bluuebunny/crossref_metadata_2025 huggingface dataset:
Blockade of the type I IGF receptor expression in human prostate cancer cells inhibits proliferation and invasion, up‐regulates IGF binding protein‐3, and suppresses MMP‐2 expression
Authors: Grzmil Michal , Hemmerlein Bernhard , Thelen Paul , Schweyer Stefan , Burfeind Peter
Published: December 2003

The type I insulin‐like growth factor receptor (IGF‐IR) is involved in tumour cell proliferation, invasion, and cancer cell survival. Several studies indicate that the IGF axis contributes to prostate cancer pathogenesis, but there is no consensus regarding the relative expression of the IGF‐IR in benign and malignant prostate epithelium. In this study, endogenous IGF‐IR gene expression was reduced in stably transfected PC‐3 cells by employing an antisense RNA strategy which resulted in significant suppression of both PC‐3 cell invasion and proliferation in vitro. Furthermore, it was demonstrated that a direct correlation exists between the inhibition of IGF‐IR gene expression and either up‐regulation of IGF binding protein (BP)‐3 or down‐regulation of matrix metalloproteinase (MMP)‐2 expression in androgen‐independent PC‐3 cells. Moreover, inhibition of IGF‐IR gene expression in transfected PC‐3 cells leads to an enhanced rate of spontaneous apoptosis. In addition, expression analyses by quantitative RT‐PCR on RNA from laser microdissected matched normal prostate and prostate tumour samples revealed that IGF‐IR gene expression was up‐regulated in nine of 12 prostate cancers, whereas IGFBP‐3 gene expression was down‐regulated in all 12 prostate carcinomas analysed. These results indicate an important role for IGF‐IR and IGFBP‐3 in the homeostasis of prostate carcinoma cells and provide a further basis for targeting IGF‐IR or IGFBP‐3 gene expression in order to improve understanding of the IGF‐IR‐activated signalling pathways and as a potential treatment for prostate cancer. Copyright © 2004 John Wiley & Sons, Ltd.
Fetal karyotyping after 28 weeks of gestation for late ultrasound findings in a low risk population
Authors: Drummond C. L. , Gomes D. Molina , Senat M. V. , Audibert F. , Dorion A. , Ville Y.
Published: December 2003

Objective

To analyze the indications and the results of invasive testing for fetal karyotyping for ultrasound abnormality in the third trimester of pregnancy, when first‐ and second‐trimester screening tests were negative.

Methods

Retrospective study of 171 consecutive pregnancies that underwent invasive testing after 28 weeks of gestation in 2 institutions between January 1999 and December 2001. Forty‐one patients did not have any form of screening for fetal aneuploidy beforehand. One hundred and thirty of them had a normal first‐trimester scan and a low risk of fetal aneuploidy by nuchal translucency and/or maternal serum screening and were included in the statistical analysis.

Results

Mean maternal age, gestational age at diagnosis and at invasive testing were 30.5 years; 29.3 weeks and 32.5 weeks respectively. Amniocentesis and fetal blood sampling were performed in 97 and 33 cases respectively.

The most frequent indications for invasive testing in the third trimester were major fetal malformations (51%) and intrauterine growth restriction (19%) detected on routine second‐ or third‐trimester ultrasound examination. Ultrasound markers of aneuploidy and polyhydramnios accounted for 17 and 11% of the indications respectively.

Fetal karyotype was normal in 121/130 cases. A gene mutation was found in one case. The karyotype was abnormal in nine cases, including seven cases of aneuploidy (one Turner syndrome, three trisomy 18, and three trisomy 21) and two cases of structural chromosomal abnormalities (46,XX, del 4 p16.1 and 46,XX, dup1).

One hundred cases resulted in the delivery of a normal baby. Thirty cases led to termination of pregnancy or intrauterine death due to major fetal malformations (N = 25), abnormal karyotype in six of these, and severe IUGR (N = 5) with normal karyotype. Fetal US markers of aneuploidy and isolated polyhydramnios were associated with a favorable outcome in all cases.

A significant increase in the risk of chromosomal anomaly was seen when two or more anomalies were found, rising from 2% with one anomaly to 21% when two or more anomalies were present.

Conclusion

In low risk patients, fetal karyotyping in the third trimester may be justified when the diagnosis of fetal malformation is made in the third trimester of pregnancy. Two or more anomalies increase the risk of fetal aneuploidy even with a negative‐screening test in the first and second trimester of pregnancy. Copyright © 2003 John Wiley & Sons, Ltd.
Ossification timing of sacral vertebrae by ultrasound in the mid‐second trimester of pregnancy
Authors: De Biasio P. , Ginocchio G. , Aicardi G. , Ravera G. , Venturini P. L. , Vignolo M.
Published: December 2003

Objectives

The aim of the study was to establish the ossification timing of sacral vertebrae by ultrasonography in the second trimester of pregnancy, for the diagnosis of caudal regression syndrome with isolated sacral agenesis.

Methods

The study was carried out on 77 normal single pregnancies, at gestational ages ranging from 15 to 21 weeks, using high‐resolution transabdominal echography. The sacral region was visualized in a coronal plane, when the fetus was in anterodorsal position. The level of ossification of sacral vertebrae (S1 to S5) at each gestational age was recorded. Each sacral region was examined three times by the same observer and the nucleus was considered as present when it was visualized at least two times out of three. Blind assessment was performed three times by a second observer, who was not present at the previous examination, for interobserver and intraobserver error analysis.

