bluuebunny/crossref_metadata_2025 huggingface dataset:
A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog–Scott syndrome)
Authors: Orrico Alfredo , Galli Lucia , Falciani Michela , Bracci Martina , Cavaliere Maria Luigia , Rinaldi Maria Michela , Musacchio Andrea , Sorrentino Vincenzo
Published: July 2002

Aarskog–Scott Syndrome (AAS) is an X‐linked disorder characterised by short stature and multiple facial, limb and genital abnormalities. A gene, FGD1, altered in a patient with AAS phenotype, has been identified and found to encode a protein with homology to Rho/Rac guanine nucleotide exchange factors (Rho/Rac GEF). However, since this original report on identification of a mutated FGD1 gene in an AAS patient, no additional mutations in the FGD1 gene have been described. We analysed 13 independent patients with clinical diagnosis of AAS. One patient presented a mutation that results in a nucleotide change in exon 10 of the FGD1 gene (G2559>A) substituting a Gln for Arg in position 610. The mutation was found to segregate with the AAS phenotype in affected males and carrier females in the family of this patient. Interestingly, Arg‐610 is located within one of the two pleckstrin homology (PH) domains of the FGD1 gene and it corresponds to a highly conserved residue which has been involved in InsP binding in PH domains of other proteins. The same residue is often mutated in the Bruton's tyrosine kinase (Btk) gene in patients with an X‐linked agammaglobulinemia. The Arg610Gln mutation represents the first case of a mutation in the PH domain of the FGD1 gene and additional evidence that mutations in PH domains can be associated to human diseases.
Lactate transport in rat adipocytes: identification of monocarboxylate transporter 1 (MCT1) and its modulation during streptozotocin‐induced diabetes
Authors: Hajduch Eric , Heyes Richard R. , Watt Peter W. , Hundal Harinder S.
Published: July 2002

We have characterised L‐lactate transport in rat adipocytes and determined whether these cells express a carrier belonging to the monocarboxylate transporter family. L‐Lactate was taken up by adipocytes in a time‐dependent, non‐saturable manner and was inhibited (by ∼90%) by α‐cyano‐4‐hydroxycinnamate. Lactate transport was stimulated by 3.7‐fold upon lowering extracellular pH from 7.5 to 6.5 suggesting the presence of a lactate/proton‐cotransporter. Antibodies against ono arboxylate ransporter 1 (MCT1) reacted positively with plasma membranes (PM), but not with intracellular membranes, prepared from adipocytes. MCT1 expression was down‐regulated in PM of adipocytes from diabetic rats, which also displayed a corresponding loss (∼64%) in their capacity to transport lactate. The data support a role for MCT1 in lactate transport and suggest that changes in MCT1 expression are likely to have important implications for adipocyte lactate metabolism.
The conformation of the main immunogenic region on the α‐subunit of muscle acetylcholine receptor is affected by neighboring receptor subunits
Authors: Fostieri Efrosini , Beeson David , Tzartos Socrates J.
Published: July 2002

Myasthenia gravis (MG) is caused by autoantibodies to the acetylcholine receptor (AChR). Experiments with fetal (α2βγδ) and adult (α2βϵδ) AChR and with recombinant subunit dimers showed that some monoclonal antibodies (mAbs) against the main immunogenic region (MIR), located on the α‐subunit of the AChR, bind better to fetal AChR and to αγ subunit dimer than to adult AChR and αϵ dimer and equally to both αβ and αδ. However, other anti‐MIR mAbs prefer adult AChR and αϵ dimer, bind well to αβ but weakly to αδ. These results suggest that the MIR conformation is affected by the neighboring γ/ϵ‐ and δ‐subunits and may contribute to understanding the antibody specificities in MG.
Identification of triphosphoribosyl‐dephospho‐CoA as precursor of the citrate lyase prosthetic group
Authors: Schneider Karin , Dimroth Peter , Bott Michael
Published: July 2002

The γ‐subunit of citrate lyase (EC 4.1.3.6) contains the prosthetic group 2′‐(5″‐phosphoribosyl)‐3′‐dephospho‐CoA and serves as an acyl carrier protein (ACP). We recently showed that in Escherichia coli the proteins CitG and CitX are essential for holo‐ACP synthesis and provided evidence that CitG catalyzes the formation of a prosthetic group precursor from ATP and dephospho‐CoA, which is subsequently attached via phosphodiester linkage to apo‐ACP by CitX. Here we prove that CitG indeed catalyzes the conversion of ATP and dephospho‐CoA to adenine and 2′‐(5″‐triphosphoribosyl)‐3′‐dephospho‐CoA, the predicted precursor of the prosthetic group. Furthermore, this precursor was transferred by CitX to apo‐ACP, yielding holo‐ACP. Thus, our proposed mechanism for holo‐ACP synthesis could be verified.
Carbamate kinase can replace in vivo carbamoyl phosphate synthetase. Implications for the evolution of carbamoyl phosphate biosynthesis
Authors: Alcántara Cristina , Cervera Javier , Rubio Vicente
Published: July 2002

The exclusive involvement of carbamate kinase (CK) in fermentative ATP production and of carbamoyl phosphate synthetase (CPS) in the production of carbamoyl phosphate (CP) for pyrimidines and arginine biosynthesis was challenged by the finding of CK as the only activity synthesising CP in the archaeaPyrococcus furiosusandPyrococcus abyssi. We now show that CK can replace CPS in vivo: transformation ofEscherichia colidevoid of the CPS gene with plasmids encoding the CK fromP. furiosusor fromEnterococcus faecalis(which uses CK for making ATP) restores the ability of CPS‐deficientE. colito grow in the absence of arginine and uracil if ammonia and bicarbonate are present.
Green tea catechins such as (−)‐epicatechin and (−)‐epigallocatechin accelerate Cu2+‐induced low density lipoprotein oxidation in propagation phase
Authors: Yamanaka Naoki , Oda Osamu , Nagao Seiji
Published: July 2002

