Hormonal activities of cytokines.
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Animals↗
Biomedical subjects
E M Smith
Publications and source records attributed to E M Smith.
One-year follow-up of survivors of a mass shooting.
OBJECTIVE: This report describes a 1-year follow-up study of survivors of a mass shooting incident. Acute-phase data from this incident were previously reported in this journal. METHOD: The Diagnostic Interview Schedule/Disaster Supplement was used to assess 136 survivors at 1-2 months and again a year later, with a 91% reinterview rate. RESULTS: In the acute postdisaster period, 28% of subjects met criteria for posttraumatic stress disorder (PTSD), and 18% of subjects qualified for another active psychiatric diagnosis. At follow-up, 24% of subjects reported a history of postdisaster PTSD (17% were currently symptomatic), and 12% another current psychiatric disorder. Half (54%) of all 46 individuals identified as having had PTSD at either interview were recovered at follow-up, and no index predictors of recovery were identified. There were no cases of delayed-onset PTSD (beyond 6 months). Considerable discrepancy in identified PTSD cases was apparent between index and follow-up. Inconsistency in reporting, rather than report of true delayed-onset, was responsible for all PTSD cases newly identified at 1 year. The majority of subjects with PTSD at index who were recovered at follow-up reported no history of postdisaster PTSD at follow-up, suggesting considerable influence of fading memory. CONCLUSIONS: This study's findings suggest that disaster research that conducts single interviews at index or a year later may overlook a significant portion of PTSD. The considerable diagnostic comorbidity found in this study was the one robust predictor of PTSD at any time after the disaster. Disaster survivors with a psychiatric history, especially depression, may be most vulnerable to developing PTSD and therefore may deserve special attention from disaster mental health workers.
Adult↗
Nonoperative treatment of major blunt renal lacerations with urinary extravasation.
PURPOSE: We determined whether nonoperative treatment of major renal lacerations with urinary extravasation adversely affects patient outcome. MATERIALS AND METHODS: We reviewed all nonoperatively treated patients who presented between 1983 and 1994 with blunt renal trauma with major lacerations on initial staging computerized tomography. Patients with major lacerations associated with (31) and without (15) extravasation were compared for complications, blood transfusions and length of hospital stay. RESULTS: Urinary extravasation spontaneously resolved in 27 of 31 patients (87.1%), while 4 (12.9%) required a ureteral stent for persistent extravasation. No complications occurred in patients without extravasation. Mean hospitalization was 8.3 and 7.7 days for patients with isolated renal injuries with and without extravasation, respectively. Blood transfusions were required in 4 patients with and none without extravasation. CONCLUSIONS: Nonoperative treatment of major renal lacerations with urinary extravasation is safe and effective. Although delayed intervention may be required, complications can often be treated with endourological or percutaneous methods.
Adolescent↗
Comparison of the Alcohol Dependence Scale and diagnostic interview schedule in homeless women.
The Alcohol Dependence Scale (ADS) is a 25 item self-report instrument designed to evaluate the degree of severity of alcohol dependence. Although previous studies have reported on the validity of the ADS, no studies using the ADS have been done on the homeless population, a special and rapidly growing population. To assess the utility of the ADS in a population of homeless, substance-abusing women, the ADS questionnaire was compared with the DSM-III-R alcohol use disorder diagnosis as measured by the Diagnostic Interview Schedule (DIS). Both the ADS and the DIS were administered to 149 homeless, substance-abusing women by trained, lay interviewers. There was good agreement between the ADS and the past-year DIS diagnosis of alcohol use disorder. The level of agreement between the ADS and DIS, as well as sensitivity and specificity, for various ADS cutoff scores are reported to facilitate selection of cutoff scores by clinicians and future researchers.
Adult↗
Connective tissue activation. XXXVII. Effects of cytokine combinations, implications for an integrated cytokine network.
