hypertension in pithed rats that is associated with increased vasoconstriction in response to sympathetic nerve stimulation and adrenal catecholamine release. Systemic vascular depressor responses to segmental sympathetic nerve stimulation are not affected, however; therefore, NO cannot be the major mediator of these responses.

Animals↗
PubMed1997

[Response rates and non-response bias in a health-related mailed survey].

A health-related mailed survey was conducted to investigate the effect of follow-up mailings to response rates. In addition, the answer distributions among early and late respondents were compared to check non-response bias. Approximately 3,000 persons aged 40-64 were randomized into two groups; a questionnaire with four pages (twenty-two questions) was assigned to the first group, and a questionnaire with eight pages (thirty-five questions) to the second group. Both questionnaires contained questions of current health status, health-related practice, smoking status, etc. Follow-up mailings were sent twice to non-respondents. Response rates were increased from 38% to 62% by the first follow-up mail, and to 71% by the second follow-up mail. Although the length of the questionnaire did not affect response rates, response rates among the older subjects was higher than the younger subjects. Positive response to current smoking status was 10% lower among early respondents than late respondents, collected after the second follow-up mailing, and response to regular participation in physical/medical checkup was 15% higher among early respondents, whereas there were few differences for answers to other questions. Odds ratios between current health status and several health-related questions may not be biased by late response. However, increased response rates are needed to prevent non-response bias, because there were some differences in responses from follow-up mailings.

Adult↗
PubMed1997

Response to second-line chemotherapy in patients with metastatic breast carcinoma previously responsive to first-line treatment: prognostic factors.

BACKGROUND: The aim of this retrospective study was to determine those prognostic factors associated with response to a second-line chemotherapy in patients with metastatic breast carcinoma (MBC) that was previously responsive to a first-line chemotherapy. METHODS: The 70 MBC patients studied had previously responded to a first-line chemotherapy, mainly anthracycline or anthracenedione-containing regimens. During first-line chemotherapy they had received treatment until the maximum response was obtained, at which time treatment was discontinued. Second-line chemotherapy regimens were of several types (48.5% with anthracycline). A study of prognostic factors associated with response to second-line chemotherapy was performed by univariate and multivariate analysis. RESULTS: Second-line chemotherapy achieved a 44% response rate, with a median response duration of 10 months. Survival was 13 months in the entire patient group, 22 months in responders, and 8 months in nonresponders. Univariate analysis identified seven factors related to patient response rate to second-line treatment. A better response rate to second-line chemotherapy was observed in patients with the following features: 1) chemotherapy free time (time between onset of metastatic disease and initiation of first-line) < 12 months (P = 0.03); 2) complete response to first-line chemotherapy (P = 0.013); 3) response duration to first-line chemotherapy > 14 months (P = 0.0001); 4) progression free interval (time between end of first-line treatment and initiation of second-line chemotherapy) > 11 months (P = 0.0001); 5) performance status at second-line treatment < 2 (P = 0.04); 6) tumor index at second-line chemotherapy < 4 (P = 0.05); and 7) treatment with an anthracycline-containing second-line regimen (P = 0.03). In multivariate analysis, only progression free interval was identified as being associated with response rate to second-line chemotherapy (P = 0.0001). CONCLUSIONS: Retained chemosensitivity appeared to be an important characteristic in patients responding to second-line chemotherapy.

Adult↗
PubMed1977

Immune responses to influenza virus in rabbits after local immunization. II. Local and systemic cell mediated response.

The development of local and systemic cell mediated immunity (CMI) was investigated in rabbits after intratracheal immunization with live or inactivated influenza A virus. Lymphocytes from bronchoalveolar washings and draining lymph nodes were used for the assay of local CMI response. Spleen cells were employed for determination of systemic responses. Since alveolar macrophages were found to be susceptible to the action of migration inhibiting factor, the development of CMI in lungs was assayed by macrophage migration inhibition test using bronchoalveolar was cells. Immunization with live virus induces beter local CMI response than inactivated virus. After primary immunization the peak responses were found between second and third week. The secondary response was detectable much earlier and peaked at one week after booster. Small amounts of inactivates virus, which was unsufficient to evoke a primary response, could elicit a strong secondary response. The development of rapid and accentuated secondary response in the local lymphoid tissues suggests the presence of memory in the local CMI response. The results also show a good correlation to exist between primary local CMI response and the skin reactivity to the immunizing antigen. However, lack of such correlation during the secondary response leaves the skin tests less reliable in the evaluation of CMI in viral infections. Some of the functions of alveolar macrophages in the local immune reponses are also discussed.

