bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of macrophage migration inhibitory factor (MIF) in human skin and its immunohistochemical localization
Authors: Shimizu Tadamichi , Ohkawara Akira , Nishihira Jun , Sakamoto Wataru
Published: April 2003

The presence and tissue localization of macrophage migration inhibitory factor (MIF) in human skin were examined. Reverse transcription‐polymerase chain reaction analysis revealed that MIF mRNA was expressed in both surgically obtained normal human epidermis and primary cultured human keratinocytes. The expression of MIF was further confirmed by Western blot analysis, which demonstrated a single band at about 12.5 kDa using a polyclonal antibody against human recombinant MIF. Immunohistochemical studies showed that MIF existed in human epidermis, especially in the basal layer. The pathophysiological role of MIF in human skin remains undefined; however, the present results indicate that MIF may play an important role in immunity, inflammation and cellular differentiation of epidermal cells.
Bisphosphorylation of cardiac troponin I modulates the Ca2+‐dependent binding of myosin subfragment S1 to reconstituted thin filaments
Authors: Reiffert Silke U. , Jaquet Kornelia , Heilmeyer Ludwig M.G. , Ritchie Marcia D. , Geeves Michael A.
Published: April 2003

We have reconstituted thin filaments comprising pyrene‐labelled actin (pyr‐actin), tropomyosin (Tm) and cardiac troponin (cTn). cTn was isolated in two defined phosphorylation states; completely dephosphorylated on all subunits and with only the cTnI subunit bisphosphorylated. The thin filament was saturated with cTn at a pyr‐actin/Tm/cTn ratio of 7:1:1. The calcium‐dependent binding of S1 to thin filaments was measured in a stopped‐flow spectrophotometer and the dependence of the observed rate constant on [Ca2+] fitted to the Hill equation. The only significant difference between the two phosphorylation states of the filaments was a 0.36 decrease in the pCa50 on bisphosphorylation.
Rice gibberellin‐binding phosphoprotein structurally related to ribulose‐1,5‐bisphosphate carboxylase/oxygenase activase
Authors: Komatsu Setsuko , Masuda Taizo , Hirano Hisashi
Published: April 2003

A gibberellin A (GA)‐binding protein was identified from rice (Oryza sativa L.) leaves by a ligand‐binding assay. The dissociation constant of GA‐binding protein and GA complex was about 100 nM. This protein has a relative molecular mass of 47 000 and an isoelectric point of 5.1. The partial amino acid sequence of the protein was determined for 54 residues from both the N‐terminal and internal regions. A sequence homology search indicated that the amino acid sequence of GA‐binding protein was homologous to that of the ribulose‐1,5‐bisphosphate carboxylase/oxygenase activase from barley, Arabidopsis, spinach and Chlamydomonas. The GA‐binding protein was immunologically detected in two polypeptides in the protein extract from leaves. The GA‐binding protein identified was phosphorylated with Ca2+, Mg2+ and ATP in the leaf protein extracts of rice grown in the presence of exogenous GA.
Inhibitors of permeability transition interfere with the disruption of the mitochondrial transmembrane potential during apoptosis
Authors: Zamzami Naoufal , Marchetti Philippe , Castedo Maria , Hirsch Tamara , Susin Santos A. , Masse Benjamin , Kroemer Guido
Published: April 2003

In a number of experimental systems, the early stage of the apoptotic process, i.e. the stage which precedes nuclear disintegration, is characterized by the breakdown of the inner mitochondrial transmembrane potential (ΔΨ
m). Here we address the question as to whether mitochondrial permeability transition (PT) pores may account for the ΔΨ
m dissipation in lymphocyte apoptosis. Drugs known for their PT‐inhibitory potential (bongkrekic acid, cyclosporin A, and the non‐immunosuppressive cyclosporin A analogue N‐methyl‐Val‐4‐cyclosporin A) are capable of preventing the apoptotic ΔΨ
m disruption. Moreover, pharmacological modulation of PT‐mediated ΔΨ
m dissipation can prevent apoptosis. Thus, while suppressing the ΔΨ
m disruption, bongkrekic acid also inhibits the apoptotic chromatinolysis. In conclusion, these data are compatible with the hypothesis that apoptotic ΔΨ
m disruption is mediated by the formation of PT pores and that PT‐mediated ΔΨ
m disruption is a critical event of the apoptotic cascade.
The 21‐residue surfactant peptide (LysLeu4)4Lys(KL4) is a transmembrane α‐helix with a mixed nonpolar/polar surface
Authors: Gustafsson Magnus , Vandenbussche Guy , Curstedt Tore , Ruysschaert Jean-Marie , Johansson Jan
Published: April 2003

The 21‐residue peptide KLLLLKLLLLKLLLLKLLLLK (KL4) has been synthesized and analyzed regarding its secondary structure and orientation in lipid environments. Fourier transform infrared and circular dichroism spectroscopy shows that the peptide exhibits approximately 80% α‐helical content both in dodecylphosphocholine micelles and in 1,2‐dipalmitoyl‐glycero‐3‐phosphocholine (DPPC)/phosphatidylglycerol (PG) 7:3 (w/w) bilayers. The positively charged lysine residues are evenly distributed over the entire, otherwise nonpolar, circumference of the helix. This is in sharp contrast to the uneven distribution of polar and nonpolar residues in amphipathic helices. Fourier transform infrared spectroscopy of the peptide inserted in DPPC/PG bilayers shows that the helical axis is oriented parallel to the lipid acyl chains. These data do not support a previous hypothesis that the KL4 peptide interacts with peripheral parts of a phospholipid monolayer and mimics the pulmonary surfactant protein SP‐B, which is composed of several amphipathic α‐helices. KL4 accelerates the spreading of phospholipid mixtures at an air/water interface but does so less efficiently than other transmembranous helical polypeptides studied.
Is there an unidentified defence mechanism against infection in human plasma?
Authors: Aejmelaeus R. , Metsä-Ketelä T. , Laippala P. , Alho H.
Published: April 2003

