bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockade of IRS1 in isolated rat pancreatic islets improves glucose‐induced insulin secretion
Authors: Araujo Eliana P , Amaral Maria E.C , Souza Cláudio T , Bordin Silvana , Ferreira Fabiano , Saad Mario J.A , Boschero Antonio C , Magalhães Everardo C , Velloso Lı́cio A
Published: January 2003

Several neural, hormonal and biochemical inputs actively participate in the balance of insulin secretion induced by blood glucose fluctuations. The exact role of insulin as an autocrine and paracrine participant in the control of its own secretion remains to be determined, mostly due to insufficient knowledge about the molecular phenomena that govern insulin signaling in pancreatic islets. In the present experiments we demonstrate that higher insulin receptor and insulin receptor substrates‐1 and ‐2 (IRS1 and IRS2) concentrations are predominantly encountered in cells of the periphery of rat pancreatic islets, as compared to centrally located cells, and that partial blockade of IRS1 protein expression by antisense oligonucleotide treatment leads to improved insulin secretion induced by glucose overload, which is accompanied by lower steady‐state glucagon secretion and blunted glucose‐induced glucagon fall. These data reinforce the inhibitory role of insulin upon its own secretion in isolated, undisrupted pancreatic islets.
The extreme N‐terminus of the calcitonin‐like receptor contributes to the selective interaction with adrenomedullin or calcitonin gene‐related peptide
Authors: Koller Daniela , Born Walter , Leuthäuser Kerstin , Flühmann Beat , McKinney R.Anne , Fischer Jan A , Muff Roman
Published: January 2003

The calcitonin (CT)‐like (CL) receptor is a CT gene‐related peptide (CGRP) receptor or an adrenomedullin (AM) receptor when co‐expressed with receptor‐activity‐modifying proteins (RAMP) 1 or 2, respectively. The CL receptor shows 57% overall sequence identity with the CT receptor, but the homology is much lower in the extreme N‐terminus. An N‐terminal deletion mutant of the human (h) CL receptor (Δ18‐hCL) and a chimeric receptor consisting of the N‐terminal amino acids of the porcine (p) CT receptor fused to the Δ18‐hCL receptor (pCT–hCL) were therefore analyzed. The Δ18‐hCL receptor function was abolished when co‐expressed with RAMP1 or ‐2. The pCT–hCL receptor was a fully functional CGRP receptor when co‐expressed with RAMP1, but the RAMP2‐dependent AM receptor function was impaired. Limited sequence similarities in the N‐terminus of the pCT and the hCL receptors rescue CGRP but not AM receptor binding and signalling.
Human pancreas protein 2 (PAN2) has a retinal reductase activity and is ubiquitously expressed in human tissues
Authors: Belyaeva Olga V , Kedishvili Natalia Y
Published: January 2003

Human gene for pancreas protein 2 (PAN2) is a novel member of the short‐chain dehydrogenase/reductase gene superfamily. The properties of PAN2 protein have not yet been characterized. We present the first evidence that human PAN2 is a ubiquitously expressed microsomal enzyme that recognizes retinoids but not steroids as substrates with the apparent K
m values between 0.08 μM and 0.4 μM. PAN2 is ∼4‐fold more efficient in the reductive than in the oxidative direction. The apparent K
m values for NADP+ and NADPH are 0.65 μM and 0.32 μM versus 1200 μM and 1060 μM for NAD+ and NADH, respectively. Kinetic constants and expression pattern of PAN2 suggest that it is likely to function as a reductase in vivo and might contribute to the reduction of retinaldehyde to retinol in most human tissues.
Significant levels of extracellular reactive oxygen species produced by brown rot basidiomycetes on cellulose
Authors: Cohen Roni , Jensen Kenneth A , Houtman Carl J , Hammel Kenneth E
Published: January 2003

It is often proposed that brown rot basidiomycetes use extracellular reactive oxygen species (ROS) to accomplish the initial depolymerization of cellulose in wood, but little evidence has been presented to show that the fungi produce these oxidants in physiologically relevant quantities. We used [14C]phenethyl polyacrylate as a radical trap to estimate extracellular ROS production by two brown rot fungi, Gloeophyllum trabeum and Postia placenta, that were degrading cellulose. Both fungi oxidized aromatic rings on the trap to give monohydroxylated and more polar products in significant yields. All of the cultures contained 2,5‐dimethoxyhydroquinone, a fungal metabolite that has been shown to drive Fenton chemistry in vitro. These results show that extracellular ROS occur at significant levels in cellulose colonized by brown rot fungi, and suggest that hydroquinone‐driven ROS production may contribute to decay by diverse brown rot species.
Antimicrobial action of achacin is mediated by L‐amino acid oxidase activity
Authors: Ehara Tatsuya , Kitajima Seiji , Kanzawa Nobuyuki , Tamiya Toru , Tsuchiya Takahide
Published: January 2003