Results

Interobserver and intraobserver error calculation demonstrated the reproducibility of the method. Concordance between the two observers as evaluated by Cohen Kappa index was 0.77 (C.I. 95%, 0.69–0.85).

S1 ossification nuclei were visualized in all fetuses at 15 weeks and S2 nucleus was found in all fetuses within 17 weeks. S3 nucleus was detected in 45% of fetuses by the beginning of the 16th week. S4 was visualized in 55% of the cases at 18 weeks and progressively in a higher percentage of cases during the following weeks of gestation.

Conclusion

The data obtained showed that the sequence of development of sacral region ossification was related to gestational age. This observation allows clinicians to accurately exclude isolated sacral agenesis at 16 to 17 weeks of gestation, when the S1–S2 ossification nuclei are visualized. This opportunity may be of particular value in the offspring of diabetic mothers. Copyright © 2003 John Wiley & Sons, Ltd.
Earliest gestational age for fetal sexing in cell‐free maternal plasma
Authors: Rijnders R. J. P. , Van Der Luijt R. B. , Peters E. D. J. , Goeree J. K. , Van Der Schoot C. E. , Ploos Van Amstel J. K. , Christiaens G. C. M. L.
Published: December 2003

Objectives

To evaluate at what gestational age fetal DNA can reliably be detected at the earliest in maternal plasma.

Methods

We performed consecutive blood sampling in the first trimester of pregnancy in 17 women who were pregnant after in vitro fertilization (IVF) or intrauterine insemination (IUI). DNA was isolated and the Y‐chromosome specific SRY was amplified by real‐time polymerase chain reaction (PCR).

We likewise studied 31 women prior to invasive prenatal diagnosis procedures for test validation purposes. All test results were compared to cytogenetic sex or sex at birth.

Results

The earliest SRY detection was at a gestational age of 5 weeks and 2 days. In none of 4 pregnancies ending in a miscarriage was SRY detected. We detected SRY in maternal plasma in 1 of 2 patients (50%) carrying a male fetus at a gestational age of 5 weeks, in 4 of 5 (80%) at a gestational age of 7 weeks, in 4 of 4 (100%) at a gestational age of 9 weeks. In all 7 women pregnant with a male fetus, the correct fetal sex was detected by 10 weeks. In none of the 6 patients who delivered a girl was SRY detected. In the validation group, SRY was detected in 13 of the 13 male, and none of the 18 female fetuses.

Conclusions

We conclude that real‐time PCR of the SRY gene promises to be a reliable technique for early fetal sexing in maternal plasma. Copyright © 2003 John Wiley & Sons, Ltd.
The influence of needle and syringe size on chorionic villus sampling of term placentae: a randomised trial
Authors: Cochrane Lindsay , Ainscough Magdalen , Alfirevic Zarko
Published: December 2003

Objective

To determine the effect of needle and syringe size on the amount of tissue obtained at chorionic villus sampling

Methods

Two needle sizes, 18 and 20 gauge, and two syringe sizes 5 mL and 20 mL, were used to assess samples from term post‐partum placentae. Each of the four combinations was tested by 25 aspirations. The placentae were divided into 100 grid spaces and each grid space was randomly allocated to a needle/syringe combination. The resulting samples were cleaned to separate the chorionic villi (CV), centrifuged and then weighed.

Results

Significantly more tissue was obtained with an 18‐g needle compared with a smaller 20‐g needle (median weight difference 1.5 mg, 95% CI 0.8–2.3 mg). More tissue was also obtained with the larger 20‐mL syringe though the impact of the syringe size was less than that of the needle size (median difference 0.8 mg, 95% CI 0–1.6).

Conclusion

A larger syringe and needle size yields a larger quantity of chorionic villi from the post‐partum term placenta. Copyright © 2003 John Wiley & Sons, Ltd.
First report of prenatal diagnosis of genetic congenital deafness in a routine prenatal genetic test
Authors: Santoro M. L. , Mobili L. , Mesoraca A. , Giorlandino C.
Published: December 2003

Objective

We aimed to screen for connexin26 gene (GJB2) mutations associated with autosomal recessive non‐syndromic neurosensory deafness (NSRD) in a general risk population.

Methods

Screening for the most common connexin26 gene mutations was offered to all women undergoing a second‐trimester amniocentesis for fetal karyotype analysis in our Center. After rapid DNA extraction from amniotic fluid, PCR amplification was performed and products analysed to detect mutations of GJB2 gene by a sequencing technique. In particular, we searched for the 20 most frequently reported mutations (out of the approximately 90 so far described) and for which there are commercially available tests.

Results

From a total of 4819 consecutive amniotic fluids examined, the following five different heterozygous mutations were detected: 35delG in 80 cases, 167delT in 3 cases and 1 occurrence of each of the following mutations: M34T, 35insG and W77R. From these data, a prevalence of 1 : 56 (1.78%) for the heterozygous condition can be estimated in the Mediterranean general risk population. The striking predominance of 35delG mutation is confirmed. In addition, we detected a homozygous 35delG mutation condition in a foetus of no risk parents. In this case, the early diagnosis permitted prompt application of an acoustic prosthesis allowing for cochlear implantation in due time, with significant improvement of the prognosis.

