bluuebunny/crossref_metadata_2025 huggingface dataset:
Live Imaging of Regenerating Lamprey Spinal Axons
Authors: Zhang Guixin , Jin Li-Qing , Sul Jai-Yoon , Haydon Philip G. , Selzer Michael E.
Published: January 2005

The sea lamprey has been used as a model for the study of axonal regeneration after spinal cord injury. Although the growing tips of developing axons in lamprey have not been described, in all species studied, growth cones are complex in shape, consisting of a lamellipodium and filopodia, rich in F-actin and lacking neurofilaments (NF). By contrast, static immunohistochemical and electron microscopic observations of fixed tissue suggested that the tips of regenerating lamprey spinal axons are simple in shape, densely packed with NF, but contain very little F-actin. Thus, it has been proposed that regeneration of axons in the CNS of mature animals is not based on the canonical pulling mechanism of growth cones but involves an internal protrusive force, perhaps generated by the transport and assembly of NF. To eliminate the possibility that these histological features are due to fixation artifact, fluorescently labeled regenerating axon tips were imaged live. Methods. Spinal cords were transected, and after 0 to 10 weeks, the CNS was isolated in lamprey Ringerat5°Cto12°Candthelargereticulospinalaxons were microinjected with fluorescent tracers. The proximal axon tips were imaged with a fluorescence dissecting microscope repeatedly over 2 to 5 days and photographed with confocal microscopy. Experiments were also performed through a dorsal incision in the living animal. Axon tips were microinjected as above or retrogradely labeled with tracer applied to the transection site and photographed through the fluorescence dissecting scope or with two-photon microscopy. The spinal cords were then fixed and processed for wholemount NF immunohistochemistry. Results. The living axon tips were simple in shape, not significantly different from those in fixed spinal cords, and filled with NF. In isolated CNS preparations, very little axon retraction and no regeneration was observed. In the living animal, rapid retraction, up to 3 mm/day, was seen during the 1st few days posttransection. At more than 2 weeks posttransection, some fibers showed regeneration of up to 35 μ m/day. Conclusions. 1) The tips of regenerating lamprey axons are simple in shape and filled with NF. 2) Both axon retraction and axon extension are active processes, requiring factors present in the living animal that are missing in the isolated CNS.
Non-metamict betafite from Le Carcarelle (Vico volcanic complex, Italy): occurrence and crystal structure
Authors: Cámara F. , Williams C. T. , Della Ventura G. , Oberti R. , Caprilli E.
Published: January 2005

Non-metamict betafite, a pyrochlore-group mineral with general formulaA2−mB2XO6Y(O,OH,F)1−n·pH2O and 2 Ti > Nb+Ta and U > 20% at theAsite, has been found at Le Carcarelle, (Latium, Italy). It occurs within miarolitic cavities of a foid-bearing syenitic ejectum enclosed within the pyroclastic formation known as “ignimbrite C”, which belongs to the main effusive phase of the Vico volcanic complex. The host rock is composed of K-feldspar, biotite, augitic clinopyroxene, magnetite and minor sodalite. Electron microprobe analyses gave the following crystal-chemical formula: (Ca1.24Na0.17U0.49REE0.03)Σ=1.93(Ti1.05Nb0.76Zr0.14Fe0.04Ta0.01)Σ=2.00O6(O,OH). Compared with other occurrences reported in the mineralogical literature, betafite from Le Carcarelle is extremely enriched in U and depleted in Th. Due to its young age of formation (∼150 k.y.), this betafite sample is highly crystalline, thus allowing structure refinement of unheated material. Betafite from Le Carcarelle is cubicFdm, witha= 10.2637(13) Å, andV= 1081.21(35) Å3, and has a smallerAsite (consistent with the higher U content), and a larger and more distortedBsite (consistent with the higher Ti content) than calciobetafite from Campi Flegrei, Italy (Mazzi and Munno, 1983). Analysis of the atomic displacement parameters provides evidence for static disorder at theXsite.
Euhedral crystals of ferroan platinum, cooperite and mertieite-II from alluvial sediments of the Darya river, Aldan Shield, Russia
Authors: Shcheka G. G. , Solianik A. N. , Lehmann B. , Bieniok A. , Amthauer G. , Topa D. , Laflamme J. H. G.
Published: January 2005

Idiomorphic crystals (up to 3.5 mm) of ferroan platinum, cooperite and mertieite-II were found in a heavy-mineral concentrate from stream sediments of the Darya river in the Aldan Shield, Russia. Pt-Fe crystals display cubic and thin platy habits; occasionally they are twinned. The chemical composition ranges from Pt2.64Fe1.00to Pt2.88Fe1.00with Os, Ru, Ir, Rh and Pd below the analytical detection limit of the electron microprobe. X-ray diffractometry of Pt-Fe crystals suggests a F-centred cubic lattice, characteristic of ferroan platinum. Some of the ferroan platinum crystals have large (about 100 μm wide) cooperite overgrowth rims or are covered by a Au-Ag alloy. Cooperite also occurs as large euhedral crystals (up to 3 mm across, partly twinned). Crystals of mertieite-II are speckled with μm-sized (2–5 μm) inclusions of sperrylite and intergrown with minerals of cooperite-braggite solid solution, Pt-Pd-Hg alloy, keithconnite and Au-Ag alloy. Fractures along crystallographic planes of the mertieite-II crystals are filled with Pd-Pt-Fe-Sb-As-Hg-Te-Bi-bearing oxides. The coarse-grained PGM from the Darya have a geological setting similar to the Kondyor PGE placer 75 km to the northeast and are probably related to clinopyroxenite-hornblende-magnetite units of Alaskan-/Uralian-type intrusions.
Seismic-frequency attenuation at first-order phase transitions: dynamical mechanical analysis of pure and Ca-doped lead orthophosphate
Authors: Harrison R. J. , Redfern S. A. T. , Bismayer U.
Published: January 2005

