bluuebunny/crossref_metadata_2025 huggingface dataset:
The geographical field course as active archive
Authors: Lorimer Hayden
Published: June 2003

This paper narrates a collaborative effort to re-place a local culture of ‘the field’. By oscillating between two geography field courses in Glenmore, Scotland - one in 1951, the other in 2002 - it traces a route through different residues of fieldwork: material objects (photographs, log-books, diaries, equipment), mnemonic devices (biography, oral narrative, re-enactment, technology) and physical phenomena (footpaths, landscape features, field sites). Framed as an ongoing and mobile event, overlapping versions of the field course(s) are then recounted through embodied methodological strategies, or ‘taskscapes’. These close observations of the processes of field practice focus on walking, sensing, talking and archiving. They resist easy interpretation, and do not always register a resolved narrative. What is more pertinent, I argue, is to understand them as an unfinished and active archive that speaks of the localized, everyday conditions in which geography’s history is made.
Natural history societies, fieldwork and local knowledge in nineteenth-century Scotland: towards a historical geography of civic science
Authors: Withers Charles W.J. , Finnegan Diarmid A.
Published: June 2003

This paper examines the role of fieldwork in the activities of natural history societies in Victorian Scotland. Fieldwork, it is argued, was an important constituent in the making of local natural knowledge. Being and doing ‘in the field’ was a means to establish through fieldwork given scientific fields and, in turn, to promote civic identity through scientific conduct.
Original theories: science and the currency of the local
Authors: Matless David
Published: June 2003

In 1960 the Royal Geographical Society published The making of the Broads: a reconsideration of their origin in the light of new evidence. This monograph, the work of an interdisciplinary team, argued that the shallow lakes of the Norfolk Broads in eastern England had their origins in the medieval peat-digging industry. This paper shows how the origins work can be understood in terms of debates and tensions concerning the cultural authority of science over landscape and the nature of local knowledge, and addresses the implications for the currency of the local within studies of scientific knowledge. Drawing on archival work and oral history, the paper shows how local acceptance or rejection of the theory turned on assertions of scientific or non-scientific cultural authority. First publication of the theory in 1953 triggered angry exchanges in the local press over the next decade; the paper reconstructs these debates in terms of their claims to local knowledge, and the constitution of authority over the field. Science and local knowledge are opposed categories for some but mutually constituted for others, such that science itself becomes a matter of local pride. The paper concludes by considering the relationship between the origins research and debates over the past, present and future of the region.
Older community residents with depression: long-term treatment with sertraline
Authors: Wilson K. C. M. , Mottram P. G. , Ashworth L. , Abou-Saleh M. T.
Published: June 2003

Background

Despite a growing use of selective serotonin reuptake inhibitors in older people, only one trial has examined their prophylactic efficacy in people aged 65 years and over.

Aims

To examine the efficacy of sertraline in preventing the recurrence of depression in older people living in the community.

Method

Participants were openly treated with sertraline and then randomised into a double-blind, placebo-controlled continuation/maintenance study of about 2 years duration. Drug dosage was maintained at levels that achieved remission.

Results

No significant difference between the sertraline and placebo groups was found in the proportion of recurrences (–7.9%; 95% CI –28.06 to 12.23). Increased age and minor residual symptoms during the continuation phase were associated with recurrence.

Conclusions

Sertraline at therapeutic dosage does not provide significant protection against recurrence.
Modelling the impact of clozapine on suicide in patients with treatment-resistant schizophrenia in the UK
Authors: Duggan Andy , Warner Juliet , Knapp Martin , Kerwin Robert
Published: June 2003

Background

Schizophrenia is a major cause of suicide, and symptoms characteristic of treatment-resistant disease are strong risk factors. Clozapine reduces symptoms in 60% of such patients and significantly decreases the risk of suicide.

Aims

To model the impact of increased clozapine prescribing on lives saved and resource utilisation.

Method

A model was built to compare current levels of clozapine prescribing with a scenario in which all suitable patients with treatment-resistant schizophrenia received clozapine.

Results

It was estimated that an average of 53 lives could be saved in the UK each year. If clozapine is cost-neutral, the cost per life-year saved is $.5108. If clozapine achieves a 10% reduction in annual support costs, the net saving is $8.7 million per annum. An average of 167 acute beds would be freed each year.

Conclusions

The use of clozapine in treatment-resistant schizophrenia saves lives, frees resources and is cost-effective.
Morphology of the anterior cingulate cortex in young men at ultra-high risk of developing a psychotic illness
Authors: Yücel Murat , Wood Stephen J. , Phillips Lisa J. , Stuart Geoffrey W. , Smith Deidre J. , Yung Alison , Velakoulis Dennis , Mcgorry Patrick D. , Pantelis Christos
Published: June 2003

Background

The anterior cingulate cortex (ACC) is consistently implicated in the pathophysiology of schizophrenia, and our own work has identified morphological anomalies in the ACC of people with this disorder.

Aims

To examine whether ACC morphological anomalies are present in a group at ultra-high risk of psychosis and whether such anomalies can be used to predict the subsequent development of a psychotic illness.

Method

Magnetic resonance imaging of 75 healthy volunteers and 63 people at ultra-high risk of developing a psychotic disorder (all right-handed males) was used to examine ACC sulcal and gyral features.

