bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptation of mammalian protein metabolism to amino acid
supply
Authors: Munro Hamish N.
Published: December 2005

The metabolism of the animal is equipped to adapt to changes in both the
internal and the external environment. Among internal factors are activity
versus rest and sleep, and the menstrual cycle in the case of the female.
Metabolism must also respond to variations in the external environment, such
as heat and cold, and notably the availability of food. Metabolic adaptation
to nutrient supply is of two kinds. First, there are transient physiological
adaptations to the intermittent intake of nutritionally adequate meals.
These short-lived adaptations account for a large part of the diurnal
variations that have been observed in the protein metabolism of mammals
(Wurtman, 1969). Secondly, long-term adaptive reactions occur when there is
a decrease in availability of an essential nutrient in the diet. Under such
circumstances, tissue constituents are lost to varying degrees from
different parts of the body. It is proposed to discuss here mainly
short-term physiological adaptations to variations in amino acid supply and
their relevance to the needs of the body for dietary protein. Adaptive
changes resulting from long-term protein deficiency are considered in the
paper by Waterlow & Stephen (1969).
Assessment of protein requirements by nitrogen
balance
Authors: Miller D. S. , Payne P. R.
Published: December 2005

The earliest estimates of protein requirements, such as those of Smith
(1863) and Pavy (1874) who recommended about 125 g per day for the average
working man, were based on studies of the diets of individuals or of groups
of subjects who were considered to be healthy and leading normal active
lives. Such estimates were simply a reflection of the dietary habits of
those under study, but helped to establish minimum standards of feeding in
institutions. About the turn of the century, similar recommendations ranging
from 118 to 150 g were made by Voit (1881), Atwater (1895) and Rubner (1903)
(Fig. 1), and these came to be vigorously defended as representing not
merely feeding standards but as irreducible minima below which a proper
state of health and vigour could not be maintained.
The control of haemoglobin synthesis: factors controlling the
output of α and β chains
Authors: Hunt R. T. , Hunter A. R. , Munro A. J.
Published: December 2005

Analysis of the effects of amino acid starvation in reticulocytes is
comparatively simple compared with similar analysis in other tissues of
whole organisms. This is mainly because of the absence of RNA synthesis in
reticulocytes, but also because the bulk of the protein being synthesized is
haemoglobin, a protein whose structure is completely known. The absence of
RNA synthesis eliminates complications that would otherwise arise through
RNA-mediated control mechanisms which in turn might mask the effects of
amino acid starvation on the protein synthetic machinery in the cells
(Munro, 1969). Consequently reticulocytes have been used to study the effect
of amino acid starvation on the actual process of protein synthesis and
assembly.
Complementary ways of meeting the world’s protein need
Authors: Pirie N. W.
Published: December 2005

Before considering the various possible protein sources, we must make some sort of estimate of the possible protein need by—say—the end of the century. That estimate controls the amount of effort we should put into work on protein supplies and the degree of novelty that we should envisage. The estimate depends on the number of people to be fed and the amount of protein that each needs. Both quantities are uncertain: the first because it must be guessed, the second because it is hotly disputed.
Cell Cycle-regulated Trafficking of Human Telomerase to Telomeres
Authors: Tomlinson Rebecca L. , Ziegler Tania D. , Supakorndej Teerawit , Terns Rebecca M. , Terns Michael P.
Published: December 2005

Telomerase synthesizes telomeres at the ends of human chromosomes during S phase. The results presented here suggest that telomerase activity may be regulated by intranuclear trafficking of the key components of the enzyme in human cells. We examined the subcellular localization of endogenous human telomerase RNA (hTR) and telomerase reverse transcriptase (hTERT) in HeLa cervical carcinoma cells. Throughout most of the cell cycle, we found that the two essential components of telomerase accumulate at intranuclear sites separate from telomeres. However, during S phase, both hTR and hTERT are specifically recruited to subsets of telomeres. The localization of telomerase to telomeres is dynamic, peaking at mid-S phase. We also found complex associations of both hTR and hTERT with nucleoli and Cajal bodies during S phase, implicating both structures in the biogenesis and trafficking of telomerase. Our results mark the first observation of human telomerase at telomeres and provide a mechanism for the cell cycle-dependent regulation of telomere synthesis in human cells.
TRAP: automated classification, quantification and annotation of tandemly repeated sequences
Authors: Sobreira Tiago José P. , Durham Alan M. , Gruber Arthur
Published: December 2005

Summary: TRAP, the Tandem Repeats Analysis Program, is a Perl program that provides a unified set of analyses for the selection, classification, quantification and automated annotation of tandemly repeated sequences. TRAP uses the results of the Tandem Repeats Finder program to perform a global analysis of the satellite content of DNA sequences, permitting researchers to easily assess the tandem repeat content for both individual sequences and whole genomes. The results can be generated in convenient formats such as HTML and comma-separated values. TRAP can also be used to automatically generate annotation data in the format of feature table and GFF files.

Availability: TRAP is available under the GNU General Public License at

Contact:  argruber@usp.br

Supplementary Information: Supplementary data are available at
A support vector machine-based method for predicting the propensity of a protein to be soluble or to form inclusion body on overexpression in Escherichia coli
Authors: Idicula-Thomas Susan , Kulkarni Abhijit J. , Kulkarni Bhaskar D. , Jayaraman Valadi K. , Balaji Petety V.
Published: December 2005

Motivation: Inclusion body formation has been a major deterrent for overexpression studies since a large number of proteins form insoluble inclusion bodies when overexpressed in Escherichia coli. The formation of inclusion bodies is known to be an outcome of improper protein folding; thus the composition and arrangement of amino acids in the proteins would be a major influencing factor in deciding its aggregation propensity. There is a significant need for a prediction algorithm that would enable the rational identification of both mutants and also the ideal protein candidates for mutations that would confer higher solubility-on-overexpression instead of the presently used trial-and-error procedures.