The total peroxyl radical scavenging capacity (TRAP) of human plasma was measured from pneumonia patients and controls. TRAP and its main components, ascorbic acid, alpha‐tocopherol, uric acid or protein thiol groups, were unaltered, but the concentration of unidentified antioxidants in pneumonia patients was significantly reduced. Our results indicate that human plasma may contain so far unidentified antioxidants depleted in infection.
Transduction signals induced in rat brain cortex astrocytes by the HIV‐1 gp120 glycoprotein
Authors: Codazzi F. , Racchetti G. , Grohovaz F. , Meldolesi J.
Published: April 2003

Cultures of rat brain cortex astrocytes were exposed to 10−10−10−9 M of the HIV‐1 envelope glycoprotein, gp120. No specific binding was revealed by the iodinated protein, suggesting expression of only a few sites onto the cells. In contrast, two transduction signals were rapidly induced by gp120: increased tyrosine phosphorylation of a ∼56 kDa protein and increased [Ca2+]i. This latter effect, present in of the investigated astrocytes, consisted in: discrete or biphasic peaks; slowly rising plateaus; and various types of oscillations. Moreover, in apparently unresponsive cells [Ca2+]i rose slowly (45 min) to double the resting levels. Rat brain cortex astrocytes thus appear highly sensitive to gp120. The induced array of signals might contribute to neurotoxicity during HIV infection.
Catalytic activities of hammerhead ribozymes with a triterpenoid linker instead of stem/loop II
Authors: Sugiyama Hiroshi , Hatano Ken , Saito Isao , Amontov Sergei , Taira Kazunari
Published: April 2003

A minizyme is a hammerhead ribozyme with short oligonucleotide linkers instead of stem/loop II. In a previous study we demonstrated that a minizyme with high‐level activity forms a dimeric structure with a common stem II (Amontov and Taira, J. Am. Chem. Soc., 118 (1996) 1624–1628). As a continuation of this study, we recently examined whether a short oligonucleotide linker at stem/loop II could be replaced by a triterpenoid linker and whether the resulting minizymes with bulky hydrophobic groups would form dimeric structures. In contrast to the minizyme with high‐level activity that we characterized in the previous study, minizymes that contained a triterpenoid group had low cleavage activities. The nature of the dependence of the activity on the concentration of ribozyme revealed that these minizymes with a triterpenoid group do not form dimeric structures. Thus, the low activities of these structures can be attributed to their failure to form dimers.
The p15 matrix protein of moloney murine leukemia virus is a phosphotyrosine protein
Authors: Seri Iftach , Priel Esther
Published: April 2003

Retroviruses have been etiologically implicated with leukemia in humans and animals. Understanding the virus life cycle, the proteins and enzymes involved in its replication, is essential for developing potent anti‐viral drugs. Phosphorylation of retroviral proteins may alter their shape in such a way as to increase or inhibit their biological activities and thus influence the replication and pathogenic potential of the retroviruses. In our previous work, we demonstrated that non‐cytotoxic doses of tyrphostins (protein tyrosine kinase blockers) inhibit moloney murine leukemia virus (Mo‐MuLV) replication in acutely and chronically infected cells. In an attempt to understand their mode of action as anti‐MoMuLV drugs, we examined the possibility that a viral protein is phosphorylated in tyrosine. Indeed, in our present work, we show that the p15 matrix protein (MA) of MoMuLV is a phosphotyrosine protein and is the only viral protein which is phosphorylated on tyrosine. Moreover, treatment of Mo‐MuLV/NIH/ 3T3 chronically infected cells with tyrphostin AG‐555 specifically inhibits the synthesis of p15 and other viral proteins but does not affect the synthesis of cellular proteins. Our results suggest that tyrosine phosphorylation of p15 MA protein may play a pivotal role in Mo‐MuLV replication.
Expression of ribonucleolytic toxin restrictocin in Escherichia coli: purification and characterization
Authors: Rathore Dharmendar , Nayak Surendra K. , Batra Janendra K.
Published: April 2003

Restrictocin is a toxin produced by the fungus Aspergillus restrictus. The DNA coding for restrictocin was isolated from the host by polymerase chain reaction and cloned into a T7 promoter‐based expression vector. The protein was overproduced in Escherichia coli and remained insoluble in the cell in the form of inclusion bodies. Recombinant restrictocin was purified in large amounts, by a simple denaturation‐renaturation protocol involving a redox system, with typical yields of 45 mg/l of original culture. Restrictocin could be secreted into the bacterial medium using ompA, pelB and LTB signal sequences. Among the three signal sequences, ompA was found to be the most efficient in secreting the recombinant protein. The protein secreted into the extracellular medium was properly processed as evident by the amino‐terminal sequencing. Recombinant restrictocin was readily purified to homogeneity from either the medium or inclusion bodies by simple chromatographic techniques and was found to be functionally as active as the native fungal protein in inhibiting the eukaryotic translation.
Site‐directed mutagenesis of Flaveria trinervia phosphoenolpyruvate carboxylase: Arg450 and Arg767 are essential for catalytic activity and Lys829 affects substrate binding
Authors: Gao Y. , Woo K.C.
Published: April 2003