Results

Compared with the controls, significantly fewer people in the ultra-high risk group had a well-developed left paracingulate sulcus and significantly more had an interrupted left cingulate sulcus. There was no difference between those who did (n=21) and did not (n=42) subsequently develop a psychotic illness.

Conclusions

Although ACC anomalies are present in young people considered to be at ultra-high risk of psychosis, they do not identify individuals who subsequently make the transition to psychosis.
Engagement of brain areas implicated in processing inner speech in people with auditory hallucinations
Authors: Shergill Sukhwinder S. , Brammer Michael J. , Fukuda Rimmei , Williams Steven C. R. , Murray Robin M. , McGuire Philip K.
Published: June 2003

Background

The neurocognitive basis of auditory hallucinations is unclear, but there is increasing evidence implicating abnormalities in processing inner speech. Previous studies have shown that people with schizophrenia who were prone to auditory hallucinations demonstrated attenuated activation of brain areas during the monitoring of inner speech.

Aims

To investigate whether the same pattern of functional abnormalities would be evident as the rate of inner speech production was varied.

Method

Eight people with schizophrenia who had a history of prominent auditory hallucinations and eight control participants were studied using functional magnetic resonance imaging while the rate of inner speech generation was varied experimentally.

Results

When the rate of inner speech generation was increased, the participants with schizophrenia showed a relatively attenuated response in the right temporal, parietal, parahippocampal and cerebellar cortex.

Conclusions

In people with schizophrenia who are prone to auditory hallucinations, increasing the demands on the processing of inner speech is associated with attenuated engagement of the brain areas implicated in verbal self-monitoring.
Suicide following deliberate self-harm: long-term follow-up of patients who presented to a general hospital
Authors: Hawton Keith , Zahl Daniel , Weatherall Rosamund
Published: June 2003

Background

Deliberate self-harm (DSH) is the strongest risk factor for future suicide. Up-to-date information on the extent of risk is lacking.

Aims

To investigate the risk of suicide after DSH during a long follow-up period.

Method

A mortality follow-up study to 2000 was conducted on 11583 patients who presented to hospital after DSH between 1978 and 1997. Data were obtained from a general hospital DSH register in Oxford and the Office for National Statistics, and from equivalent mortality registers in Scotland and Northern Ireland.

Results

Three hundred patients had died by suicide or probable suicide. The risk in the first year of follow-up was 0.7% (95% CI 0.6–0.9%), which was 66 (95% CI 52–82) times the annual risk of suicide in the general population. The risk after 5 years was 1.7%, at 10 years 2.4% and at 15 years 3.0%. The risk was far higher in men than in women (hazard ratio 2.8, 95% CI 2.2–3.6). In both genders it increased markedly with age at initial presentation.

Conclusions

Following DSH there is a significant and persistent risk of suicide, which varies markedly between genders and age groups. Reduction in the risk of suicide following DSH must be a key element in national suicide prevention strategies.
Risk assessment: ‘numbers' and ‘values’
Authors: Szmukler George
Published: June 2003

Risk assessment has two components, which I shall term ‘numbers' and ‘values'. ‘Numbers' refer to the estimation of the likelihood that an adverse event will occur in a stated period of time. The methods are mathematical and statistical. ‘Values' refer to the processes of attaching a value to the risk and deciding what should be done about it. Benefits are weighed against costs in what is largely a moral enterprise. Maden (2003, this issue) asks ‘why all the fuss?’ about standardised risk assessment. My fuss is largely about the ‘values', not so much about the ‘numbers'.
Prescribing errors in psychiatry
Authors: Paton Carol , Gill-Banham Stuart
Published: June 2003

Aims and Method

The Department of Health would like to see serious prescribing errors reduced by 40% by 2005. Little is currently known about prescribing errors made by psychiatrists. The aim of this study was to describe prescribing errors within psychiatry by analysing interventions made by pharmacists. Members of the SouthEast Thames Psychiatric Pharmacists' Network were asked to record details of prescribing errors made in their trusts during the month of May 2002.

Results

Five hundred and seventy-nine errors were reported during the study period. The majority of errors were due to clerical oversights or failure to apply clinical knowledge. In 63 cases (11%), the error could have resulted in a serious outcome.

Clinical Implications

Prescribing errors are a daily occurrence in Mental HealthTrusts, and a potentially serious error is likely to occur on a weekly basis in an average trust. Steps need to be taken to minimise the chances of errors occurring.
Drug and alcohol misuse among in-patients with psychotic illnesses in three inner-London psychiatric units
Authors: Phillips Prashant , Johnson Sonia
Published: June 2003

Aims and Method

Ward staff were asked to rate whether in-patients with a diagnosis of functional psychotic illness also met criteria for a diagnosis of alcohol or drug misuse or dependence during the preceding 6 months. Those who demonstrated such evidence were then asked to report the nature and extent of their substance use and whether they continued to use as in-patients.

Results

264 in-patients with psychotic illness were screened for evidence of recent or current alcohol or drug misuse. According to staff reports, 127 (48.9%) met the criteria for substance misuse or dependence. The mean age of those with ‘dual diagnosis' was 34.7 years and 72% were male. Eighty-three (83%) of those with a history of current or recent alcohol or drug misuse reported that they had continued to use alcohol and/or illicit drugs in the in-patient wards during their current admission.

