bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic intraperitoneal endotoxin treatment in rats induces resistance to d‐tubocurarine, but does not produce up‐regulation of acetylcholine receptors
Authors: Hinohara H. , Morita T. , Okano N. , Kunimoto F. , Goto F. 
Published: December 2004

Background: Chronic systemic inflammation resulting from intraperitoneal Eschevichia coli endotoxin administration or Corynebacterium injections induces tolerance to non‐depolarizing neuromuscular blockers in rodents. Although this has been explained as up‐regulation of muscle acetylcholine receptors (AChR), the numbers of involved receptors have not been documented. The aim of this study was to determine the effects of chronic endotoxin administration on rat muscle AChR.Methods: One day after one, seven, or 14 daily intraperitoneal doses of lipopolysaccharide endotoxin (0 or 0.5 mg kg−1), we studied in vivo dose–response relationships for d‐tubocurarine (d‐Tc) and AChR binding using [125I]α‐bungarotoxin as a ligand.Results: One day after seven and 14 daily intraperitoneal doses of endotoxin, the effective dose of d‐Tc required to suppress the twitch response to 50% of the control (ED50) was significantly increased compared with that of time‐matched control rats (146.5 ± 38.2 vs. 76.1 ± 9.0 µg kg−1 for seven doses; 116.4 ± 51.3 vs. 74.4 ± 9.6 µg kg−1 for 14 doses, P < 0.05). However, this was not associated with an increase in the number of AChR in the anterior tibial muscle or diaphragm.Conclusions: Mechanisms other than AChR up‐regulation might be responsible for the increased d‐Tc requirement during chronic intraperitoneal endotoxin administration.
Epidemiology and natural course of social fears and social phobia
Authors: Wittchen H.‐U. , Fehm L. 
Published: December 2004

Objective: To summarize epidemiological studies providing data on prevalence, incidence, comorbidity, natural course, risk factors and consequences of social phobia (SP).Method: Data from cross‐sectional studies and prospective longitudinal studies in particular are considered.Results: These studies portray SP as a frequent mental disorder, which begins typically in early adolescence, and is highly comorbid with other anxiety disorders, as well as secondary depression and substance abuse disorders. Several possible risk factors have already been identified for the onset and unfavorable course of SP; some of them have been tested in prospective longitudinal studies. SP is a chronic disorder when compared with other mental disorders and when subclinical symptomatic levels are considered. Impairment caused by SP is considerable and increases over a patient's life span. The negative impact of SP is not only reflected in subjective well‐being and reduced quality of life but also in social role functioning, and it impacts negatively on career progression.Conclusion: Prospective longitudinal studies in representative samples drawn from the general population provide information that allows the overall direct and indirect costs of the disorder (treatment costs, disability, social welfare) to be determined, and enables an improvement in long‐term care strategies as well as preventive efforts to be established.
The impairments caused by social phobia in the general population: implications for intervention
Authors: Kessler R. C. 
Published: December 2004

Objective: Although social phobia is common, treatment remains low. In order to gauge public health implications of this low treatment, information is needed on the impairments caused by social phobia.Method: A computer literature review searched for the terms ‘social anxiety disorder’ and ‘social phobia’ in the MEDLINE and PsycLIT databases. New analyses were carried out in the US National Comorbidity Survey.Results: The literature shows that social phobia has serious effects on role functioning and quality of life. These effects are least severe for pure non‐generalized social phobia and most severe for comorbid generalized social phobia with avoidant personality disorder. The most direct impairments involve social interactions and information processing errors in these interactions. Indirect effects are even more important. Three indirect effects are highlighted: effects on secondary mental (e.g. depression), substance (e.g. alcoholism) and physical (e.g. cardiovascular disease) disorders; effects on normative role transitions (e.g. educational attainment); and effects on help‐seeking.Conclusion: Given the early age of onset and impacts on secondary disorders and early adult life course transitions, the greatest public health impact of increasing treatment of social phobia is likely to be achieved by developing programs targeted at early identification and treatment through schools.
Neuroanatomical circuits modulating fear and anxiety behaviors
Authors: Charney D. S. 
Published: December 2004