Results: Six physicochemical properties together with residue and dipeptide-compositions have been used to develop a support vector machine-based classifier to predict the overexpression status in E.coli. The prediction accuracy is ∼72% suggesting that it performs reasonably well in predicting the propensity of a protein to be soluble or to form inclusion bodies. The algorithm could also correctly predict the change in solubility for most of the point mutations reported in literature. This algorithm can be a useful tool in screening protein libraries to identify soluble variants of proteins.

Avalibility: Software is available on request from the authors.

Contact:  balaji@iitcb.ac.in; vk.jayaraman@ncl.res.in

Supplementary information: Supplementary data are available at Bioinformatics Online web site.
In silico sequence evolution with site-specific interactions along phylogenetic trees
Authors: Gesell Tanja , von Haeseler Arndt
Published: December 2005

Motivation: A biological sequence usually has many sites whose evolution depends on other positions of the sequence, but this is not accounted for by commonly used models of sequence evolution. Here we introduce a Markov model of nucleotide sequence evolution in which the instantaneous substitution rate at a site depends on the states of other sites. Based on the concept of neighbourhood systems, our model represents a universal description of arbitrarily complex dependencies among sites.

Results: We show how to define complex models for some illustrative examples and demonstrate that our method provides a versatile resource for simulations of sequence evolution with site-specific interactions along a tree. For example, we are able to simulate the evolution of RNA taking into account both secondary structure as well as pseudoknots and other tertiary interactions. To this end, we have developed a program Simulating Site-Specific Interactions (SISSI) that simulates evolution of a nucleotide sequence along a phylogenetic tree incorporating user defined site-specific interactions. Furthermore, our method allows to simulate more complex interactions among nucleotide and other character based sequences.

Availability: We implemented our method in an ANSI C program SISSI which runs on UNIX/Linux, Windows and Mac OS systems, including Mac OS X. SISSI is available at

Contact:  sissi@cs.uni-duesseldorf.de
BALLView: a tool for research and education in molecular modeling
Authors: Moll Andreas , Hildebrandt Andreas , Lenhof Hans-Peter , Kohlbacher Oliver
Published: December 2005

Summary: We present BALLView, a molecular viewer and modeling tool. It combines state-of-the-art visualization capabilities with powerful modeling functionality including implementations of force field methods and continuum electrostatics models. BALLView is a versatile and extensible tool for research in structural bioinformatics and molecular modeling. Furthermore, the convenient and intuitive graphical user interface offers novice users direct access to the full functionality, rendering it ideal for teaching. Through an interface to the object-oriented scripting language Python it is easily extensible.

Availability: BALLView is an open source software and runs on all major platforms (Windows, MacOS X, Linux and most Unix flavors). It is available free of charge under the GNU Public License at

Contact:  amoll@bioinf.uni-saarland.de
Evaluating phylogenetic footprinting for human–rodent comparisons
Authors: Sauer Tilman , Shelest Ekaterina , Wingender Edgar
Published: December 2005

Motivation: ‘Phylogenetic footprinting’ is a widely applied approach to identify regulatory regions and potential transcription factor binding sites (TFBSs) using alignments of non-coding orthologous regions from two or more organisms. A systematic evaluation of its validity and usability based on known TFBSs is needed to use phylogenetic footprinting most effectively in the identification of unknown TFBSs.

Results: In this paper we use 2678 human, mouse and rat TFBSs from the TRANSFAC® database for this evaluation. To ensure the retrieval of correct orthologous sequences, we combine gene annotation and sequence homology searches. Demanding a sequence identity of at least 65% is most effective in discriminating TFBSs from non-functional sequence parts, while different alignment algorithms only have a minor influence on TFBS identification by human–rodent comparisons. With this threshold ∼72% of the known TFBSs are found conserved, a number which varies significantly between different transcription factors and also depends on the function of the regulated gene. TFBSs for certain transcription factors do not require strict sequence conservation but instead may show a high pattern conservation, limiting somewhat the validity of purely sequence-based phylogenetic footprinting.

Availability: Scripts are available from the authors upon request.

Contact:  tsa@bioinf.med.uni-goettingen.de

Supplementary information:
Gene network inference from incomplete expression data: transcriptional control of hematopoietic commitment
Authors: Missal Kristin , Cross Michael A. , Drasdo Dirk
Published: December 2005

Motivation: The topology and function of gene regulation networks are commonly inferred from time series of gene expression levels in cell populations. This strategy is usually invalid if the gene expression in different cells of the population is not synchronous. A promising, though technically more demanding alternative is therefore to measure the gene expression levels in single cells individually. The inference of a gene regulation network requires knowledge of the gene expression levels at successive time points, at least before and after a network transition. However, owing to experimental limitations a complete determination of the precursor state is not possible.