Effects of (−)‐epicatechin (EC) and (−)‐epigallocatechin (EGC) on Cu2+‐induced low density lipoprotein (LDL) oxidation were studied in initiation and propagation phases. When 1.5 μM EC or EGC was added to the mixture of isolated human LDL and Cu2+ in the initiation phase, the oxidation of LDL was inhibited in agreement with previous findings. In contrast, in the propagation phase, 1.5 μM of EC or EGC worked as an accelerator of the oxidation, and acceleration ratios (maximum about 6 times) were modified depending on the concentrations of catechin used and the oxidation process in the propagation phase. The evidence was obtained from formation of thiobarbituric acid reactive substances (TBARS), detecting conjugated diene measured by absorbance at 234 nm and investigating fragmentation of apoprotein B (apo B) in LDL. Even in the propagation phase of LDL oxidation, the elevated concentrations of EC or EGC worked as inhibitors: after 40 min incubation of LDL with Cu2+, 10.0 μM EC or 2.0 μM EGC inhibited LDL oxidation. Yet, nitric oxide (NO) released from 5 μM zwitterionic polyamine/NO adducts had an inhibitory in all phases of LDL oxidation. These results indicate that catechins such as EC and EGC can act as free radical terminators (reducing agents) or accelerators (oxidizing agents) under oxidation circumstances, which is a different character from NO. From the above evidence, further investigations are needed on many natural flavonoids, the most potent antioxidative compounds in foods.
Communication between the extracellular environment, cytoplasmic signalling cascades and the nuclear cell‐cycle machinery
Authors: Peeper Daniel S , Bernards René
Published: July 2002

In the past decade, we have gained considerable insight into the identities of various cytoplasmic signal transduction cascades and the manner in which they operate in response to changes in the extracellular environment. Moreover, we have begun to understand what the key players are in cell‐cycle regulation and how they, in turn, function to promote cell division. A long‐standing question, however, has been how communication between signalling routes and the cell‐cycle machinery occurs. This review highlights some recent observations that provide possible links between signal transduction and the cell‐cycle machinery.
Heterogeneity of water‐soluble amyloid β‐peptide in Alzheimer's disease and Down's syndrome brains
Authors: Russo Claudio , Saido Takaomi C. , DeBusk Laura M. , Tabaton Massimo , Gambetti Pierluigi , Teller Jan K.
Published: July 2002

Water‐soluble amyloid β‐peptides (sAβ), ending at residue 42, precede amyloid plaques in Down's syndrome (DS). Here we report that sAβ consists of the full‐length Aβ1–42 and peptides truncated and modified by cyclization of the N‐terminal glutamates, Aβ3(pE)–42 and Aβ11(pE)–42. The Aβ3(pE)–42 peptide is the most abundant form of sAβ in Alzheimer's disease (AD) brains. In DS, sAβ3(pE)–42 concentration increases with age and the peptide becomes a dominant species in the presence of plaques. Both pyroglutamate‐modified peptides and the full‐length Aβ form a stable aggregate that is water soluble. The findings point to a crucial role of the aggregated and modified sAβ in the plaque formation and pathogenesis of AD.
Effects of melatonin in isolated rat papillary muscle
Authors: Abete Pasquale , Bianco Sabatino , Calabrese Claudio , Napoli Claudio , Cacciatore Francesco , Ferrara Nicola , Rengo Franco
Published: July 2002

In conclusion, we found that melatonin possess anti‐adrenergic effect in isolated rat papillary muscle. This phenomenon was abolished in the presence of its receptor antagonist N‐acetyltryptamine demonstrating that melatonin operates through a specific cardiac receptor. The reduction of contractility increase, induced by forskolin‐stimulated adenylate cyclase, shows that melatonin may act through a reduction of cyclic AMP accumulation.
Does the nuclear envelope contain two types of ligand‐gated Ca2+ release channels?
Authors: Guihard Gilles , Proteau Sonia , Rousseau Eric
Published: July 2002

The nuclear envelope is composed of two membranes deliminating a perinuclear space which displays functional properties similar to those of a Ca2+‐storing compartment. ATP‐driven Ca2+ uptake and InsP3‐induced Ca2+ release processes have been described in isolated nuclei. Recently, it was reported that cADP‐ribose and InsP3 can trigger a nucleoplasmic Ca2+ increase. It was hypothesized that the inner nuclear membrane possesses Ca2+ channels that are regulated by ryanodine or InsP3. Radio‐ligand binding assays and Western blot experiments were performed in order to investigate their presence in sheep cardiac and rat liver nuclear envelopes. Ryanodine receptors (RyR) were not detected in liver nuclear envelopes by either binding assay or Western blot analysis. However, cardiac nuclear envelopes were found to retain a very low level of specific ryanodine binding, which was not detected on immuno‐blots obtained with three types of isoform‐specific RyR antibodies. In contrast, nuclear InsP3‐binding sites were consistently detected in both cardiac and liver nuclear envelopes. Altogether, these results provide evidence for the major contributor InsP3‐gated Ca2+ channels in control of Ca2+ release from the perinuclear space in liver and cardiac cells.
Disruption of the outer mitochondrial membrane as a result of large amplitude swelling: the impact of irreversible permeability transition
Authors: Petit Patrice X , Goubern Marc , Diolez Philippe , Susin Santos A , Zamzami Naoufal , Kroemer Guido
Published: July 2002