Phosphoenolpyruvate carboxylases (PEPC) of all known sequences contain 11 conserved arginine and two lysine residues located in highly conservative regions. Previous chemical modifications show that arginine and lysine residues are essential for catalytic activity. Three conserved residues, Arg450, Arg767 and Lys829, in PEPC of Flaveria trinervia were converted to glycine. All three mutant PEPC proteins were similarly expressed in Escherichia coli. However, mutant Gly450 and Gly767 PEPCs had no catalytic activity and Gly829 PEPC showed increased K

m
for PEP and Mg2+. It seems that Arg450 and Arg767 are essential for PEPC function while Lys829 might be associated with PEP and/or Mg2+ binding domain.
The effect of the length of the 3′‐untranslated region on expression in plants
Authors: Tanguay Robert L. , Gallie Daniel R.
Published: April 2003

The effect of increasing the length of the 3′‐untranslated region (UTR) on expression of luciferase mRNA was examined in transiently transfected carrot protoplasts. The effect of the 3′‐UTR on both poly(A)− and poly(A)+ mRNA was examined. A nested set of constructs in which the 3′‐UTR increased from 4 to 104 bases was generated by the introduction and reiteration of a 20 base sequence downstream of the luc stop codon. For poly(A)− mRNA, there was a consistent increase in expression when the length of the 3′‐UTR was increased from 4 to 104 bases. For poly(A)+ mRNA, expression increased 18‐fold when the length of the 3′‐UTR was increased from 7 to 27 bases. Further increases in the length of the 3′‐UTR did not affect expression. The increase in expression was largely due to an increase in translational efficiency. These data suggest that the length of the 3′‐UTR plays an important role in determining the extent to which a poly(A) tall can stimulate the translation of an mRNA.
Expression and pharmacological characterization of the human μ‐opioid receptor in the methylotrophic yeast Pichia pastoris
Authors: Talmont Franck , Sidobre Stéphane , Demange Pascal , Milon Alain , Emorine Laurent J.
Published: April 2003

The human μ‐opioid receptor cDNA from which the 32 amino‐terminal codons were substituted by the Saccharomyces cerevisiae α‐mating factor signal sequence has been expressed in the methylotrophic yeast Pichia pastoris using the host promoter of the alcohol oxidase‐1 gene. Cell membranes exhibited specific and saturable binding of the opioid antagonist [3H]diprenorphine (K
d = 0.2 nM and B
max = 400 fmol/mg protein or 800 sites/cell). Competition studies with non‐selective, and μ‐, δ‐ and κ‐selective opioid agonists and antagonists revealed a typical μ‐opioid receptor binding profile, suggesting proper folding of the protein in yeast membranes.
Hyperactivity of cathepsin B and other lysosomal enzymes in fibroblasts exposed to azithromycin, a dicationic macrolide antibiotic with exceptional tissue accumulation
Authors: Gerbaux Cécile , Van Bambeke Françoise , Montenez Jean-Pierre , Piret Jocelyne , Morlighem Grégory , Tulkens Paul M.
Published: April 2003

Azithromycin accumulates in lysosomes where it causes phospholipidosis. In homogenates prepared by sonication of fibroblasts incubated for 3 days with azithromycin (66 μM), the activities of sulfatase A, phospholipase A1, N‐acetyl‐β‐hexosaminidase and cathepsin B increased from 180 to 330%, but not those of 3 non‐lysosomal enzymes. The level of cathepsin B mRNA was unaffected. The hyperactivity induced by azithromycin is non‐reversible upon drug withdrawal, prevented by coincubation with cycloheximide, affects the V
max but not the K
m, and is not reproduced with gentamicin, another drug also causing lysosomal phospholipidosis. The data therefore suggest that azithromycin increases the level of lysosomal enzymes by a mechanism distinct from the stimulation of gene expression but requiring protein synthesis, and is not in direct relation to the lysosomal phospholipidosis.
BS‐RNase tetramers: An example of domain‐swapped oligomers
Authors: Adinolfi Salvatore , Piccoli Renata , Sica Filomena , Mazzarella Lelio
Published: April 2003

In the ribonuclease superfamily, dimericity is a unique feature of bovine seminal RNase (BS‐RNase). In about two‐thirds of native BS‐RNase molecules, the two subunits interchange their N‐terminal tails, thus generating domain‐swapped dimers (MxM), which mostly responsible for enzyme biological activities and allostericity. Higher molecular weight BS‐RNase oligomers can also be prepared [Libonati, M. (1969) Ital. J. Biochem. 18, 407–417.]. This paper reports on BS‐RNase tetrameric derivatives which were isolated and enzymatically characterized. The data collected and the analysis of the crystal packing of MxM dimers suggested a structural model for tetramer assembly, in which the four subunits are enchained by multiple domain‐swapping events.
Bandeiraea (Griffonia) simplicifolia lectin‐I, isolectin A4, reacting with Tn (GalNAαl → Ser/Thr or galabiose (Galα1 → 4Gal) containing ligands
Authors: Albert M. Wu , June H. Wu , Shuh-Chyung Song  , Kabat Elvin A.
Published: April 2003

Bandeiraea (Griffonia) simplicifolia lectin‐I, isolectin A4(GS I‐A4) reacting with the Tn(GalNAcα1 → Ser/Thr) sequence or human blood group P
k
active dissacharide (E, Galα1 → 4Gal, galabiose) was studied by quantitative precipitin (QPA) and precipitin‐inhibition assays. When human blood group P1 or Tn active glycoproteins were tested by QPA, GS IA4 reacted strongly with both the Tn active glycoproteins purified from asialo porcine, ovine and armadillo submandibular glands and a P1 active glycoprotein isolated from sheep hydatid fluid. They precipitated over 80% of the lectin nitrogen added. The asialo porcine salivary glycoprotein‐GS I‐A4 interaction was inhibited by both Tn containing glycopeptides and Galα1 → 4Gal indicating that GS I‐A4 not only reacts with human blood group A(GalNAcα1 → 3Gal) and B(Galα1 → 3Gal) active dissacharides, but also recognizes the Tn sequence and the E(Galα1 → 4Gal) ligand. From these results, the carbohydrate specificity of GS I‐A4 can be defined as A, Tn ≥ B and E.
Primary structure of a putative serine protease specific for IGF‐binding proteins
Authors: Zumbrunn Jürg , Trueb Beat
Published: April 2003