Achacin is an antibacterial glycoprotein purified from the mucus of the giant snail, Achatina fulica Férussac, as a humoral defense factor. We showed that achacin has L‐amino acid oxidase activity and can generate cytotoxic H2O2; however, the concentration of H2O2 was not sufficient to kill bacteria. The antibacterial activity of achacin was inhibited by various H2O2 scavengers. Immunochemical analysis revealed that achacin was preferentially bound to growth‐phase bacteria, accounting for the important role in growth‐phase‐dependent antibacterial activity of achacin. Achacin may act as an important defense molecule against invading bacteria.
Anthrax toxin: a tripartite lethal combination1
Authors: Ascenzi Paolo , Visca Paolo , Ippolito Giuseppe , Spallarossa Andrea , Bolognesi Martino , Montecucco Cesare
Published: January 2003

Anthrax is a severe bacterial infection that occurs when Bacillus anthracis spores gain access into the body and germinate in macrophages, causing septicemia and toxemia. Anthrax toxin is a binary A–B toxin composed of protective antigen (PA), lethal factor (LF), and edema factor (EF). PA mediates the entry of either LF or EF into the cytosol of host cells. LF is a zinc metalloprotease that inactivates mitogen‐activated protein kinase kinase inducing cell death, and EF is an adenylyl cyclase impairing host defences. Inhibitors targeting different steps of toxin activity have recently been developed. Anthrax toxin has also been exploited as a therapeutic agent against cancer.
The complex relationship between soluble and insoluble tau in tauopathies revealed by efficient dephosphorylation and specific antibodies
Authors: Hanger D.P , Gibb G.M , de Silva R , Boutajangout A , Brion J.-P , Revesz T , Lees A.J , Anderton B.H
Published: January 2003

Phosphorylated tau is deposited as insoluble inclusion bodies in the tauopathies. We have used a new efficient method to dephosphorylate tau extracted from control and tauopathy brain. In some tauopathies, including Alzheimer's disease and progressive supranuclear palsy, the pattern of insoluble tau isoforms reflected that of soluble tau. In contrast, in corticobasal degeneration, Pick's disease, and some forms of fronto‐temporal dementia, specific tau isoforms were selectively sequestered into insoluble inclusion‐forming tau. Therefore the overall expression of individual tau isoforms does not predict which tau isoforms are deposited in all tauopathies and different mechanisms must operate that result in the deposition of specific tau isoforms.
Increasing the conformational stability by replacement of heme axial ligand in c‐type cytochrome
Authors: Satoh Tadashi , Itoga Akito , Isogai Yasuhiro , Kurihara Masaaki , Yamada Seiji , Natori Miwa , Suzuki Noriko , Suruga Kohei , Kawachi Ryu , Arahira Masaomi , Nishio Toshiyuki , Fukazawa Chikafusa , Oku Tadatake
Published: January 2003

To investigate the role of the heme axial ligand in the conformational stability of c‐type cytochrome, we constructed M58C and M58H mutants of the red alga Porphyra yezoensis cytochrome c
6 in which the sixth heme iron ligand (Met58) was replaced with Cys and His residues, respectively. The Gibbs free energy change for unfolding of the M58H mutant in water (ΔG°unf=1.48 kcal/mol) was lower than that of the wild‐type (2.43 kcal/mol), possibly due to the steric effects of the mutation on the apoprotein structure. On the other hand, the M58C mutant exhibited a ΔG°unf of 5.45 kcal/mol, a significant increase by 3.02 kcal/mol compared with that of wild‐type. This increase was possibly responsible for the sixth heme axial bond of M58C mutant being more stable than that of wild‐type according to the heme‐bound denaturation curve. Based on these observations, we propose that the sixth heme axial ligand is an important key to determine the conformational stability of c‐type cytochromes, and the sixth Cys heme ligand will give stabilizing effects.
Amphioxus homologs of Go‐coupled rhodopsin and peropsin having 11‐cis‐ and all‐trans‐retinals as their chromophores
Authors: Koyanagi Mitsumasa , Terakita Akihisa , Kubokawa Kaoru , Shichida Yoshinori
Published: January 2003

Because of low contents in the native organs and failure of the expression in cultured cells, the chromophore configurations of the pigments in Go‐coupled opsin and peropsin groups in the opsin family are unknown. Here we have succeeded in expression of the amphioxus homologs of these groups in HEK293s cells and found that they can be regenerated with 11‐cis‐ and all‐trans‐retinals, respectively. Light isomerized the chromophores of these opsins into the all‐trans and 11‐cis forms, respectively. The results strongly suggest that the physiological function of peropsin would be a retinal photoisomerase, while 11‐cis configuration is necessary for the Go‐coupled opsin groups.
A recessive mutant cell line with a constitutive IκB kinase activity
Authors: Chinanonwait Netnaphis , Miura Hideyasu , Yamamoto Naoki , Yamaoka Shoji
Published: January 2003

To search for negative regulatory components of the NF‐κB activation pathways, we mutagenized Rat‐1 fibroblasts and established a stable mutant cell line with a constitutive NF‐κB activity. This mutant cell line, designated as TK26, showed permanently elevated I kappa B kinase (IKK) activity and a genetically recessive phenotype revealed by somatic cell hybridization between TK26 and Rat‐1. Our results suggested that lack of a negative regulation of IKK could lead to permanent NF‐κB activation. The TK26 cell line will be useful to genetically identify a component necessary for keeping the IKK complex under an inactive form in resting cells.
Mutations affecting phosphorylation, ubiquitination and turnover of the ABC‐transporter Ste6
Authors: Kölling Ralf
Published: January 2003