The low-frequency mechanical properties of pure and Ca-doped lead orthophosphate, (Pb1–xCax)3(PO4)2, have been studied using simultaneous dynamical mechanical analysis, X-ray diffraction (XRD), and optical video microscopy in the vicinity of the first-order ferroelastic phase transition. Both samples show mechanical softening at T > Tc, which is attributed to the presence of dynamic short-range order and microdomains. Stress-induced nucleation of the low-temperature ferroelastic phase within the hightemperature paraelastic phase was observed directly via optical microscopy at T ≈ Tc. Phase coexistence is associated with rapid mechanical softening and a peak in attenuation, P1, that varies systematically with heating rate and measuring frequency. A second peak, P2, occurs ≈3–5°C below Tc, accompanied by a rapid drop in the rate of mechanical softening. This is attributed to the change in mode of anelastic response from the displacement of the paraelastic/ferroelastic phase interface to the displacement of domain walls within the ferroelastic phase. Both the advancement/retraction of needles (W walls) and wall translation/rotation (W′ walls) modes of anelastic response were identified by optical microscopy and XRD. A third peak, P3, occurring ≈ 15°C below Tc, is attributed to the freezing-out of local flip disorder within the coarse ferroelastic domains. A fourth peak, P4, occurs at a temperature determined by the amplitude of the dynamic force. This peak is attributed to the crossover between the saturation (high temperature) and the superelastic(low temperature) regimes. Both samples display large superelastic softening due to domain wall sliding in the ferroelastic phase. Softening factors of 20 and 5 are observed in the pure and doped samples, respectively, suggesting that there is a significant increase in the intrinsic elastic constants (and hence the restoring force on a displaced domain wall) with increasing Ca content. No evidence for domain freezing was observed down to −150°C in either sample, although a pronounced peak in attenuation, P5, at T ≈ −100°C is tentatively attributed to the interaction between domain walls and lattice defects.

Both samples show similar high values of attenuation within the domain-wall sliding regime. It is concluded that the magnitude of attenuation for ferroelastic materials in this regime is determined by the intrinsic energy dissipation caused by the wall-phonon interaction, and not by the presence of lattice defects. This will have a large impact on attempts to predict the effect of domain walls on seismic properties of mantle minerals at high temperature and pressure.
The development of X-ray photo-emission electron microscopy (XPEEM) for valence-state imaging of mineral intergrowths
Authors: Smith A. D. , Schofield P. F. , Cressey G. , Cressey B. A. , Read P. D.
Published: January 2005

We demonstrate the potential of X-ray photo-emission electron microscopy (XPEEM) to reveal valence-state images of the spatial distribution and relative concentration of metals in specific oxidation states. Additionally, XPEEM allows X-ray absorption spectra to be extracted from chosen pixel areas of the images. Using an in-house-built XPEEM instrument we show an application of the method in providing valence-state images of complex mineral intergrowths. The image resolution achieved with this instrument of simple design was ∼5 μm and reasonable quality X-ray absorption spectra were extracted from areas of ∼5×5 μm. These initial results suggest that by using commercial XPEEM instruments on 3rd generation, high-brightness synchrotron sources a spatial resolution of 100 nm or better could be achieved, with the ability to extract high-quality X-ray absorption spectra from areas of 0.1 μm2. Given that standard thin sections or polished blocks can be studied by XPEEM, and that each XPEEM image records ∼1000 μm2, XPEEM can be used in conjunction with other analytical methods such as EMPA and TEM-EELS/PEELS.
Low-temperature aqueous alteration of crystalline pyrochlore: correspondence between nature and experiment
Authors: Geisler T. , Berndt J. , Meyer H.-W. , Pollok K. , Putnis A.
Published: January 2005

Pyrochlore has been considered as a waste form to immobilize high-level nuclear waste such as excess weapons-grade plutonium. In order to study the aqueous stability of pyrochlore, we have carried out hydrothermal experiments with a natural microlite (Nb + Ta > 2Ti; Ta ⩾ Nb) at 175°C in a neutral and acidic solution for 14 days. The starting material and the experimental products were studied by electron microprobe, backscattered electron (BSE) imaging, powder infrared (IR) and micro-Raman spectroscopy, and powder X-ray diffractrometry (XRD). The microlite has small U (∼200 ppm) and Th (∼800 ppm) contents and is crystalline. The hydrothermal treatment in a solution containing l mol/l HCl and l mol/l CaCl2 causes the partial replacement of the microlite (up to ∼10 μm) by a new pyrochlore phase. This new phase is characterized by a larger unit-cell volume and contains a large number of vacancies at the A site (A = Ca, Na) as well as anion vacancies, molecular water, and possibly OH groups. Analyses of the experimental fluid further revealed that U was also selectively lost to the solution. Treatment in pure water did not produce reaction zones detectable by BSE imaging or powder XRD. However, significant spectral changes in powder IR spectra of the reaction product and the detection of Na and Ca in the solution indicate that the microlite has also reacted in pure water. The experimental alteration features bear a remarkable resemblance to those seen in naturally altered microlite samples, suggesting that short-term experimental results can be applied to natural systems and vice versa in order to evaluate the long-term stability of a pyrochlore waste form.
Ore genesis at La Colorada Ag-Zn-Pb deposit in Zacatecas, Mexico
Authors: Chutas N. I. , Sack R. O.
Published: January 2005