From a subtracted cDNA library we have isolated a cDNA clone coding for a novel transformation‐sensitive protein which is expressed by human fibroblasts, but not by their matched SV40 transformed counterparts. This protein has a molecular mass of 51 kDa and is highly related to the HtrA family of serine proteases from bacteria. At the N‐terminal end, it contains an IGF‐binding domain which may modulate the activity of the associated serine protease. Our data are consistent with the assumption that the novel protein represents one of the proteases that regulate the availability of IGFs by cleaving IGF‐binding proteins.
Structure and organ specificity of an anionic peroxidase from Arabidopsis thaliana cell suspension culture
Authors: Østergaard Lars , Abelskov Anne Katrine , Mattsson Ole , Welinder Karen G.
Published: April 2003

The predominant peroxidase (pl 3.5) (E.C. 1.11.1.7) of an Arabidopsis thaliana cell suspension culture was purified and partially sequenced. Oligonucleotides were designed and a specific probe was obtained. A cDNA clone was isolated from an Arabidopsis cell suspension cDNA library and completely sequenced. The cDNA clone comprised 1194 bp and encodes a 30 residue signal peptide and a 305 residue mature protein (M

r
31 966). The sequence of the mature protein is 95% identical to the well‐characterized horseradish peroxidase HRP A2 and has therefore been designated ATP A2. Three introns at positions identical to those found in Arabidopsis and horseradish genes encoding cationic peroxidases were identified. RT‐PCR analysis revealed root‐specific expression.
Identification of the quinone cofactor in a lysyl oxidase from Pichia pastoris
Authors: Dove Joanne E. , Smith Alan J. , Kuchar Jason , Brown Doreen E. , Dooley David M. , Klinman Judith P.
Published: April 2003

A copper amine oxidase from Pichia pastoris is the only known non‐mammalian lysyl oxidase [Tur, S.S. and Lerch, K. (1988) FEBS Lett. 238, 74–76]. Recently, the cofactor in mammalian lysyl oxidase has been identified as a novel lysine tyrosylquinone moiety [Wang, S.X., Mure, M., Medzihradszky, K.F., Burlingame, A.L., Brown, D.E., Dooley, D.M., Smith, A.J., Kagan, H.M. and Klinman, J.P. (1996) Science 273, 1078–1082]. In order to identify the cofactor in P. pastoris lysyl oxidase, we have isolated the phenylhydrazone‐derivative of the active‐site peptide. This peptide has the active‐site sequence conserved among topa quinone containing amine oxidases. The resonance Raman spectra of the phenylhydrazone derivatives of the enzyme, active‐site peptide, and a topa quinone model compound are essentially identical. Collectively, these results establish that P. pastoris lysyl oxidase is a topa quinone enzyme.
Ultraviolet resonance Raman evidence for the absence of tyrosinate in octopus rhodopsin and the participation of Trp residues in the transition to acid metarhodopsin
Authors: Hashimoto Shinji , Takeuchi Hideo , Nakagawa Masashi , Tsuda Motoyuki
Published: April 2003

The ultraviolet (244 nm) resonance Raman spectra of octopus rhodopsin and its photoproduct, acid metarhodopsin, do not give any evidence for a tyrosinate. This finding excludes the possibility that Tyr‐112 serves as the counter anion to the protonated Schiff base as does Glu‐113 in bovine rhodopsin. Upon photoconversion from rhodopsin to acid metarhodopsin, Trp and Tyr Raman bands decrease in intensity and concomitantly a Trp band shifts in frequency. The changes of Trp Raman bands are ascribed to changes in hydrophobic interactions and conformation, suggesting a possible role of Trp in the photoconversion process of octopus rhodopsin.
Oxidized low‐density lipoprotein induces the production of interleukin‐8 by endothelial cells
Authors: Claise Catherine , Edeas Marvin , Chalas Jacqueline , Cockx Anélie , Abella Annie , Capel Liliane , Lindenbaum Albert
Published: April 2003

The concentration of interleukin‐8 (IL‐8) and RANTES was measured in culture supernatants of human EA.hy 926 endothelial cells incubated with oxidized low‐density lipoproteins (LDL). Oxidized LDL induced a 3‐fold increase in IL‐8 production (p < 0.01), whereas RANTES was not detected. Native LDL did not stimulate IL‐8 production. IL‐8 production in oxidized‐LDL‐treated cells was mediated by reactive oxygen species, as it was partially inhibited by catalase and completely inhibited by glutathione peroxidase and N‐acetylcysteine (p < 0.01).
Mutants of Escherichia coli lacking disulphide oxdoreductases DsbA and DsbB cannot synthesise an exogenous monohaem c‐type cytochrome except in the presence of disulphide compounds
Authors: Sambongi Yoshihiro , Ferguson Stuart J.
Published: April 2003

Absence through mutation of two proteins involved in periplasmic disulphide bond formation, DsbA and DsbB, results in failure of anaerobically grown Escherichia coli to synthesise the holo forms of either its endogenous c‐type cytochrome nitrite reductase or exogenous cytochrome c
550 from Paracoccus denitrificans. The synthesis of both cytochromes can be restored to the mutants by inclusion in the growth media of compounds containing disulphide bonds, e.g., the oxidised form of glutathione. The results suggest that the attachment of haem to the CXXCH motif of a periplasmic c‐type cytochrome may be preceeded by the formation of one or more intra‐ or intermolecular disulphide bonds involving the cysteine residues of this motif.
GnRH analogues as an adjuvant therapy for ovarian cancer patients
Authors: Rzepka‐Górska I. , Chudecka‐Glaz A. , Kosmider M. , Malecha J.
Published: April 2003

