bluuebunny/crossref_metadata_2025 huggingface dataset:
A screen for mutations in human homologues of mice exencephaly genes Tfap2α and Msx2 in patients with neural tube defects
Authors: Stegmann Karolin , Boecker Julia , Richter Bärbel , Capra Valeria , Finnell Richard H. , Ngo Ernestine T.K.N. , Strehl Elisabeth , Ermert August , Koch Manuela C.
Published: August 2002

Background

Very little is known about the identity of genetic factors involved in the complex etiology of nonsyndromic neural tube defects (NTD). Potential susceptibility genes have emerged from the vast number of mutant mouse strains displaying NTD. Reasonable candidates are the human homologues of mice exencephaly genes Tfap2α and Msx2, which are expressed in the developing neural tube.

Methods

A single‐strand conformation analysis (SSCA) mutation screen of the coding sequences of TFAP2α and MSX2 was performed for 204 nonsyndromic NTD patients including cases of anencephaly (n = 10), encephalocele (n = 8), and spina bifida aperta, SBA (n = 183). A selected number of SBA patients was additionally tested for specific mutations in MTHFD, FRα, and PAX1 already shown to be related to NTD.

Results

Two TFAP2α point mutations in individual SBA patients were silent on the amino acid level (C308C, T396T). On nucleic acid level, these mutations change evolutionary conserved codons and thus may influence mRNA processing and translation efficiency. One SBA patient displayed an exonic 9‐bp deletion in MSX2 leading to a shortened and possibly less functional protein. None of these mutations was found in 222 controls. Seven polymorphisms detected in TFAP2α and MSX2 were equally distributed in patients and controls. Patients with combined heterozygosity of an exonic MSX2 and an intronic TFAP2α polymorphism were at a slightly increased risk of NTD (OR 1.71; 95% CI 0.57–5.39).

Conclusions

Although several new genetic variants were found in TFAP2 and MSX2, no statistically significant association was found between NTD cases and the new alleles or their combinations. Further studies are necessary to finally decide if these gene variants may have acted as susceptibility factors in our individual cases. Teratology 63:167–175, 2001. © 2001 Wiley‐Liss, Inc.
Association of prenatal phenobarbital and phenytoin exposure with genital anomalies and menstrual disorders
Authors: Dessens Arianne B. , Cohen‐Kettenis Peggy T. , Mellenbergh Gideon J. , Koppe Janna G. , Poll Nanne E. V.D. , Boer Kees
Published: August 2002

Background

Animal studies demonstrated that early exposure to phenobarbital decreases reproductive function. This study investigates whether prenatal exposure to these anticonvulsants affects human genital tract development.

Methods

Genital anomalies at birth were studied retrospectively in 90 phenobarbital‐exposed, 108 phenobarbital plus phenytoin‐exposed, and 198 matched control infants. Of this group, 72 drug‐exposed males, 75 drug‐exposed females, and 147 matched control subjects participated in a follow‐up and were interviewed at age 19–35. Differences between groups were tested by chi‐square and t‐tests.

Results

A total of 15% of the phenobarbital‐exposed boys versus 2.8% control boys had undescended testes at birth. More anticonvulsant‐exposed (24%) than control males (11%) had received medical treatment for genital anomalies. Anticonvulsant‐exposed females more often had irregularities in menstrual cycles (31% vs 17%) and bleeding (15% vs 3%) and reported more problems during pregnancy.

Conclusions

Prenatal exposure to anticonvulsants seems to induce minor genital anomalies and may affect reproductive function. Teratology 64:181–188, 2001. © 2001 Wiley‐Liss, Inc.
MFO induction potential of fish species native to the Swan–Canning Estuary, Western Australia
Authors: Webb D. , Gagnon Marthe Monique
Published: August 2002

The use of mixed function oxygenase (MFO) enzymes as a potential biomarker of pollution in the Swan‐Canning Estuary was investigated in four indigenous fish species, Perth herring (Nematalosa vlaminghi), sea mullet (Mugil cephalus), yellowtail trumpeter (Amniataba caudavittata), and black bream (Acanthopagrus butcheri). Each experimental fish was intraperitoneally injected with 10 μg/kg of 3,3′,4,4′,5‐pentachlorobiphenyl per kilogram of fish using corn oil as a carrier. Controls were injected with 1 mL corn oil per kilo. Induction of the hepatic ethoxyresorufin‐O‐deethylase (EROD) activity was measured 10 days post injection. Perth herring did not survive the experimental period due to the poor ability of this fish to endure captivity and handling. Yellowtail trumpeter demonstrated a low EROD induction response (2‐fold relative to controls), while sea mullet displayed a moderate EROD induction potential (3.5‐fold relative to controls). Because of their lower EROD induction potential, yellowtail trumpeter and sea mullet were not considered the most suitable bioindicator species for Western Australian estuarine waters. Black bream has desirable population traits and had a relatively high MFO induction potential response (9‐fold relative to controls). From the results it was concluded that, when using EROD induction as a biomarker, black bream is a suitable fish to use as a bioindicator species for investigations into the health of the Swan‐Canning Estuary. © 2002 by Wiley Periodicals, Inc. Environ Toxicol 17: 87–92, 2002
Detection of nodularin in flounders and cod from the Baltic Sea
Authors: Sipiä Vesa , Kankaanpää Harri , Lahti Kirsti , Carmichael Wayne W. , Meriluoto Jussi
Published: August 2002