In this report, the role of phosphorylation in the regulation of ubiquitination and turnover of the ABC‐transporter Ste6 was investigated. We demonstrate that Ste6 is phosphorylated in vivo and that this phosphorylation is dependent on the presence of an acidic stretch (‘A‐box’) in the linker region previously shown to be important for ubiquitination and fast turnover of Ste6. By mutagenesis, two serine/threonine residues were identified in the A‐box region that are crucial for ubiquitination and trafficking to the yeast vacuole. In the mutants there was no simple correlation between phosphorylation and ubiquitination levels, suggesting that the two events may not be coupled.
In vivo and in vitro activation of temperature‐responsive plant map kinases
Authors: Sangwan Veena , Dhindsa Rajinder S
Published: January 2003

Alfalfa cells possess two temperature‐responsive Mitogen‐Activated Protein Kinases (MAPKs), SAMK (Stress‐Activated MAP Kinase) activated at 4°C and HAMK (Heat shock‐Activated MAP Kinase) activated at 37°C. Both are inactive at 25°C. We show here that SAMK is activated when cells are transferred from 37°C to 25°C, and HAMK is activated when cells are transferred from 4°C to 25°C. Moreover, we show that heat activation of HAMK also occurs in cell‐free extracts. We conclude that (i) SAMK or HAMK activation does not require a particular temperature but a relative temperature shift, and (ii) that either HAMK itself or one or more of its upstream activators can sense temperature change directly.
The effect of recombinant human osteogenic protein‐1 (bone morphogenetic protein‐7) impregnation on allografts in a canine intercalary bone defect
Authors: Cullinane Dennis M. , Lietman Steven A. , Inoue Nozomu , Deitz Luke W. , Chao Edmund Y. S.
Published: January 2003

The utility of cortical allografts in repairing large bone defects is limited by their slow and incomplete incorporation into host bone. In order to determine the effects of recombinant human osteogenic protein‐1 (rhOP‐1) impregnation on allograft incorporation, we used a canine intercalary bone defect model. Bilateral resection of a 4 cm segment of the femoral diaphysis and reconstruction with structural bone allografts were performed. In one limb, the allograft was soaked in solution with rhOP‐1 for 1 h before implantation. In the other limb, the allograft was soaked in the same solution without rhOP‐1. Dynamic load‐bearing, radiographic analysis, biomechanical testing, and histomorphometric analysis were conducted. Radiographic analysis showed significantly larger periosteal callus area in the rhOP‐1 treated group at week 2. The rhOP‐1 significantly increased allograft bone porosity and significantly increased the number of active osteons in the allografts. There were no significant differences between the rhOP‐1 treated and non‐treated allografts in load bearing and biomechanical analyses. These findings indicate that rhOP‐1 increases intercalary allograft remodeling without deleterious effects in mechanical and functional strength.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Expression of monocyte chemoattractant protein‐1 in primary cultures of rabbit intervertebral disc cells
Authors: Yoshida Masakazu , Nakamura Takafumi , Kikuchi Taro , Takagi Katsumasa , Matsukawa Akihiro
Published: January 2003

Macrophages are considered essential for herniated disc resorption, and chemokines may play a role in their recruitment. Here we demonstrate that intervertebral disc cells are capable of producing monocyte chemoattractant protein‐1 (MCP‐1), a CC chemokine that is chemotactic for macrophages. Nucleus pulposus cells and anulus fibrosus cells were harvested from intervertebral discs of healthy rabbits, and the cells were stimulated with either interleukin (IL)‐1β or tumor necrosis factor (TNF)α. Reverse transcriptase polymerase chain reaction demonstrated that IL‐1β and TNFα induced mRNA expression for MCP‐1 in nucleus pulposus and anulus fibrosus cells. Protein concentrations of MCP‐1 in the culture supernatants were quantitated by fluoroim‐munoassay, which showed that nucleus pulposus and anulus fibrosus cells dose‐ and time‐dependently produced MCP‐1 after IL‐1β‐and TNFα‐stimulation, an event that was completely abrogated by IL‐1 receptor antagonist and anti‐TNFα monoclonal antibody, respectively. Nucleus pulposus cells produced significantly higher levels of MCP‐1 than did anulus fibrosus cells. Immunohisto‐chemically, the intensity of MCP‐1 positive cells in nucleus pulposus cells was stronger than that in anulus fibrosus cells. Altogether, our data clearly demonstrated the production of MCP‐1 in intervertebral disc cells, suggesting the possible involvement of disc cells in an early stage of macrophage infiltration.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Wrist kinetics after luno‐triquetral dissociation: the changes in moment arms of the flexor carpi ulnaris tendon
Authors: Tang Jin Bo , Xie Ren Gou , Yu Xiao Wei , Chen Feng
Published: January 2003