La Colorada, in Zacatecas State, Mexico is an epithermal Ag-Zn-Pb system hosted in Mesozoic calcareous sedimentary rocks overlain by Tertiary volcanic rocks. The dominant vein is associated with a fault system that accommodates Tertiary normal and strike-slip faulting. The ore consists of fahlore [(Cu,Ag)10(Zn,Fe)2(Sb,As)4S13], polybasite [(Ag,Cu)16Sb2S11]–pearceite [(Ag,Cu)16As2S11] solid solution, pyrargyrite [Ag3SbS3]–proustite [Ag3AsS3] solid solution, acanthite-argentite [Ag2S], and native silver; associated sulphides include galena, sphalerite, chalcopyrite and pyrite. The Ag:Sb of the bulk concentrate from the mine is 1.076 and the Ag:Pb is 0.088. Compositions of the assemblages fahlore + pyrargyrite-proustite + sphalerite, and fahlore + polybasite-pearceite solid solution + (Ag,Cu)2S solid solution + sphalerite encapsulated in quartz and sphalerite indicate a primary depositional temperature of ∼325°C for a depth between 725 and 960 m below the inferred palaeosurface, which is in accord with fluid-inclusion data for higher elevations in the mine.
Surface expression, single-channel analysis and membrane topology of recombinant Chlamydia trachomatis Major Outer Membrane Protein
Authors: Findlay Heather E , McClafferty Heather , Ashley Richard H
Published: January 2005

Background

Chlamydial bacteria are obligate intracellular pathogens containing a cysteine-rich porin (Major Outer Membrane Protein, MOMP) with important structural and, in many species, immunity-related roles. MOMP forms extensive disulphide bonds with other chlamydial proteins, and is difficult to purify. Leaderless, recombinant MOMPs expressed in E. coli have yet to be refolded from inclusion bodies, and although leadered MOMP can be expressed in E. coli cells, it often misfolds and aggregates. We aimed to improve the surface expression of correctly folded MOMP to investigate the membrane topology of the protein, and provide a system to display native and modified MOMP epitopes.

Results

C. trachomatis MOMP was expressed on the surface of E. coli cells (including "porin knockout" cells) after optimizing leader sequence, temperature and medium composition, and the protein was functionally reconstituted at the single-channel level to confirm it was folded correctly. Recombinant MOMP formed oligomers even in the absence of its 9 cysteine residues, and the unmodified protein also formed inter- and intra-subunit disulphide bonds. Its topology was modeled as a (16-stranded) β-barrel, and specific structural predictions were tested by removing each of the four putative surface-exposed loops corresponding to highly immunogenic variable sequence (VS) domains, and one or two of the putative transmembrane strands. The deletion of predicted external loops did not prevent folding and incorporation of MOMP into the E. coli outer membrane, in contrast to the removal of predicted transmembrane strands.

Conclusions

C. trachomatis MOMP was functionally expressed on the surface of E. coli cells under newly optimized conditions. Tests of its predicted membrane topology were consistent with β-barrel oligomers in which major immunogenic regions are displayed on surface-exposed loops. Functional surface expression, coupled with improved understanding of MOMP's topology, could provide modified antigens for immunological studies and vaccination, including live subunit vaccines, and might be useful to co-express MOMP with other chlamydial membrane proteins.
Survey of general practitioners' knowledge about Helicobacter pylori infection
Authors: Canbaz Sevgi , Sunter Ahmet Tevfik , Peksen Yildiz , Leblebicioglu Hakan
Published: January 2005

Background

Helicobacter pylori, occurring throughout the world and causing gastroduodenal diseases, is one of the most common chronic bacterial agents in humans. The purpose of this study was to measure the general practitioners' (GPs) knowledge and practices pertaining to H. pylori infection.

Methods

A cross-sectional type questionnaire survey was conducted in all of 19 primary health care centres (PHCC) in Samsun, Turkey, between November 1 and December 31, 2003. The questionnaire was sent to 124 GPs and 109 (87.9 %) of those filled in. They were requested to answer the questions on the knowledge, sources of medical information, diagnostic tests and treatment to H. pylori.

Results

Medical journals were the most frequently used source of information on H. pylori, being cited by 86 (78.9%) of GPs. Ninety-two (84.4%) of the GPs reported having used one or more tests and 17 (15.6%) never used any test for the diagnosis of H. pylori infection. Only 9.8% had used stool antigen test for diagnosis. GPs reported that they would prescribe symptomatic treatment without ordering diagnostic tests for 29 (26.6%). 54.1% of the GPs explain that they sent patients with H. pylori infection to a specialist, and most used a triple drug regimen containing a PPI. Treatment duration varies between 7 to 28 days. 80.7 of the GPs treat patients for 14 days.