Results: We investigate a strategy for the inference of gene regulatory networks from incomplete expression data based on dynamic Bayesian networks. This permits prediction of the number of experiments necessary for network inference depending on parameters including noise in the data, prior knowledge and limited attainability of initial states. Our strategy combines a gradual ‘Partial Learning’ approach based solely on true experimental observations for the network topology with expectation maximization for the network parameters. We illustrate our strategy by extensive computer simulations in a high-dimensional parameter space in a simulated single-cell-based example of hematopoietic stem cell commitment and in random networks of different sizes. We find that the feasibility of network inferences increases significantly with the experimental ability to force the system into different initial network states, with prior knowledge and with noise reduction.

Availability: Source code is available under:

Contact:  drasdo@izbi.uni-leipzig.de

Supplementary information: Supplementary Data are available at Bioinformatics online.
Potential mechanism of resistance to TRAIL‐induced apoptosis in Burkitt's lymphoma
Authors: Tafuku Senji , Matsuda Takehiro , Kawakami Hirochika , Tomita Mariko , Yagita Hideo , Mori Naoki
Published: December 2005

Abstract:  Objectives: Members of the tumor necrosis factor family are potent inducers of apoptosis in sensitive cells and may be suitable for novel anti‐cancer therapies aimed at inducing apoptosis via the activation of receptors with the death domain on malignant cells. We characterized the sensitivity of Burkitt's lymphoma (BL) cell lines to tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) and anti‐Fas agonist, and investigated the mechanism of resistance of BL cell lines to TRAIL and Fas apoptotic pathways. Methods: Epstein–Barr virus (EBV) status in BL cell lines was determined by PCR. The extent of apoptosis following exposure to TRAIL and anti‐Fas agonist was measured by 7A6 antigen staining. Expression of TRAIL receptors and Fas was determined by flow cytometry and reverse transcriptase‐PCR. Western blot analyses were used to determine the expression of proapoptotic and antiapoptotic proteins. NF‐κB activity was evaluated by electrophoretic mobility shift assay. Results: The sensitivity of BL cell lines to anti‐Fas agonist depended on the expression of Fas. In contrast, the expression of TRAIL receptors did not correlate with the sensitivity to TRAIL‐induced apoptosis. Interestingly, EBV‐infected BL cell lines which showed constitutive levels of NF‐κB activation, were TRAIL‐resistant. NF‐κB inhibitors reversed the resistance to TRAIL‐induced apoptosis. Conclusions: Our results suggest that activation of NF‐κB by EBV infection plays an important role in resistance of BL cell lines to TRAIL‐induced apoptosis, and that NF‐κB inhibitors may be useful adjuncts in clinical use of TRAIL against BL.
Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging
Authors: Jensen Jens‐Michael , Förl Michael , Winoto‐Morbach Supandi , Seite Sophie , Schunck Michael , Proksch Ehrhardt , Schütze Stefan
Published: December 2005

Abstract:  In aged skin, decreased levels of stratum corneum ceramides have been described. Epidermal ceramides are generated by sphingomyelin hydrolysis or synthesis from sphingosin and fatty acids and are degraded by ceramidase. We recently showed that epidermal acid sphingomyelinase (A‐SMase) generates ceramides with structural function in the stratum corneum lipid bilayers, which provide for the permeability barrier function of the skin. Here, we examined the activities of epidermal A‐SMase, ceramide synthase, and ceramidase in chronologically aged versus young hairless mouse skin. We found reduced A‐SMase and ceramide synthase activities in the epidermis of aged mice. However, studies on enzyme localization revealed unchanged, ongoing high A‐SMase activity in the outer epidermis, which correlated with reported normal barrier function found in aged skin under basal conditions. Reduced A‐SMase and ceramide synthase activity was noted in the inner epidermis, correlating with reduced capacity for permeability barrier repair in aging. Ceramidase activity was not age dependent. In summary, we found reduced activities of ceramide‐generating SMase and ceramide synthase in the inner epidermis of aged skin, explaining its reduced capacity in barrier repair. In contrast, A‐SMase activity in the outer epidermis was unchanged, indicating that this enzyme is crucially involved in basal permeability barrier homeostasis.
Premature termination of hair follicle morphogenesis and accelerated hair follicle cycling in Iasi congenital atrichia (fzica) mice points to fuzzy as a key element of hair cycle control
Authors: Mecklenburg Lars , Tobin Desmond J. , Cirlan Marius V. , Craciun Constantin , Paus Ralf
Published: December 2005

Abstract:  Inbred laboratory mice have proven to be useful model systems for studying hair biology and pathomechanisms of hair loss. Fuzzy (fz) is an autosomal recessive mutation that results in hair coat abnormalities. Though this mutant has long been known, its cutaneous abnormalities still await systematic analysis. Here, we provide a systematic skin phenotype analysis of mice that are homozygous for Iasi congenital atrichia (fzica/fzica), which is allelic to fz. Homozygous mice exhibit a sparse hair coat after birth and completely loose their hair at around postnatal day 120. Although early and mid stages of hair follicle morphogenesis are normal, late hair follicle morphogenesis reveals multifocal cell degeneration within the Huxley layer of the inner root sheath (IRS) and a complete lack of the hair shaft medulla. In addition, hair follicle development is prematurely terminated by induction of the first postnatal hair cycle with premature entry into catagen. Subsequently, a dramatically shortened telogen is immediately followed by premature anagen development, resulting in a marked, generalized acceleration of hair follicle cycling. This suggests that fuzzy is not only involved in structural hair shaft integrity and differentiation of the IRS and medulla, but also plays an important role in the control of hair follicle cycling. Our data show that fuzzy is involved in controlling both catagen and anagen initiation, designating fuzzy an exciting target for characterizing the intracutaneous oscillator system that drives hair follicle cycling.
Hair growth inhibition by psychoemotional stress: a mouse model for neural mechanisms in hair growth control
Authors: Peters Eva M. J. , Arck Petra C. , Paus Ralf
Published: December 2005