Conclusions

In a general risk population, a carrier status for congenital deafness can be observed in 1 : 56 (1.78%) amniotic fluids; this is mostly due to the presence of a 35delG mutation of the connexin26 gene. Occasional identification of homozygous states, although rare, allows the best therapeutic approach. Copyright © 2003 John Wiley & Sons, Ltd.
ADAM12: a novel first‐trimester maternal serum marker for Down syndrome
Authors: Laigaard Jennie , Sørensen Tina , Fröhlich Camilla , Pedersen Bent Nørgaard , Christiansen Michael , Schiøtt Kirsten , Uldbjerg Niels , Albrechtsen Reidar , Clausen Helle V. , Ottesen Bent , Wewer Ulla M.
Published: December 2003

Objectives

The concentration of bioavailable insulin‐like growth factor (IGF) I and II is important to foetal growth. It is regulated by insulin‐like growth factor binding proteins (IGFBP) 1 through 6. Proteolytic cleavage of IGFBP‐3 takes place in human pregnancy serum; accordingly, IGFBP‐3 serum levels decrease markedly during pregnancy. ADAM12 (A disintegrin and metalloprotease) is an IGFBP‐3 and IGFBP‐5 protease and is present in human pregnancy serum. The goal of this study was to determine whether ADAM12 concentration in maternal serum is a useful indicator of foetal health.

Methods

We developed an enzyme‐linked immunosorbent assay (ELISA) for the quantification of ADAM12 in serum. The assay range was 42 to 667 µg/L. Recombinant ADAM12 was used as the standard for calibration.

Results

We found that ADAM12 was highly stable in serum. Serum concentration increased from 180 µg/L at week 8 of pregnancy to 670 µg/L at 16 weeks, and reached 12 000 µg/L at term. In 18 first‐trimester Down syndrome pregnancies, the concentration of ADAM12 was decreased, thus the median multiple of mean (MoM) value was 0.14 (0.01–0.76). A detection rate for foetal Down syndrome of 82% for a screen‐positive rate of 3.2% and a 1:400 risk cut‐off was found by Monte Carlo estimation using ADAM12 and maternal age as screening markers.

Conclusion

ADAM12 is a promising marker for Down syndrome. Copyright © 2003 John Wiley & Sons, Ltd.
Establishing long‐term permafrost observatories for active‐layer and permafrost investigations in Alaska: 1977–2002
Authors: Osterkamp T. E.
Published: December 2003

Twenty‐five years ago a programme was initiated to establish a statewide system of permafrost observatories that included boreholes drilled for the express purpose of investigating the effects of changes in climate on continuous and discontinuous permafrost. A total of 22 permafrost observatories have been established with boreholes 15 to 80 m in depth. These sites are primarily along a north‐south transect of Alaska paralleling the Alyeska oil pipeline from Prudhoe Bay to Glennallen and are visited and serviced annually. There are seven additional borehole sites with holes 15 to 80 m in depth that are visited occasionally. The sites are in undisturbed locations with nearly uniform conditions in a wide variety of environmental settings except for a few, purposefully placed in disturbed areas (e.g. farm field, burn, etc.). Proximity to meteorological stations with long weather records has allowed reconstruction of past active‐layer and permafrost conditions using calibrated site‐specific models. The sites have been used to document a recent warming trend in permafrost and active‐layer temperatures and to investigate the characteristics of the permafrost and active layer and processes that occur in them. Recommendations are made for establishing future observatories. Copyright © 2003 John Wiley & Sons, Ltd.
Application of differential global positioning systems to monitor frost heave and thaw settlement in tundra environments
Authors: Little Jonathon D. , Sandall Heath , Walegur Michael T. , Nelson Frederick E.
Published: December 2003

Technological advances in Differential Global Positioning Systems (DGPS), used in conjunction with specially designed survey targets, provide a means for accurately detecting frost heave and thaw settlement in cold environments, and for relating positions precisely in worldwide geodetic reference systems. Under ideal conditions, DGPS technology is capable of measuring vertical change of 1 cm or less. The inexpensive platform targets developed for this study were designed to support a DGPS antenna, to move in concert with the ground surface in response to changes within the active layer, and to function with minimal disturbance. The targets are unlikely to be affected adversely by flooding, cold weather, snow, or animal disturbance. Although the DGPS/target methodology can be strenuous and time consuming in comparison with traditional surveying methods, preliminary results indicate that it can be used to detect frost heave and thaw settlement at very fine resolution. Post‐processed rapid static carrier‐phase DGPS measured a mean value of vertical heave of 1 cm and mean subsidence of 4 cm during 2001–2002 at Prudhoe Bay, Alaska. Traditional profile leveling techniques confirmed these measurements. DGPS is a promising tool for measurement of periglacial phenomena, and is applicable over a wide range of spatial scale. Copyright © 2003 John Wiley & Sons, Ltd.
Simulation of freezing‐thawing cycles in a permafrost microcosm for assessing microbial methane production under extreme conditions
Authors: Wagner D. , Wille C. , Kobabe S. , Pfeiffer E.‐M.
Published: December 2003