Clinical Implications

It appears difficult to prevent in-patients with drug or alcohol misuse problems from continuing to use substances in hospital. Further consideration and investigation of how best to manage this group is therefore required.
Reading about self-help books on obsessive –compulsive and anxiety disorders – a review
Authors: Graham Candida
Published: June 2003

Many treatment manuals were originally introduced for research purposes in psychotherapy to standardise treatment programmes among researchers. On the tail of these treatment manuals came the development of self-help manuals for patients. An example is Barlow & Craske's (1994) self-help publication for anxiety and panic, which was born out of their therapist manual.
Evaluating and Upgrading Welded Steel Moment-Frame Buildings Using FEMA-351
Authors: Hooper John D.
Published: June 2003

In July 2000, the SAC Joint Venture (a joint venture of the Structural Engineers Association of California, the Applied Technology Council, and California Universities for Research in Earthquake Engineering) prepared a series of recommendations regarding welded steel moment-frame design, evaluation, and upgrade procedures. FEMA-351, Recommended Seismic Evaluation and Upgrade Criteria for Existing Welded Steel Moment-Frame Buildings, was developed to evaluate the probable performance of existing steel moment-frame buildings in future earthquakes and to provide guidance or upgrading these buildings. The procedures introduced in FEMA-351 allow the determination of the level of confidence a structure will be able to achieve based on a specified performance objective, using simplified analytical methods. Simplified procedures for estimating the probable post-earthquake repair costs and nonstructural damage, based on the losses incurred in the 1994 Northridge earthquake, are presented as well. This paper provides a brief chapter-by-chapter overview of the information contained in FEMA-351 and emphasizes the performance evaluation procedures by stepping through the process using an example building.
Rehabilitation of a 1985 Steel Moment-Frame Building
Authors: Haskell Gregg
Published: June 2003

A 1985 steel moment frame is seismically upgraded using passive energy dissipation, without adding stiffness to the system. The design and analysis techniques for sizing the Velocity Braces™ and their impact on the demand capacity ratios are reviewed. The structure was built in the San Francisco Bay Area in compliance with the 1985 Uniform Building Code (UBC). The moment frame contains the classic pre-Northridge nonductile moment connection, complete with weld backup bars left attached. Nonlinear time-history analysis procedures were implemented to verify the demand capacity ratios at the critical beam-column connections. Flexural demand capacity ratios of .6 achieve elastic behavior in the design basis earthquake with R=1.0. The response spectra of the time history chosen for design exceed the requirements of the 1997 UBC Zone 4. Torsional response to earthquake excitation is minimized by strategic placement of nonlinear viscous dampers. Nonlinear dampers that reduce the flexural demand on joints and control interstory drift without inelastic excursions of the beam flanges are achieved. Floor spectral accelerations and maximum drift limits are reduced to be consistent with immediate occupancy performance. The damper driver mechanism, being velocity driven, reduces moment frame demands and allows flexibility in configuration.
Earthquake Loss Estimation Methods for Welded Steel Moment-Frame Buildings
Authors: Kircher Charles A.
Published: June 2003

This paper describes procedures that may be used by experienced structural engineers to develop earthquake damage and related loss functions for welded steel moment-frame (WSMF) buildings. The damage and loss functions are based on and compatible with the loss estimation methods of HAZUS, a technology developed by Federal Emergency Management Agency (FEMA) for assessing regional impacts of earthquakes. The loss estimation procedures were developed by the SAC Steel Program as described in SAC Joint Venture Topical Report SAC/BD-99/13. These procedures form the basis for Appendix B of FEMA-351, Recommended Seismic Evaluation and Upgrade Criteria for Existing Welded Steel Moment-Frame Buildings. The procedures for developing damage and loss functions for WSMF building response are general in nature and applicable to WSMF buildings designed to different seismic criteria and having different connection details. Default values of damage and loss function parameters are provided for typical 3-story, 9-story, and 20-story WSMF buildings, designed for Los Angeles, Seattle, or Boston seismic criteria and having pre-Northridge, post-Northridge, or damaged pre-Northridge connection conditions.
Translating Research to Practice: FEMA/SAC Performance-Based Design Procedures
Authors: Hamburger Ronald O. , Foutch Douglas A. , Cornell C. Allin
Published: June 2003

The extensive research on steel moment-frame performance developed by the FEMA/SAC program was implemented in a probabilistic reliability framework to develop performance-based design and evaluation procedures. These procedures, presented in a familiar demand and resistance factor engineering format provide engineers with the ability to define a level of confidence associated with the prediction that a building design will be able to meet a desired performance objective. This approach builds upon and extends the performance-based design procedures developed under the SEAOC Vision 2000 and FEMA 273 projects in two important ways. First, it provides a direct method for structural performance to be evaluated on the basis of global, as opposed to local behaviors. Second, it permits quantification of the likelihood that desired performance will actually be achieved, potentially alleviating liability concerns related to implementation of performance-based design approaches. Perhaps more important, the procedures implemented by the FEMA/SAC project provide a direct method for the incorporation of analytical and laboratory research into design procedures with defined reliability.
Post-earthquake Evaluation and Repair of Welded Steel Moment-Frame Buildings
Authors: Phipps Maryann T.
Published: June 2003