Objectives: Lowering gonadotropin levels with gonadotropin‐releasing hormone (GnRH) analogues in patients with ovarian cancer remains open to debate. The aim of this study was to assess the results of treatment in stage III and stage IV ovarian cancer patients who had surgery supplemented with chemotherapy, radiotherapy, and GnRH analogues. Gonadotropin levels were monitored during treatment. Methods: The study group comprised 69 patients aged 27–70 years, stratified according to the type of treatment. The overall disease‐free, 5‐year survival rates and the frequency of remissions were analyzed. Hormonal tests [follicle‐stimulating hormone (FSH) and luteinizing hormone (LH)] were performed in 58 patients. Associations were checked between gonadotropin levels, clinical findings, and survival. The results were statistically compared. Results: Statistically significant differences were noted when chemotherapy was supplemented with GnRH analogues and/or radiotherapy. Administration of GnRH analogues resulted in significantly lower levels of LH than of FSH. Levels of FSH were significantly lower in patients surviving at least 5 years or in complete remission at the time of this study. Conclusions: Combined therapy can produce favorable results in late‐stage ovarian cancer, and GnRH analogues have an important role in treatment strategy.
The Vecchietti procedure for surgical treatment of vaginal agenesis: comparison of laparoscopy and laparotomy
Authors: Borruto F , Chasen S.T , Chervenak F.A , Fedele L
Published: April 2003

Objective: Our goal was to describe the outcomes of women with vaginal agenesis who had surgical creation of a neovagina using the Vecchietti technique over a 20‐year period. We also sought to determine whether the laparoscopic approach would result in similar outcomes as laparotomy. Method: Retrospective analysis of 76 women with vaginal agenesis treated at the University of Verona Hospital between 1976 and 1996 with the Vecchietti procedure. Operative and postoperative records were reviewed, and sexual histories were obtained. Data were analyzed based on surgical approach and postoperative sexual satisfaction. Continuous data were analyzed with student's t‐test, and categoric data were analyzed using Fisher's exact test. Result: Those who underwent the Vecchietti procedure with a laparoscopic approach (N=7) had similar complication rates (0% vs. 13.0%, P=0.59) and postoperative neovaginal depth (74.9 mm vs. 73.7 mm, P=0.93) as those with laparotomy (N=69). Similar proportions of women reported inadequate vaginal lubrication (28.6% vs. 17.4%, P=0.61) and sexual satisfaction (100% vs. 78.3%) in the laparoscopy and laparotomy groups as well. Operative complications, neovaginal depth, or degree of lubrication were not good predictors of sexual satisfaction. Conclusion: Outcomes in those women who underwent the Vecchietti technique via the laparoscopic approach are comparable to those who underwent laparotomy.
Biophysical profile score in late pregnancy and timing of delivery
Authors: Archibong E.I
Published: April 2003

Objective: To determine if the Biophysical Profile Score (BPS) as a screening procedure on patients without antenatal care (unbooked patients), seen in late pregnancy, is of value in providing an insight into the mode of delivery and fetal outcome. Design: Prospective case study of pregnant mothers, data collection and analysis over 2 years at Abha Maternity Hospital, Saudi Arabia. Subjects: Unbooked patients with abnormal BPS (Group I), and patients with normal BPS (Group II) used as control subjects, delivered in the hospital from January 1996 through December 1997. Results: The number of normal deliveries was significantly higher (P<0.01) in the control group than in the study group patients. Cesarean section rate was significantly higher in the study group than in the control group (P<0.01, OR=4.48). There was a significant increase in the number of asphyxiated and meconium aspirated babies in the study group than in the control group. Neonates that needed mechanical ventilation were significantly higher in the study group than in the control group (P<0.01, OR=10.38). Conclusion: These findings suggest that abnormal BPS is invaluable in effecting delivery, particularly in women without antenatal care, who present in late pregnancy to an obstetric unit. Patients with abnormal BPS are four times more likely to be delivered by cesarean section than those with normal BPS.
Paleomagnetic correlations between Scandinavian Ice-Sheet fluctuations and Greenland Dansgaard–Oeschger events, 45,000–25,000 yr B.P.
Authors: Mangerud Jan , Løvlie Reidar , Gulliksen Steinar , Hufthammer Anne-Karin , Larsen Eiliv , Valen Vidar
Published: April 2003

Two paleomagnetic excursions, the Skjong correlated with the Laschamp (about 41,000 GISP2 yr B.P.) and the Valderhaug correlated with the Mono Lake (about 34,000 GISP2 yr B.P.), have been identified in stratigraphic superposition in laminated clay deposited in ice-dammed lakes in three large caves in western Norway. During both periods the margin of the Scandinavian Ice Sheet advanced and reached the continental shelf beyond the outermost coastline. The mild, 4000-yr-long Ålesund interstade, when the coast and probably much of the hinterland were ice-free, separated the two glacial advances. The two paleomagnetic excursions have also been indirectly identified as increased fluxes of36Cl and10Be in the GRIP ice core, Greenland. This article presents a correlation between ice-margin fluctuations of the Scandinavian Ice Sheet and the stratigraphy of GRIP/GISP cores, using the paleomagnetic excursions and the36Cl and10Be peaks and thus circumventing the application of different dates or time scales. Some of the fluctuations of the Scandinavian Ice Sheet were of the “Allerød/Younger Dryas type” in the sense that its margin retreated during mild interstades on Greenland and readvanced during cold stades. However, some fluctuations were apparently not in phase with the Greenland climate.
Chronology of glacial Lake Agassiz meltwater routed to the Gulf of Mexico
Authors: Fisher Timothy G.
Published: April 2003