Conclusion

GPs may not have enough knowledge about the importance of stool antigen test or possibility of usage of this test. GPs have not sufficient knowledge about the difference between symptomatic and asymptomatic individuals. It is thought that GPs preferred to treat the patients with suspected ulcer empirically or to send them to a specialist because of the limited diagnostic conditions. The efforts to educate the GPs about the algorithms regarding the management of H. pylori infection during post-graduation period should be improved in PHCCs.
Human cytomegalovirus plasmid-based amplicon vector system for gene therapy
Authors: Mahmood Kutubuddin , Prichard Mark N , Duke Gregory M , Kemble George W , Spaete Richard R
Published: January 2005

We have constructed and evaluated the utility of a helper-dependent virus vector system that is derived from Human Cytomegalovirus (HCMV). This vector is based on the herpes simplex virus (HSV) amplicon system and contains the HCMV orthologs of the two cis-acting functions required for replication and packaging of HSV genomes, the complex HCMV viral DNA replication origin (oriLyt), and the cleavage packaging signal (the a sequence). The HCMV amplicon vector replicated independently and was packaged into infectious virions in the presence of helper virus. This vector is capable of delivering and expressing foreign genes in infected cells including progenitor cells such as human CD34+ cells. Packaged defective viral genomes were passaged serially in fibroblasts and could be detected at passage 3; however, the copy number appeared to diminish upon serial passage. The HCMV amplicon offers an alternative vector strategy useful for gene(s) delivery to cells of the hematopoietic lineage.
In memoriam: Celso-Ramon Garcia, M.D. (1922–2004), reproductive medicine visionary
Authors: Strauss Jerome F , Mastroianni Luigi
Published: January 2005

This article traces the career of Celso-Ramon Garcia (1922–2004), noted physician, educator, and internationally renowned pioneer in the field of reproductive endocrinology. His work helped to formulate oral contraceptives used by millions of women throughout the world. Garcia's research collaborators included Gregory Pincus and John Rock, who together finalized the landmark clinical data needed to secure initial FDA approval for "the pill" in 1960. In addition to Garcia's monumental work in contraceptive endocrinology, his scholarly interests encompassed physiology of the menopause, minimally invasive reproductive surgery, as well as psychological aspects of infertility. Closely identified with the University of Pennsylvania, Garcia was instrumental in establishing the first formal clinical program in reproductive biology and influenced countless young scientists whose training he supervised and mentored. His distinguished career was emblematic of the best of the medical profession, characterized by compassion, intellect, and a sincere desire to help others. Our manuscript outlines Garcia's wide range of interests, acknowledges his superior fund of knowledge, and honors his humanitarian spirit – all of which contributed to an impressive legacy of medical discoveries. The impact of Prof. Garcia's work will continue to be felt for many years.
Long-term prognostic significance of HER-2/neu in untreated node-negative breast cancer depends on the method of testing
Authors: Schmidt Marcus , Lewark Barbara , Kohlschmidt Nikolai , Glawatz Christiane , Steiner Erik , Tanner Berno , Pilch Henryk , Weikel Wolfgang , Kölbl Heinz , Lehr Hans-Anton
Published: January 2005

Introduction

The prognostic significance of HER-2/neu in breast cancer is a matter of controversy. We have performed a study in 101 node-negative breast cancer patients with long-term follow-up not treated in the adjuvant setting, and analysed the prognostic significance of immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), both separately and in combination, in comparison with traditional prognostic factors.

Methods

Overexpression was classified semiquantitatively according to a score (0 to 3+) (HER-2_SCO). FISH was used to analyse HER2/neu amplification (HER-2_AMP). Patients classified 2+ by IHC were examined with FISH for amplification (HER-2_ALG). Patients with 3+ overexpression as well as amplification of HER-2/neu were positive for the combined variable HER2_COM. These variables were compared with tumour size, histological grade and hormone receptor status.

Results

HER-2_SCO was 3+ in 20% of all tumours. HER-2_ALG was positive in 22% and amplification (HER-2_AMP) was found in 17% of all tumours. Eleven percent of the tumours showed simultaneous 3+ overexpression and amplification. Only histological grade (relative risk [RR] 3.22, 95% confidence interval [CI] 1.73–5.99, P = 0.0002) and HER-2_AMP (RR 2.47, 95% CI 1.12–5.48, P = 0.026) were significant for disease-free survival in multivariate analysis. For overall survival, both histological grade (RR 3.89, 95% CI 1.77–8.55, P = 0.0007) and HER-2_AMP (RR 3.08, 95% CI 1.24–7.66, P = 0.016) retained their independent significance.

Conclusion

The prognostic significance of HER-2/neu in node-negative breast cancer depends on the method of testing: only the amplification of HER-2/neu is an independent prognostic factor for the long-term prognosis of untreated node-negative breast cancer.
Practice of sedation and analgesia in German intensive care units: results of a national survey
Authors: Martin Jörg , Parsch Axel , Franck Martin , Wernecke Klaus D , Fischer Matthias , Spies Claudia
Published: January 2005

Introduction

Sedation and analgesia are provided by using different agents and techniques in different countries. The goal is to achieve early spontaneous breathing and to obtain an awake and cooperative pain-free patient. It was the aim of this study to conduct a survey of the agents and techniques used for analgesia and sedation in intensive care units in Germany.

Methods

A survey was sent by mail to 261 hospitals in Germany. The anesthesiologists running the intensive care unit were asked to fill in the structured questionnaire about their use of sedation and analgesia.

Results

A total of 220 (84%) questionnaires were completed and returned. The RAMSAY sedation scale was used in 8% of the hospitals. A written policy was available in 21% of hospitals. For short-term sedation in most hospitals, propofol was used in combination with sufentanil or fentanyl. For long-term sedation, midazolam/fentanyl was preferred. Clonidine was a common part of up to two-thirds of the regimens. Epidural analgesia was used in up to 68%. Neuromuscular blocking agents were no longer used.