The brackish water cyanobacterium Nodularia spumigena regularly forms waterblooms in the Baltic Sea. Many N. spumigena strains can produce nodularin, a hepatotoxic penta‐peptide, which has caused several animal poisonings in the Baltic Sea area. To improve our understanding of nodularin bioaccumulation in aquatic organisms this study measured nodularin in flounder and cod caught from the Baltic Sea. Flounders were collected from the western Gulf of Finland in July 1996, September 1997, and September 1998, and from the Gulf of Bothnia in August 1997 and September 1998. Flounders were also collected from the coastal areas of Sweden in the Baltic Proper during September 1998. Cod were caught from the southern Baltic Sea in August 1998. Livers and muscles of the 1997 fish were isolated, extracted, and analysed for nodularin using high‐performance liquid chromatography (HPLC) and enzyme‐linked immunosorbent assay (ELISA) and protein phosphatase 1 (PP1) inhibition assay. Approximately 30–70 ng of nodularin/g dry weight (maximum value 140 ng/g) were found in the liver tissue samples by ELISA and PP1 inhibition. These concentrations were below the detection limit of HPLC. PP1 assay showed inhibition also in muscle samples, but this may due to other compounds present in the muscle extracts rather than NODLN or due to matrix interference. The recovery of nodularin from liver tissue with ELISA and PP1 assays was about 30%. Nodularin concentrations in samples are not corrected for recovery. Although the concentrations of nodularin found in this study are low further studies of nodularin are needed to assess possible bioaccumulation in brackish water food webs. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 121–126, 2001
Interlaboratory study for the validation of an ecotoxicological procedure to monitor the quality of septic sludge received at a wastewater treatment plant
Authors: Robidoux Pierre Yves , Choucri Achraf , Bastien Christian , Sunahara Geoffrey I. , López‐Gastey José
Published: August 2002

Septic tank sludge is regularly hauled to the Montreal Urban Community (MUC) wastewater treatment plant. It is then discharged and mixed with the wastewater inflow before entering the primary chemical treatment process. An ecotoxicological procedure integrating chemical and toxicological analyses has been recently developed and applied to screen for the illicit discharge of toxic substances in septic sludge. The toxicity tests used were the Microtox, the bacterial‐respiration, and the lettuce (Lactuca sativa) root elongation tests. In order to validate the applicability of the proposed procedure, a two‐year interlaboratory study was carried out. In general, the results obtained by two independent laboratories (MUC and the Centre d'expertise en analyse environnementale du Québec) were comparable and reproducible. Some differences were found using the Microtox test. Organic (e.g., phenol and formaldehyde) and inorganic (e.g., nickel and cyanide) spiked septic sludge were detected with good reliability and high efficiency. The relative efficiency to detect spiked substances was >70% and confirms the results of previous studies. In addition, the respiration test was the most efficient toxicological tool to detect spiked substances, whereas the Microtox was the least efficient (<15%). Efficiencies to detect spiked contaminants were also similar for both laboratories. These results support previous data presented earlier and contribute to the validation of the ecotoxicological procedure used by the MUC to screen toxicity in septic sludge. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 158–171, 2001
Effect of linear alkylbenzene sulfonate on population growth of Daphnia galeata: A life table evaluation
Authors: Tanaka Y. , Nakanishi J.
Published: August 2002

The chronic effect of linear alkylbenzene sulfonate (LAS12) on a daphnid species (Daphnia galeata) was examined by the life table experiment. The estimated responses in the intrinsic rate of population growth r were analyzed with two alternate concentration–response functions, i.e., the power function and the quadratic function. Based on the best‐fit power function model with biases corrected by the jackknife procedure, the population‐level EC50, which is defined as the concentration of chemicals that reduces the population growth rate (the intrinsic rate of natural increase) by 50%, was estimated as 2.5 mg/L. The 48‐h acute immobility test yielded EC50 of 4.6 mg/L. The population‐level effect of LAS12 on this test species is considerably more sensitive than the acute lethal effects to neonates. © 2001 John Wiley & Sons, Inc. Environ Toxicol 16: 344–348, 2001
Wind hybrid electrical supply system: behaviour simulation and sizing optimization
Authors: Notton G. , Cristofari C. , Poggi P. , Muselli M.
Published: August 2002

Using a global approach, a wind hybrid system operation is simulated and the evolution of several parameters is analysed, such as the wasted energy, the fuel consumption and the role of the wind turbine subsystem in the global production. This analysis shows that all the energies which take part in the system operation are more dependent on the wind turbine size than on the battery storage capacity. A storage of 2 or 3 days is sufficient, because an increase in storage beyond these values does not have a notable impact on the performance of the wind hybrid system. Finally, a cost study is performed to determine the optimal configuration of the system conducive to the lowest cost of electricity production. Copyright © 2001 John Wiley & Sons, Ltd.
A telescopic local grid refinement technique for wind flow simulation over complex terrain
Authors: Theodorakakos A. , Bergeles G.
Published: August 2002

A telescopic local grid refinement technique is developed in order to enhance the accuracy level of wind field predictions in a subregion of a complex topography. A 3D simulation of the wind flow field over complex terrains has been carried out. The governing Navier–Stokes conservation equations of the flow field are solved numerically in a three‐dimensional generalized curvilinear non‐orthogonal grid, using Cartesian velocity components, following the finite volume approximation and a pressure correction method. Turbulence is simulated by a two‐equation transport model. The reliability of the general flow solver is first tested by simulating the flow past a cube. The second test case simulated is the flow over the Askervein hill, with a detailed comparison of predicted and measured velocities. The third case presented concerns flow field simulation over a complete island. Comparison with measurements reveals the significance of the accurate discretization of the topography and the use of telescopic meshes on the results. Copyright © 2001 John Wiley & Sons, Ltd.
Modelling and analysis of the flow field around a coned rotor
Authors: Mikkelsen R. , Sørensen J. N. , Shen W. Z.
Published: August 2002

