bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the Autoimmune Regulator (AIRE) gene in alopecia areata: Strong association of a potentially functional AIRE polymorphism with alopecia universalis
Authors: Tazi‐Ahnini R. , Cork M.J. , Gawkrodger D.J. , Birch M.P. , Wengraf D. , McDonagh A.J.G. , Messenger A.G. 
Published: March 2003

Abstract: Alopecia areata is characterized by a reversible form of patchy or complete hair loss associated with T‐cell infiltration of hair follicles. The lifetime disease risk of ∼1.4% in the general population is increased to more than 30% in autoimmune polyendocrinopathy candidiasis ectodermal dysplasia syndrome (APECED), a recessive condition resulting from a mutation of the autoimmune regulator (AIRE) gene on chromosome 21q22.3. Aire protein is thought to have transcriptional regulatory activity but its role is not well defined at present. In this study, we have examined the possible involvement of AIRE in the pathogenesis of alopecia areata.On screening the AIRE coding sequence, we identified 20 variants. Two of these at positions, G961C and T1029C, give rise to amino acid changes, S278R and V301A, located in the DNA‐binding segment (SAND) and PHD1 zinc finger motif, respectively. We found no difference in the frequency of the AIRE T1029C polymorphism between the control and patient groups. We genotyped 202 alopecia areata patients and 175 matched Caucasian controls for the AIRE G961C alleles. The frequency of the rare allele (961G) was 0.08 in the controls and there was a significant increase to 0.13 in alopecia areata overall and 0.20 in severe disease (alopecia universalis). We found no association between the AIRE G961G variant and mild (patchy) alopecia areata or alopecia totalis. However, the AIRE 961G allele is a potent risk factor (> 3) for the severest form of alopecia areata, and for disease of early age at onset (at 30 years). The change from serine to arginine in the SAND domain of AIRE protein may have a significant effect on AIRE DNA‐binding activity. Moreover, our results could provide a rational explanation of the unusually high frequency of AA in APECED patients, supporting the concept of AA as an autoimmune disease.
Activated oxygen‐mediated metabolic functions of leaf peroxisomes
Authors: Del Río Luis A. , Sandalio Luisa M. , Corpas Francisco J. , López‐Huertas Eduardo , Palma José M. , Pastori Gabriela M. 
Published: March 2003

Peroxisomes are subcellular organelles with an essentially oxidative type of metabolism. The presence in these organelles of superoxide dismutases and the generation of superoxide radicals (O2•−) was first demonstrated in plant tissues and in recent years different experimental evidence has suggested the existence of cellular functions related to activated oxygen species. Some of these functions are analyzed in this work.In purified intact peroxisomes from pea (Pisum sativum L.) leaves, xanthine oxidase and urate oxidase were found to be present. The occurrence and the level of the metabolites xanthine, hypoxanthine, uric acid, and allantoin were studied in extracts of pea leaf peroxisomes by HPLC. Xanthine, uric acid, and allantoin were detected in peroxisomes. These results suggest a cellular role for leaf peroxisomes in the catabolism of purines.In peroxisomal membranes, 3 polypeptides (PMPs) with molecular masses of 18, 29 and 32 kDa, respectively, have been shown to generate superoxide radicals. These PMPs were purified from pea leaf peroxisomal membranes and characterized. While the 18‐ and 32‐kDa PMPs use NADH as electron donor for O2•− production, the 29‐kDa PMP was clearly dependent on NADPH.Very recently, the occurrence in pea leaf peroxisomes of all the enzymes of the ascorbate‐glutathione cycle has been demonstrated. NADPH is required for the glutathione reductase activity of the cycle and this implies the reduction of NADP+ to NADPH. This recycling function could be carried out by the NADP‐dependent glucose‐6‐phosphate dehydrogenase (G6PDH), 6‐phosphogluconate dehydrogenase (6PGDH), and isocitrate dehydrogenase (ICDH). These 3 dehydrogenases have been demonstrated to be present in the matrix of pea leaf peroxisomes.The catabolism of purines, the superoxide‐generating PMPs, the ascorbate‐glutathione cycle, and the dehydrogenase‐mediated recycling of NADPH, are activated oxygen roles of leaf peroxisomes that add to other functions previously known for peroxisomes from eukaryotic cells.
What are the driving forces for water lifting in the xylem conduit?
Authors: Zimmermann Ulrich , Schneider Heike , Wegner Lars H. , Wagner Hans‐Jürgen , Szimtenings Michael , Haase Axel , Bentrup Friedrich‐Wilhelm 
Published: March 2003