OBJECTIVE: Since many cytokines have been identified in chronically inflamed human synovium, it is possible that particular cytokines or combinations of cytokines play dominant roles in driving or inhibiting metabolic processes important to inflammation. To assess these possibilities, we compared selected effects of individual cytokines and their binary, ternary, and higher combinations in human synovial cell cultures. METHODS: Cytokines studied known to occur in human synovial tissue included: interleukin 1beta (IL-1beta), IL-6, tumor necrosis factor-alpha, granulocyte macrophage colony stimulating factor, interferon-gamma, acidic fibroblast growth factor (aFGF), basic FGF (bFGF), platelet derived growth factor, transforming growth factor-beta1, connecting tissue activating peptide-III, and epidermal growth factor. The growth related effects of these agents singly and in combinations were assessed by measuring newly synthesized [3H]DNA and [14C]GAG (glycosaminoglycan) in human synovial cell cultures. Cytokine induced synthesis of prostaglandin E2 (PGE2) was measured by ELISA. RESULTS: Most cytokine combinations resulted in additive/synergistic anabolic effects, except when IL-1beta was present; IL-1beta was markedly antagonistic to the mitogenic effects of other cytokines tested. Combinations of platelet derived cytokines were the most potent stimulators of DNA synthesis, while combinations of synovial derived cytokines were more active in stimulating GAG synthesis. Synovial cells exposed simultaneously to both platelet and synovial derived cytokines produced large quantities of [14C]GAG and showed a modest increase in [3H]DNA synthesis. IL-1beta, alone or in combinations, was dominant with respect to stimulation of PGE2 synthesis. Acetylsalicylic acid substantially interfered with all the effects of cytokine combinations measured. CONCLUSION: Quantitative alterations in synovial cell synthesis of GAG and DNA varied greatly depending on the ambient mixture of cytokines. Virtually all combinations of cytokines tested gave rise to large increases in synovial cell synthesis of GAG. Four platelet derived cytokines, a "physiologic combination," appeared to be dominant agents in stimulating DNA synthesis. This effect was profoundly reduced by the antagonistic effect of IL-1beta, mediated in part by PGE2. The patterns of cytokine combination induced metabolic effects suggest that the "cytokine network" has a significant measure of redundancy with respect to control of synovial cell metabolism.
Arthritis, Rheumatoid↗
Surgical anticipatory stress manifests itself in immunocyte desensitization: evidence for autoimmunoregulatory involvement.
The immunocyte behavior (conformational changes and locomotion in response to signal molecule challenge) in patients about to undergo elective cardiac surgery was studied to elucidate the effect of psychological anticipatory stress on the immune system. Granulocytes and monocytes from 10 patients and 35 non-surgical controls were examined. Computer-assisted microscopic image analysis, capable of measuring cellular conformational and velocity changes, was used to measure the responsiveness of these immunocytes to peptidergic and cytokine stimulation. Immunocyte desensitization would appear to account for the reduction in their abilities to respond to chemotaxic challenge associated with the pre-cardiac surgery state. Their abilities to respond to D-Ala2-Met-enkephalinamide (DAMA) were observed only at much higher concentrations than previously reported (10-11 M vs. 10-9 M prior to surgery). This finding, together with the observed decrease in adrenocorticotropin levels compared to non-surgical controls, suggests that neutral endopeptidase activity was elevated just prior to surgery. Indeed, neutral endopeptidase activity is statistically elevated in the pre-cardiac surgery state. Furthermore, glucocorticoid levels remained constant, within normal resting limits, in both groups. Thus, surgical anticipatory stress may manifest itself, in part, as a desensitization of various immunocytes. Thus, a psychological anticipatory stress response may be a precipitant of the desensitization. Although this desensitization seemed not to involve the entire hypothalamic-pituitary-adrenal axis, the data suggest that psychological anticipatory stress may initially involve and influence autoimmunoregulation.
Adrenocorticotropic Hormone↗
The presence and effects of mammalian signal molecules in immunocytes of the insect Leucophaea maderae.
Opioid peptides activate immunocytes and opiate alkaloids inhibit this activation in the mussel, Mytilus edulis. Here we present evidence that cells of another invertebrate, Leucophaea maderae, can be influenced in a similar way by the Met-enkephalin analogue D-Ala2-Met5-enkephalin (DAMA) and morphine. Effects of different signal molecules on Leucophaea hemocytes were evaluated by computer-assisted image analysis of their conformational state. A small percentage of the untreated cells were found to display spontaneous conformational changes after 25 min of incubation without pharmacological agents which was noted as a decrease in both circularity factor and shape factor values. Activation caused the cells to become elliptical, a feature that appears to be characteristic of Leucophaea immunocytes. Administration of DAMA induced a similar activation of most of the cells. After 30 min these DAMA-activated cells started to display distinct locomotory activity not seen in the controls. alpha-Melanocyte-stimulating hormone (MSH, 10(-7)) added to the incubation medium after DAMA-activation caused the cells to return to their original "rounded" conformation. In addition, the presence of immunoreactive interleukin (IL-1), adrenocorticotropin (ACTH) and tumor necrosis factor (TNF) in the hemolymph was demonstrated. These data suggest an interaction between both vertebrate-type immunological signal molecules and neuropeptides in the regulation of immunological cells in Leucophaea.