The influence of coning a wind turbine rotor is analysed numerically using the blade element momentum (BEM) method and an actuator disc model combined with the Navier–Stokes equations. The two models are compared and shortcomings of the BEM model are discussed. As a first case, an actuator disc with a constant normal loading of CT = 0·89 is considered. In accordance with theoretical predictions and investigations by Madsen and Rasmussen (European Wind Energy Conference, Nice, 1999; 138–141), the computations demonstrate that the power coefficient based on the projected area of the actuator disc is invariant to coning. The induced velocities, however, are no longer constant, but vary as a function of spanwise position. Next, the flow past the 2 MW Tjæreborg wind turbine is computed with and without coning. The most important findings from this study are that, although the power is reduced when the rotor is coned, the power coefficient based on the projected area is only slightly changed. The computations show that upstream coning results in a 2%–3% point higher power production than the corresponding downstream coning of the rotor. The Navier–Stokes computations show that the integrated loading, i.e. the root shear force, is higher than the one predicted by the BEM method, which is reduced approximately in proportion to the projected area. Copyright © 2001 John Wiley & Sons, Ltd.
Local structure around phosphorus atoms in nickel–phosphorus alloy films studied by total electron yield x‐ray absorption fine structure
Authors: Watanabe Takashi , Kato Jun , Matsuo Shuji , Wakita Hisanobu , Umesaki Norimasa
Published: August 2002

Nickel– phosphorus alloy films, deposited on titanium by electroless NiP plating, were studied by means of total electron yield (TEY) x‐ray absorption fine structure (XAFS) and x‐ray diffraction (XRD). XAFS spectra were analyzed by the discrete variational Xα (DV‐Xα) molecular orbital method and XAFS spectral simulation using photoelectron multiple scattering theory (FEFF8), in order to clarify the deposition mechanism of Ni3P from NiP alloy films under various heating conditions. As for the electroless NiP plating, the quasi‐intermetallic compounds of Ni3P were formed under as‐deposited conditions before the heat treatment. The samples obtained after the heat treatment were in the form of larger crystal grains of Ni3P structure. Copyright © 2001 John Wiley & Sons, Ltd.
Quantitative elemental mapping and characterization of the homogeneity of element distribution in polymer foils by microbeam x‐ray fluorescence spectrometry
Authors: Wȩgrzynek Dariusz
Published: August 2002

Microbeam XRF measurements of polymer foils of different thickness were performed to compare the homogeneity of the distributions of element admixtures in plastics (polycarbonate foils). The measurements were performed with an energy‐dispersive x‐ray fluorescence spectrometer utilizing capillary optics. The spatial resolution of the spectrometer set‐up was about 30 µm. The distributions of Ti, Cr, Fe, Sr and Ba were investigated. The samples were prepared from plastic foils having different thickness ranging from about 90 to 2600 µm. For each sample, line scan measurements were carried out, each line scan consisting of 128 points. The local concentrations of elements along the scanned path were calculated using the modified backscatter fundamental parameter method. The influence of the foil thickness on the element distributions obtained was observed. It was found that of the investigated elements, barium had the most uneven distribution. Copyright © 2001 John Wiley & Sons, Ltd.
Extension of PROZA96 to conditions of non‐perpendicular incidence of the electron beam
Authors: Bastin G. F. , Oberndorff P. J. T. L. , Dijkstra J. M. , Heijligers H. J. M.
Published: August 2002

An extension of our double Gaussian PROZA96 correction program for EPMA is presented, which can handle non‐perpendicular incidence of the electron beam. The description of the changes in the primary intensity generated in the specimen and of the changes in the integral of φ(ρz) with tilt are taken from the literature. The extreme changes in the shape of φ(ρz) are modeled by a gradual transition of the original double Gaussian shape at zero tilt, through a mixed Gaussian/single‐exponential (for tilt angles up to 60°), to finally a mixed Gaussian/double‐exponential shape (for tilt angles exceeding 60°). The left‐hand (rising) branch of φ(ρz) is assumed to retain its original Gaussian form during tilting. Tests on the limited data available in the literature have shown that the performance of this new extended model is very promising. Copyright © 2001 John Wiley & Sons, Ltd.
Quantitative analysis of metallic ultra‐thin films by grazing‐exit electron probe x‐ray microanalysis
Authors: Spolnik Z. , Tsuji K. , Saito K. , Asami K. , Wagatsuma K.
Published: August 2002

Grazing‐exit electron probe x‐ray microanalysis (GE‐EPMA) was used for the quantitative analysis of films with thicknesses of 10 and 4 nm. First‐order calibration curves were obtained for the determination of Ti and Cr over a wide range of concentrations. The results confirmed that matrix effects are negligible when the film thickness is below some critical value. The minimum detection limits were obtained at the small exit angles (0.75° for the 10 nm thick film on the gold and 0.53° for the 4 nm thick film on the silicon substrate). Detection limits were improved by a factor of 6.5 under grazing exit conditions for the film with a thickness of 10 nm and by a factor of 2 for the film with a thickness of 4 nm, compared with detection limits obtained at 45°. Copyright © 2002 John Wiley & Sons, Ltd.
Gene order in a 10 275 bp fragment of Yarrowia lipolytica, including adjacent YlURA5 and YlSEC65 genes conserved in four yeast species
Authors: Sánchez Manuel , Domínguez Angel
Published: August 2002