Upon induction of permeability transition with different agents (Ca2+, tert‐butyl hydroperoxide, atractyloside), mouse hepatocyte mitochondria manifest a disruption of outer membrane integrity leading to the release of cytochrome c and apoptosis‐inducing factor (AIF), two proteins which are involved in programmed cell death (apoptosis). Chelation of Ca2+ shortly (within 2 min) after its addition to isolated mitochondria reestablished the mitochondrial transmembrane potential (ΔΨm), prevented induction of large amplitude swelling and release of both cytochrome c and AIF. In contrast, late Ca2+ chelation (10 min after addition of Ca2+) failed to affect these parameters. Cytochrome c appears to be released through a mechanically damaged outer mitochondrial membrane rather than via a specific release mechanism. These findings clarify the mechanisms through which irreversible permeability transition occurs with subsequent large amplitude swelling culminating in the release of intermembrane proteins from mitochondria. Moreover, they confirm the hypothesis formulated by Skulachev [FEBS Lett. 397 (1996) 7–10 and Q. Rev. Biophys. 29 (1996) 169–202] linking permeability transition to activation of the apoptogenic catabolic enzymes.
Peptidyl‐prolyl‐cis/trans‐isomerase activity may be necessary for memory formation
Authors: Bennett Pauleen C , Singaretnam Lloyd G , Zhao Wei-Qin , Lawen Alfons , Ng Kim T
Published: July 2002

At present, evidence for a plethora of physiological roles for the different classes of peptidyl‐prolyl‐cis/trans‐isomerases (PPIases, EC 5.2.1.8) is emerging. Cyclosporin A (CyA) has been previously reported to disrupt memory formation in a temporally specific manner, when administered intracranially to day‐old chicks trained on a single‐trial, passive‐avoidance task [Bennett, P.C., Zhao, W., Lawen, A. and Ng, K.T. (1996) Brain Res. 730, 107–117]. CyA is known to inhibit both the PPIase activity of cyclophilin and, indirectly, the protein phosphatase activity of calcineurin. Therefore to begin to distinguish between these two functions we studied the effects on memory formation of three non‐immunosuppressive CyA analogues, in order to study the involvement of cyclophilins. These drugs retain the capacity to bind to and inhibit the PPIase activity of cyclophilin, but do not bind in the complex with cyclophilin to calcineurin and, therefore, do not inhibit its phosphatase activity. All three drugs exert effects on memory formation comparable to those induced by CyA, significantly inhibiting memory formation when injected intracranially (50 fmol per hemisphere) immediately following training. Brain extracts from chicks treated with [MeVal4]CyA show a strong inhibition of cyclophilin activity. These data show a requirement for the PPIase activity of a cyclophilin for successful memory formation and constitute the first set of data establishing a physiological role for a cyclophilin.
Drosophila ferritin mRNA: alternative RNA splicing regulates the presence of the iron‐responsive element
Authors: Lind Maria I. , Ekengren Sophia , Melefors Öjar , Söderhäll Kenneth
Published: July 2002

Several mRNAs encoding the same ferritin subunit of Drosophila melanogaster were identified. Alternative RNA splicing and utilisation of different polyadenylation sites were found to generate the transcripts. The alternative RNA splicing results in ferritin transcripts with four unique 5′ untranslated regions. Only one of them contains an iron‐responsive element. The iron‐responsive element was found to bind in vitro specifically to human recombinant iron regulatory protein 1. Furthermore, the ferritin subunit mRNAs are differentially expressed during development. Our data provides the first molecular evidence that the presence of iron‐responsive element in a ferritin mRNA is regulated by alternative RNA splicing.
The complete sequence of the mitochondrial genome of Saccharomyces cerevisiae
Authors: Foury Françoise , Roganti Tiziana , Lecrenier Nicolas , Purnelle Bénédicte
Published: July 2002

The currently available yeast mitochondrial DNA (mtDNA) sequence is incomplete, contains many errors and is derived from several polymorphic strains. Here, we report that the mtDNA sequence of the strain used for nuclear genome sequencing assembles into a circular map of 85 779 bp which includes 10 kb of new sequence. We give a list of seven small hypothetical open reading frames (ORFs). Hot spots of point mutations are found in exons near the insertion sites of optional mobile group I intron‐related sequences. Our data suggest that shuffling of mobile elements plays an important role in the remodelling of the yeast mitochondrial genome.
Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy, inhibit the proinflammatory transcription factor NF‐κB
Authors: Riehemann Kristina , Behnke Bert , Schulze-Osthoff Klaus
Published: July 2002

Activation of transcription factor NF‐κB is elevated in several chronic inflammatory diseases and is responsible for the enhanced expression of many proinflammatory gene products. Extracts from leaves of stinging nettle (Urtica dioica) are used as antiinflammatory remedies in rheumatoid arthritis. Standardized preparations of these extracts (IDS23) suppress cytokine production, but their mode of action remains unclear. Here we demonstrate that treatment of different cells with IDS23 potently inhibits NF‐κB activation. An inhibitory effect was observed in response to several stimuli, suggesting that IDS23 suppressed a common NF‐κB pathway. Inhibition of NF‐κB activation by IDS23 was not mediated by a direct modification of DNA binding, but rather by preventing degradation of its inhibitory subunit IκB‐α. Our results suggests that part of the antiinflammatory effect of Urtica extract may be ascribed to its inhibitory effect on NF‐κB activation.
Cloning of a cDNA encoding diacylglycerol acyltransferase from Arabidopsis thaliana and its functional expression
Authors: Hobbs Douglas H , Lu Chaofu , Hills Matthew J
Published: July 2002