Conclusion

In contrast to the US 'Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult', our survey showed that in Germany different agents, and frequently neuroaxial techniques, were used.
Protection and Damage from Acute and Chronic Stress: Allostasis and Allostatic Overload and Relevance to the Pathophysiology of Psychiatric Disorders
Authors: MCEWEN BRUCE S.
Published: January 2005

Abstract: Stress promotes adaptation, but prolonged stress leads over time to wear‐and‐tear on the body (allostatic load). Neural changes mirror the pattern seen in other body systems, that is, short‐term adaptation vs. long‐term damage. Allostatic load leads to impaired immunity, atherosclerosis, obesity, bone demineralization, and atrophy of nerve cells in the brain. Many of these processes are seen in major depressive illness and may be expressed also in other chronic anxiety disorders. The brain controls the physiological and behavioral coping responses to daily events and stressors. The hippocampal formation expresses high levels of adrenal steroid receptors and is a malleable brain structure that is important for certain types of learning and memory. It is also vulnerable to the effects of stress and trauma. The amygdala mediates physiological and behavioral responses associated with fear. The prefrontal cortex plays an important role in working memory and executive function and is also involved in extinction of learning. All three regions are targets of stress hormones. In animal models, neurons in the hippocampus and prefrontal cortex respond to repeated stress by showing atrophy, whereas neurons in amygdala show a growth response. Yet, these are not necessarily “damaged” and may be treatable with the right medications.
Allostatic Load, Perceived Stress, and Health: A Prospective Study in Two Age Groups
Authors: HELLHAMMER J , SCHLOTZ W , STONE A A , PIRKE K M , HELLHAMMER D
Published: January 2005

Abstract: Overactivity of the hypothalamus‐pituitary‐adrenal axis (HPAA) has been observed in the presence of acute stress and, under chronic conditions, in disorders such as depression and anorexia nervosa as well as in cardiovascular and metabolic disorders. However, there may be other stress‐related disorders (fatigue, pain, etc) that seem to be associated with mild hypocortisolism. This suggests that two major subtypes of the HPAA response to stress need to be discriminated. In this study, we investigated 76 subjects with and without hypocortisolism, respectively, over a 1‐year period. Surprisingly, hypocortisolemic subjects had a lower allostatic load but they scored higher on measures of depression, perceived stress, and physical complaints. We propose a protective role of the hypocortisolemic stress response on cardiovascular and metabolic disorders, particularly in the elderly.
Signaling Pathways in Brain Involved in Predisposition and Pathogenesis of Stress‐Related Disease: Genetic and Kinetic Factors Affecting the MR/GR Balance
Authors: de KLOET E RONALD , DERIJK ROEL
Published: January 2005

Abstract: Optimal regulation of the stress response is a prerequisite for adaptation, homeostasis, and health. There are two modes of operation in the stress response. First, an immediate response mode mediated by corticotrophin‐releasing hormone‐1 (CRH‐1) receptors that organizes the behavioral, sympathetic, and hypothalamic‐pituitary‐adrenal (HPA) response to a stressor. Second, a slower mode, which facilitates behavioral adaptation, promotes recovery, and reestablishes homeostasis. Corticosteroid hormones are implicated in both stress system modes. On the one hand, cortisol and corticosterone determine the threshold or sensitivity of the fast responding mode, whereas the very same hormones in high concentrations facilitate termination of the stress response. In the brain, these actions exerted by the corticosteroid hormones are mediated by two distinct nuclear receptor types, that is, mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs). Whereas MRs maintain neuronal homeostasis and limit the disturbance by stress, GRs help to recover after the challenge and to store the experience for coping with future encounters. Imbalance in MR/GR‐mediated actions compromises homeostatic processes in these neurons, which is thought to underlie maladaptive behavior and HPA dysregulation that may lead to aberrant metabolism, impaired immune function, and altered cardiovascular control. The balance in MR/GR‐mediated actions depends on bioavailability of corticosteroids, access to the receptors, the stoichiometry of co‐regulators, and other proteins as well as genetic factors, among which single nucleotide polymorphisms (SNPs) of the GRs are extensively documented. Stress can bias the receptor signaling pathways, changing “good” corticosteroid actions into “bad” ones.
Trauma, Genes, and the Neurobiology of Personality Disorders
Authors: GOODMAN MARIANNE , NEW ANTONIA , SIEVER LARRY
Published: January 2005

Abstract: A model for personality dysfunction posits an interaction between inherited susceptibility and environmental factors such as childhood trauma. Core biological vulnerabilities in personality include dimensions of affective instability, impulsive aggression, and cognition/perceptual domains. For the dimension of impulsive aggression, often seen in borderline personality disorder (BPD), the underlying neurobiology involves deficits in central serotonin function and alterations in specific brain regions in the cingulate and the medial and orbital prefrontal cortex. The role of trauma in the development of personality disorder and especially for BPD remains unclear. Although recent studies suggest that BPD is not a trauma‐spectrum disorder and that it is biologically distinct from posttraumatic stress disorder, high rates of childhood abuse and neglect do exist for individuals with personality dysfunction. Personality symptom clusters seem to be unrelated to specific abuses, but they may relate to more enduring aspects of interpersonal and family environments in childhood. Whereas twin and family studies indicate a partially heritable basis for impulsive aggression, studies of serotonin‐related genes to date suggest only modest contributions to behavior. Gene‐environment interactions involving childhood maltreatment are demonstrated in recent studies on antisocial behaviors and aggressive rhesus monkeys and highlight the need for further research in this important area.
Posttraumatic Stress Disorder and Physical Illness: Results from Clinical and Epidemiologic Studies
Authors: BOSCARINO JOSEPH A.
Published: January 2005

