bluuebunny/crossref_metadata_2025_split huggingface dataset:
Severe Monilethrix Associated with Intractable Scalp Pruritus, Posterior Subcapsular Cataract, Brachiocephaly, and Distinct Facial Features: A New Variant of Monilethrix Syndrome?
Authors: Erbagci Zulal , Erbagci Ibrahim , Erbagci Hulya , Erkılıc Suna , Tuncel A. Almila 
Published: July 2004

Abstract:  Monilethrix is a rare developmental hair shaft defect characterized by small elliptical node‐like deformities with increased hair fragility resulting in partial or diffuse alopecia. The disorder is usually transmitted in an autosomal dominant fashion with incomplete penetrance and variable expressivity, but autosomal recessive inheritance has also been reported. It is thought to be without systemic involvement, whereas keratosis pilaris and follicular papules are almost invariably associated features. We describe an instance of monilethrix in a 9‐year‐old boy from consanguineous parents, characterized by universal dystrophic alopecia associated with intractable scalp pruritus, diffuse keratosis pilaris, and bilateral posterior subcapsular cataracts. His disease was further characterized by physical underdevelopment and distinct features of hypertelorism, a wide‐based nose, long philtrum, relatively large mouth with thick lower lip, enlarged forehead, small, receding chin, short neck, and rounded (ultrabrachycranial) skull. The findings in our patient suggest that “monilethrix syndrome” is an appropriate term for defining the instances of monilethrix associated with other abnormalities. We conclude that our patient may represent a new and severe, autosomal recessive variant of monilethrix syndrome.
Therapeutic efficacy of pooled buffy‐coat platelet components prepared and stored with a platelet additive solution
Authors: Van Rhenen D. J. , Gulliksson H. , Cazenave J. P. , Pamphilon D. , Davis K. , Flament J. , Corash L. 
Published: July 2004

Summary.  Despite the introduction of platelet additive solutions for the preparation of pooled platelet components, only a few studies of limited scope have evaluated the clinical efficacy of platelets stored in these solutions. The current report presents an analysis of data to evaluate the response to the transfusion of pooled buffy‐coat components suspended in storage solution with reduced (35%) plasma content in comparison with 100% plasma products.During the euroSPRITE clinical trial of platelet components treated with a pathogen inactivation process, control treatment group platelet components were prepared in 100% allogeneic donor plasma (plasma control) or in platelet additive solution (T‐Sol™) mixed with plasma (T‐Sol control). Control group thrombocytopenic patients received either plasma control or T‐Sol control platelet components. One‐hour and 24‐h platelet count increments (CIs) and corrected count increments (CCIs) were analysed for these two types of preparation. In addition, haemostatic assessments were conducted for each transfusion.One‐hour and 24‐h mean platelet CIs and post‐transfusion haemostatic scores were not significantly different for patients receiving platelet components suspended in 100% plasma and T‐Sol plasma mixtures.Pooled buffy‐coat platelet components prepared in reduced plasma content mixtures provided therapeutic platelet CIs with effective haemostasis.
SERF: a new antigen in the Cromer blood group system
Authors: Banks J. , Poole J. , Ahrens N. , Seltsam A. , Salama A. , Hue‐Roye K. , Storry J. R. , Palacajornsuk P. , Ma B‐W. , Lublin D. M. , Reid M. E. 
Published: July 2004

Summary.  The Cromer blood group system consists of eight high incidence and three low incidence antigens carried on decay‐accelerating factor (DAF). This report describes the identification and characterization of a new Cromer high incidence antigen, named SERF.Sequence analyses of DNA from a Thai female whose serum contained the alloantibody to a high incidence antigen in the Cromer blood group system (anti‐SERF) and from her two children were performed. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and sequence analysis on cDNA from the proband and PCR‐restriction fragment length polymorphism analysis on DNA from Thais were also performed. To map the epitope, DAF deletion mutants were tested by immunoblotting with anti‐SERF.Sequence analysis revealed a substitution of 647C>T in exon 5 DAF in the proband. The proband's two children and two of 100 Thais were heterozygotes 647C/T. Analysis using DAF deletion mutants revealed the antigenic determinant to be within short consensus repeat 3 (SCR3), which is encoded by exon 5.This study describes a novel high incidence antigen (SERF) in the Cromer blood group system characterized by the amino acid proline at position 182 in SCR3 of DAF. The SERF‐negative proband has a substitution mutation that predicts for leucine at this position. SERF has been provisionally assigned the International Society of Blood Transfusion number 021·012 (CROM 12).
Controlling the release and production of renin
Authors: Persson P. B. , Skalweit A. , Thiele B. J. 
Published: July 2004