Abstract:  Stress has long been discussed controversially as a cause of hair loss. However, solid proof of stress‐induced hair growth inhibition had long been missing. If psychoemotional stress can affect hair growth, this must be mediated via definable neurorendocrine and/or neuroimmunological signaling pathways. Revisiting and up‐dating relevant background data on neural mechanisms of hair growth control, we sketch essentials of hair follicle (HF) neurobiology and discuss the modulation of murine hair growth by neuropeptides, neurotransmitters, neurotrophins, and mast cells. Exploiting an established mouse model for stress, we summarize recent evidence that sonic stress triggers a cascade of molecular events including plasticity of the peptidergic peri‐ and interfollicular innervation and neuroimmune crosstalk. Substance P (SP) and NGF (nerve growth factor) are recruited as key mediators of stress‐induced hair growth‐inhibitory effects. These effects include perifollicular neurogenic inflammation, HF keratinocyte apoptosis, inhibition of proliferation within the HF epithelium, and premature HF regression (catagen induction). Intriguingly, most of these effects can be abrogated by treatment of stressed mice with SP‐receptor neurokinin‐1 receptor (NK‐1) antagonists or NGF‐neutralizing antibodies – as well as, surprisingly, by topical minoxidil. Thus there is now solid in vivo‐evidence for the existence of a defined brain‐ HF axis. This axis can be utilized by psychoemotional and other stressors to prematurely terminate hair growth. Stress‐induced hair growth inhibition can therefore serve as a highly instructive model for exploring the brain‐skin connection and provides a unique experimental model for dissecting general principles of skin neuroendocrinology and neuroimmunology well beyond the HF.
Apoptosis induced by ultraviolet B in HPV‐immortalized human keratinocytes requires caspase‐9 and is death receptor independent
Authors: Daher Ahmad , Simbulan‐Rosenthal Cynthia M. , Rosenthal Dean S.
Published: December 2005

Abstract:  Ultraviolet B (UVB) induces both apoptosis and skin cancer. We found that human keratinocytes (KC) immortalized by Human Papillomavirus (HPV)16 E6/E7 were sensitized to UVB‐induced apoptosis, possibly representing a transient regression‐prone precancerous stage equivalent to actinic keratosis. To further examine which caspases are apical and essential, we utilized retroviral constructs expressing dominant‐negative caspase‐9 (caspase‐9‐DN) or Fas‐associated protein with death domain (FADD)‐DN as well as caspase inhibitor peptides. Caspase‐9‐DN and zLEHD‐fmk both suppressed caspase‐9, ‐3, and ‐8 activity after UVB exposure, as well as proteolytic processing of procaspase‐3 into its active form, DNA fragmentation factor 45 cleavage, and internucleosomal DNA fragmentation. By contrast, stable expression of FADD‐DN in HPV‐immortalized KC did not inhibit UVB‐induced activation of caspases‐9, ‐3, and ‐8 nor downstream apoptotic events, although inhibition of caspase‐8 with zIETD‐fmk attenuated apoptosis. This study indicates that caspase‐9 activation is upstream of caspases‐3 and ‐8 and that UVB‐induced apoptosis in HPV‐immortalized human KC is death receptor (DR) independent and requires both caspase‐9 upstream and caspase‐8 downstream for maximal apoptosis. These studies further indicate that cell type as well as transformation state determine the sensitivity and mode of cell death (DR vs. mitochondrial apoptotic pathways) in response to UVB and explain the high regression rates of premalignant lesions.
Neurogenic components of trypsin‐ and thrombin‐induced inflammation in rat skin, in vivo
Authors: Obreja Otilia , Rukwied Roman , Steinhoff Martin , Schmelz Martin
Published: December 2005

Abstract:  Activation of protease‐activated receptors (PAR) can induce vasodilation (VD) and increase of vascular permeability either directly by stimulating endothelial cells or indirectly via activation of nociceptors and subsequent release of neuropeptides (neurogenic inflammation). We aimed to estimate the relative contribution of the two pathways for stimulation with endogenous activators of PAR‐2 (trypsin) and of PAR‐1, 3 and 4 (thrombin) using in vivo dermal microdialysis in rats. Protein extravasation (PE) was assessed by increase of protein concentration in the dialysate, and VD was quantified by laser Doppler scanning. Both trypsin (10−8−10−4 M) and thrombin (10−6, 10−5.5 and 10−5 M) provoked PE and local VD in a dose‐dependent manner. Trypsin (10−4 M)‐induced PE was inhibited by 87.2 ± 21% due to the substance P (SP) NK1 receptor antagonist SR140333. VD was blocked by 58.15 ± 10.1% in response to the calcitonin gene‐related peptide (CGRP) receptor antagonist CGRP8‐37. By contrast, CGRP8‐37 did not affect thrombin‐induced VD, while blockade of SP receptors prevented the PE elicited only by low doses of thrombin (10−6 M), being ineffective at higher thrombin concentrations. In conclusion, intradermal trypsin elicits a neurogenic inflammation in rat, probably mediated via PAR‐2 activation on nociceptors and subsequent SP and CGRP release. Thrombin‐induced PE and VD are mediated mainly by a non‐neurogenic mechanism.
Transduced monocyte/macrophages targeted to murine skin by UV light
Authors: Zhang Alexandra Y. , Wu Caiyun , Zhou Lixin , Ismail Sahar A. , Tao Jianming , McCormick Laura L. , Cooper Kevin D. , Gilliam Anita C.
Published: December 2005