After Renner had shown convincingly in 1925 that the transpirational water loss generates tensions larger than 0.1 MPa (i.e. negative pressures) in the xylem of cut leafy twigs the Cohesion Theory proposed by Böhm, Askenasy, Dixon and Joly at the end of the 19th century was immediately accepted by plant physiologists. Introduction of the pressure chamber technique by Scholander et al. in 1965 enforced the general belief that tension is the only driving force for water lifting although substantial criticism regarding the technique and/or the Cohesion Theory was published by several authors. As typical for scientific disciplines, the advent of minimal‐ and non‐invasive techniques in the last decade as well as the development of a new, reliable method for xylem sap sampling have challenged this view. Today, xylem pressure gradients, potentials, ion concentrations and volume flows as well as cell turgor pressure gradients can be monitored online in intact transpiring higher plants, and within a given physiological context by using the pressure probe technique and high‐resolution NMR imaging techniques, respectively. Application of the pressure probe technique to transpiring plants has shown that negative absolute pressures (down to − 0.6 MPa) and pressure gradients can exist temporarily in the xylem conduit, but that the magnitude and (occasionally) direction of gradients contrasts frequently the belief that tension is the only driving force. This seems to be particularly the case for plants faced with problems of height, drought, freezing and salinity as well as with cavitation of the tensile water. Reviewing the current data base shows that other forces come into operation when exclusively tension fails to lift water against gravity due to environmental conditions. Possible candidates are longitudinal cellular and xylem osmotic pressure gradients, axial potential gradients in the vessels as well as gel‐ and gas bubble‐supported interfacial gradients. The multiforce theory overcomes the problem of the Cohesion Theory that life on earth depends on water being in a highly metastable state.
The biology of Epstein–Barr virus in post‐transplant lymphoproliferative disease
Authors: Hsieh W.‐S. , Lemas M.V. , Ambinder R.F. 
Published: March 2003

Abstract:Post‐transplant lymphoproliferative disease (PTLD) is a B cell proliferative disorder that is associated with Epstein–Barr virus (EBV), an ubiquitous herpesvirus. EBV‐seronegative organ transplant recipients are at highest risk. EBV infection in PTLD lesions exists in a latent rather than lytic state, making tumor regression in response to antiviral agents unlikely. Viral latency proteins drive proliferation of T cells but also allow T cells to target PTLD lesions for destruction. Augmentation of the cellular immune response via the infusion of EBV‐specific cytotoxic T cells has yielded promising results in the prevention and treatment of PTLD in bone marrow transplant recipients. Efforts to extend this strategy to solid organ transplant recipients are ongoing.Editor’s comment:The spectrum of post‐transplant lymphoproliferative disease includes both B‐ and T‐cell malignancies. While the vast majority are EBV‐associated, there is a growing subset without obvious EBV markers. Given the present state of the art, which is summarized in this paper, we are incapable of stratifying patients in terms of prognosis or the likelihood of clinical response to reduction in immune suppression or to chemotherapy. The goal for multicenter trials must include the development of uniform definitions for the clinical and virologic manifestations of PTLD, as well as further attempts to define the natural history of this group of diseases.Jay A. Fishman, M.D.
Amphotericin B and its new formulations: pharmacologic characteristics, clinical efficacy, and tolerability
Authors: Tiphine M. , Letscher‐Bru V. , Herbrecht R. 
Published: March 2003