The microbial process of methane (CH4) production during the back‐freezing of permafrost soils in autumn and the future fate of produced CH4 in the thawing phase of the following spring are not well understood. Long‐term CH4 flux studies in the Lena Delta (Siberia) indicate that back‐stored CH4 adds to the emission of newly‐produced CH4 at the beginning of the vegetation period. Further field analysis shows that microbial CH4 production already occurs at in situ temperatures of around 1°C in the bottom layer of the soil. Therefore, a permafrost microcosm was developed to simulate the influence of the annual freezing‐thawing cycles on the CH4 fluxes in the active layer of permafrost soils. Two cryostats ensure independent freezing and thawing the top and the bottom of the microcosm to simulate different field conditions. The CH4 concentration (Rhizon soil moisture samplers), the soil temperature (film platinum resistance temperature detectors [RTDs]) and the soil water content (time domain reflectometry) are analysed in different depths of the microcosm during the simulation in addition to the concentration of emitted CH4 in the headspace of the microcosm. The data obtained contribute to the understanding of microbial processes and CH4 fluxes in permafrost environments in the autumn and early winter. Copyright © 2003 John Wiley & Sons, Ltd.
Umiujaq, northern Québec: innovative techniques to monitor the decay of a lithalsa in response to climate change
Authors: Delisle Georg , Allard Michel , Fortier Richard , Calmels Fabrice , Larrivée É.
Published: December 2003

We describe the introduction of several new techniques to measure and monitor permafrost properties at a site near the east coast of the Hudson Bay, northern Québec. Eight boreholes were sunk through a lithalsa to the permafrost base. High precision temperature sensors and a pressure sensor were installed in six boreholes to monitor the long‐time changes of the thermal field of the permafrost and internal pore pressure. Two open boreholes were used to carry out a ground penetrating radar transillumination survey to provide a tomographic image of the spatial distribution of electromagnetic wave velocities within the lithalsa. Cores taken from the permafrost below the active layer of the lithalsa show numerous oblique and fractured ice lenses indicative of extensive deformation of the lithalsa during its evolution. Examples of results of the new techniques applied in this study are provided. These techniques appear as very promising for permafrost studies in general. Copyright © 2003 John Wiley & Sons, Ltd.
Assessment of chemical denudation rates using hydrological measurements, water chemistry analysis and electromagnetic geophysical data
Authors: Beylich Achim A. , Kolstrup Else , Linde Niklas , Pedersen Laust B. , Thyrsted Tage , Gintz Dorothea , Dynesius Lars
Published: December 2003

Water chemistry and chemical denudation in relation to local environmental conditions were investigated in a drainage basin of approximately 9 km2 in northernmost Swedish Lapland (Latnjavagge). Discharge and surface water electric conductivity were measured over the summer of 2001 at selected sites. The chemical investigations show differences between sub‐areas and changes over the season as well as overall rates of chemical denudation. Transects within the catchment using a radio‐magnetotelluric geophysical method describe regolith thickness and ground frost conditions at the time of measurement. This combination of methods obtains information on the influence of regolith thickness and ground frost upon sub‐surface drainage and chemical denudation, not only along the profiles but also, by extension, on areas further upslope. In this paper the techniques are outlined and the approach demonstrated for three sub‐areas with different regolith thicknesses and thaw development. Copyright © 2003 John Wiley & Sons, Ltd.
Molecular Modeling in Crystal Engineering for Processing of Energetic Materials
Authors: Bénazet Stéphane , Jacob Guy , Pèpe Gérard
Published: December 2003

Nowadays molecular modeling is available to explain molecular phenomena. This approach helps to compute crystal surface property effects that can be used both for morphology studies and optimal design of “bonding agents” to prevent filler‐binder detachment. The principles of crystal growth and of interaction energy computing have been applied to Hexanitrohexaazaisowurtzitane (HNIW). Crystallization experiments validate our calculations. Three families of additives of crystal growth are distinguished: the retarding (and inhibitor) agents, the promoters and finally the “tailor‐mades”. Retarding and inhibitor agents are the most interesting one to find bonding agents. HNIW is used to present our methodology, but engineering using molecular modeling could be generalized to other fillers.
Electron beam effects on diethylsilane‐covered Si(100) surfaces investigated by electron stimulated and temperature programmed desorption
Authors: Wang P. W. , Lozano J. , Kimberlin K. R. , Petrany P. , Young V. , Craig J. H.
Published: December 2003

The effect of low‐energy electron irradiation on adsorbed layers of diethylsilane (DES) on the Si(100) surface at 100 K were studied using temperature programmed desorption (TPD) and electron stimulated desorption (ESD). As has been observed previously, TPD studies of adsorbed DES have shown desorption of both molecular hydrogen and ethylene. Adsorption of DES at 100 K also results in a loosely bound layer that desorbs molecularly at a temperature of ∼140 K. Strong evidence exists for thermal removal of ethylene from the surface during programmed heating via a β‐hydride elimination process. Irradiation of the dosed surface with electrons results in a number of interesting effects. Electron‐induced enhancement of both hydrogen and ethylene desorption from Si(100) is observed. In addition, both neutral and ionic desorption of surface species was observed, induced by electron irradiation. Desorption of neutral species having masses of 2, 15 and 28 indicate electron‐induced removal of hydrogen and ethylene, with a methyl group appearing as a result of ethylene dissociation. Hydrogen removal occurs from two distinct states, as identified by the decay of neutral hydrogen from the surface, characterized by two decay constants. Analysis of the energy of desorbing H+ species suggests two distinct kinetic energy distributions at 1.8 and 4.1 eV, which contribute to the desorption signal. Copyright © 2003 John Wiley & Sons, Ltd.
Electron spectroscopic investigation of ethylmethylsulfide/nickel interface
Authors: Syed J. A. , Sardar S. A. , Yagi S. , Tanaka K.
Published: December 2003