Abstract:  We have selectively targeted monocyte/macrophages overexpressing an immunomodulatory molecule, latency‐associated peptide (LAP), a naturally occurring antagonist for transforming growth factor‐β1, to murine skin utilizing UV light to produce a cutaneous influx of transduced monocyte/macrophages. Bone marrow (BM) cells from BALB/c mice were transduced in vitro with a retroviral construct containing green fluorescent protein (GFP) for detection and human LAP (hLAP) as a test molecule. The transduced BM cells were then cultured in vitro with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) to produce differentiation to monocyte/macrophages. More than 80% of transduced BM cells were CD11b‐positive and MOMA‐positive by fluorescence‐activated cell‐sorter analysis and secreted LAP by ELISA after 10 days of culture in granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). Transduced monocyte/macrophages containing either GFP or hLAP‐GFP were then injected intravenously into BALB/c mice. One‐half of recipients in each group were exposed to UVB (72 mJ) to induce monocyte/macrophage infiltration into skin. Recipients were sacrificed 60 h after UV irradiation. We found transduced cutaneous macrophages expressing GFP by examining with fluorescence microscopy frozen skin sections of recipient mice immunostained with antibodies to GFP and to macrophage marker F4/80. We identified hLAP sequences by polymerase chain reaction (PCR) of total DNA in recipient blood and UV‐irradiated skin but not in unirradiated skin. LAP sequences were also detected at much lower levels in other organs (lung, spleen, and liver) by PCR. Therefore, we have shown that genetically altered monocytic cells can be injected intravenously and targeted to mouse skin by UV exposure. This macrophage‐based gene‐transfer method may be a potentially useful immunotherapeutic approach for delivering monocyte/macrophage‐derived products to skin.
Consenting to blood: what do patients remember?
Authors: Chan T. , Eckert K. , Venesoen P. , Leslie K. , Chin‐Yee I.
Published: December 2005

summary.  We sought to characterize the consent process for transfusion and determine its impact on patients' knowledge and level of comfort with receiving blood.

We identified all adult patients who had received blood transfusion at a tertiary care centre over 3 months. Patients who were discharged each received a survey that assessed their (1) recall of the consent process, (2) recall of information conveyed, (3) assessment of the discussion's understandability and (4) perceived knowledge of as well as comfort level with transfusion as a result of the discussion.

Overall, 80% of respondents recalled discussing and signing an informed consent. Information was mostly conveyed by attending physicians (35%) and consent obtained in the patient's hospital room (38%) or the preadmission clinic (19%). Although the majority recalled the consent process, many did not recall the discussion of specific transfusion risks or alternatives to donor blood (88%). Although the majority felt the discussion was at least somewhat understandable (77%), only 35% felt better informed and more comfortable with accepting blood.

Despite implementation of written informed consent for transfusion, patients' recollection and understanding of risks and alternatives remain poor. This suggests the need for improving risk communication.
Low dose erythropoietin is effective in reducing transfusion requirements following allogeneic HSCT
Authors: Fox C. P. , Pacey S. , Das‐Gupta E. P. , Russell N. H. , Byrne J. L.
Published: December 2005

summary.  Blood transfusions are frequently required for several weeks after allogeneic transplantation due to inadequate erythropoiesis and defective erythropoietin production. Because red cell transfusion is not without complications in this setting, we sought to avoid them using recombinant human erythropoietin (rhEpo) therapy.

We treated 53 patients following allogeneic transplantation for haematological malignancy, using rhEpo at a dose of 10 000 units subcutaneously twice weekly. The median time of commencement of rhEpo was 61 days post‐transplant (range 19–465 days), and the median haemoglobin (Hb) concentration was 9·4 g dL−1 (range 7·0–10·7 g dL−1). Thirty patients responded to rhEpo and required no further transfusion with a median rise in Hb after 2 weeks of therapy of 1·5 g (0·7–4·1 g dL−1). Erythropoietin (Epo) was discontinued at a median of 5 weeks (range 2–36), when the median Hb concentration was 12·3 g dL−1 (range 10·0–14·3 g dL−1). Those patients who failed to respond to rhEpo frequently had additional reasons for anaemia including cytomegalovirus (CMV) reactivation and treatment, major ABO incompatibility, disease relapse, graft rejection or other transplant‐related complications.