Sediment cores with new radiocarbon dates from the southern outlet of glacial Lake Agassiz indicate that meltwater delivery to the Mississippi valley was disrupted at 10,800 14C yr B.P. and the outlet was abandoned by 9400 14C yr B.P. These findings confirm the timing of generally accepted terminations of the Lockhart and Emerson Phases of Lake Agassiz. Additionally, the radiocarbon chronology indicates that the spillway was fully formed by 10,800 14C yr B.P. and that the occupancy in late-Emerson time was likely short-lived with minimal spillway erosion.
Biotite composition as a tool for the identification of Quaternary tephra beds
Authors: Shane Phil , Smith Victoria , Nairn Ian
Published: April 2003

Stratigraphically important Quaternary rhyolitic tephra deposits that erupted from the Okataina and Taupo volcanic centers in New Zealand can be geochemically identified using the FeO and MgO contents of their biotite phenocrysts. The FeO/MgO ratio in biotite does not correlate with FeO/MgO in the coexisting glass phase so that tephra beds with similar glass compositions can be discriminated by their different biotite compositions. Some individual tephra deposits display sequential changes in biotite composition that allow separate phases of the eruption to be identified, greatly increasing the potential precision for correlation. In addition, devitrified lavas that are unsuitable for glass analysis can be correlated to coeval tephra deposits by their biotite compositions. Biotite is common in high-K2O (>4 wt%) tephra beds and is widely dispersed in ash plumes because of its platy form, thus making it important in correlation studies.
Contagion of suicidal symptoms as a function of assortative relating and shared relationship stress in college roommates
Authors: Joiner Thomas E.
Published: April 2003

Vulnerable people may become socially contiguous via assortative relating, and thus simultaneously susceptible to the effects of shared life stress. To test this possibility, 138 undergraduates and their roommates completed questionnaires on suicidality and stress. Consistent with an assortative relating process, roommates who chose to room together were more similar on a suicide index than were roommates who were assigned to room together. Stress in the roommate relationship amplified similarity in roommates’ suicide levels. Results were consistent with the view that shared stress simultaneously affects the suicidality of people whose contiguity was pre‐arranged by an assortative relating process.
A reliable externally fixated murine femoral fracture model that accounts for variation in movement between animals
Authors: Connolly Chris K. , Li Gang , Bunn Jonathan R. , Mushipe Moses , Dickson Glenn R. , Marsh David R.
Published: April 2003

Fifty‐two CFLP mice had an open femoral diaphyseal osteotomy held in compression by a four‐pin external fixator. The movement of 34 of the mice in their cages was quantified before and after operation, until sacrifice at 4, 8, 16 or 24 days. Thirty‐three specimens underwent histomorphometric analysis and 19 specimens underwent torsional stiffness measurement. The expected combination of intramembranous and endochondral bone formation was observed, and the model was shown to be reliable in that variation in the histological parameters of healing was small between animals at the same time point, compared to the variation between time‐points. There was surprisingly large individual variation in the amount of animal movement about the cage, which correlated with both histomorphometric and mechanical measures of healing. Animals that moved more had larger external calluses containing more cartilage and demonstrated lower torsional stiffness at the same time point. Assuming that movement of the whole animal predicts, at least to some extent, movement at the fracture site, this correlation is what would be expected in a model that involves similar processes to those in human fracture healing. Models such as this, employed to determine the effect of experimental interventions, will yield more information if the natural variation in animal motion is measured and included in the analysis. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Skeletal homeostasis in tissue‐engineered bone
Authors: Schneider Abraham , Taboas Juan M. , McCauley Laurie K. , Krebsbach Paul H.
Published: April 2003

Tissue‐engineering strategies to stimulate bone regeneration may offer an alternative approach to conventional orthopaedic and maxillofacial surgical therapies. Over the last decade, significant advances have been accomplished in developing biomimetic matrices, growth factors, cell transplantation and gene delivery therapeutics to support new bone growth. However, it is not known if tissue‐engineered bone recapitulates the biology of normal skeletal tissue in response to physiologic cues. Here, we report that bone formed by the differentiation of transplanted murine bone marrow stromal cells (BMSCs) responds to a systemically delivered calciotropic hormone. Ectopic ossicles in mice exposed to catabolic doses of parathyroid hormone (PTH) had increased numbers of tartrate‐resistant acid phosphatase (TRAP)‐positive osteoclasts as compared to control mice. In contrast, treatment with anabolic doses of PTH promoted a marked increase in trabecular bone mass as analyzed by microcomputed tomography and histomorphometry. Our findings demonstrate that bone formed from transplanted BMSCs is responsive to normal physiologic signals, and can be augmented by the addition of a systemic anabolic agent. Because multiple and distinct ossicles can be generated in a single animal, this versatile system may be used to: (a) elucidate cellular/molecular mechanisms in bone regeneration; (b) study cell‐to‐cell interactions in the bone marrow microenvironment in health and disease; and (c) evaluate the efficacy of osteotropic agents that modulate bone turnover in vivo. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Fibronectin metabolism of cartilage explants in response to the frequency of intermittent loading
Authors: Wolf Amela , Raiss Ruth X. , Steinmeyer Jürgen
Published: April 2003