Abstract:Research indicates that exposure to traumatic stressors and psychological trauma is widespread. The association of such exposures with posttraumatic stress disorder (PTSD) and other mental health conditions is well known. However, epidemiologic research increasingly suggests that exposure to these events is related to increased health care utilization, adverse health outcomes, the onset of specific diseases, and premature death. To date, studies have linked traumatic stress exposures and PTSD to such conditions as cardiovascular disease, diabetes, gastrointestinal disease, fibromyalgia, chronic fatigue syndrome, musculoskeletal disorders, and other diseases. Evidence linking cardiovascular disease and exposure to psychological trauma is particularly strong and has been found consistently across different populations and stressor events. In addition, clinical studies have suggested the biological pathways through which stressor‐induced diseases may be pathologically expressed. In particular, recent studies have implicated the hypothalamic‐pituitary‐adrenal (HPA) and the sympathetic‐adrenal‐medullary (SAM) stress axes as key in this pathogenic process, although genetic and behavioral/psychological risk factors cannot be ruled out. Recent findings, indicating that victims of PTSD have higher circulating T‐cell lymphocytes and lower cortisol levels, are intriguing and suggest that chronic sufferers of PTSD may be at risk for autoimmune diseases. To test this hypothesis, we assessed the association between chronic PTSD in a national sample of 2,490 Vietnam veterans and the prevalence of common autoimmune diseases, including rheumatoid arthritis, psoriasis, insulin‐dependent diabetes, and thyroid disease. Our analyses suggest that chronic PTSD, particularly comorbid PTSD or complex PTSD, is associated with all of these conditions. In addition, veterans with comorbid PTSD were more likely to have clinically higher T‐cell counts, hyperreactive immune responses on standardized delayed cutaneous hypersensitivity tests, clinically higher immunogolobulin‐M levels, and clinically lower dehydroepiandrosterone levels. The latter clinical evidence confirms the presence of biological markers consistent with a broad range of inflammatory disorders, including both cardiovascular and autoimmune diseases.
Can Posttraumatic Stress Disorder Be Prevented with Glucocorticoids?
Authors: SCHELLING GUSTAV , ROOZENDAAL BENNO , de QUERVAIN DOMINIQUE J.‐F.
Published: January 2005

Abstract: Patients with critical illness who are treated in an intensive care unit (ICU) often report traumatic memories from ICU treatment, receive exogenously administered glucocorticoids for medical reasons, and have a relatively high incidence of chronic stress symptoms and posttraumatic stress disorder (PTSD) during follow‐up. ICU therapy could therefore represent a useful model for investigating glucocorticoid effects on traumatic memories and PTSD development. Studies in long‐term survivors of ICU treatment demonstrated a clear and vivid recall of different categories of traumatic memory such as nightmares, anxiety, respiratory distress, or pain. The incidence and intensity of PTSD symptoms increased with the number of categories of traumatic memory present. The prolonged administration of glucocorticoids (stress doses of hydrocortisone) to critically ill patients resulted in a significant reduction of PTSD symptoms measured after recovery without influencing the number of categories of traumatic memory. This protective effect of cortisol can possibly be explained by a cortisol‐induced temporary impairment in traumatic memory retrieval which has previously been demonstrated in both rats and humans. Therefore, stress doses of hydrocortisone could be useful for prophylaxis and treatment of PTSD.
Neurobiology of Memory and Dissociation in Trauma Survivors
Authors: DELAHANTY DOUGLAS , GLOVER DORIE , GOLIER JULIA
Published: January 2005

Abstract: This symposium examines the neurobiology of memory and dissociation in traumatized individuals. Several paradigms are presented that investigate the specific nature of differences in “remembering” in relation to neuroendocrine profiles among those with and without posttraumatic stress disorder (PTSD). These lines of research may help to clarify the paradox of distortion or absence of some memories and enhancement of others in PTSD.
The “Steroid Dementia Syndrome”: An Unrecognized Complication of Glucocorticoid Treatment
Authors: WOLKOWITZ OWEN M. , LUPIEN SONIA J. , BIGLER ERIN , LEVIN R BRONSON , CANICK JONATHAN
Published: January 2005

Abstract: Glucocorticoid treatment is frequently associated with transiently impaired attention, concentration, and memory. In rare cases, cognitive changes may be prominent and may persist for substantial periods of time after steroid discontinuation. This largely unrecognized complication has been termed the “steroid dementia syndrome” and may reflect steroid neuroendangerment or neurotoxicity. Several clinical cases of this syndrome, with shared phenomenological and neuropsychological features, are presented here.
Memory Consolidation during Sleep: Role of Cortisol Feedback
Authors: BORN JAN , WAGNER ULLRICH
Published: January 2005

Abstract: Nocturnal cortisol release in humans is synergistically regulated by circadian rhythm and sleep. Cortisol concentrations typically reach a nadir during the slow wave sleep‐rich periods of early nocturnal sleep, whereas during the late night, when rapid eye movement (REM) sleep predominates, cortisol levels are enhanced. Here we review a series of our own studies examining whether and how this regulation of cortisol release affects the consolidation of memories during sleep. The studies show that increasing cortisol during early slow wave sleep‐rich periods of nocturnal sleep impairs hippocampus‐dependent declarative memory formation. Preventing the natural increase in cortisol during REM sleep‐rich sleep in the late night appears to enhance amygdala‐dependent emotional memory. The findings are consistent with the view that cortisol via activation of limbic glucocorticoid receptors generally diminishes memory consolidation.
Are Stress Eaters at Risk for the Metabolic Syndrome?
Authors: EPEL ELISSA , JIMENEZ SHERLYN , BROWNELL KELLY , STROUD LAURA , STONEY CATHERINE , NIAURA RAY
Published: January 2005