We conclude that a short course of rhEpo is an effective treatment for anaemia arising following allogeneic hematopoietic cell transplantation, and can avoid the need for transfusion in this setting.
Transfusions of CPDA‐1 red blood cells stored for up to 28 days decrease donor exposures in very low‐birth‐weight premature infants
Authors: Fernandes da Cunha D. H. , Nunes dos Santos A. M. , Kopelman B. I. , Areco K. N. , Guinsburg R. , De Araújo Peres C. , Chiba A. K. , Kuwano S. T. , Terzian C. C. N. , Bordin J. O.
Published: December 2005

summary.  The goal of this research was to study the safety and the efficacy of transfusing citrate‐phosphate‐adenine anticoagulant‐preservative (CPDA‐1) RBC stored for up to 28 days to reduce donor exposures in premature infants. A prospective randomized two‐group study was conducted with very low‐birth‐weight premature infants that received at least one RBC transfusion during hospital stay. Neonates randomly assigned to Group 1 (26 infants) were transfused with CPDA‐1 RBC stored for up to 28 days; those assigned to Group 2 (26 infants) received CPDA‐1 RBC stored for up to 3 days. Demographic and transfusion‐related data were collected. Neonates from both groups showed similar demographics and clinical characteristics. The number of transfusions per infant transfused was 4·4 ± 4·0 in Group 1 and 4·2 ± 3·1 in Group 2, and the number of donors per infant transfused was 1·5 ± 0·8 (Group 1) and 4·3 ± 3·4 (Group 2), P < 0·001. RBC transfusions containing 29·7 ± 18·3 mmol L−1 of potassium (RBC stored for up to 28 days) did not cause clinical or biochemical changes and reduced donor exposures by 70·2%, compared to transfusions containing 19·8 ± 12·3 mmol L−1 of potassium (RBC stored for up to 3 days), P < 0·001. In conclusion, RBC stored for up to 28 days safely reduced donor exposures in premature infants.
The marginalist approach and the making of fuel policy in France and Britain, 1945–721
Authors: CHICK MARTIN
Published: December 2005

Focusing on the shift from coal to oil in the French and British economies between 1945 and 1972, this article analyses the influence of economists and economic concepts on fuel‐policy making in each economy. The framing of French fuel policy around marginalist principles from 1958 is examined, and the unusually direct influence of economists on policy making is ascribed to a mix of national security, industrial modernization, and political considerations.
Evaluation of intracavitary mitoxantrone and carboplatin for treatment of carcinomatosis, sarcomatosis and mesothelioma, with or without malignant effusions: A retrospective analysis of 12 cases (1997–2002)*
Authors: Charney S. C. , Bergman P. J. , McKnight J. A. , Farrelly J. , Novosad C. A. , Leibman N. F. , Camps‐Palau M. A.
Published: December 2005

Carcinomatosis, sarcomatosis and mesothelioma, with or without malignant effusions, are difficult to treat and generally carry a poor prognosis. The purpose of this study was two‐fold; first, to determine the prognosis for dogs with carcinomatosis, sarcomatosis, or mesothelioma, with or without malignant effusions; second, to evaluate the safety and efficacy of treatment with intracavitary (IC) carboplatin and mitoxantrone in dogs with these syndromes. Nineteen dogs were evaluated. Seven were untreated and 12 were treated with IC chemotherapy (mitoxantrone and/or carboplatin), and multiple factors were analysed for significance with respect to survival time. The median survival time (MST) for untreated dogs was 25 days, whereas the MST for treated dogs was 332 days (Log Rank,P < 0.0001). Treatment with IC chemotherapy was well tolerated. This study suggests that IC chemotherapy with mitoxantrone and/or carboplatin is an effective treatment for dogs with carcinomatosis, sarcomatosis or mesothelioma, with or without malignant effusion.
Vascular‐targeted photodynamic therapy (VTP) of a canine‐transmissible venereal tumour in a murine model with Pd‐bacteriopheophorbide (WST09)
Authors: Vilensky J. , Koudinova N. V. , Harmelin A. , Scherz A. , Salomon Y.
Published: December 2005

Treatment of canine‐transmissible venereal tumour (CTVT) with local vascular‐targeted photodynamic therapy (VTP) using Pd‐bacteriopheophorbide (WST09) as a drug is suggested as an alternative to conventional chemotherapy. Male CD1 nude mice were subcutaneously grafted with the xenograft‐transmissible canine venereal tumour (XTVT). The VTP protocol delivered once consisted of intravenous administration of WST09 (10 mg kg−1) followed by immediate local illumination with a diode laser (763 nm). Controls included animals treated with light or WST09 alone. Macroscopic and microscopic evaluations of tumour response were conducted 10, 24 and 48 h after treatment. Upon VTP, tumours underwent necrosis that lasted 8–10 days and exhibited complete healing by 25–35 days, reaching an overall long‐term cure rate (83%) by 90 days after treatment. This study suggests that VTP with WST09 can efficiently treat CTVT in a single session, as compared with 4–6 sessions of chemotherapy and thus may be feasible for common veterinary practice, particularly under ambulatory conditions.
Detection of centrosome amplification as a surrogate marker of dysfunction in the p53 pathway –p53 gene mutation or MDM2 overexpression
Authors: Kaneko N. , Okuda M. , Toyama N. , Oikawa T. , Watanabe M. , Kanaya N. , Yazawa M. , Hasegawa K. , Morimoto M. , Hayashi T. , Une S. , Nakaichi M. , Taura Y. , Tsujimoto H. , Inokuma H.
Published: December 2005

In human and canine cancers, the inactivation of p53 protein as well as p53 gene mutation and MDM2 overexpression result in centrosome amplification that in turn contributes to chromosomal instability. To explore the usefulness of the detection of centrosome amplification as a surrogate marker of dysfunction in the p53 pathway, we systematically analysed centrosome amplification, p53 overexpression, p53 gene mutation and MDM2 overexpression in canine tumours. Centrosome amplification was detected in 16 of 51 (31%) naturally developing tumours in dogs. All the tumour specimens with aberrations in the p53 pathway, including p53 overexpression, p53 gene mutation or MDM2 overexpression, showed centrosome amplification, suggesting that the detection of centrosome amplification could serve as a preliminary surrogate marker of dysfunction in the p53 pathway.
Measurements of hypoxia ([18F]‐FMISO, [18F]‐EF5) with positron emission tomography (PET) and perfusion using PET ([15O]‐H2O) and power Doppler ultrasonography in feline fibrosarcomas*
Authors: Allemann K. , Wyss M. T. , Wergin M. , Ohlerth S. , Rohrer‐Bley C. , Evans S. M. , Schubiger A. P. , Ametamey S. M. , Kaser‐Hotz B.
Published: December 2005