Triacylglycerols are the most important storage lipids in most plants and animals. Acyl‐CoA:diacylglycerol acyltransferase (EC 2.3.1.20) catalyzes the final step of the pathway of triacylglycerol synthesis and is the only step which is unique to this process. Diacylglycerol acyltransferase is required for the synthesis of storage oil in a wide range of oil‐bearing seeds and fruits and in floral structures such as petals, anthers and pollen. We describe the first cloning and functional expression of a cDNA encoding diacylglycerol acyltransferase from a plant. The cDNA, cloned from Arabidopsis thaliana, encodes a 520 amino acid protein with a predicted molecular mass of 59.0 kDa which shares 38% amino acid sequence identity with diacylglycerol acyltransferase from mouse. When expressed in insect cell cultures, the protein catalyzes the synthesis of [14C]triacylglycerol from [14C]diacylglycerol and acyl‐CoA. Primer extension analysis revealed that the transcription begins 225 bases before the translation start site, yielding an unusually long 5′ untranslated region. The gene is expressed in a wide range of tissues but most strongly in developing embryos and petals of flowers.
Biochemical analysis of the interaction between elongation factor 1α and α/β‐tubulins from a ciliate, Tetrahymena pyriformis
Authors: Nakazawa Masumi , Moreira David , Laurent Jacqueline , Le Guyader Hervé , Fukami Yasuo , Ito Keisuke
Published: July 2002

The interaction between elongation factor 1α (EF‐1α) and α/β‐tubulins has been analyzed in vivo and in vitro. An association of both α‐ and β‐tubulins with EF‐1α in the lysate of Tetrahymena pyriformis was detected by co‐immunoprecipitation analysis. In contrast, in vitro biomolecular interaction analysis with glutathione S‐transferase (GST) fusion proteins revealed that GST‐β‐tubulin, but not GST‐α‐tubulin, can bind to GST‐EF‐1α. Two β‐tubulin binding sites have been identified to reside in the domains I and III of EF‐1α. In addition, β‐tubulin itself seems to have two distinct interaction sites for each of the domains. Since domain II of EF‐1α did not interact with β‐tubulin, we have re‐evaluated the phylogenetic status of ciliates using EF‐1α sequences devoid of domain II. The phylogenetic tree thus obtained was significantly different from that inferred from the whole sequence of EF‐1α, suggesting the presence of functional constraints on the molecular evolution of EF‐1α.
ATP‐dependent degradation of SulA, a cell division inhibitor, by the HslVU protease in Escherichia coli
Authors: Seong Ihn Sik , Oh Ji Yeon , Yoo Soon Ji , Seol Jae Hong , Chung Chin Ha
Published: July 2002

HslVU is an ATP‐dependent protease consisting of two multimeric components, the HslU ATPase and the HslV peptidase. To gain an insight into the role of HslVU in regulation of cell division, the reconstituted enzyme was incubated with SulA, an inhibitor of cell division in Escherichia coli, or its fusion protein with maltose binding protein (MBP). HslVU degraded both proteins upon incubation with ATP but not with its non‐hydrolyzable analog, ATPγS, indicating that the degradation of SulA requires ATP hydrolysis. The pulse‐chase experiment using an antibody raised against MBP‐SulA revealed that the stability of SulA increased in hsl mutants and further increased in lon/hsl double mutants, indicating that SulA is an in vivo substrate of HslVU as well as of protease La (Lon). These results suggest that HslVU in addition to Lon plays an important role in regulation of cell division through degradation of SulA.
A FTIR spectroscopy evidence of the interactions between wheat germ agglutinin and N‐acetylglucosamine residues
Authors: Bonnin Stéphanie , Besson Françoise , Gelhausen Micaèle , Chierici Sabine , Roux Bernard
Published: July 2002

Wheat germ agglutinin (WGA), a lectin binding a N‐acetyl‐D‐neuraminic acid (NeuNAc) and/or N‐acetyl‐D‐glucosamine (GlcNAc) group, was studied by Fourier transform infrared (FTIR) spectroscopy. Deconvolution of the FTIR spectrum of WGA alone indicated the presence of few α‐helices and β‐sheets, in contrast to many other lectins. These results agree with previous WGA crystal data. The WGA conformational changes, induced by GlcNAc‐bearing liposomes or GlcNAc oligomers, were studied by infrared differential spectroscopy. The GlcNAc binding to WGA resulted in a decrease of turns and α‐helices and a concomitant appearance of β‐sheets, inducing more or less peptidic N‐H deuteration.
Oligomeric complexes involved in translocation of proteins across the membrane of the endoplasmic reticulum
Authors: Wang Lin , Dobberstein Bernhard
Published: July 2002

Proteins involved in protein translocation across the membrane of the endoplasmic reticulum assemble into different oligomeric complexes depending on their state of function. To analyse such membrane protein complexes we fractionated proteins of mammalian rough microsomes and analysed them using blue native PAGE and immunoblotting. Among the proteins characterised are the Sec61p complex, the oligosaccharyl transferase (OST) complex, the translocon‐associated protein (TRAP) complex, the TRAM and RAMP4 proteins, the signal recognition particle (SRP) and the SRP receptor (SR). Interestingly, the RAMP4 protein, SR and OST complex display more than one oligomeric form.
Glutathione peroxidase‐like activity of caeruloplasmin as an important lung antioxidant
Authors: Park Y.S. , Suzuki K. , Taniguchi N. , Gutteridge John M.C.
Published: July 2002

