Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The long term alterations of T and B lymphocytes in the peripheral blood of patients treated with regional irradiation for various malignancies were examined. Eighty patients were tested at various intervals after the completion of irradiation. Absolute lymphocyte counts, the percentages of T cells and B cells, and the blastogenic response to phocyte reaction (MLR) were determined. Nearly all patients initially had absolute lymphocytopenia and one-third of the patients tested 3 years after completion of irradiation had lymphocyte counts which were more than two standard deviations below the normal range. The depression was not specific for either the T-or B-lymphocyte subpopulations. The PHA response was impaired for extended periods of time after the completion or irradiation. Differences in the mean response of lymphocytes to PHA were noted for all concentrations of the mitogen, but were most marked with suboptimal concentrations of PHA. The MLR was below the lower limits of normal in 70% of the recently irradiated patients. There was a gradual recovery of the ability to respond in the MLR, and all patients tested more than 4.5 years after the completion of therapy had a normal response. These results were compared with those obtained in patients treated with total lymphoid irradiation for Hodgkin's disease. Although three appeared to be a difference in the effect of radiation on lymphocyte subpopulations in the two groups, the effects on lymphocyte function were similar.
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PMID:The long term effects of radiation of T and B lymphocytes in the peripheral blood after regional irradiation. 14 54

In the present study we observed a significant depression of thymocytes during pregnancy and investigated the influences of this thymic change on the immunologic capacities of peripheral lymphocytes. Thymocytes in pregnant mice began to decrease in number from Day 10 and reached about 0.1-fold of the nonpregnant level at Day 19, just before parturition. At late stage of pregnancy, thymocyte subpopulation expressing CD4+CD8+ and Thy1.2+PNA+ was selectively depressed. On the contrary, peripheral lymphocytes including splenocytes, peripheral blood lymphocytes and peripheral lymph node cells showed no depression. As to the immunologic capacities of the pregnant hosts, delayed footpad reaction and phagocytic activity of fixed liver macrophages in vivo were remarkably suppressed, but MLR reactivity and antibody response to SRBC or haptens were well preserved. Transfer of pregnant sera or administration with steroid hormones especially E3 into nonpregnant mice induced similar changes in the thymus and peripheral lymphocytes in number and subsets but this could not mimic the immunologic reactivities of the pregnant mice. These results suggest that sex steroid hormones such as E3 play an important role in the changes in cell populations of each lymphoid organ and the immune reactivities of the hosts during pregnancy. However, other factors also contribute to the immunologic capacities of the maternal hosts.
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PMID:Thymic depletion in pregnancy: kinetics of thymocytes and immunologic capacities of the hosts. 166 37

In the summer following graduation a sample of 125 female college graduates (mean age = 28) completed Cohen & Wills' ISEL (1985) which includes scales measuring four social support functions: belonging (social companionship), appraisal (availability of confidants), tangible (instrumental), and self-esteem support. In the summer and fall subject status on two outcome scales was ascertained: the Psychophysiologic Symptom Scale and the Center for Epidemiologic Studies Depression Scale (CES-D). Reliability of the difference scores suggested that the ISEL scales do not measure entirely different constructs and the ISEL Self-esteem Scale is operationally redundant with the Rosenberg Self-esteem scale and the CES-D. Cross-sectional analyses indicated that the ISEL scales were related to symptoms. By contrast, standard longitudinal and prospective MLR analyses indicated that only the Belonging Scale was significantly related to future symptoms. The issues of confounding support with symptoms and the dimensionality of the subscales were discussed. The study suggests that specific functions of support take on greater importance during major life transitions and that any one supportive behaviour often serves multiple functions.
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PMID:Dimensions of functional social support and psychological symptoms. 178 Mar 98