The aim of this study was to evaluate if hypoxia in feline fibrosarcomas can be detected. This was done using positron emission tomography (PET), two hypoxia tracers and polarographic pO2measurements. Of the seven cats included, five received [18F]‐fluoromisonidazole and two 2‐(2‐nitro‐1H‐imidazol‐1‐yl)‐N‐(2,2,3,3,3‐pentafluoropropyl) acetamide. Perfusion was evaluated with [15O]‐H2O (n = 4) and with contrast‐enhanced power Doppler ultrasonography (n = 5). Hypoxia was detected in three cats. Polarographic pO2measurements did not confirm PET results. In the ultrasonographic evaluation, low vascularity and low perfusion were seen with a peripheral vascular pattern and no perfusion in the centre of the tumour. This was in contrast to the [15O]‐H2O scans, where central perfusion of the tumour was also found. In conclusion, it appears that hypoxia exists in this tumour type. The presence of tumour necrosis and heterogeneous hypoxia patterns in these tumours may explain the found discrepancies between the applied techniques.
Transplantation of umbilical cord blood‐derived endothelial progenitor cells: a promising method of therapeutic revascularisation
Authors: Zhang Lei , Yang Renchi , Han Zhong Chao
Published: December 2005

Abstract:  Therapeutic neovascularisation by endothelial progenitor cells (EPCs) mediated vascular regeneration is becoming a novel option for the treatment of ischaemic diseases. Recently, human umbilical cord blood (CB) has been found to contain a large number of EPCs and transplantation of CB EPCs led to a successful salvage of the ischaemic limbs through improvement in blood perfusion, indicating the feasibility of using CB cells for therapeutic revascularisation. This review will summarise recent studies in therapeutic revascularisation using CB cells and discuss the potential clinical utilisation of CB cells in ischaemic diseases.
Comparison of T Cell Subsets Between Somatic Cloned and Normal Cow
Authors: Tanaka Sachi , Miyazawa Kohtaro , Watanabe Kouichi , Ohwada Shyuichi , Aso Hisashi , Yonai Miharu , Saito Norio , Yamaguchi Takahiro
Published: December 2005

Problem  Somatic cloning technology is beneficial for genetically producing excellent animals. However, many developmental problems of somatically cloned animals have been described. Some of them may cause disorders of the immune system, resulting in the fluctuation of the proportion of white blood cells (WBC), different from that of normal animals in peripheral blood.

Method of study  In Holstein‐ cloned and normal cows, the fluctuation of granulocytes, monocytes, B cells and T cells, and further T cell subsets (CD4+, CD8+, γδ, CD8+γδ and WC1+γδ T cell) in peripheral blood were analyzed in early lactation stage (ELS) and mid to late lactation stage (MLS) by flow cytometry using specific monoclonal antibodies for cell surface markers.

Results  In both ELS and MLS, there were no significant differences in the proportions of granulocytes, monocytes, B cells and T cells between cloned and normal cows. In T cell subsets, γδ and WC1+γδ T cells in cloned cows were significantly less frequent than in normal cows in ELS. The decreased proportions of γδ and WC1+γδ T cells recovered to the level of normal cows in MLS.

Conclusions  The population of granulocytes, monocytes, B cells and T cells, and T cell subsets except for γδ and WC1+γδ T cells in cloned cows fluctuated in a manner similar to those of normal cows during lactation. In ELS, the proportions of γδ and WC1+γδ T cells temporarily declined in cloned cows, suggesting that cloned cows may fall into an immunosuppressive state in ELS.
Aspirin Desensitization in the Treatment of Antiphospholipid Syndrome during Pregnancy in ASA‐sensitive Patients
Authors: Alijotas‐Reig Jaume , Miguel‐Moncín Mar San , Cisteró‐Bahíma Anna
Published: December 2005

Problem Antiphospholipid syndrome (APS) is associated with thrombosis and poor pregnancy outcome in the presence of antiphospholipid antibodies (aPL). Patients with aPL have a high risk of foetal loss. However, with low‐dose aspirin (acetylsalicylic acid; ASA) in combination with subcutaneous heparin, the chances of full‐term delivery increase. Nevertheless, ASA treatment is avoided in pregnant, ASA‐sensitive women with APS.

Methods Rapid oral challenge‐desensitization to ASA was performed in four pregnant women with a history of APS and aspirin sensitivity. In three patients, desensitization was performed during pregnancy and before the next pregnancy in the fourth. Desensitization was carried out in the ICU using increasing doses of aspirin (0.1–125 mg) over a 24‐hr period.

Results Successful ASA desensitization was achieved in all the patients. No severe side effects occurred during the desensitization test. Only one patient required a small oral dose of antihistamines.