In the wake of a potentially damaging earthquake, every affected welded steel moment-frame building should be assessed to determine whether it poses a safety risk. A straightforward, multi-step process has been developed to streamline this formidable task. This paper provides an overview of this procedure and repair techniques as published in FEMA-352, Recommended Post-earthquake Evaluation and Repair Criteria for Welded Steel Moment-Frame Buildings. The evaluation procedure, developed as part of the SAC Steel Project, begins with screening to rapidly identify those buildings unlikely to have been damaged. Subsequent steps help identify buildings that have sustained sufficient structural damage to compromise future performance and to determine appropriate actions regarding building occupancy and repair.
Project Specifications for New Steel Moment-Frame Building Construction
Authors: Shaw Robert E.
Published: June 2003

FEMA-353, Recommended Specifications and Quality Assurance Guidelines for Steel Moment-Frame Construction for Seismic Applications, contains numerous provisions related to the materials, details, quality, and inspection of steel moment-frame buildings in seismic regions. These provisions continue to evolve as industry standards and practices are reviewed, modified, and adopted to meet the need for good seismic performance. Those writing project specifications must remain current with new industry developments and standards.
Northridge Welded Steel Moment-Frame Damage Data and Its Use for Rapid Loss Estimation
Authors: Bonowitz David , Maison Bruce F.
Published: June 2003

FEMA-351, Recommended Seismic Evaluation and Upgrade Criteria for Existing Welded Steel Moment-Frame Buildings, offers two methods for estimating seismic losses in pre-Northridge WSMFs: detailed and rapid. The rapid method uses empirical relationships between seismic demand parameters and either damage levels or repair costs. The relationships are based on actual damage data collected after the 1994 Northridge earthquake. This paper summarizes the Northridge data, explains the FEMA-351 rapid method loss functions, and comments on the nature of the damage data and its application to loss estimation. Use of the loss functions can be enhanced by understanding their inherent assumptions and uncertainties and by considering how the underlying data was collected and interpreted in the years following the 1994 earthquake.
International Visions and Goals for the Earthquake Engineering Research Institute
Authors: Poland C. D. , Alcocer S. M.
Published: June 2003

The Earthquake Engineering Research Institute (EERI) has recently added public advocacy for seismic safety to its rich history of facilitating the discussion amongst earthquake scientists and engineers. In recognition of its unique role as the authoritative source for information in the United States, EERI also seeks to partner with other nations to develop information for use worldwide. In 2002, EERI began forming cooperation agreements with organizations in other countries that encourage the exchange of information, collaborative efforts in learning from earthquakes, joint memberships, development of mitigation tools and techniques, and access to seminars, conferences, and technical publications. The ultimate goal of the program is to arrest the growth of seismic vulnerability worldwide and thereby save lives, protect capital investments, and minimize economic impacts.
Prequalification of Steel Moment-Frame Connection Performance
Authors: Roeder Charles W.
Published: June 2003

Welded-flange/bolted-web connections were damaged during the Northridge earthquake, and the SAC Steel Project was funded by the Federal Emergency Management Agency to find solutions to the problems caused by this damage. The Connection Performance Technical Advisory Panel was one of several groups completing the project research, and this group examined all connection performance issues. Many connections were evaluated, and some were prequalified for future use without detailed testing or evaluation. This prequalification criteria and the methods used to satisfy the criteria are described. Some connections that satisfy the prequalification criteria are summarized and the general basis for the prequalification limits are noted. Prequalification requires an adequate experimental database for understanding and evaluating all yield mechanisms and failure modes for each connection type. The concept of the yield mechanisms and failure modes, and the application of the experimental data toward meeting the prequalification requirements are described. A wide range of connections including fully bolted connections, welded connections, and a range of partial-strength and partial-stiffness connections are included.
Overview of the U.S. Program for Reduction of Earthquake Hazards in Steel Moment-Frame Structures
Authors: Mahin Stephen A. , Malley James O. , Hamburger Ronald O. , Mahoney Michael
Published: June 2003

Considerable research has been conducted worldwide to assess the unexpected damage to welded steel moment-frame buildings during the 1989 Loma Prieta, 1994 Northridge, and 1995 Hyogo-ken Nanbu earthquakes, as well as to find effective and economical remedies that can be incorporated into analysis, design, and construction practices. A major six-year program has been undertaken with the sponsorship of the U.S. Federal Emergency Management Agency (FEMA) to synthesize and interpret the results of this research, and to conduct additional investigations to develop reliable, practical, and cost-effective guidelines for the design and construction of new steel moment-frame structures, as well as for the inspection, evaluation and repair or upgrading of existing ones. Topics investigated as part of this program include (1) performance of steel buildings in past earthquakes; (2) material properties and fracture issues; (3) joining and inspection; (4) connection performance; (5) system performance; (6) performance prediction and evaluation; and (7) social, economic, and political impacts. The project utilizes a performance-based engineering framework and addresses issues pertaining to various types of steel moment-resisting frames including those utilizing welded, bolted, and partially restrained connections. The guidelines are applicable to regions of low, medium, and high seismicity throughout the United States. This paper reviews the overall organization and management of this program of research, guideline development, training and peer evaluation, the scope of the investigations undertaken, and the general organization and contents of the guidelines developed.
Design Guidelines for Steel Moment Frames for New Buildings
Authors: Saunders C. Mark
Published: June 2003