To further define the role of arachidonic acid (AA) metabolites in transfusion-induced immunosuppression (TII), the effects of pharmacological manipulation of AA metabolism were examined in a rodent model. If the prostaglandins of the E series are mediators of TII, as has been recently hypothesized, then inhibition of cyclooxygenase (indomethacin) should abrogate whereas inhibition of lipoxygenase (nordihydroguaiaretic acid [NDGA]), or thromboxane synthetase (4-63557A) could potentiate the transfusion effect. Lewis rats received donor-specific transfusions from Buffalo rats in conjunction with one of the above inhibitors. Two weeks later they received intraabdominal Buffalo heart allografts or were used for one-way mixed lymphocyte reactions. Cyclooxygenase inhibition partially abrogated TII with shortened cardiac allograft survival. Lipoxygenase inhibition augmented TII, with depression of MLR and prolongation of allograft survival. Thromboxane synthetase inhibition had no effect. These results indicate that AA metabolites play a role in TII, and that immunoregulation via pharmacological manipulation of AA metabolism is possible.
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PMID:Immunoregulation of transfusion-induced immunosuppression with inhibitors of the arachidonic acid metabolism. 250 21

Excess body fat has been clearly associated with an increased risk of oligo-ovulation and endometrial/breast carcinoma. The connection has been assumed to lie within derangements of the metabolic/endocrine compartments, particularly of estrogens and androgens. To differentiate the effect of obesity from its related disease process, an attempt has been made to define the reproductive-endocrinologic alterations encountered in otherwise asymptomatic obese women. Androgen metabolism is accelerated in obesity. It is not clear whether the increased clearance precedes or follows the accelerated production of androgens. A servocontrol mechanism appears to be operative in these asymptomatic individuals, maintaining plasma steroid levels normal. The unbound fraction of T may be somewhat increased in overweight women with predominantly upper body fat deposition. The increased clearance of androgen may arise from an obesity-related depression in SHBG concentration (e.g., for T, E2, delta 5-diol, etc.). Adipose tissue, by virtue of the lipid solubility of most of these steroids, concentrates androgens, estrogens, and progesterone. This steroid sequestration not only contributes to the obesity-related increase in androgen clearance but also leads to an extremely enlarged total body steroid pool. Fat tissue sequestration also increases the concentration of androgens in the vicinity of adipose stromal cells, possibly encouraging their aromatization. Adipose tissue also has a moderate degree of 17-hydroxysteroid dehydrogenase activity, which appears to stimulate the conversion of A to T. Finally, alterations in peripheral and hepatic conjugation and an accelerated urinary excretion may contribute to the elevated clearance of androgens. The accelerated PR of androgens may simply result as compensation for the elevated MCR in obesity. Nonetheless, evidence of alteration(s) in adrenocortical steroidogenesis has been presented suggesting a selective obesity-related enhancement in adrenal androgen secretion. These remain to be confirmed. Nonetheless, adrenocortical abnormalities may arise secondary to the influence of other circulating and intra-adrenal factors, including insulin, prolactin, estrogens, and androgens. It is not known whether the accelerated androgen metabolism or the aberrant adrenal steroidogenesis improve with weight reduction. Excess body fat increases androgen aromatization which, together with an obesity-related decrease in SHBG, is associated with mildly elevated levels of E1 and free E2 in postmenopausal women. Although premenopausal obese individuals have the same tendency, the far greater ovarian estrogen secretion overshadows any differences. The bulk of aromatization activity in fat lies in the stromal comportment. The major substrate for peripheral estrogen production is A. Testosterone also contributes to the estrogen pool via its conversion to E2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reproductive endocrinologic alterations in female asymptomatic obesity. 268 Jun 25

Cellular immune response was studied longitudinally for a period of 1 month in a group of 51 patients sustaining burns between 20 and 55 per cent of their body surface area. The results indicated lymphocytopenia and significant depression in the total T cells in all the patients. T cells showed a significant rise in their levels in those patients who showed clinical improvement. Further, the loss of expression of 'E' receptor correlated with the lowering of the protein-synthesizing capacity of the mononuclear cells. The functional integrity of the lymphocytes also showed an inability to recognize and stimulate normal alloantigens in an MLR reaction. Investigation of the mechanisms responsible for immunosuppression revealed the generation of T suppressor activity.
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PMID:Cellular immune response following thermal injury in human patients. 294 27