We have determined the sequence of a 10275 bp DNA segment of Yarrowia lipolytica located on chromosome VI. The sequence contains six complete open reading frames (ORFs) longer than 100 amino acids and two more partial ORFs at both ends. Two of the ORFs encode for the well‐characterized genes YlURA5 (orotate phosphoribosyltransferase) and YlSEC65 (encoding a subunit of the signal recognition particle). These two genes show an identical organization—located on opposite strands and in opposite orientations—in four yeast species: Saccharomyces cerevisiae, Kluyveromyces lactis, Candida albicans and Y. lipolytica. One ORF and the two partial ORFs code for putative proteins showing significant homology with proteins from other organisms. YlVI‐108w (partial) and YlVI‐103w show 39% and 54% identity, respectively, with YDR430c and YHR088w from S. cerevisiae. YlVI‐102c (partial) shows significant homology with a matrix protein, lustrin A from Haliotis rufescens, and with the PGRS subfamily (Gly‐rich proteins) of Mycobacterium tuberculosis. The three remaining ORFs show weak or non‐significant homology with previously sequenced genes. The nucleotide sequence has been submitted to the EMBL database under Accession No. AI006754. Copyright © 2001 John Wiley & Sons, Ltd.
A minisatellite sequence in the upstream region of the DURA3 gene from the halotolerant yeast Debaryomyces hansenii
Authors: Bansal Parmil K. , Sharma Pratima , Mondal Alok K.
Published: August 2002

The URA3 gene of Debaryomyces hansenii, encoding orotidine 5′‐phosphate decarboxylase enzyme, was isolated by complementation in the yeast Saccharomyces cerevisiae. The deduced amino acid sequence is highly similar to Ura3 proteins from other yeast and fungal species. Analysis of the region upstream of the coding sequence revealed the presence of AG‐rich minisatellite DNA sequences. In addition, upstream of the DURA3 sequence, we have found the 3′‐terminal of a gene encoding a GEA2‐like protein. The GenBank Accession No. of this sequence is AY033329. Copyright © 2001 John Wiley & Sons, Ltd.
Characterization of the sec1‐1 and sec1‐11 mutations
Authors: Brummer Mirko H. , Kivinen Katja J. , Jäntti Jussi , Toikkanen Jaana , Söderlund Hans , Keränen Sirkka
Published: August 2002

Sec1 proteins are implicated in positive and negative regulation of SNARE complex formation. To better understand the function of Sec1 proteins we have identified the nature of the temperature‐sensitive mutations in sec1‐1 and sec1‐11. The sec1‐1 mutation changes a conserved glycine443 to glutamic acid. The sec1‐11 mutation changes a highly conserved arginine432 to proline. Based on homology and the crystal structure of the mammalian nSec1p, the corresponding amino acids localize to the 3b domain of nSec1p. Compared to the wild‐type Sec1p the mutant proteins are less abundant even at the permissive temperature. Thus, the R432P and G443E mutations may cause structural alterations that affect folding and make the mutant proteins more susceptible to degradation. The remaining part is sufficient for growth and protein secretion at 24°C and thus is likely to be properly folded. At 37°C the mutant proteins become non‐functional. In pulse–chase‐type experiments the newly synthesized Sec1‐1 and Sec1‐11 proteins decayed similarly with the wild‐type protein. Thus, the non‐functionality of the mutant proteins cannot be explained by denaturation‐induced degradation only. It is possible that the newly synthesized mutant proteins fold slowly and are susceptible to degradation before they have managed to fold and associate with other proteins. The mutant proteins were unable to interact with the Sec1p‐interacting proteins Mso1p and Sso2p in the two‐hybrid assay, even at the permissive temperature. These results localize sec1‐1 and sec1‐11 mutations to a domain of Sec1p and suggest a mechanism by which sec1‐1 and sec1‐11 cells become temperature‐sensitive. Copyright © 2001 John Wiley & Sons, Ltd.
In vivo selectively infective phage as a tool to detect protein interactions: evaluation of a novel vector system with yeast Ste7p–Fus3p interacting proteins
Authors: Hertveldt Kirsten , Robben Johan , Volckaert Guido
Published: August 2002

The selectively infective phage (SIP) approach allows rapid identification of interacting proteins by linking protein–protein interaction to phage infectivity. Infection of E. coli by filamentous phage depends on viral g3p. This protein consists of three domains, N1, N2 and CT. Phages lacking the N1 domain are non‐infective unless a bait (X)–prey (Y) interaction links it to phage anchored N2–CT domains. We have developed all the vectors required for an in vivo selectively infective phage strategy (SIP). This includes a bait vector, pG3N1, a prey vector, pHOS41, and a gene III deletion helper phage, HPd3. The bait vector pG3N1 allows expression of a bait protein (X) fused to the C‐terminus of the N1 domain. The prey vector pHOS41 allows expression of prey (Y) proteins, fused to the N‐terminus of the N2–CT domains. The gene III deletion helper phage delivers all phage proteins necessary for phage production, except g3p. Escherichia coli transformed with these three vectors produces non‐infective phages unless a bait–prey interaction links the g3p domains. Fus3p and Ste7p, two proteins from the Saccharomyces cerevisiae pheromone‐responsive pathway have been cloned to evaluate the SIP strategy. The presence of the interacting N1–Fus3p adapter increased the infectivity of Ste7p–N2–CT phages ∼1400‐fold, which makes SIP a promising technology for the detection and further investigation of interacting proteins. Copyright © 2002 John Wiley & Sons, Ltd.
Mutations in the Lcb2p subunit of serine palmitoyltransferase eliminate the requirement forthe TSC3 gene in Saccharomyces cerevisiae
Authors: Monaghan Erin , Gable Ken , Dunn Teresa
Published: August 2002