The damage to steel moment frames observed in the Northridge earthquake of 1994 led to requirements in codes for use of tested connections, when these systems were to be employed in new buildings. One of the primary goals of the FEMA/SAC project was to develop guidelines for the design of steel moment frames that would return the design process to a relatively simple set of procedures similar to those used in the design of other lateral force-resisting systems. Recommended Seismic Design Criteria for New Steel Moment-Frame Buildings, FEMA-350, presents design guidelines for use of steel moment frames in new buildings, developed from the FEMA/SAC research. This paper provides a general summary of the criteria, and a description of the prequalified connections and recommendations for their use.
Steel and Composite Structures in European Seismic Areas: Research, Codification, Design, and Applications
Authors: Mazzolani Federico M.
Published: June 2003

This paper focuses on the present situation of research, codification, design, and applications in the field of steel and composite structures in the European earthquake-prone countries. Emphasis is first given to recent research projects developed in cooperation among European institutions, providing the basis of the research activity and the main conclusions. Then codification rules are focused on, by examining basic principles and new amendments of Eurocode 8, in relation with the current design methodologies adopted in Europe for both steel and steel-concrete composite structures. Finally, some applications of earthquake-resistant structures recently built in Europe are illustrated.
Leptin Signaling in the Hypothalamus during Chronic Central Leptin Infusion
Authors: Pal Rekha , Sahu Abhiram
Published: June 2003

Using a rat model of chronic central leptin infusion in which neuropeptide Y neurons develop leptin resistance, we examined whether leptin signal transduction mechanism in the hypothalamus is altered during central leptin infusion. Adult male rats were infused chronically into the lateral cerebroventricle with leptin (160 ng/h) or vehicle via Alzet pumps for 16 d. In the leptin-infused group, the initial decrease in food intake was followed by a recovery to their preleptin levels by d 16, although food intake remained significantly lower than in artificial cerebrospinal fluid controls; and body weight gradually decreased reaching a nadir at d 11 and remained stabilized at lower level thereafter. Phosphorylated leptin receptor and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) remained elevated in association with a sustained elevation in DNA-binding activity of STAT3 in the hypothalamus throughout 16-d period of leptin infusion. However, phosphorylated Janus kinase-2 was increased during the early part of leptin infusion but remained unaltered on d 16. Although hypothalamic suppressors of cytokine signaling-3 (SOCS3) mRNA levels were increased throughout leptin infusion, SOCS3 protein levels were increased only on d 16. This study demonstrates a sustained elevation in hypothalamic leptin receptor signaling through Janus kinase-STAT pathway despite an increased expression of SOCS3 during chronic central leptin infusion. We propose that an alteration in leptin signaling in the hypothalamus through pathways other than STAT3 and/or a defect in downstream of STAT3 signaling may be involved in food intake recovery seen after an initial decrease during chronic central leptin infusion.
Mineralocorticoid Action and Sodium-Hydrogen Exchange: Studies in Experimental Cardiac Fibrosis
Authors: Young Morag , Funder John
Published: June 2003

There is increasing evidence that the trigger for cardiac fibrosis in response to mineralocorticoid/salt administration is coronary vasculitis and that effects can be seen within days of deoxycorticosterone acetate (DOCA) administration. Furthermore, rapid, nongenomic mineralocorticoid effects on the sodium-hydrogen exchanger (NHE-1) in vascular smooth muscle cells have recently been described. That this mechanism may act as an inflammatory or profibrotic signal was tested by comparing the specific NHE-1 antagonist cariporide and the mineralocorticoid receptor antagonist K canrenoate in the rat model of mineralocorticoid/salt perivascular fibrosis over 8 d of DOCA/salt administration. Interstitial collagen, inflammatory cell infiltration, and inflammatory markers were determined. DOCA elevated blood pressure above control, cariporide +DOCA, or K canrenoate +DOCA rats, without cardiac hypertrophy. At 8 d interstitial collagen was significantly elevated in the DOCA-alone group, with levels in cariporide- and K canrenoate-treated rats not different from control. Expression of osteopontin, cyclooxygenase-2, and ED-1 were elevated by DOCA treatment, blocked by potassium canrenoate, and (for ED-1 and osteopontin) partially reduced by cariporide. These results suggest mineralocorticoid/salt-induced cardiac fibrosis may involve coronary vascular smooth muscle cell NHE-1 activity as a possible contributor to the cascade of transcriptional events that produce the characteristic coronary vasculitis seen with excess mineralocorticoid and salt.
Inhibition of the Stem Cell Factor-Induced Migration of Mast Cells by Dexamethasone
Authors: Jeong Hyun-Ja , Na Ho-Jeong , Hong Seung-Heon , Kim Hyung-Min
Published: June 2003