The blood MCR of estradiol (MCRE2) was measured in 34 experiments with 10 adult (4.7-8.2 kg) and 13 prepubertal (1.8-3.0 kg; 13-23 months old) female rhesus monkeys using the constant infusion technique. Twenty-six of the studies were performed using an adult and an immature animal simultaneously. Twenty-four of the studies were performed in pentobarbital-anesthetized animals, while the remainder used conscious animals restrained in primate chairs. The blood MCRE2 in the adult female was 167.5 +/- 9.5 liters/day (mean +/- SE; n = 14) or 27.5 +/- 1.4 liters/day x kg BW, and was not altered by anesthesia, stage of the menstrual cycle, amenorrhea of more than 60 days duration, or the site of origin of the blood used to calculate the MCR (radial artery, femoral artery, femoral vein, or saphenous vein). While the absolute MCRE2 in the immature animal (either anesthetized or conscious) was less than that in the adult, when corrected for body weight, the relative MCRE2 (in liters per day/kg BW) of the conscious immature animal was double that seen in the adult [48.4 +/- 5.2 (n = 6) vs. 27.5 +/- 1.4 (n = 1.4)]. Anesthesia caused a profound depression of the MCRE2 in the immature animal, which could be prevented if the body temperature of the animal was maintained at 37 C during the prolonged period of anesthesia. The production rate of estradiol (PRE2) was calculated as the product of the serum estradiol concentration (in micrograms per liter; measured by RIA techniques) and the plasma MCRE2 (blood MCRE2 x 1 - hematocrit). In the adult animals, the PRE2 ranged from 1.9 - 35.5 micrograms/day, and was lowest in the amenorrheic animals and highest during the late follicular phase. The PRE2 in the immature animals ranged from unmeasurable to 1.7 micrograms/day, averaging 0.7 +/- 0.2 micrograms/day (n = 12) in those animals where it could be measured. These data support the hypothesis that the low circulating estradiol levels in the immature animal are the consequence of a low PRE2 coupled with a high MCRE2.
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PMID:The metabolic clearance rate and the production rate of estradiol in sexually immature and adult female rhesus monkeys. 683 72

This study evaluated the efficacy and mode of action of rapamycin (RPM) in a model of accelerated (24-hr) rejection of LBNF1 cardiac allografts in specifically sensitized LEW rats. RPM treatment (0.25 mg/kg/day i.p.) between the day of sensitizing skin grafts (day -7) and subsequent heart (day 0) transplantation (Tx), abrogated fulminant rejection and prolonged cardiac allograft survival to 46 +/- 22 days (mean +/- SD, P < 0.0001). The delayed introduction of RPM until day -2 or day -1 was equally effective, whereas treatment initiated after cardiac Tx was ineffectual. Untreated accelerated rejection was associated with strong production of circulating IgM, whereas an IgG alloantibody response was not detected until after rejection was complete. RPM therapy (day -7 to -1) diminished this systemic IgM response and prevented the switch from IgM to IgG alloantibody production. Immunohistologic evaluation at 24 hr after cardiac Tx showed that compared with untreated hosts RPM treatment largely abolished intragraft cellularity, and was associated with decreased mononuclear and endothelial cell activation. Specifically, Ia and ICAM-1 upregulation was abolished, and no cells elaborating IL-2 or IFN-gamma were detected. In addition, RPM treatment prevented intragraft production of the proinflammatory cytokines IL-1 beta, IL-6, and IL-8. The effects of RPM therapy on recipient cellular responses were evaluated in vitro by mixed lymphocyte reaction. Surprisingly, the donor-specific proliferative response of cells from RPM-treated hosts at 1 or 7 days after Tx was markedly increased, compared with cells from rejecting, untreated controls, and bioassay of IL-2 within supernatants of MLR cultures showed comparable levels of IL-2 in both groups. The effects of RPM upon adhesion properties of lymph node lymphocytes were also tested in an in vitro binding assay. The binding of naive cells to sections of cardiac allografts collected from RPM-treated hosts at 24 hr post-Tx was decreased compared with that in untreated recipients. Interestingly, the binding of mononuclear cells to high endothelial venules of peripheral lymph nodes in RPM-treated hosts remained relatively high. Thus, treatment with RPM prevents and/or erases the sensitization, which otherwise leads to accelerated allograft rejection. Abrogation of allograft injury by RPM was associated with profound and long-lasting depression of host IgM and IgG alloantibody responses in the circulation, and selective downregulation of host cellular immunity and endothelial activation at the graft site. In contrast, antigen alloreactivity and endothelial adhesivity in peripheral lymphoid tissues were spared, indicating novel and potent selective effects of RPM therapy in allograft recipients.
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PMID:Abrogation by rapamycin of accelerated rejection in sensitized rats by inhibition of alloantibody responses and selective suppression of intragraft mononuclear and endothelial cell activation, cytokine production, and cell adhesion. 815 43