Objective:  Our understanding of the neurobiology of anxiety disorders, although not complete, has advanced significantly with the development and application of genetic, neuroimaging and neurochemical approaches.Method:  The neuroanatomical basis of anxiety disorders is reviewed with particular focus on the amygdala and the temporal and prefrontal cortex. The functional anatomical correlates of anxiety disorders such as panic disorder, specific phobias and post‐traumatic stress disorder are also discussed.Results:  Functional neuroimaging studies in patients with anxiety disorders have shown neurophysiological abnormalities during symptom provocation tests, implicating the limbic, paralimbic and sensory association regions. The involvement of neurotransmitters such as serotonin and norepinephrine in depressive disorders is well established. Antidepressants that affect these neurotransmitter systems have also been shown to be useful in the treatment and management of patients with anxiety disorders. The role of serotonin and norepinephrine in the pathophysiology of anxiety disorders is reviewed. In addition, the involvement of the stress hormone corticotropin‐releasing hormone, the peptide cholecystokinin and the amino acid transmitter γ‐amino butyric acid in anxiety disorders is reviewed.Conclusion:  The inconsistency in the results of biologic investigations of anxiety disorders highlights the importance of addressing the neurobiologic heterogeneity inherent within criteria‐based, psychiatric diagnoses. Understanding of this heterogeneity will be facilitated by the continued development and application of genetic, neuroimaging and neurochemical approaches that can refine anxiety disorder phenotypes and elucidate the genotypes associated with these disorders. Application of these experimental approaches will also facilitate research aimed at clarifying the mechanisms of anti‐anxiety therapies.
The neurobiology of social anxiety disorder: the relevance of fear and anxiety
Authors: Marcin M. S. , Nemeroff C. B. 
Published: December 2004

Objective: Social anxiety disorder (SAD) is a ubiquitous anxiety disorder. Despite being the third most common psychiatric disorder, little is known about the interaction between genetic predisposition and environmental factors in the development of SAD. The available literature on SAD has been compared with data on the genetics and environmental impact on the phenotypic expression of fear and anxiety, and its implicated neurobiology, in order to explore the neurobiology of SAD as understood through the neurochemical dysregulation expressed in fear and anxiety.Method:A systematic review of the literature was employed for the years from 1966 to 2001.Results:SAD does indeed have much overlap with fear and anxiety. This is best demonstrated by the interactions of the noradrenergic and serotonergic systems with each other and the hypothalamic–pituitary–adrenal axis.Conclusion:SAD may well be understood as one potential outcome for predisposed individuals who are exposed to the proverbial ‘second hit’, or environmental insult, in childhood. Behavioral inhibition may be an early expression of this predisposition, with natural progression to SAD occurring via a disruption of neurochemical homeostasis. Through animal and human data it has become evident that fear and anxiety have shared, as well as distinct, neurochemical and neuroanatomical pathways. These similarities are expressed as symptoms and objective signs that are common to many individuals with social anxiety disorder.
Family and high‐risk studies of social anxiety disorder
Authors: Merikangas K. R. , Lieb R. , Wittchen H.‐U. , Avenevoli S. 
Published: December 2004

Objective:  To present data on the role of familial factors in the etiology of social anxiety disorder.Method:  Findings presented from a family/high‐risk study (the Yale Family Study) and a prospective community study of youth (the Munich Early Developmental Stages of Psychopathology (EDSP) Study).Results:  The Yale Family Study demonstrated a substantial degree of familial aggregation of social anxiety disorder and specificity with respect to other anxiety subtypes among adult relatives. The Yale high‐risk component and the EDSP Study confirm the association between parental and offspring social anxiety, but did not yield consistent evidence for an association between familial environmental factors and social anxiety.Conclusion:  Future studies are needed to examine mechanisms for the specificity of social anxiety disorder aggregation, to identify vulnerability factors for its development and to pinpoint environmental conditions that may enhance or suppress expression of underlying vulnerability.
Pharmacotherapy of social phobia
Authors: Davidson J. R. T. 
Published: December 2004