Mast cell accumulation can be causally related to several allergic inflammations. Previous work has demonstrated that glucocorticoids decreased tissue mast cell number, and stem cell factor (SCF)-induced migration of mast cells required p38 MAPK activation. In the present study we investigated the effects of dexamethasone on SCF-induced migration of rat peritoneal mast cells (RPMCs). SCF significantly induced the migration of RPMCs at 4 h. Dexamethasone dose-dependently inhibited SCF-induced migration of RPMCs (∼90.1% at 100 nm; P < 0.05). The MAPK p38 inhibitor SB203580 (20 μm) also inhibited the SCF-induced migration. The ability of SCF to enhance morphological alteration and filamentous actin formation was also abolished by treatment with dexamethasone. Dexamethasone inhibited SCF-induced p38 MAPK activation to near-basal levels and induced MAPK phosphatase-1 expression. In addition, SCF-induced inflammatory cytokine production was significantly inhibited by treatment with dexamethasone or SB203580 (P < 0.01). Our results show that dexamethasone potently regulates SCF-induced migration, p38 MAPK activation, and inflammatory cytokine production through the expression of MKP-1 protein in RPMCs. Such modulation may have functional consequences during dexamethasone treatment, especially mast cell-mediated allergic inflammation disorders.
Thyroid Hormones Interact with Glucocorticoids to Affect Somatotroph Abundance in Chicken Embryonic Pituitary Cells in Vitro
Authors: Liu Lixin , Dean Carlton E. , Porter Tom E.
Published: June 2003

Our laboratory has reported that somatotroph differentiation occurs between d 14 and d 16 of chicken embryonic development and that corticosterone (CORT) can induce somatotroph differentiation at an earlier age in vitro and in vivo. The objective of the present study was to test for thyroid hormone-CORT interactions on somatotroph differentiation in vitro. Pituitary cells from d 11 chicken embryos were treated with CORT and thyroid hormones, and GH-producing somatotrophs were detected by reverse hemolytic plaque assays and immunocytochemistry. We found that thyroid hormones can act synergistically with CORT to further augment the abundance of somatotrophs in vitro but have little to no effect on their own. Both T4 and T3 could act synergistically with CORT to increase somatotroph abundance, but the effects of T3 were biphasic, inhibiting CORT actions at higher concentrations. The monodeiodination inhibitor iopanoic acid inhibited the synergistic effect of T4 on CORT induction of GH cells in vitro but not the synergistic effect of CORT and T3 or the effect of CORT alone. Furthermore, T3 treatment overcame the iopanoic acid-induced reduction in the T4-CORT effect. Our findings indicate that thyroid hormones act synergistically with CORT to further augment the abundance of somatotrophs in vitro and that conversion of T4 to T3 within the pituitary is involved in T4 modulation of somatotroph abundance. Somatotroph differentiation during normal development may be regulated by complex interactions of hormones produced by the embryonic thyroid and adrenal glands.
Novel Neuropeptides Related to Frog Growth Hormone-Releasing Peptide: Isolation, Sequence, and Functional Analysis
Authors: Ukena Kazuyoshi , Koda Aya , Yamamoto Kazutoshi , Kobayashi Tetsuya , Iwakoshi-Ukena Eiko , Minakata Hiroyuki , Kikuyama Sakae , Tsutsui Kazuyoshi
Published: June 2003

We previously identified in the bullfrog a novel hypothalamic RFamide peptide (SLKPAANLPLRF-NH2) that stimulated GH release in vitro and in vivo and therefore was designated frog GH-releasing peptide (fGRP). Molecular cloning of cDNA encoding the deduced fGRP precursor polypeptide further revealed that it encodes fGRP and its related peptides (fGRP-RP-1, -RP-2, and -RP-3). In this study immunoaffinity purification using the antibody against fGRP was therefore conducted to determine whether these three putative fGRP-RPs exist as mature endogenous ligands in the frog brain. The mass peaks of the isolated immunoreactive substances were detected at 535.78, 1034.14, and 1079.71 m/z ([M+2H]2+), and their sequences, SIPNLPQRF-NH2, YLSGKTKVQSMANLPQRF-NH2, and AQYTNHFVHSLDTLPLRF-NH2, were revealed by the fragmentation, showing mature forms encoded in the cDNA sequences of fGRP-RP-1, -RP-2, and -RP-3, respectively. All of these fGRP-RPs contained a C-terminal -LPXRF-NH2 (X = L or Q) sequence, such as fGRP. This study further analyzed hypophysiotropic activities of the identified endogenous fGRP-RPs. Only fGRP-RP-2 stimulated, in a dose-related way, the release of PRL from cultured frog pituitary cells; its threshold concentration ranged from less than 10−7m. A similar stimulatory action of fGRP-RP-2 on GH release was evident. It was ascertained that fGRP-RP-2 was also effective in elevating the circulating GH and PRL levels when administered systemically. In contrast, fGRP-RPs did not have any appreciable effect on the release of gonadotropins. Thus, fGRP-RP-2 may act as a novel hypothalamic factor on the frog pituitary to stimulate the release of GH and PRL.
Deletion, But Not Antagonism, of the Mouse Growth Hormone Receptor Results in Severely Decreased Body Weights, Insulin, and Insulin-Like Growth Factor I Levels and Increased Life Span
Authors: Coschigano Karen T. , Holland Amy N. , Riders Markus E. , List Edward O. , Flyvbjerg Allan , Kopchick John J.
Published: June 2003