AbstractThe renin–angiotensin system (RAS) plays a pivotal role for a variety of cardiovascular functions. The diversity of renin actions is reflected by its complex control. The major stimulus for the release of renin from the vesicles in juxtaglomerular cells is determined by stretch, as induced by changes in arterial pressure. The production of renin underlies a vastly complex control network, which takes place at different levels, such as transcription and translation. With regard to transcription, important regions for binding transcription factors have been identified several years ago, but the conservation of nucleotide sequences throughout different species suggests that there might be additional binding regions of importance. At the post‐transcriptional level, the modulation of renin mRNA stability is seems pivotal. The half‐life of renin mRNA appears to be controlled by the interaction between several regulatory proteins, most of which are well known in other systems. Moreover, in addition to the modulation of mRNA stability, the translation efficiency seems to play a key role in determining the amount of renin to be produced.
Structure of renal afferent arterioles in the pathogenesis of hypertension
Authors: Skov K. , Mulvany M. J. 
Published: July 2004

AbstractRenal vascular resistance is increased in essential hypertension, as in genetic models of hypertension. Here we review the evidence that this is at least in part due to structural changes in the afferent arterioles. Rat studies show that the renal afferent arteriole is structurally narrowed in young and adult spontaneously hypertensive rats (SHR). Furthermore, in the second generation of crossbred SHRs/normotensive rats (SHR/WKY F2‐hybrids), a narrowed afferent arteriole lumen diameter at 7 weeks is a predictor of later development of high blood pressure. The reduced lumen diameter of resistance vessels is accompanied by a decrease in media cross‐sectional area in SHR and could therefore be due to inhibited growth. Evidence from a primate model of hypertension has shown a negative correlation between left ventricular hypertrophy and afferent arteriole diameter, but apparently no relation to blood pressure. In SHR, the antihypertensive effect of angiotensin converting enzyme (ACE) inhibitors is mediated through renal vascular mechanisms, while ACE inhibitors (like AT1 antagonists) have a more persistent effect on blood pressure after treatment withdrawal compared with other antihypertensive drugs. Taken together, the evidence suggests that structural narrowing of the renal afferent arteriole could be an important link in the pathogenesis of primary hypertension, at least in the SHR.
Nitric oxide counteracts angiotensin II induced contraction in efferent arterioles in mice
Authors: Patzak A. , Kleinmann F. , Lai E. Y. , Kupsch E. , Skelweit A. , Mrowka R. 
Published: July 2004

AbstractAim:  Efferent arterioles (Ef) are one of the final control elements in glomerular haemodynamics. The influence of nitric oxide (NO) on Ef remains ambiguous.Methods:  To test the hypothesis that endothelial NO plays an important role in this context, afferent arterioles (Af) and Ef of wild‐type mice (WT), and Ef of mice lacking the endothelial NO synthetase [eNOS(−/−)] were perfused. Perfusion was performed in Ef via Af (orthograde) as well as from the distal end of Ef (retrograde), which provides an estimate for the importance of substances derived from the glomerulus. Angiotensin II (Ang II) was added in doses ranging from 10−12 to 10−6 mol L−1 to the bath solution.Results:  Ang II reduced the luminal diameter of Af to 68 ± 7 and in Ef to 55 ± 8% during orthograde, and to 35 ± 6% during retrograde perfusion (10−6 mol L−1 Ang II) in WT. Pre‐treatment with NG‐Nitro‐l‐arginine‐methylester (l‐NAME) (10−4 mol L−1) increased the Ang II sensitivity in retrograde (17 ± 9%) and orthograde perfused Ef (19 ± 9%). The Ang II sensitivity was enhanced in eNOS(−/−) mice compared with WT, too. Already at a dose of Ang II 10−9 mol L−1, luminal diameters diminished to 8 ± 7 and 7 ± 4%.Conclusion:  The increased Ang II sensitivity during l‐NAME pre‐treatment and in eNOS(−/−) mice indicates a strong counteraction of endothelial derived NO on Ang II induced contraction in Ef. Moreover, Ef are similarly sensitive to Ang II during either retrograde or orthograde perfusion in the absence of NO effects, suggesting that NO mediates, at least in part, the action of potential vasodilatory substances from the glomerulus.
Renal autoregulation in P2X1 knockout mice
Authors: Inscho E. W. , Cook A. K. , Imig J. D. , Vial C. , Evans R. J. 
Published: July 2004