Chondrocytes within articular cartilage experience complete unloading between loading cycles and in so doing utilize mechanical signals to regulate their own metabolic activities. A strongly elevated fibronectin content is an early feature in osteoarthritis and appears to be related to increases in both the synthesis and retention of this glycoprotein. The objectives of this study were to investigate systematically whether the frequency of intermittently applied cyclic mechanical loading of cartilage explants alters the biosynthesis and retention of fibronectin, and to assess whether it is possible to induce in vitro osteoarthritic‐like changes of this metabolic parameter by mechanical means over a period of 6 days. Cartilage plugs consisting of viability‐checked chondrocytes were exposed to sinusoidal cyclic compressive pressure alterations of 0.1, 0.5 or 1.0 Hz frequency with a peak stress of 0.5 MPa for a period of 5, 10 or 20 s, followed by an unloading period of 10, 100 or 1000 s, and compared to unloaded reference plugs from the same joint and topographic origin. The incorporation of radioactive precursor into fibronectin during the last 18 h, the content of fibronectin, and the viability of chondrocytes were determined. Our data revealed that (a) the fibronectin synthesis was selectively, but non‐linearly affected by the frequency of intermittent loads applied (as defined by the frequency of the applied force, the duration of the loading cycle and the duration of the force‐free period between each loading cycle), and that (b) the retention of endogenous fibronectin and proteins within loaded cartilage explants is strongly elevated. These data support our hypothesis that the mechanical factor “frequency of intermittent loading” seems to be the crucial mechanical parameter controlling the metabolism of chondrocytes. The effect of the frequency of intermittent loading cannot be described by a simple statistical correlation, so that no specific predictions are possible. However, our results imply that distinct loading protocols have been established that can induce alterations of the fibronectin metabolism similar to those observed in human and animal osteoarthritis. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Eurasianism: Past and Present
Authors: Shlapentokh Dmitry V.
Published: April 2003

Eurasianism is a quasi-political and intellectual movement. Its representatives state that Russia is a unique blend of Slavic and non-Slavic cultures and ethnic groups. Eurasianists also emphasize the corporate nature of the Russian state which makes it quite different from the West. Eurasianism emerged in the 1920s as an anti-Bolshevik movement. Yet, through its evolution, Eurasianism has become closer and closer to the Soviet brand of Marxism. In its blending of Marxism with nationalism, Eurasianism was one of the precursors to the present-day ideology of post-Soviet Russia.
Documented Homicides and Excess Deaths: New Insights into the Scale Killing in the USSR During the 1930S
Authors: Rosefielde Steven
Published: April 2003

Getty, Rittersporn and Zemskov recently claimed that no more than 2 million people could have perished from collectivization, famine, execution, terror, and forced labor in the USSR during the 1930s. Prior demographic confirmation of this estimate was provided by Anderson and Silver who contended that killings were unlikely to exceed a few million and could not be more than 4.8 million victims. This essay disproves both these contentions by introducing new demographic evidence proving that Stalin killed at least 5.2 million Soviet citizens 1927-1938, with a best estimate in the vicinity of 10 million.
Reducing Genital Tract Trauma at Birth: Launching a Clinical Trial in Midwifery
Authors: Albers Leah L.
Published: April 2003

Genital tract trauma is a common outcome of vaginal birth, and can cause short‐term and long‐term problems for new mothers. Preventive measures have not been fully explicated. Midwives use a variety of hand maneuvers late in the second stage of labor, in the belief that genital trauma can be reduced. However, none of these care measures have been rigorously tested to determine if they are effective. A midwifery practice offers an ideal setting to study the relationship of hand techniques by the birth attendant to reduction of genital tract trauma.
One‐to‐one Midwifery: Restoring the “with Woman” Relationship in Midwifery
Authors: Page Lesley
Published: April 2003

One‐to‐One Midwifery, a model of care developed in the United Kingdom, provides a continuous and personal relationship between each woman and her midwife. The organization of care and the outcomes are relevant to midwifery policy in all industrialized countries. One‐to‐One Midwifery is not solo practice. An important principle of the organization of the practice is to enable individual midwives to take time off and to provide supportive structures for the midwives. Here the implications of One‐to‐One Midwifery for childbearing women and their families, and the midwives involved, are explored. The One‐to‐One Midwifery model has particular relevance for Canada because it is very similar to the model of practice being developed in at least two provinces. It may also be of importance in the United States, particularly for midwives working shifts in hospitals who may want to develop a system that allows them to provide continuity to the women they serve.
Pharmacological discrimination between muscarinic receptor signal transduction cascades with bethanechol chloride
Authors: Liu Liwang , Rittenhouse Ann R
Published: April 2003

Muscarinic agonist specificity is limited, making it difficult to match receptor subtypes with signal transduction cascades that mediate ion channel modulation. We have characterized the inhibitory effects of two muscarinic agonists, oxotremorine‐M (Oxo‐M) and bethanechol chloride (BeCh), on Ca2+ currents in neonatal rat superior cervical ganglion neurons.

Oxo‐M‐mediated (10 μM) inhibition occurred via two signaling pathways. The first pathway inhibited whole cell peak currents, consisting primarily of N‐type current, but not FPL 64176‐induced, long‐lasting tail currents, comprised entirely of L‐type current. Inhibited currents displayed slowed activation kinetics and voltage dependence, characteristics of membrane‐delimited inhibition. Current inhibition was blocked by the selective M2 receptor antagonist, methoctramine (METH; 100 nM), or following pertussis toxin (PTX) pretreatment.

Activation of the second pathway inhibited both peak and long‐lasting tail currents. This pathway was voltage‐independent, PTX‐insensitive, but sensitive to internal Ca2+ chelator concentration. Muscarinic toxin 7 (MT‐7, 100 nM), an irreversible M1 receptor antagonist, eliminated this inhibition. Oxo‐M (100 μM) decreased L‐ and N‐type channel activities in cell‐attached patches, indicating that a diffusible second messenger is involved.

BeCh (100 μM) also inhibited whole cell currents via the membrane‐delimited pathway. Blocking M4 receptors with 100 nM pirenzepine (in the presence of MT‐7) had no effect, while antagonizing M2 receptors with METH abolished inhibition. Concentrations of BeCh as high as 3 mM failed to inhibit either peak or long‐lasting tail currents following PTX pretreatment.