Serine palmitoyltransferase catalyses the committed step in sphingolipid synthesis, the condensation of serine with palmitoyl‐CoA to form 3‐ketosphinganine. Two proteins, Lcb1p and Lcb2p, are essential for enzyme activity and a third protein, the 80‐amino acid Tsc3p, stimulates the activity of serine palmitoyltransferase several‐fold. Tsc3p physically associates with a complex of Lcb1p–Lcb2p and stimulates enzyme activity post‐translationally, but its precise function is not known. Tsc3p is essential for cell viability only at elevated temperatures, although serine palmitoyltransferase activity is reduced in the tsc3Δ mutant, even at permissive growth temperatures. Tsc3p is apparently not required for any essential process besides stimulation of serine palmitoyltransferase at 37°C, since providing sphingoid bases to the growth medium reverses the temperature‐sensitive growth phenotype of the tsc3Δ mutant. To gain further insight into the function of Tsc3p, suppressor mutants that eliminate the Tsc3p requirement for growth at 37°C were isolated and characterized. These studies show that dominant mutations in the Lcb2p subunit of serine palmitoyltransferase suppress the temperature‐sensitive growth phenotype of the tsc3Δ null mutant by increasing the Tsc3p‐independent serine palmitoyltransferase activity. Copyright © 2002 John Wiley & Sons, Ltd.
Lories and lorikeets in field and aviary
Authors: Mejeur James H.
Published: August 2002

A review of Hancock House Encyclopedia of the Lories, by Rosemary Low. Blaine, Washington, Hancock House Publishers LTD, 1998, 432 pp, $70.00, hardbound.
Long‐term administration of α‐tocopherol in captive Asian elephants (Elephas maximus)
Authors: Kenny David E.
Published: August 2002

After the loss of an African elephant (Loxodonta africana) in February 1989 at the Denver Zoological Gardens (DZG) with very low circulating serum α‐tocopherol, a long‐term study was initiated with three Asian elephants (Elephas maximus) to evaluate the effect of an oral micellized, water‐soluble, natural source d‐α‐tocopherol supplement. Baseline α‐tocopherol levels were evaluated and found to be approximately 3.75‐fold less than those reported for semi‐free‐ranging Asian Nepalese work camp and free‐ranging African elephants. The DZG elephants were then administered a liquid d‐α‐tocopherol (Emcelle®) at 2.2 IU/kg body weight orally once daily. Serum samples were obtained and analyzed at 1, 2, 8, and 12 months and then annually for 96 months. The oral vitamin E supplement significantly elevated serum levels above baseline and were found to be comparable with levels reported for semi–free‐ranging and free‐ranging elephants. Zoo Biol 20:245–250, 2001. © 2001 Wiley‐Liss, Inc.
The effects of prorating risk in the development of life‐tables
Authors: Odum R. Andrew , Smith Brandie R.
Published: August 2002

This study used computer models to investigate two different strategies for assessing risk in the development of age‐based life‐tables from studbook data sets. One methodology is similar to that currently employed in American Zoo and Aquarium Association population management, which prorates animals at risk within age‐classes. The other follows the method used in human life‐tables that assumes animals are at risk for the entire age‐class. This study concludes that prorating risk may invalidate population growth projections by significantly and unequally over‐estimating fecundity and mortality rates. This effect is most pronounced in species that have distinct breeding seasons (birth pulse populations), seasonal mortality, and small data sets. Recommendations include using a non‐prorated methodology, tabulating life‐tables using only completely known age‐class data, and combining population parameters for emigrations, releases, and deaths for population growth projections. Zoo Biol 20:279–291, 2001. © 2001 Wiley‐Liss, Inc.
Landmarks in the Development of Hematopoietic Cell Transplantation
Authors: Thomas E. Donnall
Published: August 2002

The field of bone marrow transplantation has evolved over a period of 50 years. Reports of beneficial treatment of murine leukemia by irradiation and injection of marrow cells from another mouse stimulated interest in attempting to use these techniques to treat patients with leukemia. The first few bold attempts at human application were generally met with a total lack of success except for a few transplants involving identical twins. Understanding the HLA system led to the ability to select compatible sibling donors. The first successful long‐term survivors were reported at the end of the 1960s. During the 1970's patients were given transplants for leukemia after failure of all other treatment. Survivals were poor, but some patients were cured. Transplantation early in the course of the disease resulted in greatly improved survival. During the 1980s improved control of infections, the use of peripheral blood as the source of stem cells, and the ability to select donors other than family members resulted in wide application of hematopoietic cell grafting.
Screening for Early Colorectal Cancer
Authors: Kronborg Ole
Published: August 2002