Adrenocorticotropic Hormone↗
Adrenocorticotropin--a central trigger in immune responsiveness: tonal inhibition of immune activation.
Adrenocorticotropin is known for its key role in mediating neuroendocrine responses, especially in response to stress. Recently, it has been recognized to have direct immunomodulatory actions, most of which are suppressive. This is a widely conserved action which occurs in invertebrates and vertebrates. This conservation illustrates the fundamental nature of adrenocorticotropin's immunomodulatory action. Such a mechanism of action helps explain why the immunocytes themselves can serve as a source of adrenocorticotropin. Regulation of adrenocorticotropin production and action is complex and the result is an integration of multiple mechanisms. Serum adrenocorticotropin levels fluctuate in response to stimulatory and inhibitory factors. Further, peptidases can specifically process adrenocorticotropin into smaller active fragments, inactive peptides or into peptides with different activities. These proteolytic enzymes have a differential tissue and cellular distribution. Immune stimulating factors such as interleukin-1 can overcome adrenocorticotropin inhibition and secondarily, block adrenocorticotropin production through the release of corticosteroids. With an endogenous presence and complex regulation it has been difficult to characterize adrenocorticotropin's role in the immune system. Here, we propose that adrenocorticotropin is a tonis regulator of immune response, i.e. it tonally inhibits immunocytes which undergo disinhibition as the result of exposure to stimulatory signals, e.g. cytokines, neuropeptides, etc. Thus, adrenocorticotropin appears to set the threshold for immunoactivation by controlling the degree of immunoexcitability.
Adjuvants, Immunologic↗
The genetic program of genital human papillomaviruses in infection and cancer.
Human papillomavirus (HPV) infection has been recognized as the major cause of cervical cancer. This article summarizes the functions of HPV gene products that cause abnormal cell growth--E6 and E7--and reviews how cellular and viral factors influence their synthesis. E6 and E7 inactivate two cellular tumor-suppressor gene products, p53 and RB. In cervical cancer, E6-E7 gene control is deranged by mutations in viral control sequences and in integrated HPV fragments by the disruption of the viral repressor E2. Elimination of this sequence makes E6-E7 mRNAs unstable, and deranges cellular regulation at the integration site. It is apparent that an intricate interplay of cellular and viral factors determines whether the outcome is active papillomavirus infection, viral latency, or ultimately, genital cancer.
DNA, Viral↗
Human immunodeficiency virus envelope glycoprotein 120 alters sleep and induces cytokine mRNA expression in rats [published errata appear in Am J Physiol 1996 Aug;271(2 Pt 2):section R following table of contents and 1996 Dec;271(6 Pt 3):section R following table of contents].
Sleep is altered during the course of viral infection, including that in which the human immunodeficiency virus (HIV) is the etiologic agent. Alterations in the sleep of HIV-infected individuals occur early in the course of infection, prior to the onset of AIDS. The mechanisms for such alterations in sleep are not known. The HIV envelope glycoprotein 120 (gp120) induces the synthesis and secretion of cytokines that enhance [e.g., interleukin (IL)-1 and tumor necrosis factor] and suppress (e.g., IL-10 and IL-1 receptor antagonist) sleep. We used a well-defined rat model to test the hypothesis that the HIV gp120 alters sleep. Recombinant HIV-1IIIB gp120 was injected intracerebroventricularly (20- 500 ng) into rats prior to dark onset. Sleep-wake behavior was not altered after the 20-ng dose, whereas both non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) were initially enhanced and subsequently suppressed after the 100-ng dose. NREMS was enhanced for 8 h after the 500-ng dose; REMS was not affected by this dose. Brain temperature was not altered by any of the gp120 doses used in this study. In addition, mRNA expression for IL-1 beta and IL-10 was induced in the hypothalamus by gp120; this brain region is crucial for the regulation of sleep. These new data support the hypothesis that altered cytokine concentrations within the central nervous system play a pivotal role in the complex alterations in sleep observed during HIV infection.
Animals↗
Opioid and opiate immunoregulatory processes.