AbstractAutoregulation of renal blood flow is an established physiological phenomenon, however the signalling mechanisms involved remain elusive. Autoregulatory adjustments in preglomerular resistance involve myogenic and tubuloglomerular feedback (TGF) influences. While there is general agreement on the participation of these two regulatory pathways, the signalling molecules and effector mechanisms have not been identified. Currently, there are two major hypotheses being considered to explain the mechanism by which TGF signals are transmitted from the macula densa to the afferent arteriole. The adenosine hypothesis proposes that the released adenosine triphosphate (ATP) is hydrolysed to adenosine and this product stimulates preglomerular vasoconstriction by activation of A1 receptors on the afferent arteriole. Alternatively, the P2 receptor hypothesis postulates that ATP released from the macula densa directly stimulates afferent arteriolar vasoconstriction by activation of ATP‐sensitive P2X1 receptors. This hypothesis has emerged from the realization that P2X1 receptors are heavily expressed along the preglomerular vasculature. Inactivation of P2X1 receptors impairs autoregulatory responses while afferent arteriolar responses to A1 adenosine receptor activation are retained. Autoregulatory behaviour is markedly attenuated in mice lacking P2X1 receptors but responses to adenosine A1 receptor activation remain intact. More recent experiments suggest that P2X1 receptors play an essential role in TGF‐dependent vasoconstriction of the afferent arteriole. Interruption of TGF‐dependent influences on afferent arteriolar diameter, by papillectomy or furosemide treatment, significantly attenuated pressure‐mediated afferent arteriolar vasoconstriction in wild‐type mice but had no effect on the response in P2X1 knockout mice. Collectively, these observations support an essential role for P2X1 receptors in TGF‐mediated afferent arteriolar vasoconstriction.
The role of the RAS in programming of adult hypertension
Authors: Rasch R. , Skriver E. , Woods L. L. 
Published: July 2004

AbstractThe aetiology of cardiovascular disease originally included two components: a genetic component and an environmental or lifestyle component. Increasing epidemiologic evidence has been accumulating during the last decades indicating the importance of a third component: the influence of the environment during foetal development. Poor living conditions resulted in a high infant mortality and influenced the incidence of cardiovascular diseases in adulthood despite better living conditions (A. Forsdahl. Br J Prev Soc Med 1977; 31, 91–95). An association between pre‐natal growth pattern and the rate of death from cardiovascular disease in adulthood was reported (D.J. Barker, P.D. Winter, C. Osmond, B. Margetts & S.J. Simmonds. Lancet 1989; 2, 577–580). Men from Hartfordshire (UK), born between 1911 and 1930 were investigated. The investigations showed that men with the lowest weight at birth and at 1 year of age had the highest risks of death from cardiovascular disease (D.J. Barker, P.D. Winter, C. Osmond, B. Margetts & S.J. Simmonds. Lancet 1989; 2, 577–580). These findings suggested that factors in the perinatal environment could programme an individual for later risk of development of cardiovascular disease compared with someone born with a normal weight. Numerous studies have since confirmed these initial findings of an inverse relationship between early growth pattern and cardiovascular disease in adulthood.
Exploring type I angiotensin (AT1) receptor functions through gene targeting
Authors: Crowley S. D. , Tharaux P.‐L. , Audoly L. P. , Coffman T. M. 
Published: July 2004

AbstractThe renin–angiotensin system (RAS) modulates a diverse set of physiological processes including development, blood pressure, renal function and inflammation. The principal effector molecule of this system, angiotensin II, mediates most of these actions. The classically recognized functions of the RAS are triggered via the type 1 (AT1) class of angiotensin receptors. Pharmacological blockade of the AT1 receptor lowers blood pressure and slows the progression of cardiovascular and renal diseases. Gene‐targeting technology provides an experimental approach for precisely dissecting the physiological functions of the RAS. Here, we review how gene‐targeting experiments have elucidated AT1 receptor functions.
Consomic rat model systems for physiological genomics
Authors: Cowley A. W. , Liang M. , Roman R. J. , Greene A. S. , Jacob H. J. 
Published: July 2004