Objective:  To review placebo‐controlled medication trials in social phobia (SP).Method:  Published and/or presented placebo‐controlled trials of medication were reviewed and summarized.Results:  Phenelzine is effective in 60–70% of patients with SP and always superior to placebo. Although reversible inhibitors of monoamine oxidase type A (RIMAs) are safer, their benefits are unpredictable. SSRIs, fluvoxamine, paroxetine and sertraline are superior to placebo in generalized SP. Gabergic drugs are useful, e.g. clonazepam, gabapentin and pregabalin. Promising effects have been found with venlafaxine, a serotonin–norepinephrine reuptake inhibitor, and the results of larger studies should be forthcoming in the next 2 years. Drugs such as buspirone, tricyclics and beta‐blockers are either ineffective or have limited use. SP is a chronic disorder, and early termination of successful pharmacotherapy is associated with a greater likelihood of relapse. Studies with paroxetine, clonazepam, sertraline and brofaromine show that continued treatment is associated with better maintenance of response. Special populations that require further study include children, those with comorbid Axis I disorders and the population with discrete (non‐generalized) SP.Conclusion:  MAOI and SSRI are most uniformly effective in treating SP. Clonazepam and gabapentin may also be useful. Other drugs are of more limited value. Long‐term treatment is recommended to reduce rates of relapse.
Non‐pharmacologic treatments for social anxiety disorder
Authors: Zaider T. I. , Heimberg R. G. 
Published: December 2004

Objective:  The purpose of this paper is to present a review of research on the efficacy of psychotherapeutic interventions for children, adolescents and adults with social anxiety disorder. Data are presented on the relative efficacy of cognitive‐behavioral therapies (CBTs), pharmacotherapy and combination treatments. We also discuss research on specific clinical conditions that are likely to influence treatment success.Method:  Relevant studies were identified through literature searches, reference lists and research databases.Results:  Non‐pharmacologic treatments for social anxiety disorder, particularly CBTs, have gained substantial empirical support over the last two decades. However, questions remain about how to maximize the benefit of available treatments.Conclusion:  New directions for future research in this area are discussed.
Necrotic Feature of the Trophoblasts Lacking HLA‐G Expression in Normal and Pre‐eclamptic Placentas
Authors: Sageshima Noriko , Ishitani Akiko , Omura Motoko , Akasaki Masayoshi , Umekage Hideshi , Katabuchi Hidetaka , Okamura Hitoshi , Hatake Katsuhiko 
Published: December 2004

PROBLEM:  Human leukocyte antigen (HLA)‐G is thought to be expressed in all placental extravillous trophoblasts (EXTs). In pre‐eclamptic placentas, a lack of HLA‐G expression on EXTs had been found, and deduced as a possible cause of pre‐eclampsia. However, a subset of EXTs lacking expression of HLA‐G can also be found in normal placenta. Therefore, we sought to compare these cells in normal and pre‐eclamptic placentas.METHODS OF STUDY:  Frozen sections of normal and pre‐eclamptic placentas were examined by immunohistochemical staining using HLA‐G monoclonal antibody 87G, histochemical enzymatic analysis of succinate dehydrogenase (SDH) and ultrastructural analysis.RESULTS:  A subset of EXTs lacking HLA‐G expression was found in both normal and pre‐eclamptic placentas. These cells showed necrotic features such as the swelling of cells, eosin‐achromatophilia, the loss of SDH activity and swelling mitochondria. Cells from both tissues were identical with regard to these features.CONCLUSION:  The features of the EXTs lacking HLA‐G expression indicated they had undergone necrosis and thus could not express HLA‐G protein. Therefore, an alternative interpretation to the lack of HLA‐G expression in pre‐eclamptic placentas is that it is the result of cell death and not the cause.
Estrogen and Progesterone Modulate Monocyte Cell Cycle Progression and Apoptosis
Authors: Thongngarm T. , Jenkins J. K. , Ndebele K. , McMurray R. W. 
Published: December 2004

PROBLEM:  Pregnancy is characterized by dramatic immunologic changes most commonly characterized as suppression of cell‐mediated immunity. Mechanisms of this immunosuppression are obscure but may be caused by increases in pregnancy‐associated sex steroids such as 17‐β‐estradiol or progesterone.METHOD OF STUDY:  Using five myelomonocytic cell lines in various stages of differentiation, the effects of 17‐β‐estradiol and progesterone on cell cycling, apoptosis, and bcl‐2 expression in randomly cycling cells before and after lipopolysaccharide (LPS) activation were examined.RESULTS:  Lipopolysaccharide alone inhibited cell cycle progression in THP‐1 monocyte‐like cells and U‐937 histiocyte‐like cells. Estrogen alone produced cell cycle arrest in all myelomonocytic cells except HL‐60 pro‐myelocyte‐like cells. Progesterone had effects predominantly on pro‐myelocytic‐like HL‐60 cells, inducing apoptosis. Estrogen and progesterone both decreased levels of bcl‐2 in KG‐1α, HL‐60, and THP‐1 cells. LPS partially antagonized both estrogen‐induced THP‐1 apoptosis and its suppression of bcl‐2 protein.CONCLUSIONS:  Sex steroid‐induced effects on cell cycle transition and apoptosis are potential mechanisms by which pregnancy‐induced cell‐mediated immune suppression may occur. Further investigation should provide a better understanding of pregnancy‐induced immune changes and, perhaps, sex‐based differences in monocyte function and immunologic responses.
Natural Killer (NK) Cell Receptors' Repertoire in Couples with Recurrent Spontaneous Abortions
Authors: Varla‐Leftherioti Marighoula , Spyropoulou‐Vlachou Maria , Niokou Demetra , Keramitsoglou Theodora , Darlamitsou Areti , Tsekoura Christina , Papadimitropoulos Miltiadis , Lepage Virginia , Balafoutas Christos , Stavropoulos‐Giokas Catherine 
Published: December 2004