Wrist biomechanics after luno‐triquetral (LT) dissociation is important for understanding the clinical sequelae of the disease and for determining its treatment options. The LT interosseous ligament plays an important role in stabilizing the joint and damage to the ligament would be expected to significantly increase moment arms of tendon of the flexor carpi ulnaris (FCU), the principal ulnar wrist flexor. We investigated the changes in moment arms of FCU tendon after various amounts of sectioning of the ligaments proven to be associated with LT dissociation. In six fresh frozen cadaveric upper extremities, excursions of the FCU tendon were recorded simultaneously with wrist joint angulation during wrist flexion‐extension and radioulnar deviation. Tendon excursions were measured in intact wrists, in wrists with sectioning of the dorsal portion of the LT interosseous ligament, in wrists with sectioning of the entire LT interosseous ligament, and finally in wrists with further sectioning of the dorsal radiotriquetral and intercarpal ligaments. Moment arms of the tendon were calculated from tendon excursions and joint motion angulations and expressed as percentage changes from those in the intact wrist. During wrist flexion‐extension, moment arms of the FCU tendon after sectioning of the entire LT interosseous ligament and after sectioning of the two capsular ligaments were 112 ± 7% and 114 ± 8%, respectively; these values were significantly greater than those in the intact wrist. During radioulnar deviation, the moment arms were 114 ± 11% after sectioning of the dorsal portion of the LT interosseous ligament, 134 ± 15% after sectioning of the entire ligament, and 153 ± 18% after sectioning of the capsular ligaments, again being significantly greater than the normal wrist. Increase in moment arms of the FCU tendon after loss of integrity of the LT interosseous ligament and dorsal capsular ligaments may contribute to clinical sequelae of LT dissociation and difficulty in treating this disorder.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Cyclic compression of cartilage/bone explants in vitro leads to physical weakening, mechanical breakdown of collagen and release of matrix fragments
Authors: Thibault Marc , Robin Poole A. , Buschmann Michael D.
Published: January 2003

Mechanical loading of articular cartilage can produce catabolic and anabolic changes in tissue metabolism. Most previous studies in this area have focussed on aggrecan. Little information concerning load‐induced collagen modifications has been obtained. We have therefore conducted studies where mechanical loads are applied in vitro to full thickness cartilage explants retaining a thin layer of bone, in order to investigate mechanically induced collagen breakdown and consequent turnover, in addition to aggrecan changes and mechanical property alterations. Tissue explant disks were subjected to unconfined compression and either immediately frozen or kept in static culture for 10 days. Mechanical tests of the disks immediately prior to and just after the cyclic loading period were also performed. They showed a weakening of the collagen network and an increased hydraulic permeability due to the cyclic loading. Load‐induced alterations of the extracellular matrix was then clearly evidenced by an increase in denatured collagen in the disks frozen immediately after loading compared to unloaded controls. Loaded disks maintained in culture for 10 additional days following cyclic loading no longer expressed this increase in denatured collagen suggesting that mechanically denatured collagen II had undergone a removal process which could represent turnover or repair, or the beginning of progressive degradation. Indeed matrix fragments of collagen II and glycosaminoglycans were found to be released to post‐loading culture medium in increased quantities compared to unloaded controls. Our data further demonstrates the ability of mechanical load of articular cartilage to modulate turnover and metabolism of collagen and proteoglycan in a complex and multifactorial manner that may be of particular significance in the pathogenesis of osteoarthritis and in the development of pharmacological agents to modulate its progression.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Tenofovir treatment at 30 mg/kg/day can inhibit cortical bone mineralization in growing rhesus monkeys (Macaca mulatta)
Authors: Castillo Alesha B. , Tarantal Alice F. , Watnik Mitchell R. , Bruce Martin R.
Published: January 2003

The acyclic nucleoside phosphonate analog, 9‐[2‐(R)‐(phosphonomethoxy)propyl]adenine (PMPA; Tenofovir; Gilead Sciences, Inc., Foster City, CA), has been shown to effectively inhibit simian immunodeficiency virus (SIV) replication in rhesus macaques by blocking reverse transcription. However, chronic long‐term tenofovir treatment at 30 mg/kg/day, intended to reduce viral replication and illness, has been shown to result in bone deformities and spontaneous fractures in rhesus monkeys. Based on these findings, we studied the effects of tenofovir treatment and pathogenic SIV infection on cortical bone remodeling in rhesus monkeys. Tibiae from tenofovir‐treated or untreated, SIV‐infected or uninfected, rhesus macaques were evaluated for bone microdamage and remodeling. We found that tenofovir treatment had a significant effect on osteoid (unmineralized bone) seam width in tibial cross‐sections. Regardless of SIV infection status, half of the tenofovir‐treated animals had significantly increased osteoid seam widths in tibial cortical bone resulting in an osteomalacia‐like condition. Pathogenic SIV infection significantly increased tibial resorption cavity density, and this increase was normalized by tenofovir treatment. These results suggest that tenofovir treatment at 30 mg/kg/day inhibits mineralization of newly formed bone. SIV infection results in increased tibial resorption cavity density, while tenofovir treatment tends to minimize this increase. Both defective mineralization of newly formed bone and increased resorption cavity density may result in greater bone fragility.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
CDMP‐2 induces bone or tendon‐like tissue depending on mechanical stimulation
Authors: Forslund Carina , Aspenberg Per
Published: January 2003