The copper‐containing plasma protein caeruloplasmin (Cp) has been shown to possess several oxidase activities, but with the exception of its ferrous ion oxidising (ferroxidase) activity which so far appear to be of minor biological relevance. Recently, Kim and colleagues (Kim et al. (1998) FEBS Lett. 431, pp. 473–475) observed that Cp can catalytically remove hydrogen peroxide in the presence of thiols. Here, we show that Cp can remove both hydrogen peroxide and lipid hydroperoxides at physiologically relevant concentrations of reduced glutathione known to be present in lung and lung lining fluid. The glutathione peroxidase‐like activity of Cp together with its ferroxidase activity would completely remove the primary reactants required for both Fenton chemistry and lipid peroxidation.
Structure and mechanism of proton‐translocating transhydrogenase
Authors: Jackson J.Baz , Peake Sarah J. , White Scott A.
Published: July 2002

Recent developments have led to advances in our understanding of the structure and mechanism of action of proton‐translocating (or AB) transhydrogenase. There is (a) a high‐resolution crystal structure, and an NMR structure, of the NADP(H)‐binding component (dIII), (b) a homology‐based model of the NAD(H)‐binding component (dI) and (c) an emerging consensus on the position of the transmembrane helices (in dII). The crystal structure of dIII, in particular, provides new insights into the mechanism by which the energy released in proton translocation across the membrane is coupled to changes in the binding affinities of NADP+ and NADPH that drive the chemical reaction.
Induction of labor in breech presentation
Authors: Rojansky N , Tsafrir A , Ophir E , Ezra Y
Published: July 2002

Objective: Induction of labor in breech presentation, although not contraindicated, has rarely been reported. We have undertaken to evaluate the safety and outcome of this practice in two Israeli institutions along with a literature review of this controversial subject. Method: The research design was a retrospective case control study covering the years: 1980–1999. We have studied 53 term (>37 weeks) breech deliveries induced for various medical and obstetrical reasons, in two major regional hospitals in Israel. Induction was performed with prostaglandin E2 for the unripe cervix and with oxytocin for induction or augmentation when the cervix was ripe. Six women were induced by nipple stimulation. Controls were 53 women with spontaneous labor in breech presentation that had a trial of vaginal delivery, and 54 women with breech presentation who delivered by elective cesarean section. Result: No significant difference in the various maternal and fetal outcomes was observed. CS rate was comparable in both study and control groups (34% vs. 32%) and two‐thirds gave birth vaginally. Conclusions: In properly selected and carefully managed cases of breech presentation, induction of labor seems a safe and reasonable option.
The AMDD program: history, focus and structure
Authors: Maine D , Rosenfield A
Published: July 2002

The AMDD (Averting Maternal Death and Disability) Program was established at the Mailman School of Public Health in 1999. In this article, we discuss four key aspects of the program: the focus on emergency obstetric care; the use of process indicators; working with partners; and applying human rights.
The mediating role of caspase‐3 protease in the intracellular mechanism of genistein‐induced apoptosis in human prostatic carcinoma cell lines, DU145 and LNCaP
Authors: Kumi‐Diaka James , Sanderson Naeyhi‐Aelei , Hall Alexis
Published: July 2002

Summry— A series of in vitro studies were carried out to investigate genistein‐induced cell death, and the nature of cell death, in two human prostate cancer cell lines (LNCaP and Du145), and the possible involvement of caspase‐3 protease in genistein‐induced apoptosis in the target cells. The major findings of these studies are: i) genistein inhibits growth and proliferation of both LNCaP and DU145 cells via apoptosis mainly, and necrosis at higher concentrations; ii) genistein induces activation and expression of caspase‐3 (CPP32) in both target cells; iii) genistein‐induced apoptosis and CPP32 activation could be significantly inhibited by the caspase‐3 inhibitor, z‐VAD‐fmk (N—benzyloxycarbonyl‐Val‐Asp‐fluoromethyl—ketone), thus confirming a mediator role of CPP32 in the genistein‐induced apoptotic pathway in the target cells. The potency of most known chemopreventive drugs for cancer is due to induction of apoptosis in solid tumors (Thompson, Science 267 (1995) 1456; Gurney et al., Science 288 (2000) 283). Inevitably, agents that increase transcription of caspase‐3 protease could reinforce cell death via CPP32‐mediated apoptosis. In this regard, genistein may find an application in the treatment of human prostate carcinoma, independently of hormone sensitivity.
Service design and operations strategy formulation in multicultural markets
Authors: Pullman Madeleine E , Verma Rohit , Goodale John C
Published: July 2002

Businesses that service multicultural customer segments face unique challenges in developing the appropriate service strategy. While the strategic implications of expanding services from a domestic market to an international location have been well documented, multicultural customer segments at one location is a unique problem that has largely been neglected by researchers. This paper attempts to fill this gap by presenting a conceptual framework and method for determining the extent of service product and process attribute standardization versus customization in these settings. The paper presents an approach for modeling the preferences of different cultural segments, evaluating the differences between the segments and determining the appropriate service strategy for service providers. We evaluate the effects of competitors adopting their revenue maximizing strategy both independently of each other and simultaneously while assuming the size of the market is viewed as a zero sum game. In an actual application at an international airport terminal, one food‐service vendor implemented the suggested operations strategy and the result was a significant revenue gain over the previous year’s sales during the same period. The method has valuable implications for managers when developing strategies for delivering a service to multicultural customer segments.
Proton magnetic resonance spectroscopy (1H-MRS) of the thalamus in schizophrenia
Authors: Delamillieure P , Constans J.M , Fernandez J , Brazo P , Dollfus S
Published: July 2002

This study applied1H-MRS in the thalamus of schizophrenic patients and healthy subjects.