PROBLEM:  Natural killer (NK) cell receptors (NKRs) have been suggested to protect trophoblast, but their function at the fetomaternal interface remains unknown. To investigate if the outcome of pregnancy depends on women's NKRs, we studied the NKR repertoire in couples with recurrent spontaneous abortions (RSA).METHODS:  Twenty‐six childless couples with ≥2 abortions, characterized by alloimmune abnormalities, and 26 control couples were genotyped for five killer immunoglobulin‐like receptors (KIR) and two CD94/NKG receptors, known to have as ligands human leukocyte antigen (HLA) class I molecules with trophoblastic expression: inhibitory 2DL1,2,3 and activating 2DS1,4 KIRs, inhibitory NKG2A and activating NKG2C. Detected repertoires of women and partners were compared between the two groups.RESULTS:  Less aborters than controls were found to have all three inhibitory KIRs (30.77% versus 69.23%, P = 0.01), some of them had only one inhibitory KIR (19.23% versus 3.85%, P = 0.08) and most of them were lacking inhibitory KIRs possessed by their husbands (57.69% versus 15.38%, P = 0.001).CONCLUSIONS:  Women with alloimmune abortions have a limited inhibiting KIR repertoire and such miscarriages may occur because trophoblastic HLA class I molecules are recognized by decidual NK cells lacking the appropriate inhibitory KIRs.
Intracellular Expression of CD69 in Endometrial and Peripheral T cells Represents a Useful Marker in Women with Recurrent Miscarriage: Modulation After Allogeneic Leukocyte Immunotherapy
Authors: Ramhorst R. , García V. , Agriello E. , Corigliano A. , Etchepareborda E. , Irigoyen M. , Pasanante Gómez , Fainboim L. 
Published: December 2004

PROBLEM:  To characterize in fertile women and women with recurrent spontaneous abortions (RSA) the expression and functional status of T cells expressing the CD69 molecule.METHOD OF STUDY:  We analyzed by flow cytometry in peripheral blood and endometrium from fertile and RSA women, the surface and cytoplasmic expression of CD69 on gated T cells. In addition, we investigated by three‐color flow cytometry the expression of cytokines, and subsets of memory T cells.RESULTS:  In T cells, CD69 was restricted to the intracellular compartment with a higher frequency in RSA than in fertile women (68.2 ± 12% versus 23.7 ± 22%, P < 0.001, and 20 ± 9.5% versus 2.1 ± 3.8%, P < 0.005, in endometrium and peripheral blood, respectively). In contrast, the number of interferon‐γ+ (IFN‐γ+) secreting cells was higher (16 ± 5% versus 6 ± 1%) in fertile women. All 11 RSA women alloimmunized with parental leukocytes reached values of CD3+ CD69+ cells similar to those observed in fertile women.CONCLUSIONS:  CD69 might represent a useful marker in the diagnosis and the follow up of RSA patients.
The Cellular Immune Response of Children is Specifically Decreased Against their Parents but not Vice versa, Independent of Pregnancy, age, or HLA or HY Antigens
Authors: Brune Thomas , Riepe Felix G. , Garritsen Henk , Exeler Rita , Louwen Frank , Harms Erik 
Published: December 2004