To demonstrate the interaction of ethylmethylsulfide (C2H5SCH3) with an Ni(110) surface, we use x‐ray photoelectron spectroscopy and x‐ray absorption near‐edge structure measurements to identify the adsorbed sulfur species and their orientation on the surface at low temperature. The S–C2H5 and S–CH3 bonds are found to be oriented at angles of 46 ± 5° and 14 ± 5° from the surface, respectively. A qualitative estimation of charge transfer from substrate to molecule is carried out by S 1s XPS measurements. Copyright © 2003 John Wiley & Sons, Ltd.
History of the annual Symposium on Applied Surface Analysis
Authors: Grant J. T.
Published: December 2003

The annual Symposium on Applied Surface Analysis started in 1979 at the University of Dayton. A colleague of mine had suggested such a meeting to me, because at that time there was no scientific division of the American Vacuum Society devoted to applications of surface analysis. I sent a proposal to the Air Force Office of Scientific Research for Sponsorship and this was accepted. The first symposium had 40 oral presentations over 3 days (13–15 June 1979), a vendor exhibit and a reception. A total of 129 people registered for the symposium. Eight of the first nine symposia were held at the University of Dayton, and then it became a topical conference of the American Vacuum Society, with site selection being decided by its newly formed Applied Surface Science Division. This year is the 25th anniversary of the Symposium on Applied Surface Analysis, and this paper is a brief history of the symposium. Copyright © 2003 John Wiley & Sons, Ltd.
Interactions of cisplatin with calcium phosphate nanoparticles: In vitro controlled adsorption and release
Authors: Barroug A. , Kuhn L. T. , Gerstenfeld L. C. , Glimcher M. J.
Published: December 2003

A new system for the local delivery of chemotherapy to malignant solid tumors has been developed based on calcium phosphate (CaP) nanoparticles. The adsorption of the anti‐neoplastic drug cis‐diamminedichloroplatinum (cisplatin) was characterized on three types of apatitic CaP (poorly and well crystallized hydroxyapatite, and carbonated apatite). Adsorption isotherms obtained in chloride‐free phosphate solutions at pH = 7.4 (24 and 37°C) indicate that cisplatin adsorption increases with temperature and increases with decreasing crystallinity. Release studies in phosphate buffer saline (containing the chloride ion essential for release) showed that while the cumulative amount of released drug was the same for all apatites at 20 days (∼70% of the total bound), the least crystalline material released the drug more slowly. The drug release rate increased slightly with temperature. Cytotoxicity testing was conducted in a K8 clonal murine osteosarcoma cell line to verify that drug activity was retained after adsorption onto the apatite crystals. K8 cells were plated onto dried films of the apatite/cisplatin conjugates and after 24 h, viability was measured with tritiated uridine. The apatite/cisplatin formulations exhibited cytotoxic effects with a dose dependent diminishment of cell viability. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Placental growth factor induces FosB and c‐Fos gene expression via Flt‐1 receptors
Authors: Holmes David I.R. , Zachary Ian
Published: December 2003

Placental growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family that binds specifically to Flt‐1. The biological roles of PlGF and Flt‐1 have not yet been defined and the signalling mechanisms mediating cellular actions of PlGF remain poorly understood. In human umbilical vein endothelial cells, VEGF and PlGF induced expression of both full‐length FosB mRNA and an alternatively spliced variant, ΔFosB, with similar efficacy and kinetics. In contrast, PlGF induced c‐Fos expression less strongly than VEGF, and whereas VEGF strongly upregulated tissue factor mRNA, PlGF had a negligible effect. PlGF induced c‐Fos expression in porcine aortic endothelial cells specifically expressing Flt‐1, and FosB expression in the monocytic RAW 264.7 cell line expressing endogenous Flt‐1. These findings show for the first time that VEGF and PlGF induce mRNA expression of the transcription factors FosB and c‐Fos, and suggest that these factors may play a role in the biological responses mediated by PlGF and Flt‐1.
Snake and snail toxins acting on nicotinic acetylcholine receptors: fundamental aspects and medical applications
Authors: Tsetlin V.I , Hucho F
Published: December 2003

This review covers recent data on interactions of nicotinic acetylcholine receptors (AChR) with snake venom proteins (α‐ and κ‐neurotoxins, ‘weak’ toxins recently shown to act on AChRs), as well as with peptide α‐conotoxins from Conus snails. Mutations of AChRs and toxins, X‐ray/nuclear magnetic resonance structures of α‐neurotoxin bound to AChR fragments, and the X‐ray structure of the acetylcholine‐binding protein were used by several groups to build models for the α‐neurotoxin–AChR complexes. Application of snake toxins and α‐conotoxins for pharmacological distinction of muscle, neuronal and neuronal‐like AChR subtypes and for other medical purposes is briefly discussed.
Quantitative measurements of Ca2+/calmodulin binding and activation of myosin light chain kinase in cells
Authors: Geguchadze Ramaz , Zhi Gang , Lau Kim S , Isotani Eiji , Persechini Anthony , Kamm Kristine E , Stull James T
Published: December 2003