Cartilage derived morphogenetic proteins (CDMPs, also known as growth and differentiation factors, GDFs) are a subgroup of the bone morphogenetic protein (BMP) gene family. As most BMPs, they are known to induce cartilage or bone formation when implanted subcutaneously or intramuscularly on an appropriate carrier. However, similar implantation experiments with CDMPs have also reported the formation of a tendon‐like tissue, without any cartilage or bone. A solution to this apparent contradiction might be offered by the mechanical tissue differentiation theory, suggesting that tissue differentiation depends on the mechanical environment. This study analyzes the response to CDMP‐2 implants at different sites and under different loading conditions in the rat. Collagen sponges carrying CDMP‐2 were implanted subcutaneously, intramuscularly or inside a freshly created defect in the achilles tendon. Large amounts of bone were induced subcutaneously, smaller amounts intramuscularly, and in the tendons, only small amounts of bone or cartilage were seen in few animals. Thus, the amount of bone appeared inversely related to the degree of mechanical stimulus. To confirm this, CDMP was also injected into tendon defects that were either loaded or partially unloaded. All the unloaded tendons showed bone induction after one CDMP‐2 injection, whereas only 4 of 10 loaded ones showed any cartilage or bone (p = 0.0005). Single injections of a similar dose of CDMP‐2 have previously been shown to augment tendon repair by increasing the size of the tendon callus. This study suggests that the response to CDMP‐2 is dependent on the mechanical situation at the site where it is applied.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
In situ strain and stress of nerve conduction blocking in the brachial plexus
Authors: Takai Shinro , Dohno Hidefumi , Watanabe Yoshinobu , Yoshino Nobuyuki , Ogura Taku , Hirasawa Yasusuke
Published: January 2003

The objective of the present study was to determine the in situ strain and stress of nerve conduction blocking in the brachial plexus. The measurement of the in situ tension stress inducing functional failure of the brachial plexus consisted of two steps. Step I (in vivo): The brachial plexus of the rabbit was stretched laterally until electrophysiological conduction blocking occurred. The distance between two dye marks placed on the lower trunk was simultaneously recorded using a video dimensional analyzer system. Step II (in vitro): The lower trunk that was removed was loaded again, and the nerve tension was recorded. The load at complete conduction blocking was determined by a load‐elongation curve. The results showed that when the in situ nerve strain reached 8.1 ± 0.5%, the compound muscle action potential was not evoked. The in situ load and stress were 2.5 ± 0.4 N and 0.89 ± 0.14 MPa, respectively, at complete conduction blocking. These findings should be helpful in understanding the mechanism of brachial plexus traction injury.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Development‐associated differences in integrative cartilage repair: Roles of biosynthesis and matrix
Authors: Giurea Alexander , Dimicco Michael A. , Akeson Wayne H. , Sah Robert L.
Published: January 2003

A recurring problem in tissue transplantation therapies for articular cartilage defects is the lack of integration between the implant and the host cartilage. Previous studies have shown that in vitro integration between explants of calf cartilage is markedly higher than that between fetal cartilage, despite similarly high levels of deposition of newly synthesized collagen. The aim of this study was to determine if cellular biosynthesis and extracellular matrix each contribute to these development‐associated differences in integrative repair in vitro. The approach taken was to examine integration between specific combinations of cartilage explants that were apposed for two weeks. The cartilage matrix showed different propensities for repair, as integration of calf live cartilage to calf devitalized cartilage was greater than that of calf live cartilage to fetal devitalized cartilage. An inhibiting factor appeared to be present in fetal cartilage matrix since guanidine treatment of fetal devitalized cartilage was able to enhance its integration. The difference between integration to living cartilage and integration to devitalized cartilage, for calf and fetal tissue, indicated that the biosynthetic contribution to integration by calf cartilage was greater than the biosynthetic contribution by fetal cartilage. Thus, the increasing level of integration between fetal and fetal cartilage, fetal and calf cartilage, and calf and calf cartilage appeared to reflect both biosynthetic and matrix differences. Therapeutic strategies to enhance integration to cartilage may thus target both the extracellular components and the cellular biosynthetic activities of implants and host cartilage.

© 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Are social fears and DSM-IV social anxiety disorder associated with smoking and nicotine dependence in adolescents and young adults?
Authors: Sonntag H. , Wittchen H.U. , Höfler M. , Kessler R.C. , Stein M.B.
Published: January 2003

To investigate associations between social anxiety and smoking behaviour in order to explore whether social anxiety predicts the first onset of cigarette smoking, regular smoking and the development of nicotine dependence.

Baseline and four-year follow-up data from the Early Developmental Stages of Psychopathology Study (EDSP), a prospective-longitudinal community study of 3,021 adolescents and young adults, are used. Smoking behaviour and psychopathology were assessed with the M-CIDI and its DSM-IV algorithms. At baseline, 35.7% of the sample were regular smokers, and 18.7% fulfilled criteria for DSM-IV nicotine dependence. Twenty-seven point two percent reported at least one social fear, and 7.2% met criteria for DSM-IV social phobia, most of whom reported first onset of social fear problems clearly prior to smoking initiation. Cross-sectional retrospective baseline analyses based on retrospective reports revealed that social fears and DSM-IV social phobia were both significantly associated with higher rates of nicotine dependence. Prospective-longitudinal analyses that were conducted in an attempt to confirm cross-sectional retrospective results showed that baseline non-users with social fears (OR = 3.85) and baseline non-dependent users with social fears (OR = 1.5) had an increased risk of onset of nicotine dependence during the follow-up period of four years. These findings remained significant even when controlling for co-morbid depressive disorders. Social anxiety was found to be significantly associated with nicotine dependence in both cross-sectional retrospective and prospective-longitudinal analyses. It is suggested that social fears could lead to heavy tobacco use as smoking is a socially acceptable behaviour that relieves anxiety in social situations. Possible differential effects of social anxiety on the early stages of smoking behaviour compared to effects on nicotine dependence are discussed. These findings should stimulate a continued search into potentially causal links between social fear symptoms and the development of tobacco consumption and nicotine dependence in adolescence.
Cognitive aspects of social phobia: a review of theories and experimental research
Authors: Musa C.Z. , Lépine J.P.
Published: January 2003