There is now solid evidence from randomized trials suggesting that it is possible to reduce mortality from colorectal cancer by 15% to 25% by screening with fecal occult blood tests (FOBTs). The major benefit results from detection of early cancer in average‐risk persons above 50 years of age who have a positive test followed by colonoscopy. However, it has to be demonstrated that the same acceptability can be reached in the general population as that obtained in trials. Many countries must establish a screening organization in a limited area to learn how satisfactory quality assurance can be obtained before a country‐wide screening program is set up. So far, screening has not resulted in a reduced incidence of colorectal cancer in true population studies despite removal of two to three times as many possible precursors compared to controls. Cost‐effectiveness will probably be as good as that known from screening for breast cancer with mammography and better than that for cervical cancer. However, the calculations are based on the unhydrated Hemoccult‐II test in randomized trials. More sensitive methods would be attractive, but none has yet been evaluated properly in average‐risk persons. There is no general agreement how to screen high risk groups such as patients with previous colorectal adenomas and carcinomas, one or two first‐degree relatives with colorectal neoplasia, or ulcerative colitis. Families with familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, however, are presented with firm guidelines. Genetic screening has been helpful in no more than these two small groups in the colorectal carcinoma universe.
Contribution to the History of Plastic and Reconstructive Surgery from Dubrovnik and Split during the Fourteenth to Sixteenth Centuries
Authors: Bacic Jurica , Skrobolja Ante , Kojic Niksa , Polanda‐Bacic Gordana
Published: August 2002

Medieval contracts for medical treatment are, without doubt, evidence of proper and adequate insight into the quality of operations performed centuries ago. Historical archives in Dalmatian cities have preserved a certain number of such contracts. Their contents assist in better understanding our historical heritage. This paper submits contracts, kept in Dubrovnik and Split, for the operation of inguinal hernia. A case depicting a defective palate treated by Amatus Lusitanus, who lived in Dubrovnik from 1555 to 1558, is also presented.
Study of Three Patients with Congenital Adrenal Hyperplasia Treated by Bilateral Adrenalectomy
Authors: Warinner Sonja A. , Zimmerman Donald , Thompson Geoffrey B. , Grant Clive S.
Published: August 2002

Medical management of congenital adrenal hyperplasia (CAH) patients has led to suboptimal results in most cases. High glucocorticoid doses, often needed to suppress adrenal androgen production, may lead to signs of Cushing syndrome. Incompletely suppressed androgen levels commonly lead to premature closure of growth centers, acne, virilization, precocious puberty, irregular or absent menses, and decreased fertility in female CAH patients. A newly proposed therapy for CAH patients is bilateral adrenalectomy. Three Caucasian female patients with 21‐hydroxylase deficiency were treated with bilateral adrenalectomy. Two of the three procedures were accomplished laparoscopically. In each patient, medical management alone was unsuccessful. Two patients had salt‐losing 21‐hydroxylase deficiency. The third patient had uncontrolled hyperandrogenism complicated by obesity and glucose intolerance. All patients had low height percentiles with respect to their normalized percentiles for weight. Bone age was advanced in one patient. Androgen and renin levels were well controlled in two patients, whereas the third patient had persistent hyperandrogenism. Bilateral adrenalectomy was performed at the ages of 14, 19, and 30 years with follow‐up, to date, of 25 months, 10 months, and 26 months, respectively. Postoperatively, all patients were free from hyperandrogenism. One patient experienced one episode of urosepsis precipitating an addisonian crisis. Bilateral adrenalectomy may successfully address the problems of increasing steroid requirements and hyperandrogenism in patients with severe CAH. The ability to perform this operation laparoscopically coupled with the overall metabolic benefits make bilateral adrenalectomy a reasonable alternative to lifelong androgen suppression in select patients.
Advances in the Staging of Intrathoracic Malignancies
Authors: Whyte Richard I.
Published: August 2002

Heading

Conventional staging of lung and esophageal tumors has consisted of a thorough history and physical examination, screening laboratory studies, computed tomography, and radionuclide imaging. Newer modalities including positron emission scanning, endoscopic ultrasonography, minimally invasive surgery (laparoscopy and thoracoscopy), and immunohistochemical staining of lymph node tissue. The roles of these techniques are subject to much current debate, and they may ultimately add information that is valuable for staging and optimally treating patients with intrathoracic malignancies.
Temporary Pancreatic Duct Occlusion by Ethibloc: Cause of Microcirculatory Shutdown, Acute Inflammation, and Pancreas Necrosis
Authors: Plusczyk Thorsten , Westermann Simone , Bersal Björn , Menger Michael , Feifel Gernot
Published: August 2002

Temporary obliteration of the pancreatic duct has been suggested to be beneficial in chronic pancreatitis, segmental pancreatic transplantation, and following Roux‐Y pancreaticojejunostomy. Little is known, however, as to whether obliteration of the duct alters exocrine pancreatic physiology. Therefore we studied in male inbred Lewis rats the immediate effects of Ethibloc‐induced duct obliteration (Ethibloc: Ethicon, Norderstedt, Germany) on pancreatic microcirculation, inflammation, and tissue injury (n= 8), and compared these effects with those caused by experimental pancreatitis (4% sodium taurocholate; n= 8). Animals receiving an intraductal infusion of saline served as controls (n= 8). Duct occlusion with Ethibloc resulted in a marked decrease (p < 0.05) in capillary red blood cell (RBC) velocity and functional capillary density (FCD) to 88 ± 39 μm/s (baseline 716 ± 40 μm/s) and 72 ± 33 cm−1 (baseline 493 ± 21 cm−1), respectively, which was even more pronounced when compared with that observed in experimental pancreatitis (333 ± 62 μm/s and 195 ± 44 cm−1, respectively). In parallel, the manifestation of tissue damage was found to be more severe after Ethibloc; and chloracetate esterase staining showed a larger number of infiltrating leukocytes [555 ± 86/high power field (HPF) versus pancreatitis: 160 ± 12/HPF; p < 0.05). We conclude that intraductal application of Ethibloc induces significant microcirculatory failure and a marked inflammatory response, which are even more pronounced when compared with the changes observed with experimental pancreatitis. Based on these results and the fact that there is no direct proof for a benefit of temporary duct occlusion by Ethibloc, it is proposed that the procedure be reevaluated for its use in pancreatic surgery.
Liver Metastatic Model for Human Gastric Cancer Established by Orthotopic Tumor Cell Implantation
Authors: Yamaguchi Koji , Ura Hideki , Yasoshima Takahiro , Shishido Takayuki , Denno Ryuichi , Hirata Koichi
Published: August 2002