Animals↗
PubMed1998

Newborn mice develop balanced Th1/Th2 primary effector responses in vivo but are biased to Th2 secondary responses.

Newborn mice are impaired in their abilities to mount protective immune responses. For decades, it was generally held that the poor responses of newborns were largely due to the developmentally immature state of the T cells. In vitro studies showing that neonatal T cells were deficient in Th1 cytokine production, proliferation, and secondary responsiveness strongly supported this idea. Recently, several studies have challenged this view; animals exposed to Ag as neonates were shown to have mature Th1 responses in adulthood. However, it is not clear whether the mature immune responses were actually mounted by T cells generated after the neonatal stage. We have reexamined this issue by analyzing the capabilities of neonatal lymph node T cells to develop into Ag-specific effector cells during the actual neonatal period. Our results demonstrate that the capacity to develop a balanced Th1/Th2 primary effector response is fully mature within the first week of life. However, while neonatal and adult primary cytokine profiles were very similar, Th2 secondary responses predominated in animals first immunized as newborns. Moreover, we have observed other differences between adults and neonatal responses, including 1) the kinetics of cytokine production and responsiveness to adjuvant during the primary response, and 2) the contribution of spleen and lymph node to secondary responses. We propose that these differences reflect developmental regulation of effector cell function that has important consequences to neonatal immune function.

Animals↗
PubMed2000

Sp1, steroidogenic factor 1 (SF-1), and early growth response protein 1 (egr-1) binding sites form a tripartite gonadotropin-releasing hormone response element in the rat luteinizing hormone-beta gene promoter: an integral role for SF-1.

Recently, several cis-regulatory elements that play roles in LHbeta gene expression, and their cognate DNA-binding transcription factors, have been identified. These factors include Sp1, steroidogenic factor-1 (SF-1), and early growth response protein 1 (Egr-1). Using the GH3 pituitary cell line (which lacks SF-1) as a model, we demonstrate that expression of SF-1 or Egr-1 increases rat LHbeta gene promoter activity but has little effect on the fold response to GnRH. However, expression of both SF-1 and Egr-1 synergistically enhances LHbeta gene promoter activity and prevents further stimulation of activity by GnRH. Mutations in the Sp1 binding sites of the rat LHbeta gene promoter decrease GnRH responsiveness, whereas mutations in the SF-1 and/or Egr-1 binding sites alone have little effect on the GnRH response. Combinatorial mutations in both the Sp1 and Egr-1 binding elements result in almost complete loss of the GnRH response. In contrast, in GH3 cells cotransfected with SF-1, mutations in the Sp1, SF-1, or Egr-1 binding elements independently decrease GnRH responsiveness. In LbetaT2 cells, a gonadotrope-derived cell line that expresses SF-1 endogenously, mutations in either the Sp1 or Egr-1 binding elements decrease GnRH responsiveness. These data suggest that the Sp1, SF-1, and Egr-1 binding sites form a tripartite GnRH response element in the rat LHbeta gene promoter. Changes in the spacing between the upstream Sp1 binding sites and the downstream SF-1/Egr-1 binding elements reduce the response to GnRH. SF-1, while having little direct effect on GnRH responsiveness, has a critical role in integrating the effects of Sp1 and Egr-1.

Animals↗
PubMed1982

Evidence for distinct polygenic regulation of antibody responses to some unrelated antigens in lines of mice selected for high or low antibody responses to somatic antigen of Salmonella.

The effect of the selective breeding of mice for high or low antibody production to complex immunogens is largely "nonspecific", since it modifies the responsiveness of high (H) and low (L) lines to many antigens unrelated to the selection antigen. However, the nonspecific effect of the polygenic control operating in these lines is not a general feature. For example, the group of genes in selection IV, carried out for responsiveness to somatic antigen of Salmonella, does not modify the responses to sheep erythrocytes (SE). Despite equivalent responses in H and L mice of selection IV, a large variability was found in individual responses of F2 interline hybrids, which demonstrates the presence of alleles with high or low effect on responses to SE. A selective breeding (Selection IV-A) was therefore initiated from this F2 population for responsiveness to SE.A progressive interline divergence occurred during the first seven generations of selection; the interline separation was due to polygenic regulation (about four independent loci from a preliminary estimate). Equivalent responses to the s antigen of Salmonella are observed in the two lines. This constitutes additional evidence for distinct polygenic regulation of responses to SE and to somatic antigen. Moreover, the pattern of responses to several unrelated antigens (nonspecific effect) also differs between Selections IV and IV-A.