The discovery of the ability of the nervous system to communicate through "public" circuits with other systems of the body is attributed to Ernst and Berta Scharrer, who described the neurosecretory process in 1928. Indeed, the immune system has been identified as another important neuroendocrine target tissue. Opioid peptides are involved in this communication (i.e., neuroimmune) and with that of autoimmunoregulation (communication between immunocytes). The significance of opioid neuropeptide involvement with the immune system is ascertained from the presence of novel delta, mu, and kappa receptors on inflammatory cells that result in modulation of cellular activity after activation, as well as the presence of specific enzymatic degradation and regulation processes. In contrast to the relatively uniform antinociceptive action of opiate and opioid signal molecules in neural tissues, the presence of naturally occurring morphine in plasma and a novel mu3, opiate-specific receptor on inflammatory cells adds to the growing knowledge that opioid and opiate signal molecules may have antagonistic actions in select tissues. In examining various disorders (e.g., human immunodeficiency virus, substance abuse, parasitism, and the diffuse inflammatory response associated with surgery) evidence has also been found for the involvement of opiate/opioid signaling in prominent mechanisms. In addition, the presence of similar mechanisms in man and organisms 500 million years divergent in evolution bespeaks the importance of this family of signal molecules. The present review provides an overview of recent advances in the field of opiate and opioid immunoregulatory processes and speculates as to their significance in diverse biological systems.
Animals↗
Are the mentally ill homeless a distinct homeless subgroup?
The question has been raised whether it is useful or meaningful to dichotomize the homeless population by mental illness - i.e., to consider the mentally ill homeless as distinct from other homeless people. The current article presents evidence from a single data set to address this question empirically. Data from a randomly sampled population of 900 homeless men and women systemically interviewed using the Diagnostic Interview Schedule were examined to determine associations of mental illness with the problems of homelessness, controlling for the presence of substance abuse in the analyses. Although a few clinically meaningful associations with mental illness were found that might suggest directions for appropriate interventions, mental illness did not differentiate individuals in many important demographic and biographic respects. Individual diagnoses did not perform much better in differentiating the homeless by mental illness. Schizophrenia and bipolar mania showed a few significant associations not identified by the "major mental illness" construct. Major depression, constituting the majority of nonsubstance Axis I disorder in the homeless, provided no association beyond that obtained with the "major mental illness" category. The data provide little support for conceptualizing homeless subgroups or homelessness in general on the basis of mental illness alone. To do so also risks neglecting the emotional distress of the majority without major mental illness and the other problems that homeless persons share regardless of psychiatric illness. While serious mental illness is overrepresented among the homeless, it represents just one of many important vulnerability factors for homelessness. Substance abuse is far more prevalent than other Axis I disorders. Media images equating homelessness with major mental illness unnecessarily stigmatize homeless people and encourage oversimplified and narrowly conceived psychiatric interventions. While continuing attention is needed on improving identification and management of serious mental illness among the homeless, this must be accomplished within the broader context of social and economic aspects of homelessness.
Adult↗
Presence of interleukin-10 transcripts in human pituitary and hypothalamus.
1. Recent data have shown that interleukin-10 (IL-10) is expressed and acts in mouse pituitary tumor cells and freshly isolated mouse pituitaries. 2. In this study, we show that poly(A+) RNA derived from normal human pituitary and hypothalamus expresses IL-10 message. 3. The majority of transcripts was likely from the pituitary and hypothalamus, and not from lymphocytes in the pituitary and hypothalamic vasculature, since both IL-10 and interferon-gamma mRNA levels, compared to equivalent amounts of RNA from peripheral blood lymphocytes, were much lower. 4. These results indicate that IL-10 may function in human neuroendocrine process as it does in the murine system, thus serving as an important signal molecule for bidirectional communication between the neuroendocrine and the immune systems.
Adolescent↗
Interleukin-10 (cytokine synthesis inhibitory factor) acts in the central nervous system of rats to reduce sleep.
Interleukin-10 (IL-10), originally designated a cytokine synthesis inhibitory factor, inhibits the synthesis of the pro-inflammatory cytokines IL-1 and tumor necrosis factor by stimulated human and mouse monocytes/macrophages; these cytokines are involved in the regulation of sleep. To determine if IL-10 reduces spontaneous sleep, we injected murine recombinant IL-10 intracerebroventricularly into rats prior to light onset. Non-rapid eye movements sleep was reduced. The behavioral responses to IL-10 were abolished by heat-inactivation of this cytokine. We believe these to be the first observations of central nervous system actions for this cytokine. These results further support the hypothesis that cytokines are involved in the regulation of sleep, and suggest an additional mechanism whereby sleep may be altered in response to an activated immune system.