We have established an orthotopic implantation model that is highly metastatic to the liver. A human gastric carcinoma cell line, AZ521, with low capacity for liver metastasis was implanted as a single‐cell suspension in the stomach of nude mice. The tumor cells derived from a few liver metastatic foci were subsequently implanted orthotopically, and we established a cell line, AZH5G, by repeating the in vivo stepwise selection method. This metastasizing line (AZH5G) developed liver metastasis in seven of eight (87.5%) cases, whereas parental AZ521 developed in 3 of 20 (15.0%). The in vitro growth activities of AZH5G were lower than that of AZ521, although the in vivo tumorigenicity of AZH5G was clearly higher than that of AZ521. Motility assays demonstrated higher motility of AZH5G than of AZ521. Flow cytometric analysis demonstrated that the expression of α6‐integrin significantly decreased in AZH5G (4.9% ± 4.1%) compared to in AZ521 (17.7% ± 8.1%) (p < 0.05). The adhesive activity of AZH5G cells to laminin was lower than that of AZ521 cells. In contrast, the adhesive activity of AZH5G cells to fibronectin was clearly higher than that of AZ521 cells. These findings suggested that changes in the expression of integrins on the cell surface might play an important role in metastatic ability. This well characterized line and its in vivo experimental model should be useful to investigate the mechanisms of liver metastasis and to develop a new therapeutic approach for human gastric cancer.
Inguinal Hernia Repair in the New Millennium: Plug and Patch Repair with Local Anesthesia
Authors: Zieren Jürgen , Hoksch Beatrix , Wenger Frank A. , Opitz Isabell , Müller Jochen M.
Published: August 2002

Plug and patch repair is a safe, economic method for repairing inguinal hernias, with patient comfort comparable to that with laparoscopic hernia repair. The technique is simple to perform under local anesthesia and easily learned without a learning curve. Complications are rare, and recovery and return to work are rapid. After performing plug and patch repair on 400 patients with a follow‐up examination rate of 93% and a median postoperative observation time of 42 months, we have recorded a recurrence rate of only 0.25%.
Can the Use of Growth Hormone Reduce the Postoperative Fatigue Syndrome?
Authors: Vara‐Thorbeck R. , Guerrero J. A. , Ruiz‐Requena E. , García‐Carriazo M.
Published: August 2002

Convalescence after surgery is characterized by a period of fatigue (POF). If we assume that the POF syndrome has a multifactorial etiology, it is clear that the aim of therapeutic measures should be to reduce the response to surgical stress. The purpose of the present study was to determine if administering exogenous human growth hormone (hGH) can prevent the development or reduce the duration of the POF. We carried out a placebo‐controlled randomized double‐blind trial with 48 patients after elective cholecystectomy (placebo, or control group,n= 26; hGH‐treated group,n= 22). Eligibility criteria were strict so as to introduce as few variables as possible. The results obtained in the study show that for moderate surgical injury (cholecystectomy in metabolically healthy subjects) the administering of low doses of hGH (8 IU/day) minimized the POF syndrome (Christensen score). Furthermore, a positive nitrogen balance was achieved in the hGH‐treated group during the postoperative period from the first 24 hours onward. This finding correlates with the significant increase in serum levels of hGH (p< 0.05) and insulin‐like growth factor 1 (IGF‐1) (p< 0.001). On the other hand, anthropometric measurements in the hGH‐treated group revealed a slight but continuous decrease in body weight and thickness of the triceps skinfold; however, arm muscle circumference did not significantly change during the postoperative period. These findings are related to the effects of the application of exogenous growth hormone, which preserves or increases lean body mass and reduces adipose tissue mass. The serum transferrin level proved to be a reliable biochemical indicator of POF.
Stromal Fibroblasts Adjacent to Invasive Thyroid Tumors: Expression of Gelatinase A But Not Stromelysin 3 mRNA
Authors: Zedenius Jan , Ståhle‐Bäckdahl Mona , Enberg Ulla , Grimelius Lars , Larsson Catharina , Wallin Göran , Bäckdahl Martin
Published: August 2002

Thyroid tumors vary widely in biologic behavior; they range from benign adenomas to rapidly growing anaplastic carcinomas. Among thyroid neoplasms, the follicular tumor is especially suited as a model for studies of tumor cell invasion; the distinction between adenomas and carcinomas relies mainly on the presence of capsular and vascular invasion. Matrix metalloproteinases play an important role in tumor cell invasion, as they are able to degrade basement membrane and extracellular matrix components. Twenty‐nine thyroid tumors of varying type and aggressiveness were selected for analysis of relative molecular weight 72,000‐dalton type IV collagenase (gelatinase A) expression by mRNA in situ hybridization. Strong gelatinase A mRNA expression was seen in 10 of 14 follicular carcinomas, in none of six follicular adenomas, in all four anaplastic carcinomas, and in four of five papillary carcinomas. The expression was restricted to fibroblasts in the stroma adjacent or close to invading tumor cells. Twelve of the tumors were also investigated for expression of stromelysin 3 mRNA, no expression of which was detected in any tumor. The findings suggest that gelatinase A contributes to the invasive process and spread of aggressive thyroid tumors.
Management of Carcinoid Tumors of the Stomach, Duodenum, and Pancreas
Authors: Åkerström Göran
Published: August 2002