Cognitive theories of social phobia have largely been inspired by the information-processing models of anxiety. They propose that cognitive biases can, at least partially, explain the etiology and maintenance of this disorder. A specific bias, conceived as a tendency to preferentially process socially-threatening information, has been proposed. This bias is thought to intervene in cognitive processes such as attention, memory and interpretation. Research paradigms adopted from experimental cognitive psychology and social psychology have been used to investigate these hypotheses. The existence of a bias in the allocation of attentional resources and the interpretation of information seems to be confirmed. A memory bias in terms of better retrieval for threat-relevant information appears to depend on specific encoding activities.
Disability and quality of life in pure and comorbid social phobia. Findings from a controlled study
Authors: Wittchen H.U. , Fuetsch M. , Sonntag H. , Müller N. , Liebowitz M.
Published: January 2003

Social phobia is increasingly recognized as a prevalent and socially impairing mental disorder. However, little data is available regarding the general and disease-specific impairments and disabilities associated with social phobia. Furthermore, most studies have not controlled for the confounding effects of comorbid conditions.

This study investigates: (a) the generic quality of life; (b) work productivity; and, (c) various other disorder-specific social impairments in current cases with pure (n = 65), comorbid (n = 51) and subthreshold (n = 34) DSM-IV social phobia as compared to controls with no social phobia (subjects with a history of herpes infections).

Social phobia cases reported a mean illness duration of 22.9 years with onset in childhood or adolescence. Current quality of life, as assessed by the SF-36, was significantly reduced in all social phobia groups, particularly in the scales measuring vitality, general health, mental health, role limitations due to emotional health, and social functioning. Comorbid cases revealed more severe reductions than pure and subthreshold social phobics. Findings from the Liebowitz self-rated disability scale indicated that: (a) social phobia affects most areas of life, but in particular education, career, and romantic relationship; (b) the presence of past and current comorbid conditions increases the frequency and severity of disease-specific impairments; and, (c) subthreshold social phobia revealed slightly lower overall impairments than comorbid social phobics. Past-week work productivity of social phobics was significantly diminished as indicated by: (a) a three-fold higher rate of unemployed cases; (b) elevated rates of work hours missed due to social phobia problems; and (c) a reduced work performance.

Overall, these findings underline that social phobia in our sample of adults, whether comorbid, subthreshold, or pure was a persisting and impairing condition, resulting in considerable subjective suffering and negative impact on work performance and social relationships. The current disabilities and impairments were usually less pronounced than in the past, presumably due to adaptive behaviors in life style of the respondents. Data also confirmed that social phobia is poorly recognized and rarely treated by the mental health system.
Anxiety disorders in anorexia nervosa and bulimia nervosa: co-morbidity and chronology of appearance
Authors: Godart N.T. , Flament M.F. , Lecrubier Y. , Jeammet P.
Published: January 2003

The objectives of the study were to assess lifetime prevalence of specific anxiety disorders, and their age of onset relative to that of eating disorders (ED), in a French sample of patients with anorexia nervosa (AN) or bulimia nervosa (BN). We assessed frequencies of seven anxiety disorders and childhood histories of separation anxiety disorder among 63 subjects with a current DSM-IV diagnosis of an ED, using the Composite International Diagnostic Interview (CIDI). Eighty-three percent of subjects with AN and 71% of those with BN had at least one lifetime diagnosis of an anxiety disorder. By far, the most frequent was social phobia (55% of the anorexics and 59% of the bulimics). When present, the co-morbid anxiety disorder had predated the onset of the ED in 75% of subjects with AN, and 88% of subjects with BN. Our results are consistent with those of studies conducted in other countries, and show that an anxiety disorder frequently exists before an ED. This has to be taken in consideration for successful treatment of patients with AN or BN.
Trends in the prevalence of social phobia in the United States: a synthetic cohort analysis of changes over four decades
Authors: Heimberg R.G. , Stein M.B. , Hiripi E. , Kessler R.C.
Published: January 2003