Animals↗
PubMed1997

Secobarbital in humans discriminating triazolam under two-response and novel-response procedures.

Humans were trained to discriminate the benzodiazepine triazolam (0.32 mg/70 kg) from placebo under a two-response (drug vs. placebo) drug discrimination procedure. Dose-effect curves for several drugs were then determined in a crossover design using the two-response procedure and a 'novel-response procedure' that provided a novel-appropriate response for drugs unlike triazolam or placebo. Three subjects were tested with triazolam (0.1-0.32 mg/70 kg), the barbiturate secobarbital (56-177 mg/70 kg), and caffeine (320 and 560 mg/70 kg). Triazolam dose dependently increased triazolam-appropriate responding under both procedures and generally did not occasion novel-appropriate responding under the novel-response procedure. Secobarbital substituted for triazolam in the two-response procedure and dose-dependently increased novel-appropriate responding as well as occasioned some triazolam-appropriate responding in the novel-response procedure. Caffeine generally occasioned placebo-appropriate responding under the two-response procedure and a mix of novel- and placebo-appropriate responding under the novel-response procedure. Triazolam and secobarbital produced qualitatively similar self-reported drug effects. These results suggest that the novel-response procedure for human drug discrimination may enhance the pharmacological selectivity of triazolam- and placebo-appropriate responding.

Adult↗
PubMed2001

Der p 1 and Der p 2 induce less severe late asthmatic responses than native Dermatophagoides pteronyssinus extract after a similar early asthmatic response.

BACKGROUND: The models for exposure to house dust in research and clinical practice are selected with respect to their role in IgE-mediated immediate hypersensitivity. The use of isolated major allergens instead of complex allergen extracts is becoming increasingly popular as it offers some important advantages for quantitative measures in diagnosis and research. OBJECTIVE: To compare house dust mite extract and isolated mite major allergens with respect to their ability to induce early and late asthmatic responses and bronchial hyperreactivity. METHODS: Bronchial responses to house dust mite (HDM, Dermatophagoides pteronyssinus) extract and isolated major allergens from HDM (Der p 1 and Der p 2) were compared in a double-blind, randomized, cross-over study in 20 patients with mild to moderate asthma who were allergic to HDM. Allergen was titrated to a standardized early asthmatic response. Bronchial hyper-responsiveness to histamine (PC20histamine) was determined before and after allergen inhalation to assess allergen-induced bronchial hyper-responsiveness and IL-5 was measured in serum. In addition, the allergens were applied in intracutaneous skin tests and activation of basophil leucocytes and proliferation of peripheral blood mononuclear cells was tested in vitro. RESULTS: After a similar early asthmatic response (mean Deltaforced expiratory volume in 1 s (FEV1),max -29.4 (SD 7.2) vs. -33.1 (8.6) %; mean difference 3.6 (95% CI -0.9 to 8.2) %), the late asthmatic response (mean DeltaFEV1,max -45.9 (21.9) vs. -32.7 (22.3) %; mean difference 13.2 (3.8-22.3) %), the degree of allergen-induced bronchial hyper-responsiveness (mean DeltaPC20histamine, 1.8 (1.0) vs. 1.2 (0.9) doubling dose; mean difference 0.6 (0.2-1.1) doubling dose) and serum IL-5 at 6 h were found to be significantly higher after bronchial challenge with HDM extract than after challenge with an isolated HDM major allergen. Likewise, there was an increased late skin reaction with HDM compared with isolated major allergen after a similar early skin reaction. CONCLUSION: Constituents of HDM extract, other than Der p 1 or Der p 2, with no significant influence on the IgE-mediated early asthmatic response contribute significantly to the allergen-induced late asthmatic response and bronchial hyper-reactivity.

Adolescent↗
PubMed1999

Functional disparity of distinct CD28 response elements toward mitogenic responses.