Carcinoids of the stomach, duodenum, and pancreas are represented by a variety of tumors with variable histologic and clinical features. Multicentric gastric carcinoids and concomitant nonantral argyrophilic hyperplasia are common in chronic atrophic gastritis, more rarely due to a multiple endocrine neoplasia (MEN)‐related Zollinger‐Ellison syndrome (ZES). These tumors are infrequently associated with metastases and may generally be dealt with by repeated endoscopic fulguration. Sporadic carcinoids tend to be larger, invasive, and more often metastatic, especially in the presence of atypical histology. Small tumors may be removed by endoscopy, but larger lesions need to be surgically excised. In association with metastases a histamine‐related atypical carcinoid syndrome may evolve and require treatment with a somatostatin analog. Poorly differentiated neuroendocrine carcinomas of the stomach constitute markedly aggressive tumors that rarely are suitable for radical surgery. Gastrinomas are the most prevalent duodenal carcinoids and a common cause of ZES especially in MEN‐I. Despite a marked tendency for regional lymph node dissemination, liver metastases occur late and duodenal gastrinomas are often excisable, thereby offering favorable odds for cure in ZES. Unusual somatostatin‐rich carcinoids in the ampulla of Vater relate to von Recklinghausen’s disease and may be the cause of obstructive jaundice; depending on their size, these tumors may be removed by local excision or pancreaticoduodenectomy. Gangliocytic paragangliomas are unusual, generally benign lesions of the duodenum. Rare pancreatic tumors with serotonin immunoreactivity may be classified as carcinoids and constitute an unusual cause of the carcinoid syndrome.
Acute Surgical Treatment of Complicated Peptic Ulcers with Special Reference to the Elderly
Authors: Bulut Orhan , Rasmussen Christian , Fischer Anders
Published: August 2002

The results of 136 consecutive patients treated surgically for the acute complications of peptic ulcers between 1990 and 1993 are reviewed. All patients required emergency operation. Among 136 patients, 91 had perforations, 42 hemorrhage, and 3 a penetrated peptic ulcer. The median age was 77 years; 65% were women; and 83% were more than 60 years old. Concurrent disease requiring medical treatment were present in 92 patients; 79 patients (58%) were currently or recently taking antiinflammatory drugs at the time of admission; 66% of the patients had duodenal ulcer. Only 46 patients (34%) had no postoperative complications; pneumonia, arrhythmia, bleeding, and septic complications were the most frequent. The overall mortality was 30%. Sepsis and multiple organ failure was the leading cause of death in most of the patients. It was concluded that elderly individuals using two or more antiinflammatory drugs should be considered potential peptic ulcer patients and should be treated prophylactically with ulcer‐healing drugs.
Endovascular Repair of Abdominal Aortic Aneurysms Using the EGS Tube and Bifurcated Graft Systems
Authors: Colburn Michael D. , Moore Wesley S.
Published: August 2002

Left untreated, aneurysmal disease of the abdominal aorta is a highly lethal condition. Standard transabdominal repair of aortic aneurysm, although successful and durable, continues to be plagued by significant morbidity, mortality, and cost. Placement of an endovascular graft through a femoral arteriotomy is a new technique that could potentially reduced this morbidity and cost without sacrificing efficacy. This report details the development of a U.S. Food and Drug Administration (FDA)‐approved endovascular grafting device. In addition, we describe our experience screening patients and summarize our clinical experience with the placement of both tube and bifurcated endovascular graft systems. To date, 16 patients have undergone endovascular repair with a tube graft at UCLA, and three bifurcated grafts have been placed. Two patients required conversion to conventional open aneurysm repair. All the remaining procedures were successful, and there were no perioperative deaths or major complications. We conclude that endovascular grafting of aortic aneurysms is both feasible and safe. Long‐term patency and the ability of this technique to prevent the known complications of aortic aneurysmal disease remain unanswered questions at this time.
Retroperitoneal Nephrectomy: Comparison of Laparoscopy with Open Surgery
Authors: Doublet Jean D. , Barreto Helio S. , Degremont Anne C. , Gattegno Bernard , Thibault Philippe
Published: August 2002

Retroperitoneal laparoscopic nephrectomy (RLN) is a relatively recent technique whose performance needs to be firmly established. The aim of this study was to compare the results of RLNs in 19 patients with retrospective results for 10 cases of open surgery. Ten of the RLN patients had transplanted kidneys. We used a slightly modified, already published technique with only three trocars that did not require balloon dilatation of the retroperitoneal space. It was successful in patients with and without transplants. The average operative times of RLN and open surgery were 115 and 110 minutes, respectively. In no instance did the laparoscopic procedure need to be converted to open surgery. There were no peri‐ or postoperative complications that could be related to the RLN technique. The average length of hospitalization after RLN was considerably shorter (3.8 days) than after open surgery (7.9 days). In conclusion, our experience shows that RLN is a safe, reproducible technique that reduces recovery time. It has become our first‐line approach for simple nephrectomy, nephroureterectomy for ureteral tumors, and removal of the native kidney in transplant recipients.