PROBLEM:  The fetal immune response against the mother and the father is specifically altered. Up to now it is unclear whether the immune response between adult children and their parents is also specifically altered.METHODS:  Seven female and seven male adults and five male and five female newborns and all their parents were enrolled in the study. Cyotoxicity, apoptosis and proliferation properties of the parents' lymphocytes were measured against those of their children and vice versa using two‐way mixed lymphocyte cultures (MLCs).RESULTS:  The immune response of adult children against both their parents is reproducibly decreased compared with that of both parents against their children in cytotoxicity, apoptosis and proliferation, independent of sex or age.CONCLUSION:  The cellular immune response of children is decreased against both their parents but not vice versa independent of pregnancy, age, or HLA or HY antigens. This might be acquired during pregnancy or genetically determined.
Pro‐inflammatory Maternal Cytokine Profile in Preterm Delivery
Authors: Makhseed M. , Raghupathy R. , El‐Shazly S. , Azizieh F. , Al‐Harmi J. A. , Al‐Azemi M. M. K. 
Published: December 2004

PROBLEM:  The objective of this study was to determine the levels of cytokines produced by maternal peripheral blood mononuclear cells (PBMC) upon stimulation with a mitogen, with autologous placental cells and with a trophoblast antigen extract.METHOD OF STUDY:  Peripheral blood mononuclear cells from 54 women with a history of successful pregnancy and 30 women undergoing preterm delivery (PTD) were stimulated with the mitogen and antigens, and the cytokine levels in mitogen‐stimulated culture supernatants assessed.RESULTS:  Significantly higher levels of the type 1 cytokines, interferon (IFN)‐γ and interleukin (IL)‐2, were produced by the PTD group than by the normal pregnancy group, which on the contrary showed significantly greater production of the type 2 cytokines, IL‐4, IL‐5 and IL‐10. A comparison of the ratios of type 2 to type 1 cytokines is indicative of a type 1 cytokine bias in PTD.CONCLUSIONS:  These data are suggestive of a maternal type 1 cytokine bias in PTD.
Uterine Response to Infectious Bacteria in Estrous Cyclic Ewes
Authors: Seals Richard C. , Wulster‐Radcliffe Meghan C. , Lewis Gregory S. 
Published: December 2004

PROBLEM:Luteal‐phase uteri are susceptible to infections, and PGE2and exogenous progesterone can down‐regulate, whereas PGF2αcan up‐regulate, uterine immune functions.METHOD OF STUDY:Uteri of follicular‐ or luteal‐phase ewes were inoculated with either saline or bacteria (Arcanobacterium pyogenesandEscherichia coli). Vena caval blood was collected for the next 3 days, and progesterone, PGE2, and PGF2αwere measured. The effects of 10−7 mPGE2(Experiment 1), 10−7 mPGF2α(Experiment 2), 10−7 mindomethacin (INDO), and diluent on proliferation of lymphocytes from the vena caval blood in response to mitogens was quantified.RESULTS:Experiment 1: Progesterone was greater (P < 0.01) in luteal than in follicular ewes (3.4 versus 0.4 ng/mL), and only luteal ewes inoculated with bacteria developed infections.Lymphocyte proliferation was least (P = 0.08) in follicular ewes (2.6 versus 4.5 pmol for follicular and luteal, respectively). Concanavalin A (Con A)‐stimulated proliferation was less (P < 0.05) for ewes inoculated with bacteria and for cells cultured with diluent (5.9 versus 3.1 pmol for saline and bacteria, respectively) or with INDO (6.6 versus 2.8 pmol for saline and bacteria, respectively). Also, Con A‐stimulated lymphocytes from ewes inoculated with bacteria tended to proliferate less (P < 0.1) when cultured with PGE2(4.9 versus 3.7 pmol for saline and bacteria, respectively) or PGE2 + INDO (5.5 versus 3.8 pmol for saline and bacteria, respectively). Experiment 2: Progesterone was greater (P < 0.01) in luteal than in follicular ewes (6.5 versus 1.2 ng/mL), and only luteal ewes inoculated with bacteria developed infections. Con A‐stimulated lymphocyte proliferation was greater (P < 0.001) for follicular ewes (4.1 versus 3.1 pmol for follicular and luteal, respectively). Proliferation of lymphocytes collected from follicular ewes was greater (P < 0.01) when cells were cultured with PGF2α(3.5 versus 2.7 pmol for follicular and luteal, respectively), but INDO did not affect unstimulated or mitogen‐stimulated proliferation.CONCLUSIONS:Prostaglandin F2αenhanced lymphocyte proliferation, whereas bacterial inoculation andin vitrotreatment with PGE2suppressed lymphocyte proliferation. This may signify the involvement of bacterial products and prostaglandins in regulation of uterine immunity.