GH participates in growth, metabolism, and cellular differentiation. To study these roles, we previously generated two different dwarf mouse lines, one expressing a GH antagonist (GHA) and the other having a disrupted GH receptor and binding protein gene (GHR −/−). In this study we compared the two dwarf lines in the same genetic background (C57BL/6J). One of the most striking differences between the mouse lines was their weight gain profile after weaning. The weights of the GHA dwarfs gradually approached controls over time, but the weights of the GHR −/− dwarfs remained low throughout the analysis period. Additionally, fasting insulin and glucose levels were reduced in the GHR −/− mice but normal in the GHA mice. IGF-I and IGF binding protein 3 (IGFBP-3) levels were significantly reduced, but by different degrees, in both mouse lines, but IGFBP-1 and -4 levels were reduced and IGFBP-2 levels increased in GHR −/− mice but unaltered in GHA mice. Finally, life span was significantly extended for the GHR −/− mice but remained unchanged for GHA dwarfs. These results suggest that the degree of blockade of GH signaling can lead to dramatically different phenotypes.
The Value of the Low-Dose Dexamethasone Suppression Test in the Differential Diagnosis of Hyperandrogenism in Women
Authors: Kaltsas Gregory A. , Isidori Andrea M. , Kola Blerina P. , Skelly Rob H. , Chew Shern L. , Jenkins Paul J. , Monson John P. , Grossman Ashley B. , Besser G. Michael
Published: June 2003

We studied 211 hyperandrogenic women with respect to clinical presentation, basal androgen levels, and the degree of cortisol and androgen suppression during a 48-h low-dose (2 mg) dexamethasone-suppression test (LDDST) to exclude ovarian and adrenal tumors. In 42 women with elevated testosterone levels, 21 of whom failed to suppress testosterone during the LDDST, the response of serum androgen levels during a 4-wk administration of 7.5 mg prednisolone in a reverse circadian regimen was also assessed. These results were compared with an additional 17 patients with histologically proven androgen-secreting tumors.

Clinical presentation alone was suggestive of a virilizing tumor in 70% of patients with tumors. Serum testosterone, although occasionally only marginally elevated, was the sole androgen that was elevated in every patient with a tumor. After the LDDST, none of the patients with tumors obtained either a greater than 40% reduction or normalization of the previously elevated testosterone levels, whereas 88% of patients with nontumorous hyperandrogenism showed either normalization or suppression of more than 40%. With one exception, all of the patients with nontumorous hyperandrogenism who showed inadequate suppression of testosterone during the LDDST, and were treated with prednisolone, normalized the previously elevated androgens after 1 month of administration.

In summary, in women presenting with hyperandrogenism, lack of testosterone suppression during the LDDST is associated with 100% sensitivity and 88% specificity in distinguishing patients with ovarian and adrenal androgen-secreting tumors from patients with nontumorous hyperandrogenism in this small series. The LDDST is an easy to perform screening test that can also identify causes of hyperandrogenism due to altered glucocorticoid secretion.
Developmental Changes in the Hormonal Identity of Gonadotroph Cells in the Rhesus Monkey Pituitary Gland
Authors: Meeran Dawud , Urbanski Henryk F. , Gregory Susan J. , Townsend Julie , Tortonese Domingo J.
Published: June 2003

To help elucidate the regulatory mechanism responsible for divergent gonadotrophin secretion during sexual maturation, we examined the gonadotroph population and hormonal identity of gonadotroph subtypes in pituitary glands of juvenile (age, 1.7 ± 0.2 yr) and adult (age, 12.3 ± 0.8 yr) male rhesus monkeys (Macacca mulatta). Serum LH and testosterone concentrations were, respectively, 3 and 7 times lower in juveniles than in adults, thus confirming the different stages of development. Immunohistochemistry revealed that the proportion of LH gonadotrophs in relation to the total pituitary cell population in the juvenile animals was significantly smaller than in the adults. In a subsequent study, double immunofluorescent labeling identified three distinct gonadotroph subtypes in both age groups: ones expressing either LH or FSH and another one expressing a combination of both gonadotrophins. Whereas the number of monohormonal LH cells per unit area was greater in the adults than in the juveniles, the number of monohormonal FSH gonadotrophs was remarkably lower. However, the proportion of FSH cells (whether mono- or bihormonal) within the gonadotroph population was similar between groups. Interestingly, the proportion and number of bihormonal gonadotrophs as well as the LH/FSH gonadotroph ratio were significantly greater in the adults than in the juveniles. Taken together, these data reveal that during the juvenile-adult transition period, not only does the pituitary gonadotroph population increase, but a large number of monohormonal FSH gonadotrophs are likely to become bihormonal. Because this morphological switch occurs when marked changes in plasma gonadotrophins are known to occur, it may represent an intrapituitary mechanism that differentially regulates gonadotrophin secretion during sexual development.
Increased Pulse Wave Velocity Associated with Reduced Calcaneal Quantitative Osteo-sono Index: Possible Relationship Between Atherosclerosis and Osteopenia
Authors: Hirose Ken-ichi , Tomiyama Hirofumi , Okazaki Ryo , Arai Tomio , Koji Yutaka , Zaydun Gulnisa , Hori Saburo , Yamashina Akira
Published: June 2003