Abstract:Amphotericin B (amB) remains the gold standard for the treatment of invasive fungal infections. However, the efficacy is limited, with response rates from 10% to 80%. Moreover, amB is toxic, especially for the kidneys. New formulations have been developed in an attempt to improve both efficacy and tolerability. In an attempt to reduce toxicity, a number of investigators have reconstituted amB in a lipid emulsion, but few data are available on efficacy in documented infections. An improvement in immediate and renal tolerance was obtained with equivalent daily dose regimens, but the therapeutic index does not appear to be improved. This approach cannot be recommended at present. Three lipid formulations have been developed and are now available in most countries: amB colloidal dispersion (ABCD), amB lipid complex (ABLC), and liposomal amB (AmBisome). The efficacy of ABCD on various fungal infections has been assessed in open trials, with a response rate of 49% in aspergillosis, 70% in candidiasis, and 67% in mucormycosis. In two randomized trials comparing ABCD with amB in invasive aspergillosis and in persistent febrile neutropenia, the response rates were equivalent. ABCD was less nephrotoxic. In contrast, immediate reactions to ABCD were as frequent and severe as with amB. These immediate effects are more frequent during the first infusions and lessen as treatment continues. The recommended dose is 3–4 mg/kg/day. ABLC appeared to be effective as rescue therapy in various types of invasive mycoses, with a response rate of 42% in aspergillosis, 67% in candidiasis, and 82% in fusariosis. Efficacy identical to that of amB was demonstrated in a comparative randomized trial involving patients with invasive candidiasis. General and renal tolerability is improved compared with amB. The recommended dose regimen is 5 mg/kg/day. Liposomal amB (AmBisome) is the only truly liposomal formulation. The response rates in preliminary trials were 66% in aspergillosis and 81% in candidiasis. Several comparative studies have confirmed that this formulation has similar or superior efficacy relative to amB in various fungal infections and also in the empirical treatment of febrile neutropenia. Renal and general tolerability is excellent. The optimal dosing remains unclear but is generally between 3 and 5 mg/kg/day. A double‐blind trial comparing the tolerance of liposomal amB and ABLC demonstrated that both infusion‐related events and nephrotoxicity were significantly lower for liposomal amB. In sum, the new lipid formulations of amB are effective in various invasive fungal infections. The three formulations exhibit reduced nephrotoxicity compared with conventional amB. Large‐scale comparative clinical trials may clarify issues of relative efficacy in various forms of mycotic infections.Note
Safety and efficacy of granulocyte colony‐stimulating factor in kidney and liver transplant recipients
Authors: Turgeon N. , Hovingh G.K. , Fishman J.A. , Basgoz N. , Tolkoff‐Rubin N.E. , Doran M. , Cosimi A.B. , Rubin R.H. 
Published: March 2003

Abstract:Background:Leukopenia is not infrequently encountered following solid organ transplantation, most often in the setting of cytomegalovirus (CMV) disease and/or its treatment with ganciclovir. The present study was undertaken to determine the safety and efficacy of granulocyte colony‐stimulating factor (G‐CSF) in renal and liver transplant recipients with leukopenia.Methods: Between 1 June 1991 and 1 June 1998, patients received G‐CSF for 2 indications: 1) white blood cell count (WBC) <3000/mm3, with a decline from baseline; 2) to shorten the duration of leukopenia associated with chemotherapy. A retrospective review of the outcome of such therapy was undertaken.Results:50 patients were given 100 courses of treatment with G‐CSF; 35 of 168 liver transplant recipients (20.8%), 14 of 391 kidney transplant recipients (3.6%), and 1 of 4 recipients of combined liver–kidney transplants (25.0%) received from 1 to 9 courses of G‐CSF. Presumed causes of leukopenia were identified as ganciclovir in 28 cases (28.0%), CMV in 21 (21.0%), chemotherapy in 12 (12.0%), sepsis in 11 (11.0%), azathioprine in 5 (5.0%), interferon in 3 (3.0%) and other causes in 20 cases (20.0%). The median length of therapy was 10.0 days (range 1–154 days) and the average dose of daily G‐CSF received was 3.9±1.5 μg/kg/day. The average WBC was (2.4±1.3)×103/μl at the beginning of therapy, and (13.8±9.1)×103/μl at the end of therapy. In 7 of 100 treatments (7.0%) a WBC of 5.0×103/μl was not reached during G‐CSF therapy; in 6 of these 7 cases, G‐CSF therapy lasted fewer than 4 days. The mean time needed to reach a WBC count of 5×103/μl was 3.7±3.3 days among 71 patients who had daily WBC counts sent. Eight G‐CSF treatments (8.0%) were followed by episodes of rejection appearing during or within 2 months of treatment; 5 of them were biopsy‐documented. No relation was found between the highest WBC obtained during G‐CSF therapy and the risk of rejection. Eight patients (16.0%) died while receiving G‐CSF, all from infection. Six of these 8 patients were receiving G‐CSF for leukopenia secondary to sepsis. Overall, 25 patients (50.0%) received 49 courses of G‐CSF secondary to CMV and/or ganciclovir therapy. In 40 of 49 courses (81.6%), ganciclovir could be continued at recommended doses. Twenty‐one of 22 patients (95.5%) with symptomatic CMV infection had a clinical response to ganciclovir. Sixteen of 18 patients (88.9%) treated for a CMV infection and followed with serial antigenemia assays attained microbiological cure; both patients who did not were infected with ganciclovir resistant CMV.Conclusion:G‐CSF was well tolerated in solid organ transplant recipients. It was particularly useful in patients with CMV disease, allowing optimal ganciclovir therapy (Note).
The distribution of porcine pancreatic beta‐cells at ages 5, 12 and 24 weeks
Authors: KA TR Jay , Heald  , Carless NJ , DE Topham  , Downing R. 
Published: March 2003