Abstract: Stress eating is a health behavior that has been overlooked in much of health psychology research. It is largely unknown why some tend to eat during or after stressful periods, whereas others tend to lose their appetite and lose weight. Furthermore, it is unknown if such transient changes in food intake or macronutrient composition during stress have clinically significant consequences in terms of weight and metabolic health. The Brown University Medical Student Study examined students during a baseline control period as well as during two examination periods. This design enabled an examination of weight changes in self‐proclaimed stress eaters vs stress‐less eaters over time. Stress eaters tended to gain more weight and demonstrated increases in nocturnal levels of insulin, cortisol, and blood levels of total/HDL cholesterol ratio, during exam periods, controlling for the baseline control period. These data show prospectively that stress eating may indeed have short‐term consequences on metabolic health. Future research will need to determine whether this confers a greater risk of disease over time.
Lowering Cortisol and CVD Risk in Postmenopausal Women: A Pilot Study Using the Transcendental Meditation Program
Authors: WALTON KENNETH G. , FIELDS JEREMY Z. , LEVITSKY DEBRA K. , HARRIS DWIGHT A. , PUGH NIRMAL D. , SCHNEIDER ROBERT H.
Published: January 2005

Abstract: Unlike younger women, the risk of cardiovascular disease in older women matches or exceeds that of men. Excessive cortisol may play a role in this increased risk. Here we explore the possibility that the Transcendental Meditation (TM) program may reduce the cortisol response to a metabolic stressor as a way of reducing disease risk in older women. Data from 16 women who were long‐term practitioners of transcendental meditation (mean = 23 y) were compared with data from 14 control women matched for age (mean = 75 y, range = 65‐92 y). Data on demographics, disease symptoms, and psychological variables were collected, and cortisol response to a metabolic stressor (75 g of glucose, orally) was examined in saliva and urine. Pre‐glucose levels of salivary cortisol were identical for the two groups. Post‐glucose cortisol rose faster in the controls and was significantly higher than that in the TM women (P < 1 3 10−4). Urinary excretion of cortisol during this period was 3 times higher in controls than in the TM women (2.4 ± 0.17 and 0.83 ± 0.10 μg/h, respectively; P= 2 × 10−4). In addition, the number of months practicing transcendental meditation was inversely correlated with CVD risk factors. Lower cortisol response to metabolic challenge may reflect improved endocrine regulation relevant to the disease‐preventing effects of transcendental meditation in older women.
The Neurobiology of Trust
Authors: ZAK PAUL J. , KURZBAN ROBERT , MATZNER WILLIAM T.
Published: January 2005

Abstract:This is the first report that endogenous oxytocin in humans is related to social behaviors, which is consistent with a large animal literature. Subjects are put into a social dilemma in which absent communication, cooperative behavior can benefit both parties randomly assigned to a dyad. The dilemma arises because one participant must make a monetary sacrifice to signal the degree of trust in the other before the other's behavioral response is known. We show that receipt of a signal of trust is associated with a higher level of peripheral oxytocin than that in subjects receiving a random monetary transfer of the same average amount. Oxytocin levels were also related to trustworthy behavior (sharing a greater proportion of the monetary gains). We conclude that oxytocin may be part of the human physiology that motivates cooperation.
Negative Affect in Offspring of Depressed Mothers Is Predicted by Infant Cortisol Levels at 6 Months and Maternal Depression during Pregnancy, but Not Postpartum
Authors: HUOT R L , BRENNAN P A , STOWE Z N , PLOTSKY P M , WALKER E F
Published: January 2005

Abstract: This study tests the hypothesis that maternal depression during pregnancy predicts temperament in offspring aged 6 m to 5 y. Previous studies have shown that maternal depression is related to negative affect and that certain temperament factors, such as negative affect and behavioral inhibition, in children predict affective disorders. Here, maternal depression is divided into depression during pregnancy vs. depression postpartum. Maternal depression was determined by the Beck Depression Inventory (BDI) throughout pregnancy and postpartum (prospectively) and by a diagnostic interview (SCID) at 6 months postpartum. The data show that maternal depression during pregnancy, but not postpartum, predicted the ratings of negative affect in the offspring. Importantly, symptoms of depression in the mother (BDI) were used as a control variable in the analyses in order to control for potential bias related to the mother's mood. In addition, cortisol levels in response to a mild stressor at 6 months of age predicted negative affect in infants and toddlers. We conclude that the effects of maternal depression on behavioral problems and vulnerability to mental illness may be mediated by altered temperament and enhanced stress responsiveness.
A Role for 5Alpha‐Reductase Activity in the Development of Male Homosexuality?
Authors: ALIAS A G
Published: January 2005