Activation of T cells through the antigen-specific T-cell receptor in combination with a costimulatory signal results in efficient cytokine gene transcription. The CD28-induced signal represents a major costimulatory signal for T cells. A CD28 response element, named CD28RE, was first identified in the interleukin-2 (IL-2) promoter region. Here we demonstrate that the NF-kappaB sequence in the IL-6 promoter functions as a CD28 response element. Mutations in this sequence rendered the IL-6 promoter unresponsive to CD28 costimulation. Moreover, this element could replace the IL-2 CD28RE in conferring CD28 responsiveness to the IL-2 promoter. In analogy to the known CD28 response elements IL-2 CD28RE, IL-8 CD28RE, and the human immunodeficiency virus-1 (HIV-1) NF-kappaB motif, the IL-6 NF-kappaB motif efficiently bound c-Rel, c-Rel/NFKB1, and the recently identified inducible T-cell factor NF-MATp35. However, the IL-6 NF-kappaB sequence together with the IL-8 CD28RE and HIV-1 NF-kappaB sequence differed from the IL-2 CD28RE in the binding of NF-kappaB/Rel family proteins. Although the IL-2 CD28RE exerted selective binding with c-Rel and c-Rel/NFKB1, the other CD28REs allowed efficient binding of a wide range of NF-kappaB/Rel family proteins. The difference in binding specificity correlated with the capacity of the distinct CD28 response elements to function in the context of the IL-6 promoter in response to T-cell activation. Domain swapping experiments revealed that the IL-8 CD28RE and HIV-1 NF-kappaB motif conferred similar responsiveness as the genuine IL-6 NF-kappaB motif in the transcriptional activation of the IL-6 promoter upon CD28 costimulation. In contrast, replacement of the IL-6 NF-kappaB sequence by the IL-2 CD28RE motif strongly reduced the responsiveness of the IL-6 promoter. These data indicate that despite the sequence similarity, two different classes of CD28 responsive elements exist that differ in their NF-kappaB binding capacity and the ability to confer CD28 costimulatory responsiveness toward a heterologous promoter.

Antibodies↗
PubMedDate not supplied

Hormetic dose-response relationships in immunology: occurrence, quantitative features of the dose response, mechanistic foundations, and clinical implications.

This article provides an assessment of the occurrence of immune-system-related hormetic-like biphasic dose-response relationships. Such dose-response relationships are extensive, with over 90 different immune response-related endpoints reported, induced by over 70 endogenous agonists, over 100 drugs, and over 40 environmental contaminants. Such hormetic responses were reported in over 30 animal models, over a dozen mammalian and human cell lines. These findings demonstrate that immune-system-related hormetic-like biphasic dose-response relationships are common and highly generalizable according to model, endpoint, and chemical class. The quantitative features of the dose response are generally consistent with previously published examples of hormetic dose responses for other biological endpoints. These findings were generally recognized and explicitly discussed by the original authors, often with consideration given to possible mechanistic foundations as well as numerous clinical implications. Despite the recognition by individual authors of the hormetic nature of these observed responses, the overall widespread nature of immune-related hormetic responses has been only little appreciated, with a general lack of insight into the highly generalizable nature of this phenomenon as well as the complex regulatory networks affecting biological switching mechanisms that result in the hormetic responses.

Adaptation, Physiological↗
PubMed1990

The role of adenosine in the hyperaemic response of the hepatic artery to portal vein occlusion (the 'buffer response').

1. Adenosine has been shown to be responsible for the hyperaemic response of the hepatic artery to portal vein occlusion (the hepatic arterial 'buffer response'). 2. The effect of adenosine receptor blockade and of adenosine uptake inhibition on the hepatic arterial response to portal vein occlusion was investigated in three groups of anaesthetized dogs. 3. Venous return and arterial blood pressure were maintained during periods of portal occlusion by establishing a side-to-side portacaval shunt. Hepatic artery and portal vein blood flows were measured with electromagnetic flowmeters. 4. Hepatic arterial infusions of 8-phenyltheophylline (500 micrograms kg-1 and 3-isobutyl-1-methylxanthine min-1) and 3-isobutyl-1-methylxanthine (75 micrograms kg-1 min-1), doses sufficient to block the vasodilator response of the hepatic artery to exogenously applied adenosine, reduced the magnitude of the 'buffer response' by 50% and 75%, respectively. 5. Intravenous infusion of dipyridamole (100 micrograms kg-1 min-1), a dose sufficient to potentiate the vasodilator response of the hepatic artery to exogenously applied adenosine, had little effect on the 'buffer response'. 6. It is concluded that adenosine is an important, but not the sole, agent responsible for the hepatic arterial 'buffer response'.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Growth hormone response to thyrotropin-releasing hormone in acromegalic patients: reproducibility and dose-response study.