There were no differences in the metabolite ratios (NAA/Cr, Cho/Cr or mI/Cr) between the two groups. Relationships were noted between NAA/Cr and age in patients with a trend toward this correlation in controls, suggesting an effect of age on the metabolism of the thalamus.
Family- and school-related stresses in depressed Hungarian children
Authors: Csorba J. , Rózsa S. , Vetro A. , Gadoros J. , Makra J. , Somogyi E. , Kaczvinszky E. , Kapornay K.
Published: July 2002

The aim of the study was 1) to identify recent and past life stresses as having a significant differential risk of childhood depression versus other childhood psychiatric illnesses, and 2) to establish if life stresses shared with other family members had a greater impact on the depression of the child than events of only personal relevance. Using a recently developed semi-structured interview (Diagnostic Evaluation Schedule for Children and Adolescents – Hungarian version, DESCA-H ), 68 life events of a total sample of 526 children were investigated. Two hundred and fifteen depressed preadolescents (mean age 12.73 years, SD 2.58) were compared with identical variables of 311 nondepressed mixed clinical controls (mean age: 10.91 years, SD 2.46) referred to child psychiatry care with other psychiatric symptomatology than depression. The life event questionnaire part of the DESCA-H was administered separately by means of lists of recent (within 1 year) and past stresses (events prior to 1 year before the assessment). With the two series of life stresses, two separate logistic regression analyses were performed. Of past stressors, physical punishment of the child by teachers, serious financial problems of the family and mental health problems of family members were found to be significant predictors of depression. From the series of recent stresses, moving to a new school, somatic illness, death of relatives and mental health disorders of family members were proved to be independent risk factors of depression for the children. The findings suggest that significant stresses of the child shared with other family members dominate in demarcating depressed children from nondepressed ones. School-related stresses are critically discussed.
Long-term treatment of chronic schizophrenia with risperidone: a study with plasma levels
Authors: Mauri M.C. , Laini V. , Boscati L. , Rudelli R. , Salvi V. , Orlandi R. , Papa P.
Published: July 2002

Twenty-four chronic schizophrenic outpatients with a mean age of 37.21 years ± 9.96 SD were treated with risperidone (RSP) at the dosage of 2–9 mg/die (mean 4.46 mg/die ± 1.30 SD, mean 0.06 mg/kg ± 0.01 SD) for a year.

Clinical evaluation was assessed with the Brief Psychiatric Rating Scale (BPRS), Positive and Negative Symptoms Scale (PANSS), Extrapyramidal Side Effects Rating Scale (EPSE) and a checklist for Anticholinergic Side Effects (ACS) at T0, then after 1 (T1), 2 (T2), 3 (T3), 6 (T6), 9 (T9) and 12 (T12) months. RSP and 9-hydroxy-risperidone (9OH-RSP) plasma levels were determined at T12 by the HPLC method. BPRS and PANSS mean values showed a significant improvement during the study. No correlation between RSP dosage (mg/kg) and RSP, 9OH-RSP plasma levels or active moiety resulted. A positive correlation between age and active moiety was observed. A positive correlation between RSP and 9OH-RSP plasma levels was observed. A curvilinear relationship between active moiety and PANSS improvement (%) was observed. Patients with the higher PANSS amelioration showed RSP + 9OH-RSP plasma levels ranging from 15 to 30 ng/mL. RSP seems to be quite an effective drug. It seems, however, difficult to devise appropriate dose schedules and plasma level determination seems to be necessary in some cases.
Subtyping of panic disorder patients with bradycardia
Authors: Massana J. , López Risueño J.A. , Masana G. , Marcos T. , González L. , Otero A.
Published: July 2002

Purpose

Since clinical practice suggests that panic disorder may not be a homogeneous condition, a study was carried out to test the possible existence of different groups or subgroups of panic patients.

Subjects and methods

Thirty-two panic patients (DSM-III-R) underwent lactate challenge in our laboratory and were assessed for heart rate, blood pressure, sweating and Acute Panic Inventory.

Results

During the lactate challenge, patients complaining mainly of ‘cardiorespiratory’ symptoms (N = 12) showed tachycardia and localized sweating. Conversely, patients complaining mainly of ‘pseudoneurological’ symptoms (N = 16) showed bradycardia and generalized sweating. In both groups, Acute Panic Inventory scores were significantly higher during than before the panic attack, but the distribution of the scores was markedly different.