Abstract: Higher body hair with lower mesmorphism ratings were observed in Caucasian homosexual men compared with the general male population, reflecting elevated 5alpha‐reductase (5αR) activity, and higher dihydrotestosterone‐to‐testosterone (DHT‐to‐T) ratio, in sharp contrast to 46,XY 5αR 2 deficiency subjects, who are often born with ambiguous, or female genitalia, but tend to grow up to be muscular, heterosexual men with very little body hair, or beard. One study also showed them scoring around dull normal IQs. A greater prevalence of liberal body hair growth in men with higher IQs and/or educational levels was also observed in several samples. The exceptions to this statistical trend are too unsettling, however. Nevertheless, the results of a number of published studies, including one showing higher DHT‐to‐T ratio in homosexual men, done with different objectives over a span of 80 years, together strongly support these findings. Furthermore, in an animal model, “cognitive‐enhancing effects” of “5α‐reduced androgen [metabolites]” were recently demonstrated.
Evaluating Performance of Law Enforcement Personnel during a Stressful Training Scenario
Authors: MEYERHOFF JAMES L. , NORRIS WILLIAM , SAVIOLAKIS GEORGE A. , WOLLERT TERRY , BURGE BOB , ATKINS VALERIE , SPIELBERGER CHARLES
Published: January 2005

Abstract: Police trainees who were ready to graduate from the Federal Law Enforcement Training Center (FLETC) volunteered to participate in an exercise designed to evaluate their survivability. In a highly stressful interactive scenario, which included a hostage situation, performance was evaluated for a range of responses, including: shooting judgment and accuracy, communications, and coping with a weapon malfunction. Nineteen percent of subjects shot the hostage, a failure rate that falls in the reported range of friendly fire casualties in military combat. The Spielberger Trait Anger Scale showed an association with shot placement and performance during the gunfight as well as with overall performance scores.
Neural Circuits Underlying Emotional Distress in Humans
Authors: SINHA RAJITA , LACADIE CHERYL , SKUDLARSKI PAWEL , WEXLER BRUCE E.
Published: January 2005

Abstract: Difficulties in the experiences and regulation of emotional stress have been associated with the development of psychiatric and substance use disorders. This study examined neural circuits underlying emotional distress in healthy volunteers using functional magnetic resonance imaging (fMRI) techniques. Recall of personal nontraumatic, highly stressful life events with script‐driven guided imagery was used to induce moderate levels of emotional distress in eight healthy volunteers. Subjects participated in six guided imagery trials (3 separate stress and 3 separate neutral‐relaxing scripts each) interspersed by rest periods in a 1.5T scanner. Results indicated significant activation in the medial prefrontal, anterior cingulate, caudate, putamen, thalamus, hippocampus, parahippocampal gyrus, and posterior cingulate regions during emotional distress relative to brain activation during neutral‐relaxing imagery. These findings suggest that specific striatal‐limbic‐prefrontal cortical circuits are involved in the experience and regulation of emotional stress in humans. The study also provides a feasible method to study brain correlates of emotional stress processing in healthy individuals and clinical samples.
Psychosocial Stress‐Induced Activation of Salivary Alpha‐Amylase: An Indicator of Sympathetic Activity?
Authors: ROHLEDER NICOLAS , NATER URS M. , WOLF JUTTA M. , EHLERT ULRIKE , KIRSCHBAUM CLEMENS
Published: January 2005

Abstract: Assessment of sympathoadrenal medullary system (SAM) activity is only possible to date via measurement of catecholamines in blood plasma or via electrophysiological methods. Both ways of measurement are restricted to endocrinological or psychophysiological laboratories, as both require either immediate freezing of blood samples or complex recording devices. Efforts have therefore been undertaken to find a method comparable to salivary cortisol measurements, in which noninvasive samples can be taken at any place and stored at room temperature for sufficient time before later analysis in the laboratory. Salivary alpha‐amylase (sAA) is a candidate that may prove useful in this context. We show here that sAA activity is increased by acute psychosocial stress (Trier Social Stress Test) and that increases in sAA correlate with increases in norepinephrine. We further report that sAA exhibits a stable circadian pattern that mirrors that of salivary cortisol. In conclusion, the current data show that salivary alpha‐amylase may serve as an easy‐to‐use index for SAM activity. However, some questions remain to be answered; for example, what impact does salivary flow rate exert on stress‐induced sAA activity?
Applying a Nonlinear Regression Model to Characterize Cortisol Responses to Corticotropin‐Releasing Hormone Challenge
Authors: STROUD LAURA R. , PAPANDONATOS GEORGE D. , WILLIAMSON DOUGLAS E. , DAHL RONALD E.
Published: January 2005

Abstract: We previously applied a pharmacokinetic model to characterize stress‐induced cortisol curves. In the current study, we apply this pharmacokinetic model to characterize cortisol responses to CRH challenge in children aged 6‐16. Two hundred eleven sessions were completed beginning between 4 and 5 pm. Sessions included 30‐40 minutes preinfusion baseline, 1 μg/kg CRH infusion, 90‐180 minutes of postinfusion measures, and 9‐10 plasma cortisol samples per session. A simpler version of the original oral dose model best‐fit responses to the CRH challenge: Response = alpha + beta*Time + lambda*T*exp(−kappa*T). Time was standardized so that CRH infusion was at time 0. T = max (0, Time) such that the nonlinear departure from baseline only operated in the postinfusion phase. Alpha represents baseline cortisol at time of infusion, beta is the slope of the linear approximation of the diurnal rhythm, lambda controls magnitude of peak change from baseline, and kappa is reactivity rate. The model converged and appeared to provide a good fit to “real‐world” data in healthy children. Our proposed model provides a detailed characterization of cortisol response to CRH infusion and should allow for increased flexibility in characterizing the influence of individual and situational variables on specific aspects of cortisol response curves.