Jay TR, Heald KA, Carless NJ, Topham DE, Downing R. The distribution of porcine pancreatic beta‐cells at ages 5, 12 and 24 weeks. Xenotransplantation 1999; 6: 131‐140. ©Munksgaard, CopenhagenIslet transplantation is a potential treatment for diabetes mellitus and porcine pancreata may provide a readily available source of islets. The size, number and distribution of islets within the pancreas may influence the choice of age of donor for xenotransplantation. Samples (n = 3 per age group) from the dorsal and ventral pancreas of 5‐, 12‐ and 24‐week‐old hybrid pigs were fixed in formal saline, processed in paraffin wax and stained with an avidin/biotin immunohistochemical kit for insulin, glucagon, somatostatin and pancreatic polypeptide. The arrangement of endocrine cells within the pancreata were studied and mean diameter of β‐cell groups were measured (from insulin stained sections) in 1 mm2 grid areas (n = 10 per section) and collated into groups according to size. Percentage volume density of β‐cells in relation to the whole pancreas was calculated and also the distribution of β‐cell groups, according to their size, within the total β‐cell mass. There were differences in the frequency and arrangement of endocrine cells within islets at the different ages studied. β‐Cell groups < 50 µm in diameter occupied 70 to 80% of the total β‐cell mass at 5 weeks but, as the age of the pig increased, larger cell groups were more abundant. However, the percentage volume density of β‐cells within the total pancreas did not change as the pancreas matured.This study shows that the endocrine porcine pancreas was maturing and its structure changed between the ages of 5 and 24 weeks. The relevance of these findings may have implications on the isolation and function of islets if young pigs are to be used as donors for transplantation as a treatment for diabetes mellitus.
Analysis of human CD4 T lymphocyte proliferation induced by porcine lymphoblastoid B cell lines
Authors: Bonenfant Christine , Vallée Isabelle , Sun Jishan , Brossay Angélique , Thibault Gilles , Guillaumin Jean Maurice , Lebranchu Yvon , Bardos Pierre , Butler J. E. , Watier Hervé 
Published: March 2003