Previous analysis of data from the U.S. National Comorbidity Survey (NCS) suggested that the lifetime prevalence of social phobia in the community has increased significantly in recent cohorts. Furthermore, a latent class analysis of NCS data revealed two primary classes of persons with social phobia: those with exclusive speaking fears and those with one or more other social-evaluative fears. Social phobia in the other social fear group is more persistent, more impairing, and more highly co-morbid with other DSM-III-R disorders. The current report presents data on whether the cohort effect is a general aspect of social phobia or is specific to one of the NCS social phobia subtypes, and whether the cohort effect varies as a function of socio-demographic characteristics. Data were drawn from the NCS. Social phobia was assessed with a revised version of the Composite International Diagnostic Interview. Retrospective age of onset reports were used to estimate Kaplan-Meier survival curves for first onset of social phobia in each cohort represented in the survey. Comparison of these curves allowed us to make synthetic estimates based on retrospective reports of intercohort trends in lifetime prevalence. The lifetime prevalence of social phobia appears to have increased in recent cohorts. However, this increase does not exist among social phobics with exclusive fears of speaking. The increase is most pronounced among white, educated, and married persons, and it is not explained by increased co-morbidity with other mental disorders. The fact that the cohort effect is more pronounced for social phobia with one or more non-speaking fears is important in that this is generally a more severe form of the disorder with an earlier age of onset than social phobia with pure speaking fears. The fact that the cohort effect is most pronounced among people with social and economic advantage (i.e., white, married, well-educated) is intriguing and raises questions about the etiologic process that warrant further study in future research.
Epidemiology of social phobia: a clinical approach
Authors: Faravelli C. , Zucchi T. , Viviani B. , Salmoria R. , Perone A. , Paionni A. , Scarpato A. , Vigliaturo D. , Rosi S. , D’adamo D. , Bartolozzi D. , Cecchi C. , Abrardi L.
Published: January 2003

The recent epidemiologic studies report extremely varied rates for social phobia (SP). One of the reasons for this may be the difficulty in diagnosing SP, the boundaries of which are uncertain. A community survey was carried out using doctors with experience in clinical psychiatry as interviewers, and a clinical diagnostic instrument. Two thousand three hundred and fifty-five people (out of the 2,500 randomly selected from the population) living in Sesto Fiorentino, a suburb of Florence, Italy, were interviewed by their own general practitioner, using the MINI plus six additional questions. Six hundred and ten of the 623 subjects that were found positive for any form of psychopathology at the screening interview, and 57 negative subjects, were re-interviewed by residents in psychiatry using the Florence Psychiatric Interview (FPI). The FPI is a validated composite instrument that has the format of a structured clinical research record. It was found that 6.58% of subjects showed social anxiety not attributable to other psychiatric or medical conditions during their life. Social or occupational impairments meeting DSM-IV diagnostic requirements for SP was detected in 76 subjects (lifetime prevalence = 3.27%). Correction for age raises the lifetime expected prevalence to 4%. Sex ratio was approximately (F:M) 2:1. The most common fear was speaking in public (89.4%), followed by entering a room occupied by others (63.1%) and meeting with strangers (47.3%). Eighty-six point nine percent of subjects with SP complained of more than one fear. The mean age of onset (when the subjects first fully met DSM-IV criteria for SP) was 28.8 years, but the first symptoms of SP usually occurred much earlier, with a mean age of onset at 15.5 years. Ninety-two percent of cases with SP also showed at least one other co-morbid psychiatric disorder during their life. Lifetime prevalence of avoidant personality disorder (APD) was 3.6%. Forty-two point nine percent of cases with SP also had APD, whereas 37.9% of cases with APD developed SP.
A European perspective on social anxiety disorder
Authors: Lecrubier Y. , Wittchen H.U. , Faravelli C. , Bobes J. , Patel A. , Knapp M.
Published: January 2003

Epidemiologic surveys conducted across Europe indicate that the lifetime prevalence of social anxiety disorder in the general population is close to 7%. The disorder in adulthood rarely presents in its ‘pure’ form and 70–80% of patients have at least one other psychiatric disorder, most commonly depression. Social anxiety disorder is a risk factor for the development of depression and alcohol/substance use or dependence, especially in cases with an early onset (< 15 years). Individuals with social anxiety disorder have significant functional impairment, notably in the areas of initiation and maintenance of social/romantic relationships and educational and work achievement. The economic consequences of social anxiety disorder are considerable, with a high level of diminished work productivity, unemployment and an increased utilisation of medical services amongst sufferers. Effective treatment of social anxiety disorder would improve its course and its health and economic consequences.
Is the East European “underclass” feminized?
Authors: Domanski Henryk
Published: January 2003

Results of national surveys carried out in East-European countries convincingly showed that after the fall of communism the gender gap in earnings remained substantial. Following the same analytical framework here I explore a range of issues concerning the gender gap in membership in what I define as the “underclass” in 6 post-communist societies. The basic question is to determine whether or not such a gap exits. I find considerable cross-national variation in the odds of female/male membership in the underclass: women in Poland, Russia and Hungary appear to be most heavily over-represented in this category, while in Bulgaria and Slovakia, the effect of gender does not exist. In addition, the explanation for this gap cannot be found in the intergenerational transmission of poverty, in differences in marital status, and other social–demographic attributes commonly employed in quantitative studies. It is only the lower educational status of women, living in rural areas, and older age, which significantly interact with relatively higher representation of women in the underclass. After controlling for several characteristics of a person's socio–economic position I found that in four countries, namely in Poland, Russia, Romania and Hungary, a statistically significant net effect of gender remains which provides solid evidence for the feminization of the underclass in these societies.
Intra-household gender inequality: hidden dimensions of poverty among Polish women
Authors: Tarkowska Elzbieta
Published: January 2003