Myosin II regulatory light chain (RLC) phosphorylation by Ca2+/calmodulin (CaM)‐dependent myosin light chain kinase (MLCK) is implicated in many cellular actin cytoskeletal functions. We examined MLCK activation quantitatively with a fluorescent biosensor MLCK where Ca2+‐dependent increases in kinase activity were coincident with decreases in fluorescence resonance energy transfer (FRET) in vitro. In cells stably transfected with CaM sensor MLCK, increasing [Ca2+]
i
increased MLCK activation and RLC phosphorylation coincidently. There was no evidence for CaM binding but not activating MLCK at low [Ca2+]
i
. At saturating [Ca2+]
i
MLCK was not fully activated probably due to limited availability of cellular Ca2+/CaM.
Investigations by mass isotopomer analysis of the formation of D‐2‐hydroxyglutarate by cultured lymphoblasts from two patients with D‐2‐hydroxyglutaric aciduria
Authors: Struys Eduard A. , Verhoeven Nanda M. , Brunengraber Henri , Jakobs Cornelis
Published: December 2003

D‐2‐Hydroxyglutaric aciduria is an inborn error of metabolism first described in 1980. To date, more than 40 patients have been diagnosed with this disease. To identify the metabolic precursor of D‐2‐hydroxyglutarate (D‐2‐HG), cultured human lymphoblasts from two patients with D‐2‐HG aciduria were grown in culture medium supplemented with [U‐13C6]glucose or [2H5]glutamate. Mass isotopomer distribution measurements of D‐2‐HG, 2‐ketoglutarate (2‐KG) and citrate were performed by gas chromatography‐mass spectrometry. The mass isotopomer distributions in D‐2‐HG, 2‐KG and citrate, following [U‐13C6]glucose and [2H5]glutamate incubations, revealed that 2‐KG interconverts rapidly to D‐2‐HG and that D‐2‐HG is formed within the mitochondria.
Quinacrine nonsurgical female sterilization in Baroda, India: 23 years of follow‐up of 84 women
Authors: Bhatt R.V.
Published: December 2003

Objectives: Evaluate the long‐term effectiveness and safety of transcervical insertion of quinacrine hydrochloride pellets for nonsurgical female sterilization (QS). Methods: During the period June 1979 through January 1980, 84 women were admitted to a study at the Baroda Medical College and Hospital, Baroda, India. Our protocol called for three transcervical insertions of 252 mg of quinacrine hydrochloride to be deposited in the uterus of each patient. Follow‐up was scheduled at 6, 12 and 48 months after the last administration. Results: These women were 25 to 39 years of age at the time of the QS procedure and now, 23 years later, have completed their reproductive years. There were 4 pregnancies subsequent to the completion of QS, all prior to their 4‐year follow‐up. Thus, the life‐time failure rate for these women was 3.7%. Complaints were minor, especially when compared to surgical sterilization. There were no long‐term effects suspected of being attributable to QS. Conclusions: QS appears to be a reasonably effective method that is much safer than surgical sterilization.
The effect of special training for quinacrine sterilization (QS) in Faisalabad, Pakistan: a report on an 1833‐women subset of 11,000 cases
Authors: Bashir A. , Bashir M. , Afzal S.
Published: December 2003

Objective: To determine the impact of retrained clinicians on the efficacy of transcervical quinacrine sterilization. Method: Retraining of clinicians in the accepted insertion technique was conducted in 1996. From 1 January 1997 through 2001, they performed 1089 quinacrine sterilizations in 11 MCH clinics of the Mother & Child Welfare Association at Faisalabad, Pakistan. Of these, 885 women had a recorded follow‐up visit (81.4%) by 31 December 2001. Results: Reported pregnancy failures declined after retraining from 5.4% (SE 2.3) for one year of use to 1.1% (SE 0.4) for 5 years of use. The rates at 4 years of use showed the expected increase in failures for women 30 years old or younger of 1.5% (SE 0.7) compared to 0.9% (SE 0.4) for those over 30; a lower rate of 0.8% (SE 0.4) for breastfeeding subjects and 2.2% (SE 1.1) for mothers not breastfeeding; but rates were similar for uterine length and post insertion traumatic bleeding. Conclusion: Quinacrine sterilization appears safe with acceptable efficacy.
A 22‐year experience with quinacrine sterilization in a rural private clinic in Midnapore, India: a report on 5 protocols and 1838 cases
Authors: Roy A.
Published: December 2003

Objectives: Evaluate the safety and effectiveness of quinacrine for non‐surgical female sterilization in five different protocols. Methods: The 5 trials were conducted sequentially. The first and largest, with 985 cases, tested the use of a curved inserter to place a 50 mg dose of quinacrine near each tubal ostia. The next 3 trials were carried out to determine the effect of adjunct procedures on the efficacy of the standard recommended protocol. The three adjuncts were 75 mg of intrauterine diclofenac, 10 mg medroxyprogesterone IM and either 10 mg of atropine IM or 20 mg of hyoscine butylbromide IM. The final trial focused on the currently recommended protocol. Results: The 100 mg dose placed at the tubal ostia with the curved inserter resulted in a failure rate of 9.0% at 20 years. Diclofenac or medroxyprogesterone did not improve efficacy over quinacrine alone. Atropine or hyoscine butylbromide substantially diminished the effectiveness of the quinacrine. The failure rate with the standard protocol in our series of 122 cases was 0.8% at 3.5 years. Side effects were minor. There were no deaths nor serious complications with any of these protocols. Discussion: All 5 protocols appeared to be safe and the standard one was the most effective.
Quinacrine sterilization (QS) in Iran and the use of HSG as a measure of success
Authors: Soroodi‐Moghaddam S.
Published: December 2003