Conclusions Aspirin desensitization may be a safe alternative even during pregnancy if carefully monitored and permit patients with APS to receive treatment with ASA. This would constitute a new indication in pregnant women with APS and ASA sensitivity.
The Effect of Serum Concentration of Leukaemia Inhibitory Factor on In Vitro Fertilization Treatment Outcome
Authors: Thum Meen‐yau , Abdalla Hossam I. , Bhaskaran Shree , Harden Emily L. , Ford Brian , Sumar N. , Shehata Hassan , Bansal Amolak S.
Published: December 2005

Problem To evaluate the association of peripheral leukaemia inhibitory factor (LIF) levels on implantation and miscarriage rates after in vitro fertilization (IVF) treatment.

Methods Prospective observational study of 120 randomly selected women who underwent IVF treatment. The concentration of LIF in serum was determined by enzyme‐linked immunosorbent assay.

Results There was no significant differences with regard to the systemic mean LIF concentration between the pregnant (42 patients, LIF: 11.55 pg/mL ± 5.3 S.D.) and non‐pregnant (66 patients, LIF: 13.47 pg/mL ± 5.1 S.D.) women after IVF treatment. Likewise, for those women who have positive pregnancy after IVF treatment, the systemic mean LIF levels were not significantly different between women who have an ongoing pregnancy (34 ongoing pregnancy, LIF: 11.26 pg/mL ± 5.2 S.D.) and those who had miscarriage (eight miscarriage, LIF: 12.78 pg/mL ± 5.6 S.D.).

Conclusion The systemic levels of LIF concentration have no association with implantation rate or miscarriage rate in women undergoing IVF treatment. Measuring serum LIF concentration prior to embryo transfer in IVF treatment has no predictive value of implantation rate or miscarriage rate.
Antigen Presentation by Human Uterine Epithelial Cells to Autologous T Cells
Authors: Fahey John V. , Wallace Paul K. , Johnson Kristy , Guyre Paul M. , Wira Charles R.
Published: December 2005

Problem  Epithelial cells, as sentinels of immune protection in the endometrium, use innate immune mechanisms to protect against infection from pathogenic microbes. Our goal in this study was to assess the ability of human uterine epithelial cells to present antigen to cells of the adaptive immune system.

Method of study  Highly purified preparations of uterine epithelial cells from 11 patients were assessed for their ability to present tetanus toxoid (TT) to autologous T cells. Leukocyte contamination in the epithelial cell preparations was numerically and functionally determined. Using confocal microscopy, epithelial cells were tested for the expression of CD40 and CD1d.

Results  Purified preparations of endometrial epithelial cells isolated from every patient presented TT recall antigen to autologous T cells. Leukocyte contamination of epithelial cell preparations was insignificant. Uterine epithelial cells express CD40 and CD1d.

Conclusion  Antigen presentation is an additional aspect of uterine epithelial cell function in maintaining women's health.
Alterations in Syncytiotrophoblast Cytokine Expression Following Treatment with Lipopolysaccharide
Authors: Ma Yuehong , Mor Gil , Abrahams Vikki M. , Buhimschi Irina A , Buhimschi Catalin S , Guller Seth
Published: December 2005

Problem  The placental syncytium is a differentiated cell type on the surface of the villus that has the potential to release cytokines directly to maternal blood. Responsiveness of this cell type to inflammatory compounds remains largely unelucidated.

Method of study  Response to a pro‐inflammatory (lipopolysaccharide, LPS) and an anti‐inflammatory (dexamethasone, DEX) compound was studied in primary cultures of syncytiotrophoblasts (SCTs). Cells were incubated with and without LPS and DEX. Cytokine levels in conditioned media were determined by enzyme‐linked immunosorbent assay and proteome arrays.

Results  LPS treatment induced a fourfold increase in interleukin‐8 (IL‐8) levels in SCTs. LPS enhanced the expression of both pro‐ and anti‐inflammatory cytokines in SCTs. DEX treatment reduced IL‐8 levels in control and LPS‐treated cultures by 70–90%.

Conclusion  Cytokine expression in SCTs was enhanced by LPS treatment and this effect was suppressed by glucocorticoid treatment. This suggests that inflammatory compounds may alter cytokine expression in the syncytium throughout gestation.
Histochemical and ultrastructural analysis of the epidermal gland cells of Branchiomma luctuosum (Polychaeta, Sabellidae)
Authors: Mastrodonato Maria , Lepore Elena , Gherardi Miriam , Zizza Sara , Sciscioli Margherita , Ferri Domenico
Published: December 2005

Abstract. This histochemical and ultrastructural study describes the epidermal gland cells of a tubicolous polychaete, Branchiomma luctuosum. The histochemistry was carried out using standard techniques and FITC‐labelled lectins. Four types of secretory cells were identified in two categories: orthochromatic cells (Type 1) and metachromatic cells (Types 2, 3, and 4). The secretory product of the Type‐1 orthochromatic cells contains neutral glycoproteins with Galβ1,3GalNAc residues. Metachromatic cells produce acidic, mainly sulfated, glycoconjugates with Galβ1,3GalNAc residues (Type 2) or glucosidic and/or mannosidic residues (Types 3 and 4). In sialylated chains, terminal sialic acid is bound to the penultimate GalNAc and Galβ1,3GalNAc residues. The complex composition of the mucus produced by epidermal gland cells of B. luctuosum may be correlated with its different functions. Ultrastructural studies of the epidermal gland cells showed differing morphology, and the presence in the gland cells of Types 3 and 4 of a funnel‐shaped structure for the extrusion of the secretory material.