We tested the effects of blocking CD28-B7 T cell costimulation by using CTLA4Ig in an established transplantation model in which LBNF1 cardiac allografts are rejected in an accelerated manner (<36 h) by LEW rats presensitized with Brown-Norway skin grafts. Treatment with CTLA4Ig with or without donor alloantigen in the sensitization phase (between skin and cardiac engraftment) minimally delayed accelerated rejection. However, adjunctive infusion of CTLA4Ig and donor alloantigen in the effector phase (after cardiac engraftment) resulted in long term graft survival and donor-specific tolerance in 30 to 50% of the recipients. The mutant form of CTLA4Ig, which blocks B7-1 but not B7-2, was ineffective. The tolerant state was accompanied by reduction of cell-mediated (MLR/CTL) responses and depression of humoral (circulating IgM/IgG allo-Abs) alloreactivity in vivo. Hence, the binding of CD28 on T cells to both CD80 and CD86 ligands represents a crucial initial costimulatory step leading to accelerated graft rejection. CTLA4Ig-mediated early blockade of the CD28 signaling pathway combined with transfusion of donor cells in the perioperative period interrupts sensitization and may produce transplantation tolerance. This regimen inhibits T cell costimulation and activation to provide help to CD8+ cytotoxic T and B cells, perhaps, via CTLA4Ig-induced clonal anergy or deletion.
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PMID:CD28-B7 T cell costimulatory blockade by CTLA4Ig in sensitized rat recipients: induction of transplantation tolerance in association with depressed cell-mediated and humoral immune responses. 925 32

Escape from immune surveillance is critical for tumor progression in metastatic melanoma. We assessed the function of melanoma-derived dendritic cells (DCs) in patients presenting simultaneously with responding (rM) or progressing (pM) melanoma metastases. These rare coincidences allowed us to compare syngeneically the function of tumor DCs. CD83+ DCs were purified freshly from large responding (rDCs) or progressing (pDCs) metastases following chemoimmunotherapy. rDCs were 5 times more potent inducers of allogeneic T-cell proliferation than the pDCs that were used as control. Phenotypic analysis showed a marked depression of CD86 expression on pDCs. Culture supernatants from pM showed production of Th2-type cytokines [interleukin-10 (IL-10)], whereas a Th1 pattern [IL-2, interferon-gamma (IFN-gamma), IL-12) predominated in rM. The IL-10 detected in progressing metastases was directly derived from melanoma cells. Culture supernatants from metastases applied to DC-supported allo-MLR assays suppressed T-cell responses by 50-75% in the case of pM, but not rM. Finally, in a co-stimulation-dependent anti-CD3 tolerance assay, pDCs (but not rDCs) induced anergy in syngeneic CD4+ T cells. Anergy could be overcome by addition of IL-12 or IL-2. Our results show that melanoma-derived factors convert DC-antigen presenting cell function to tolerance induction against tumor tissue, changing tumor DCs to "silencers" of anti-tumoral immune responses.
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PMID:Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. 935 74


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