The aim of the study was to analyze 14 consecutive patients with active acromegaly who had not undergone any therapy, the dose response of growth hormone (GH) to thyrotropin-releasing hormone (TRH), the existence of reproducibility of such response as well as to rule out the possibility of spontaneous fluctuations of GH which would mimic this response. On several nonconsecutive days, we investigated the GH response to saline serum, 100, 200 (twice) and 400 micrograms of TRH administration. We also studied both basal serum prolactin, serum prolactin after TRH administration and thyrotropin values. Our results show an absence of GH response after saline serum infusion, whereas after TRH doses, 36.3 42.8 and 45.4% positive responses were obtained, respectively. All GH responders were concordant to the different doses administered. The mean of GH concentrations of the different doses at different times did not reach significant differences. The response to the administration of the same dose brought about a significative increase, although it was not identical. It demonstrated a progressive increase of the area under the response curve, as did the means of increments after each TRH administration, albeit without reaching statistical significance. Between the GH-responding and GH-nonresponding groups there were no differences in either basal serum prolactin or serum prolactin and thyroid-stimulating hormone levels after TRH stimulation. The present study clearly shows that TRH elicits serum GH release from GH-secreting pituitary tumors. The response was reproducible in qualitative terms rather than quantitative, and no dose-response relationship was found between the TRH concentrations and the amounts of GH secreted.

Acromegaly↗
PubMedDate not supplied

Attenuation of pressor responses to norepinephrine and pitressin and potentiation of pressor response to angiotensin II by captopril in human subjects.

The present study was conducted to investigate the influence of captopril on cardiochemodynamic responses in 38 normal volunteers (20- to 35-year-old men) to exogenously administered vasopressor substances. Norepinephrine (NE), 0.05, 0.1, and 0.2 micrograms/kg min-1; angiotensin II (AII), 5, 10, and 20 ng/kg min-1; and pitressin (2 mU/kg min-1) were infused for 10 minutes. Each infusion was reported twice, and the responses were reproducible. Captopril (50 mg by mouth) significantly attenuated the pressor responses to NE and pitressin, but the decrease in heart rate in response to NE and pitressin was almost the same before and after captopril treatment, suggesting that captopril potentiates reflex slowing of the heart. Captopril significantly potentiated the pressor response to AII. Attenuation of pressor response and potentiation of reflex slowing of the heart, in response to NE and pitressin, disappeared when a subdepressor dose of AII (1 ng/kg min-1) was infused in addition to captopril. Infusion of a subdepressor dose of bradykinin (BK), 0.1 microgram/kg min-1, had no influence on the pressor response to NE. In the subjects treated with indomethacin (225 mg/54 hrs), captopril still attenuated the pressor response to NE. These results suggest that captopril attenuates the pressor responses to NE and pitressin primarily by depletion of endogenous AII; decreased AII may desensitize the contraction of arterial smooth muscle and may potentiate the compensatory reflex mechanism.

Adult↗
PubMed2003

Transcutaneous immunization with cholera toxin B subunit adjuvant suppresses IgE antibody responses via selective induction of Th1 immune responses.

Topical application of cholera toxin (CT) onto mouse skin can induce a humoral immune response to CT as well as to coadministered Ags. In this study, we examined the nontoxic cell-binding B subunit of CT (CTB) as a potential adjuvant for cutaneous immune responses when coadministered with the prototype protein Ag, OVA. CTB applied onto skin induced serum Ab responses to itself with magnitudes comparable to those evoked by CT but was poorly efficient at promoting systemic Ab responses to coadministered OVA. However, transcutaneous immunization (TCI) with either CT or CTB and OVA led to vigorous OVA-specific T cell proliferative responses. Furthermore, CTB potentiated Th1-driven responses (IFN-gamma production) whereas CT induced both Th1 and Th2 cytokine production. Coadministration of the toxic subunit CTA, together with CTB and OVA Ag, led to enhanced Th1 and Th2 responses. Moreover, whereas TCI with CT enhanced serum IgE responses to coadministered OVA, CTB suppressed these responses. TCI with either CT or CTB led to an increased accumulation of dendritic cells in the exposed epidermis and the underlying dermis. Thus, in contrast to CT, CTB appears to behave very differently when given by the transcutaneous as opposed to a mucosal route and the results suggest that the adjuvanticity of CT on Th1- and Th2-dependent responses induced by TCI involves two distinct moieties, the B and the A subunits, respectively.

Adjuvants, Immunologic↗