Animals↗
Modulation of immune responses by anabolic androgenic steroids.
Anabolic androgenic steroids (AS) have recently been placed on the Food and Drug Administration's (FDA's) list of controlled substances, because of the adverse effects seen in athletes taking accelerated dosages in attempts to enhance performance. Reported deleterious effects on abusers include sterility, gynecomastia in males, acne, balding, psychological changes, and increased risks of heart disease and liver neoplasia. Considering the roles of the immune and neuroendocrine systems and their interactions in many of these pathologies, it is important to determine the effects of these derivitized androgens on this connection. Little is known in this respect. We therefore determined the effects of anabolic steroids on certain immune responses and their effects on the extrapituitary production of corticotropin by lymphocytes. We present evidence that (1) both 17-beta and 17-alpha esterified AS, nandrolone decanoate and oxymethenelone, respectively, significantly inhibited production of antibody to sheep red blood cells in a murine abuse model; (2) the control androgens testosterone and dehydroepian-drosterone (DHEA) or sesame seed oil vehicle had no significant effects on antibody production; (3) nandrolone decanoate and oxymethenelone directly induced the production of the inflammatory cytokines IL-1 beta and TNF-alpha from human peripheral blood lymphocytes but had no effect on IL-2 or IL-10 production; (4) control androgens had no direct cytokine inducing effect; (5) nandrolone decanoate significantly inhibited IFN production in human WISH and murine L-929 cells; and (6) nandrolone decanoate significantly inhibited the production of corticotropin in human peripheral blood lymphocytes following viral infection. These data indicate that high doses of anabolic steroids can have significant effects on immune responses and extrapituitary production of corticotropin. Furthermore, the mouse model should provide an effective means by which to study other deleterious effects of anabolic steroid abuse in humans.
Adjuvants, Immunologic↗
Cyclotorsion in the seated and supine patient.
We used Maddox double-rod measurements to determine if positionally induced ocular cyclotorsion occurs when a patient moves from the seated to supine position. Maddox double-rod measurements were determined twice while patients (N = 30) viewed a fixation light at a distance of 7 feet in both the seated and supine positions. The difference between axis measurements made in seated and supine positions was not statistically significant. There was also no significant difference between the two measurements made in the seated and in the supine positions. These data show that the eyes do not undergo positionally induced ocular cyclotorsion when a patient moves from a seated to a supine position.
Adult↗
Eighteen-month follow-up data on a treatment program for homeless substance abusing mothers.
In response to the dearth of data on substance abuse treatment among homeless mothers, this study breaks new ground in presenting 18-month follow-up data on 149 homeless mothers with young children enlisted in a substance abuse treatment program. The effects of residential compared to nonresidential services were evaluated over the follow-up period. Although dropout rates were high, predictors of dropout were identified, and the residential had a lower dropout rate compared to the nonresidential comparison group. Members of both residential and nonresidential groups evidenced improvement in alcohol and drug problems and in housing stability, regardless of the amount of time they spent in the program. This project demonstrated that homeless mothers can be more successfully engaged in substance abuse programs with provisions of residential placement in addition to participation in a therapeutic community. Future interventions can take advantage of this knowledge in designing more effective programs.
Adult↗
Perinatal transmission and maternal risks of human papillomavirus infection.
We conducted a prospective study to investigate whether human papillomavirus (HPV) could be vertically transmitted to neonates. Pregnant women (N = 203) were tested for HPV DNA infection during the third trimester and again during labor prior to delivery. Their newborns (N = 203) were tested 1 to 3 days after delivery. Among the mothers, 12.3% (N = 25/203) typed HPV positive at either or both maternal specimen collection periods, whereas only 1.0% of the neonates (N = 2/203) typed positive. This low transmission rate may be due in part to the fact that 65% of mothers who were HPV positive during the third trimester tested HPV negative by labor/delivery. The higher frequency of risks associated with maternal HPV infection were similar to those found in studies of cervical dysplasia and cancer: younger age at first intercourse and first pregnancy, number of sexual partners, and longer duration in use of oral contraceptives. In addition, those who were past smokers and had a shorter recency and latency period in smoking were more likely to be detected with HPV.
Adolescent↗