Although the associations between arterial calcification or advanced atherosclerosis and osteopenia have been well documented, it is not clear whether the one is the result of the other or they coprogress from the early stages through common mechanisms. Thus, we measured pulse wave velocity (PWV), which reflects earlier phase atherosclerosis, and osteo-sono assessment index (OSI), which correlates with bone mineral density, in 7865 Japanese subjects (4183 males and 3682 females, aged 50 ± 12 yr) and analyzed their association. PWV was determined by the volume rendering method; OSI was measured by the calcaneal quantitative ultrasound method. We evaluated the influence of age, gender, menopausal state, and established atherosclerotic risk factors on this association. In a linear regression analysis, OSI negatively correlated with PWV in both genders, and this association was more prominent in females (r = −0.38, P < 0.01) than in males (r = −0.17, P < 0.01). In females, this relationship was stronger after the menopause. In a multivariate analysis, PWV was significantly associated with OSI independent of age and conventional atherosclerotic risk factors. In females, this association was independent from menopause. These results suggest that common or related mechanisms, which may be accelerated after menopause, control both atherosclerosis and osteoporosis from the early stages.
Acute Temporal Regulation of Vascular Endothelial Growth/Permeability Factor Expression and Endothelial Morphology in the Baboon Endometrium by Ovarian Steroids
Authors: Albrecht Eugene D. , Aberdeen Graham W. , Niklaus Andrea L. , Babischkin Jeffery S. , Suresch Donna L. , Pepe Gerald J.
Published: June 2003

We recently showed that endometrial vascular endothelial growth/permeability factor (VEG/PF) mRNA expression was decreased by ovariectomy of baboons and restored by chronic administration of estrogen. However, it remains to be determined whether this effect of estrogen reflects genomic up-regulation of VEG/PF and leads to an increase in microvascular permeability, an early physiological event in angiogenesis. Therefore, we determined the temporal expression of VEG/PF mRNA in glandular epithelial and stromal cells isolated by laser capture microdissection from and width of microvascular paracellular clefts that regulate vessel permeability in the endometrium of ovariectomized baboons after acute estradiol and/or progesterone administration.

Endometrial VEG/PF mRNA levels were increased in five of five animals within 2 h of estradiol administration and remained elevated at 4 and 6 h. The net increase in glandular epithelial (7.31 ± 2.72 attomol/fmol 18S ribosomal rRNA) and stromal (3.13 ± 0.36) cell VEG/PF mRNA levels after estradiol administration was over 8-fold (P < 0.05) and 2.6-fold (P < 0.01) greater, respectively, than after vehicle (0.90 ± 0.30, glands and 1.20 ± 0.33, stroma). In contrast, endometrial VEG/PF mRNA expression was unaltered by progesterone. After estradiol treatment, endometrial paracellular cleft width was increased (P < 0.01) from a mean (±se) of 71.6 ± 4.6 nm at 0 h to 101.1 ± 6.4 nm at 6 h, whereas vehicle or progesterone had no effect. We suggest that estrogen has a major role in regulating VEG/PF synthesis and early events in angiogenesis in the primate endometrium.
Novel Interactions of Adiponectin with the Endocrine System and Inflammatory Parameters
Authors: Fernández-Real José Manuel , López-Bermejo Abel , Casamitjana Roser , Ricart Wifredo
Published: June 2003

Several markers of chronic immune activation have been found in association with obesity and insulin resistance. We aimed to study the interaction of adiponectin with chronic inflammation and known components of the insulin resistance syndrome.

Insulin sensitivity (minimal model analysis) and plasma soluble fractions of TNF-α receptor 1 (sTNFR1) and 2 (sTNFR2), adrenal and thyroid function, and adiponectin were evaluated in 68 apparently healthy subjects. An additional group of type 2 diabetic patients (n = 19) similarly studied, except for insulin sensitivity, were also included in the analysis.

As reported by others, serum adiponectin concentrations were higher in women than in men (13.55 ± 9.79 vs. 8.64 ± 7.83 mg/liter; P = 0.018). They were also higher in healthy subjects compared with diabetic patients (10.35 ± 8.48 vs. 7.41 ± 8.31 mg/liter; P = 0.021). As expected also, circulating adiponectin was significantly associated with waist to hip ratio (r = −0.28; P = 0.013), diastolic blood pressure (r = −0.25; P = 0.027), fasting plasma high-density lipoprotein cholesterol (r = 0.35; P = 0.001), triglycerides (r = −0.37; P = 0.001), and insulin sensitivity (r = 0.30; P = 0.011). Additionally, subjects in the higher quartile of circulating adiponectin had lower sTNFR2 concentrations (3.05 vs. 4.37 μg/liter; P = 0.012), a trend to lower sTNFR1 concentrations (1.76 vs. 2.20 μg/liter; P = 0.055), higher concentration of serum morning cortisol (16.86 vs. 13.52 μg/dl; P = 0.027), and higher serum free T4 levels (1.31 vs. 1.20 ng/dl; P = 0.038). Multiple regression analysis models were constructed to predict adiponectin concentrations. Predictive variables in these models included insulin sensitivity, waist to hip ratio and free T4, contributing to 17%, 10%, and 8% of adiponectin variance, respectively, These findings suggest that circulating adiponectin differentially modulates insulin action and that thyroid-axis, inflammatory cytokines, and the adrenal cortex might intervene in this modulation.