Objectives: To establish the safety, effectiveness and acceptability of quinacrine sterilization (QS) in Iran. To determine whether the hysterosalpingogram (HSG) performed under low pressure can be used to demonstrate success of the QS procedure rather than waiting for a pregnancy to occur in order to demonstrate failure. Methods: This study was initiated in September 1990 in a private family planning clinic in Tehran, Iran. Patient intake for this analysis was completed 31 December 1998 and the cut‐off date for follow‐up data to be included in this analysis was 30 July 2002. During this period, 268 women received QS. From inception until April 1994, 160 women entered the study. The first 62 women received 3 insertions and the remainder received 2. Short‐term side effects were closely followed in these 160 women. From 18 February 1994 until the patient intake cut‐off date, 131 women entered the study and 46 of them received an HSG. Results: With 4 to 12 years of follow‐up there have been 7 pregnancies for a gross pregnancy rate of 2.6%. However, the use of the HSG tripled the risk of pregnancy for women who underwent the procedure. Furthermore, HSG, even when performed under minimal pressure, indicated failure of the QS procedure about 6% of the time when in fact both tubes would have closed had there been no intervention. Side effects were minor when compared to the complications of surgical sterilization. Conclusions: QS was found to be safe, effective and preferred over surgical sterilization by Iranian women. HSG understated the number of patients with bilateral tubal closure, or with tubes that would have closed given a little more time.
Quinacrine sterilization of 1997 women in Daharpur, Midnapore, West Bengal, India: a comparison of 3 protocols
Authors: Pal S.K.
Published: December 2003

Objectives: Determine the efficacy of two different dosage regimens of quinacrine placed at each cornual angle, employing a curved inserter, and for fundal placement of doses from 252 mg to 360 mg of quinacrine, depending on the age of the woman. Methods: 1. The first trial involved 3 double insertions, a month apart, of 50 mg of quinacrine at each cornual angle. This trial was initiated on 14 August 1979 and completed on 26 June 1984 with 418 subjects admitted. 2. The second was a single double insertion of 100 mg at each cornual angle. This trial, initiated on 30 November 1984, was completed on 11 June 1985 with 100 subjects admitted. 3. The third trial began 2 January 1995, was completed 26 January 1998 and included 1479 subjects. There were 2 insertions, a month apart, with fundal placement of all pellets. The dose depended on the woman's age and ranged from 252 mg in the oldest to 360 mg in the youngest. The cut‐off date for this trial was 23 January 2003. Results: Only relatively minor side effects or complications were seen. None required hospitalization. Failure rates with multiple low dose or single dose cornual placement of pellets were unacceptably high. When higher doses of fundal placement of quinacrine were used at two visits, one month apart, no failures occurred. Conclusions: The third protocol shows great promise.
Quinacrine sterilization (QS) in a private practice in Daytona Beach, Florida: a preliminary report
Authors: Whitney R.B.
Published: December 2003

Objectives: To affirm that WS can be performed safely and effectively in a U.S. private office practice. Methods: The U.S. FDA Modernization Act of 1997 Pharmacy Compounding Provisions made it possible for American physicians to begin offering WS to their patients. These provisions became effective November 21, 1998. This series was initiated in October 2000. The standard protocol recommended by the International Federation for Family Health (IFFH) is followed. Information on patients is recorded on forms suggested by IFFG to accomplish good post‐marketing surveillance. The potential role of uterine septae in WS failures is of particular interst to this investigator. Results: Seven cases have been completed. There have been no failures. Side effects have been minor. Women have been exceptionally happy with this method. The Florida Agency for Health Care Administration has examined WS and found it to be an acceptable off‐label use of quinacrine. Conclusion: Preliminary results have been similar to those reported by QS researchers around the world.
8‐year follow‐up in a randomized trial of one vs two transcervival insertions of quinacrine pellets for sterilization in Indonesia
Authors: Agoestina T.
Published: December 2003

Objective: To evaluate the efficacy of one vs two insertions of quinacrine and the long‐term safety of quinacrine sterilization (QS) 8 years after the procedure in Indonesia. Methods: Between March 1993 and September 1995, a randomized trial was conducted in 6 academic centers in Indonesia. In February 2003, a follow‐up was undertaken in Bandung, one of these centers. This survey required a home visit of each woman. A questionaire was designed to elicit information regarding current general health status, method failure, pregnancy outcomes and other contraceptive methods now used by women who experienced failures. Among the 70 patients receiving a single insertion of quinacrine pellets, 14.3% had become pregnant. There were no pregnancies among the 30 who received 2 insertions. All the women were found to be in good health. No long‐term side effects or complications were identified. Conclusions: The two‐insertion protocol is unmistakably superior to the single insertion. This study provides further evidence that QS is a safe contraceptive method.
Quinacrine sterilization (QS): Informed consent
Authors:   Informed Consent Working Group
Published: December 2003

Informed consent is a basic human right for any medical procedure. It is particularly important that women know what is involved in any sterilization method, and how it will affect their health and their emotional life. Over 140,000 QS procedures have been performed in 34 countries. In no country has there been any formal effort to advance the acceptance of this method. Instead, satisfied users have been the promoters. Thoroughly informed consent is vital to patient satisfaction. A working group undertook an initiative to create an ideal consent form. The product of that initiative is presented.
Individual signatures in the frequency‐modulated sweep calls of African large‐eared, free‐tailed batsOtomops martiensseni(Chiroptera: Molossidae)
Authors: Fenton M. B. , Jacobs D. S. , Richardson E. J. , Taylor P. J. , White W.
Published: December 2003