Discussion and Conclusion

The results suggest that panic disorder may be a heterogeneous condition. Implications of these results to other phobic disorders, to Klein’s false suffocation alarm theory and to the ‘extended amygdala model’ are discussed.
Subjective effects of MDMA (‘Ecstasy’) on human sexual function
Authors: Zemishlany Z. , Aizenberg D. , Weizman A.
Published: July 2002

Sexual function following 3,4-Methylenedioxymethamphetamine (MDMA, or ‘Ecstasy’) consumption was subjectively evaluated in 35 healthy recreational users (20 men and 15 women, aged 21–48 years) with regard to four major domains of sexual activity: desire, erection (lubrication in women), orgasm and satisfaction. Desire and satisfaction were moderately to profoundly increased by MDMA in more than 90% of subjects. Orgasm was delayed but perceived as more intense. Erection was impaired in 40% of the men. It seems that MDMA impairs sexual performance, in spite of enhancement of sexual desire and the perception of greater satisfaction.
Survey of patient satisfaction in adult psychiatric outpatient clinics
Authors: Barak Y. , Szor H. , Kimhi R. , Kam E. , Mester R. , Elizur A.
Published: July 2002

A client satisfaction survey was undertaken in two adult psychiatric outpatient clinics. The anonymous self-report questionnaire covering demographic, setting and satisfaction with service variables was endorsed by 203 participants. The mean age of the subjects was 42.5 ± 19 years, with a small majority (58.6%) of females. Overall satisfaction with psychiatric care was high (79.8%). None of the demographic or setting variables correlated significantly with satisfaction. Psychoeducation was significantly correlated with level of satisfaction with services. These findings further emphasize the importance of psychoeducation by service providers in mental health.
The prognostic value of initial EDI scores in anorexia nervosa patients: a prospective follow-up study of 5–10 years
Authors: Bizeul C. , Sadowsky N. , Rigaud D.
Published: July 2002

Aim

To study in a prospective manner the long-term prognostic value of the initially recorded Eating Disorder Inventory (EDI) scores in anorexia nervosa (AN) patients.

Methods

The 5–10-year outcome of 26 consecutive malnourished AN patients was prospectively recorded according to the initial EDI score. We selected only patients with full 6-month assessments for more than 5 years (mean 8.5 years). Eating behavior, quality of life, autonomy and insight capacity were prospectively assessed by the Morgan-Russell scale and a semi-structured interview. At the end of follow-up, 13 patients recovered and the 13 others had a poor outcome.

Results

In monovariate analyses, high initial EDI total score (P < .0007) and high initial scores for perfectionism (P < .001), ineffectiveness (P < .002), interpersonal distrust (P < .004), interoceptive awareness (P < .03) and drive for thinness (P < .05) were significantly associated with a poor prognosis 5–10 years afterward. In a multivariate analysis, only high initial scores for perfectionism (F = 8.43; P = 0.008) and interpersonal distrust (F = 7.46; P = 0.012) were significantly associated with illness severity.

Discussion

High EDI total score and subscales for perfectionism and interpersonal distrust could predict a long-term severe outcome in AN.
The influence of comorbidity on the prevalence of suicidal behaviour
Authors: Lecrubier Y.
Published: July 2002

The existence of mental disorders is almost constant in subjects who try to kill themselves. In addition, a majority of attempters have more than one diagnosis.

This is especially true if Axis II or Axis I subthreshold conditions are taken into account. The existence of a disorder largely explains the association between most socioeconomic variables (sex, marriage, education level) and suicidality. Depressive disorders are the major risk factor, a risk probably linked to a current episode just before the attempt. The association to depressive episodes of an anxiety disorder or the existence of impulsive traits (and/or cluster B personality disorder or drug abuse) increases the risk of acting out. Ideation and attempts show parallel onset curves peaking between the ages of 14 and 20 years, with the existence of a previous DSM III R diagnosis as a strong predictor. The number of associated disorders linearly increases the probability of attempting suicide and is the only significant predictor for lethality. A proper treatment of mental disorders could substantially lower suicidality.
The scientific and ethical basis for placebo-controlled trials in depression and schizophrenia: an FDA perspective
Authors: Laughren T.P.
Published: July 2002

There is a tension between the need for scientifically valid trials of new psychotropic drugs and concern about conducting placebo-controlled trials, the trials psychopharmacologists consider the gold standard trial, when this requires that some patients be denied existing effective therapy. This paper will review the scientific principles supporting the need for placebo-controlled trials in depression and schizophrenia, and will provide preliminary data on failure rates of placebo-controlled trials for these disorders, as illustrations of the application of these principles. Next, the ethical issues pertinent to the conduct of placebo-controlled trials for these two serious psychiatric disorders will be reviewed. Preliminary data on suicides in placebo-controlled depression and schizophrenia trials will be presented to argue for the ethical acceptability of the conduct of placebo-controlled trials in these two conditions.
Violence and its prediction at a psychiatric hospital
Authors: Sjöström N. , Eder D.N. , Malm U. , Beskow J.
Published: July 2002

Aggressive behaviour in psychiatric inpatients was assessed before and after a training course for staff members. The Social Dysfunction Aggression Scale (SDAS) was used to report and assess aggressive behaviour over time, and the Staff Observation Aggression Scale (SOAS) to report and assess single aggressive incidents. In addition, the numbers of nursing staff members who were on sick leave because of injuries in the periods before and after the course were recorded and compared. No statistically significant reduction was found in the number of aggressive patients or in the number of staff members on sick leave. One interesting finding was a lower reporting on the SOAS of perceived aggressive incidents after the training course in comparison with the SDAS reports. Directed verbal aggressiveness and violence towards things were found to be predictors of violence.
Charles Bonnet syndrome and Parkinson’s disease
Authors: Alcántara AG , Valenciano L , Díaz-Ortuño A , Martínez-Navarro ML , Barcía D
Published: July 2002

We present two cases of Charles Bonnet syndrome in comorbidity with Parkinson’s disease. Patients developed visual hallucinosis before starting any antiparkisonian treatment. We briefly discuss the possible physiopathological mechanisms involving low visual acuity and Parkinson’s disease with visual hallucinosis.
Convertible debt: an effective financial instrument to control managerial opportunism
Authors: Isagawa Nobuyuki
Published: July 2002