AbstractA consomic rat strain is one in which an entire chromosome is introgressed into the isogenic background of another inbred strain using marker‐assisted selection. The development and physiological screening of two inbred consomic rat panels on two genetic backgrounds (44 strains) is well underway. Consomic strains enable one to assign traits and quantitative trait loci (QTL) to chromosomes by surveying the panel of strains with substituted chromosomes. They enable the rapid development of congenic strains over a narrow region and enable one to perform F2 linkage studies to positionally locate QTL on a single chromosome with a fixed genetic background. These rodent model systems overcome many of the problems encountered with segregating crosses where even if linkage is found, each individual in the cross is genetically unique and the combination of genes cannot be reproduced or studied in detail. For physiologists, consomics enable studies to be performed in a replicative or longitudinal manner to elucidate in greater detail the sequential expression of genes responsible for the observed phenotypes of these animals. They often provide the best available inbred control strains for physiological comparisons with the parental strains and they enable one to assess the impact of a causal gene region in a genome by allowing comparisons of the effect of replacement of a specific chromosome on a disease susceptible or a resistant genomic background. Consomic rat strains are proving to be a unique scientific resource that can greatly extend our understanding of genes and their role in the regulation of complex function and disease.
Hormones and pregnancy: thromboembolic risks for women
Authors: Kujovich Jody L. 
Published: July 2004

SummaryDuring their lifetimes, women face several unique situations with an increased risk of venous thromboembolism (VTE). Doctors in a variety of specialties must advise women on the risks of oral contraceptives (OC), hormone replacement or pregnancy. Modern ‘low dose’ OC are associated with a three to sixfold increased relative risk of VTE. Hormone replacement and selective oestrogen receptor modulators confer a similar two to fourfold increase in thrombotic risk. However, because the baseline incidence of thrombosis is higher in older postmenopausal women, the absolute risk is higher than in younger OC users. The risk of venous thrombosis is six to 10‐fold higher during pregnancy than in non‐pregnant women of similar age. Thrombophilic disorders increase the thrombotic risk of OC, hormone replacement and pregnancy, especially in women with homozygous or combined defects. This review focuses on recent data estimating the thrombotic risk of hormonal therapies and pregnancy in women with and without other thrombotic risk factors.
CD34+ cell selection of peripheral blood progenitor cells using the CliniMACS device for allogeneic transplantation: clinical results in 102 patients
Authors: Ringhoffer Mark , Wiesneth Markus , von Harsdorf Stephanie , Schlenk Richard F. , Schmitt Anita , Reinhardt Peter P. , Moessner Margit , Grimminger Wolfgang , Mertens Thomas , Reske Sven N. , Döhner Hartmut , Bunjes Donald 
Published: July 2004

SummaryThe present study investigated the effects of CD34+ cell selection in 102 patients using the CliniMACS device. Patients were at high risk for the development of graft versus host disease (GvHD) because of age, or the use of a haploidentical, mismatched or unrelated donor (UD). The median age of the patients was 44 years. The CliniMACS procedure yielded 8·0 × 106 CD34+ cells/kg and the number of residual T cells was 1·3 × 104/kg (median). The median follow up was 20·6 months. The probability of graft failure was 7%. The rate of acute GvHD was low (compatible family donors 10%, UDs 17%, and haploidentical donors 26%) with no patient enduring more than grade II disease. The cumulative incidence of chronic GvHD at the median follow up after transplant was 15% for the compatible family donor group, 40% for the UD group and 78% in the group transplanted from a haploidentical donor Treatment failure was mainly because of transplant‐related mortality, especially aspergillus infection, and not due to relapse. The probability of disease‐free survival, stratified for the risk of treatment failure, was 27% for the high risk, 46% for the intermediate risk and 83% for the low risk group.
Compound heterozygous mutations in the γ‐glutamyl carboxylase gene cause combined deficiency of all vitamin K‐dependent blood coagulation factors
Authors: Rost Simone , Fregin Andreas , Koch Dieter , Compes Markus , Müller Clemens R. , Oldenburg Johannes 
Published: July 2004