These results indicate that BeCh may be an effective tool for selectively activating M2 receptor stimulation of the membrane‐delimited pathway.

British Journal of Pharmacology (2003) 138, 1259–1270. doi:10.1038/sj.bjp.0705157
Can bethanechol distinguish between different muscarinic signalling pathways in neurones?
Authors: Constanti Andrew
Published: April 2003

British Journal of Pharmacology (2003) 138, 1185–1187. doi:10.1038/sj.bjp.0705158
Vasodilator actions of abnormal‐cannabidiol in rat isolated small mesenteric artery
Authors: Vanessa Ho W‐S , Hiley C Robin
Published: April 2003

The nonpsychoactive cannabinoid abnormal‐cannabidiol (trans‐4‐[3‐methyl‐6‐(1‐methylethenyl)‐2‐cyclohexen‐1‐yl]‐5‐pentyl‐1,3‐benzenediol) (abn‐cbd) produced concentration‐dependent relaxation of methoxamine‐precontracted rat small mesenteric artery. Endothelial removal reduced abn‐cbd potency six‐fold without affecting the maximum relaxation.

In endothelium‐intact vessels, abn‐cbd was less potent under 60 mM KCl‐induced tone and inhibited by combination of L‐NG‐nitroarginine methyl ester (L‐NAME) (nitric oxide synthase inhibitor; 300 μM), apamin (small conductance Ca2+‐activated K+ channels inhibitor; 50 nM) and charybdotoxin (inhibitor of intermediate conductance Ca2+‐activated K+ channels and large conductance Ca2+‐activated K+ channels BKCa; 50 nM). L‐NAME alone or in combination with either toxin alone had little effect.

In intact vessels, relaxations to abn‐cbd were inhibited by SR 141716A (cannabinoid receptor antagonist; 1 or 3 μM). Concomitant addition of L‐NAME, apamin and charybdotoxin had no further effect. Other cannabinoid receptor antagonists either had little (SR 144528; 1 μM and AM 251; 1 μM) or no effect (AM 630; 10 μM and AM 281; 1 μM). Inhibition of gap junctions, Gi/o protein coupling and protein kinase A also had no effect.

Endothelium‐independent relaxation to abn‐cbd was unaffected by L‐NAME, apamin plus charybdotoxin or capsaicin (10 μM). Abn‐cbd inhibited CaCl2‐induced contractions in vessels with depleted intracellular Ca2+ stores and stimulated with methoxamine or KCl. This was insensitive to SR 141716A (3 μM) but greatly reduced in vessels stimulated with ionomycin (Ca2+ ionophore; 1 μM).

We conclude that abn‐cbd relaxes the rat small mesenteric artery by endothelium‐dependent activation of K+ channels via SR 141716A‐sensitive pathways, which do not involve CB1 and CB2 receptors. It also causes endothelium‐independent, SR 141716A‐insensitive, relaxation by inhibiting Ca2+ entry through voltage‐gated Ca2+ channels.

British Journal of Pharmacology (2003) 138, 1320–1332. doi:10.1038/sj.bjp.0705160
An assessment of the role of the inhibitory gamma subunit of the retinal cyclic GMP phosphodiesterase and its effect on the p42/p44 mitogen‐activated protein kinase pathway in animal and cellular models of pulmonary hypertension
Authors: Murray Fiona , MacLean Margaret R , Pyne Nigel J
Published: April 2003

We have previously reported that the inhibitory gamma subunit of the rod photoreceptor type 6 cyclic GMP phosphodiesterase (PDEγ) is expressed in nonretinal tissues and is involved in the stimulation of the p42/p44 mitogen‐activated protein kinase (MAPK) pathway by growth factors and G‐protein‐coupled receptor agonists. We have now investigated whether PDEγ plays a role in modulating chronic hypoxic‐dependent mitogenic signalling pathways in pulmonary smooth muscle from rats with pulmonary hypertension (PHT).

We show for the first time that PDEγ is expressed in rat main, first, intrapulmonary and resistance pulmonary arteries. Moreover, its expression is increased in all the arteries to varying extents by chronic hypoxia. The extent of the increased expression of PDEγ is correlated with an enhanced activation of p42/p44 MAPK in these vessels.

We also report that PDEγ translation from mRNA transcript is increased in cultured human pulmonary artery smooth muscle cells subjected to chronic hypoxia for 14 days. This was correlated with hypoxic‐dependent increase in p42/p44 MAPK activation.

In conclusion, our studies identify for the first time a major chronic hypoxic‐dependent change in the phenotypic expression of an intermediate protein regulating mitogenic signalling in pulmonary arteries. This may have a significant effect on arterial remodelling in PHT. Future studies will focus on strategies designed to knockout rod PDEγ to assess whether this rescues rats from chronic hypoxic‐dependent changes in arterial remodelling and PHT.

British Journal of Pharmacology (2003) 138, 1313–1319. doi:10.1038/sj.bjp.0705190
Search of Jumping Items: Visual Marking and Discrete Motion
Authors: Olds Elizabeth S , McMurtry C Meghan
Published: April 2003

Watson and Humphreys (1997 Psychological Review104 90 – 122) showed that when searching for a target, observers can ignore a previewed set of distractors (other items), effectively decreasing the number of relevant items in a difficult search display and thus speeding performance (‘visual marking’). Other researchers have more recently investigated visual marking for continuously moving items, finding that shared features, and preserved inter-item spatial relationships, are helpful. Here, we tested whether visual marking occurs for a set of initial items that moves in one discrete jump (preserving shared features and inter-item spatial relationships). Marking did not occur in these displays, and we interpret this result in the context of previous research on visual marking.