Frequency‐modulated sweep calls ofOtomops martiensseniwere recorded from individuals as they emerged from nine different building roosts near Durban, South Africa. Multiple analyses of call features, including duration (ms), lowest frequency (kHz), highest frequency (kHz) and frequency with most energy (kHz), indicated significant inter‐individual variation. Discriminant function analysis of call features correctly classified the calls of individuals from four roosts > 70% on 19 of 28 times. Although other species of molossids (Chaerephon pumilus,Tadarida aegyptiaca, and one unidentified species) produced social calls as well as frequency‐modulated sweep calls,O. martiensseniproduced just the latter vocalizations and they were longer and lower in frequency than those of the sympatric molossids. Other species of molossids, but notO. martiensseni, produced feeding buzzes as they attacked flying insects. The frequency‐modulated sweep calls ofO. martiensseniseem to serve a communication function, but they may not be used in echolocation unlike similar calls by other molossids. Individually distinct communication signals (frequency‐modulated sweep calls) enhance communication in a species that lives in year‐round social groups (one adult male, females and dependent young).
Mating behaviour and insemination in Diplatys flavicollis, an earwig with double‐barrelled penises and a variable number of female sperm‐storage organs
Authors: Kamimura Yoshitaka
Published: December 2003

Earwigs (Insecta, Dermaptera) show astonishing diversity in penis morphology. In several families, males have a single penis (termed virga), whereas males of other families possess two functional virgae. Taxonomists have assumed that the two‐virgae state is ancestral; however, ecological reasons why the ancestor acquired two virgae have not been explored. This study investigated in detail male and female genital structures, mating behaviour and insemination processes in the earwig Diplatys flavicollis (Diplatyidae). Diplatyidae are considered to be the most primitive family of earwigs. SEM and light‐microscopy revealed that males of this species have two gonopores on each of two virgae, similar to those reported in other diplatyids (i.e. two double‐barrelled penises), while females have four to six independent sperm‐storage organs (spermathecae). Rapid fixation of mating pairs and insemination success of males from which one virga had been removed clearly revealed that only one virga was used for mating and was usually sufficient for inseminating multiple spermathecae. This finding rejects the one‐to‐one correspondence between male gonopores and female spermathecae. Based on allometric analysis of spermathecal variation, the possible significance of multiple spermathecae in relation to sperm‐storage strategies of females is discussed. Compared to studies of male genital morphology, few studies have described spermathecal morphology. Based on compiled data of spermathecal and virgal morphology among earwigs, a parallel evolutionary trend between spermathecae and virgae from complicated (multiple) to simple (single) ones is suggested, and further investigation of the phylogeny, female genital morphology and insemination processes among earwigs is encouraged.
Scaling of bird claws
Authors: Pike A. V. L. , Maitland D. P.
Published: December 2003

The claw geometry of birds can be used to predict their mode of life. Previous studies, however, have not considered how bird size might affect these predictions. Thus, in the present study, the geometric scaling relationships of bird claws are examined for a variety of extant birds with different modes of life: predatory, climbing, perching or ground‐dwelling. Measurements of hind‐limb claw radius (i.e. claw size) and claw angle (i.e. claw ‘hookedness’) of the third digit claw were made on 120 species of bird ranging from 0.0057 kg to 44 kg in body mass. Claw radius was found to be proportional to (body mass)0.34 across all species. Claw angle was found to increase with body mass for predatory and climbing birds (i.e. bigger birds have relatively more hooked claws), and decrease with body mass for ground‐dwelling birds (i.e. bigger birds have relatively less hooked or flatter claws). No significant relationship was found between claw angle and body mass for perching birds. Mode of life could not be predicted with any certainty using measurements of either claw radius or claw angle, suggesting difficulty in assigning fossil species such as Archaeopteryx to a specific locomotor category. As claw design should enable the claw to withstand the forces placed upon it, further work is needed to establish the stresses experienced by the claws of different types of bird.
Development of the beetle parasitoids,Brachinus explodensandB. crepitans(Coleoptera: Carabidae)
Authors: Saska Pavel , Honek Alois
Published: December 2003

Earlier authors demonstrated that wetland species of the genusBrachinus(Coleoptera: Carabidae) are pupal ectoparasitoids of water beetles of the families Dytiscidae, Gyrinidae and Hydrophilidae. Here we demonstrate that the dryland species,Brachinus explodensandB. crepitans, develop on pupae of ground beetles of the genusAmara(Carabidae). AsBrachinusandAmaraspecies often occur together at high densities in crops, the rearing of bothBrachinusspecies was followed in the laboratory. Females laid eggs in the soil and the first instar larva searched for a host. After finding anAmarapupa, aBrachinuslarva bit it and then fed on haemolymph exuding from the wound. The second instar larva continued feeding in this way. The third instar larva attached theAmarapupa to its dorsum and ate it completely withinc. 2 days. Feeding was followed by a resting phase and moulting to pupa and adult. The total post‐embryonic development was completed within 20 days inB. explodensand 24 days inB. crepitansat 24.7 °C.