SummaryHereditary combined deficiency of the vitamin K‐dependent coagulation factors II, VII, IX, X, protein C, S and protein Z (VKCFD) is a very rare autosomal recessive inherited bleeding disorder. The phenotype may result from functional deficiency of either the γ‐glutamyl carboxylase (GGCX) or the vitamin K epoxide reductase (VKOR) complex. We report on the third case of VKCFD1 with mutations in the γ‐glutamyl carboxylase gene, which is remarkable because of compound heterozygosity. Two mutations were identified: a splice site mutation of exon 3 and a point mutation in exon 11, resulting in the replacement of arginine 485 by proline. Screening of 100 unrelated normal chromosomes by restriction fragment length polymorphism and denaturing high‐performance liquid chromatography analysis excluded either mutation as a frequent polymorphism. Substitution of vitamin K could only partially normalize the levels of coagulation factors. It is suggested that the missense mutation affects either the propeptide binding site or the vitamin K binding site of GGCX.
Human γδ T cells as mediators of chimaeric‐receptor redirected anti‐tumour immunity
Authors: Rischer Markus , Pscherer Sibylle , Duwe Susanne , Vormoor Josef , Jürgens Heribert , Rossig Claudia 
Published: July 2004

SummaryHuman peripheral blood γδ T cells (Vγ9+ Vδ2+) can be selectively expanded in vivo by the systemic administration of aminobisphosphonates without prior antigen priming. To assess the potential of human γδ T cells to serve as effector cells of specific anti‐tumour immunity, we expanded peripheral blood‐derived γδ T cells and transduced them with recombinant retrovirus encoding GD2‐ or CD19‐specific chimaeric receptors. Flow cytometric analysis of T cells from four individual donors cultured in the presence of zoledronate at day 14 of culture showed selective enrichment of the γδ T cell population (Vγ9+ Vδ2+ CD3+ CD4− CD8−) to 73–96% of total CD3+ T cells. Retroviral gene transfer resulted in chimaeric receptor surface expression in 73 ± 12% of the population. Transduced γδ T cells efficiently recognized antigen‐expressing tumour cell targets, as demonstrated by target‐specific upregulation of CD69 and secretion of interferon‐α. Moreover, transduced γδ T cells efficiently and specifically lysed the antigen‐expressing tumour targets. They could be efficiently expanded in vitro and maintained in culture for prolonged periods. Zoledronate‐activated human γδ T cells expressing chimaeric receptors may thus serve as potent and specific anti‐tumour effector cells. Their responsiveness to stimulation with aminobisphosphonates may enable the selective re‐expansion of adoptively transferred T cells in vivo, permitting long lasting anti‐tumour immune control.
Translocations involving 6p22 in acute myeloid leukaemia at relapse: breakpoint characterization using microarray‐based comparative genomic hybridization
Authors: Tchinda Joëlle , Dijkhuizen Trijnie , Vlies Pieter van der , Kok Klaas , Horst Jürgen 
Published: July 2004

SummaryThe detection of chromosomal aberrations is essential for the diagnosis and therapy of acute myeloid leukaemia (AML). We report two cases of de novo AML with translocations involving the breakpoint 6p22 first detected at relapse. Chromosomes were identified by conventional and molecular cytogenetics. At diagnosis, one patient presented a normal karyotype and the other one a trisomy 11 and a del(7)(q31q36). In the first case, cytogenetic analyses at relapse revealed a t(3;6)(q21;p22). The second patient showed a t(1;6)(q21;p22) at relapse. Detailed characterization of the breakpoints on the short arm of chromosome 6 was performed using array comparative genomic hybridization (CGH) on a platform specific for chromosome 6. In both cases, array CGH showed a terminal deletion and a small internal duplication of the short arm of chromosome 6. The region 6p22 is involved in several aberrations in tumours. Translocation partners are distributed throughout the human genome. We identified 3q21, a recurrent breakpoint in AML, for the first time as a translocation partner. The fragile site FRA6C, located in 6p22.2, and possibly the genes that reside within it, may play a role in tumorigenesis. The occurrence of translocations involving 6p22 after chemotherapy or radiation therapy suggests that one or more therapeutic agents might play a role in their origin.