This paper challenges recent findings from quantitative studies of poverty in post-communist countries which deny the existence of gender differences in poverty in post 1989 Poland. The author uncovers hidden forms of the feminization of poverty by studying it from the micro-perspective of the family and the household. This perspective highlights gender differences in the division of labor, leisure time, as well as the fact that it is women’s primary responsibility to secure the basic needs of the family. This study presents strong evidence for a variety of ways in which men and women experience and endure poverty differently in an impoverished area in Poland, a fact which is associated with the role of culture, history and tradition in shaping gendered patterns of reaction towards poverty and hardship. The paper is based on the content analysis of in-depth interviews collected during a field research conducted within the project “Old and new forms of poverty in Poland” (2002–1998) and “Poverty, Ethnicity, and Gender inTransitional Societies (1999–2000).
Family policies and gender in Hungary, Poland, and Romania
Authors: Fodor Eva , Glass Christy , Kawachi Janette , Popescu Livia
Published: January 2003

This paper discusses changes and new directions in the gendered nature of the welfare state in three post-state socialist societies: Hungary, Poland and Romania. Relying on an analysis of laws and regulations passed after 1989 concerning child care, maternity and parental leave, family support, unemployment and labor market policies, retirement and abortion laws, the authors identify the differences and the similarities among the three countries, pointing out not only their status in 2001, but also their trajectory, the dynamics and timing of their change. The authors argue that there are essential differences between the three countries in terms of women’s relationship to the welfare state. They also specify some of the key historical and social variables which might explain variation across countries.
Up‐regulation of kinin B1 receptor in the lung of streptozotocin‐diabetic rat: autoradiographic and functional evidence
Authors: Vianna Rose Mari J , Ongali Brice , Regoli Domenico , Calixto João Batista , Couture Réjean
Published: January 2003

The function and autoradiographic binding expression of kinin B1 receptors were evaluated in the lungs of Streptozotocin (STZ)‐diabetic rats.

The intrapleural injection (i.pl.) of des‐Arg9‐bradykinin (des‐Arg9‐BK) (50 and 100 nmol per site), a selective B1 receptor agonist, increased time‐dependently the mononuclear and neutrophil cells influx in the pleural cavity of rats treated with STZ (65 mg kg−1, i.p., 4 days earlier). This effect was significantly less in control rats.

The influx of mononuclear and polymorphonuclear neutrophil cells induced by des‐Arg9‐BK was significantly inhibited by two B1 receptor antagonists (des‐Arg10‐Hoe140 or R‐715, 100 nmol per site, 5 min earlier), but not by two B2 receptor antagonists (Hoe140, 10 nmol or NPC 18884, 100 nmol per site, 5 min earlier). However, Hoe140 prevented the higher basal leukocyte influx seen in STZ‐diabetic rats.

Leukocyte infiltration induced by des‐Arg9‐BK in STZ‐diabetic rats was significantly reduced after treatment with insulin (2 U per day, s.c. over 4 days) or with an anti‐PMN antibody (0.1 ml of a 1 : 20 dilution, i.pl. 5 min earlier).

Specific B1 receptor binding sites were seen in lung sections from both control and STZ‐diabetic rats, yet the density of labelling was much greater in diabetic rats and particularly after intrapleural injection of des‐Arg9‐BK. Treatment with insulin or with the anti‐PMN antibody markedly reduced B1 receptor binding sites occurring after the injection of des‐Arg9‐BK in STZ‐diabetic rats.

Data suggest that the B1 receptor is up‐regulated in the lungs of STZ‐diabetic rats, and its activation increases leukocyte infiltration into the pleural cavity. The overexpression of B1 receptors seems to depend on neutrophils influx and appears to be associated with hyperglycaemia.

British Journal of Pharmacology (2003) 138, 13–22. doi:10.1038/sj.bjp.0704999
5‐hydroxyindole causes convulsions and increases transmitter release in the CA1 region of the rat hippocampus
Authors: Mannaioni Guido , Carpenedo Raffaella , Moroni Flavio
Published: January 2003

5‐hydroxyindole (5‐OHi) is a proposed tryptophan metabolite able to cause convulsions when systemically injected into rodents. We studied its effects using microdialysis in vivo and electrophysiological approaches in vitro.

Local administration of 5‐OHi into the CA1 region of the rat hippocampus, via a microdialysis probe, significantly increased glutamate concentrations in the dialysates.

In rat hippocampal slices, using extracellular recordings in the CA1 region, 5‐OHi (30–300 μM) increased the amplitude of population spikes and fEPSPs.

In the same preparation, using intracellular recordings in CA1 pyramidal neurons, 5‐OHi reduced the latency of firing induced by direct depolarization and increased both evoked excitatory and slow inhibitory postsynaptic potential amplitudes, without affecting the resting membrane potential, the after‐hyperpolarization or the neuronal input resistance. It also altered GABAA‐mediated neurotransmission by increasing the frequency and the amplitude of pharmacologically isolated spontaneous inhibitory postsynaptic currents (sIPSC).

In separate experiments, performed by measuring AMPA or NMDA‐induced depolarization in cortical wedges, 5‐OHi did not modify glutamate receptor agonist responses.

Our results show that 5‐OHi causes convulsions, modifies the properties and the function of the hippocampal circuitry, and facilitates the output of both excitatory and inhibitory transmitters.

British Journal of Pharmacology (2003) 138, 245–253. doi:10.1038/sj.bjp.0705007