This paper discusses the superiority of convertible debt to common debt and equity in controlling managerial opportunism. When managers have both empire‐building tendencies and fears of default, over‐investment occurs under low debt levels and under‐investment occurs under high debt levels. Convertible debt, which can adjust firms' debt levels by its convertibility, can restrict over‐investment and help firms to avoid under‐investment at the same time. In a simple setting, we show that well‐designed callable convertible debt has an important role in controlling managerial opportunistic behavior that neither common debt nor equity has.
Increasing awareness and improving the management of heart failure in Europe: the IMPROVEMENT of HF initiative
Authors:   The Study Group on Diagnosis of the Working Group on Heart Failure of The European Society of Cardiology
Published: July 2002

Background:

Previous reports suggest that patients with suspected heart failure are inadequately investigated and that patients who do have heart failure are sub‐optimally treated. Guidelines on the diagnosis and treatment of heart failure have been published by the European Society of Cardiology and provide a framework for the management of heart failure against which to judge current medical practice. Both primary care and hospital physicians are responsible for ensuring appropriate management of patients with heart failure. This programme concentrates on management of heart failure in primary care and is complementary to a similar exercise that will be conducted in 50 European regions (EUROHEART‐CHF).

Aims:

The IMPROVEMENT of HF initiative investigates, in Europe, how primary care physicians perceive heart failure should be diagnosed and treated and whether they perceive that they are provided with adequate support to implement best medical practice. Subsequently, their perceptions are compared to their actual practice by reviewing relevant case notes. The results will be used to recommend changes in practice. A future study is planned to analyse the impact of the initiative.

Methods:

The initiative comprises a research phase and an educational phase. For the research phase, 10 regional centres (to include both urban and rural areas) from each of 14 participating countries have been identified and each region has randomly selected 10 primary healthcare physicians. The primary healthcare physicians are participating in two surveys: a ‘perception’ survey and an ‘actual practice’ survey. For the ‘actual practice’ survey, the physicians are supplying case notes of nine patients who have or are at high risk of having heart failure. The results of these surveys will be used to organise an educational programme.

Conclusion:

This study is expected to provide valuable data on the perceptions of primary care physicians about heart failure, possible deficiencies in the current provision of care and how any deficiencies may be corrected.
Views on Involving a Social Support Person During Labor in Zambian Maternities
Authors: Maimbolwa Margaret C. , Sikazwe Nsama , Yamba Bawa , Diwan Vinod , Ransjö‐Arvidson Anna‐Berit
Published: July 2002

Because social support persons are excluded from modern obstetric care in Zambia, the aim of this study was to explore the views of 84 mothers and 40 health staff about allowing women to be attended by a supportive companion during labor in Zambian urban and rural maternities. Most of the mothers wanted a companion present to provide emotional and practical support. Those who were opposed to the idea had nobody to ask to be with them, or they had relatives who would interfere with the care provided.

All health staff cited hospital policy as the principal reason for prohibiting social support persons from staying with laboring women. They also said that the health staff's role is to care for laboring women, and they worried that social support persons could interfere with their work by giving the laboring women traditional medicine. However, most health staff also said that a social support person could help the laboring women and give her a sense of security.

The study concludes that Zambian maternity staff should be exposed to new research findings about the benefits of social support during childbirth and that this practice should be encouraged in Zambia. Ultimately, it should be the laboring woman who decides whether she wants to bring a social support person to the labor ward.
BEHAVIORAL INTERVENTION FOR URINARY INCONTINENCE IN WOMEN: EVIDENCE FOR PRACTICE
Authors: Sampselle Carolyn M.
Published: July 2002

In the past, clinicians have relied heavily on pharmacologic and surgical interventions for urinary incontinence in women. However, evidence now exists that less invasive, behavioral therapies can be extremely effective in helping women become continent; thus, strategies that involve bladder and pelvic floor muscle training should generally be the first line of treatment. Before behavioral intervention is initiated, it is important to assess for any medical or associated conditions that should be treated first. Bladder training enables women to accommodate increasingly greater volumes of urine in the bladder and gradually to extend the interval between voiding. Pelvic floor muscle training increases awareness of function and strengthens these voluntary muscles, promoting continence.
An Enhanced Johnson–Cook Model for Hot Compressed A356 Aluminum Alloy
Authors: Chen Xiao-Min , Lin Y. C. , Hu Hong-Wei , Luo Shun-Cun , Zhou Xiao-Jie , Huang Yi
Published: August 2020

The isothermal compression experiments with the strain rates of 0.01–10 s−1 and deformation temperature range of 300–420 °C are performed to investigate the hot deformation behavior of A356 aluminum alloy. Also, the complex deformation mechanisms are analyzed. It is found that, as the strain is gradually increased, the flow stress first rises, and then the stable stress appears without a tangible peak. The microstructures exhibit large elongated grains, and only a few small new grains appear under most deformation conditions. It is because the dynamic recovery (DRV) is the dominant softening mechanism. Based on the measured data, both the original Johnson–Cook (O–JC) model and modified Johnson–Cook model (M–JC) are built for the tested aluminum alloy. However, there are different deviations between the experimental and the predicted true stresses by O–JC model and M–JC model. Considering the obvious DRV features, an enhanced Johnson–Cook (EH–JC) model is proposed by introducing the stress–dislocation relation. The accuracy of the EH–JC model is validated because the correlation coefficient between the experimental and predicted results is as high as 0.997, whereas the average absolute relative error is merely 2.84%.