Bonenfant C, Vallée I, Sun J, Brossay A, Thibault G, Guillaumin JM, Lebranchu Y, Bardos P, Butler JE, Watier H. Analysis of human CD4 T lymphocyte proliferation induced by porcine lymphoblastoid B cell lines. Xenotransplantation 2003; 10: 107–119. © Blackwell Munksgaard, 2003Background: This study was undertaken to characterize the two porcine lymphoblastoid cell lines L23 and L35, derived from a pig inoculated by the retrovirus Tsukuba‐1, and to determine how they induce a strong human lymphocyte proliferation. Methods: Phenotypic characterization was performed by flow cytometry and reverse transcriptase‐polymerase chain reaction analyses. Xenogeneic mixed lymphocyte reactions (XMLR) were performed using unfractionated human peripheral blood mononuclear cells (huPBMC) and purified CD4+ T lymphocytes as responding cells, in the presence of blocking antibodies and fusion proteins. Results: The immunoglobulin genes were demonstrated to be rearranged in L23 and L35 cell lines, in agreement with the expression of a B cell phenotype. Both induced a similar proliferation of huPBMCs and purified human CD4+ lymphocytes from adult or cord blood (naïve cells). Proliferation of CD4+ T lymphocytes was completely blocked by anti‐SLA‐DR plus anti‐SLA‐DQ mAbs, excluding human lymphocyte transformation by porcine viruses. The frequency of proliferative precursors was inconsistent with that induced by a retroviral superantigen but similar to classical direct xenoantigen presentation as observed with other porcine antigen‐presenting cells. Extensive analysis of costimulatory signals led to the identification of the CD28 pathway, in agreement with membrane expression of B7 molecules on L23 and L35 cells, and of the CD2 pathway in L35 cells. Conclusion: These two porcine lymphoblastoid cell lines have been further characterized and clearly identified as belonging to the B cell lineage. By expressing major histocompatibility complex class II antigens and costimulatory molecules, they induce a vigorous proliferative response of human CD4+ lymphocytes through a direct presentation pathway.
Transforming growth factor‐β3 (Tgf‐β3) down‐regulates Tgf‐β receptor type I (Tβr‐I) during rescue of cranial sutures from osseous obliteration
Authors: Opperman LA , Galanis V , Williams AR , Adab K 
Published: March 2003

AbstractAppropriate biochemical regulation of intramembranous bone growth from sutures is necessary to achieve correct craniofacial morphology. Failure to form sutures (agenesis) or to maintain sutures in their unossified state (craniosynostosis) can result in severe facial dysmorphology. Several factors such as Twist, Msx2, fibroblast growth factors (Fgfs), bone morphogenetic proteins (Bmps) and transforming growth factors‐β (Tgf‐βs) regulate suture patency, likely by interacting with one another. Tgf‐β2 and Tgf‐β3 use the same cell surface receptors, yet have opposite effects on suture patency, cellular proliferation and apoptosis within the suture. One possible mechanism by which Tgf‐β3 rescues sutures from obliteration is by regulating the ability of suture cells to respond to Tgf‐β2. As Tgf‐β3 does not regulate protein levels of Tgf‐β2 in sutures, Tgf‐β3 could regulate tissue responsiveness to Tgf‐β2 by regulating Tgf‐β2 access to receptors. Tgf‐β3 is a more potent competitor than Tgf‐β2 for cell surface receptors, so it is proposed that Tgf‐β3 binds to and down‐regulates Tgf‐β receptor type I (Tβr‐I) expression by suture cells. This down‐regulation would limit the ability of cells to respond to all Tgf‐βs, including Tgf‐β2. To test this hypothesis, an in vitro culture model was used in which fetal rat sutures either remain patent or are induced to fuse when cultured in the presence or absence of dura mater, respectively. Tgf‐β3 was added to cultured calvaria and changes in the number of receptor positive cells within the suture were established. Data were compared with that seen in control sutures and in normal sutures in vivo. It was found that the numbers of cells expressing Tβr‐I within the suture matrix increased over time in sutures remaining patent. Osteoblastic cells lining the bone fronts on either side of sutures were Tβr‐I positive during early morphogenesis, but these numbers declined as sutures fused, both in vivo and in vitro. Addition of Tgf‐β3 to calvaria in culture decreased the number of Tβr‐I expressing cells in both fusing and non‐fusing sutures, with dramatic decreases in the numbers of osteoblasts expressing Tβr‐I.
Epidemiological and genetic study of 121 cases of oral clefts in Kuwait
Authors: Al‐Bustan S A , El‐Zawahri M M , Al‐Adsani A M , Bang R L , Ghunaim I , Maher B S , Weinberg S , Marazita M L 
Published: March 2003

Structured Abstract
Authors –
S Al‐Bustan, M El‐Zawahri, A Al‐Adsani, R Bang, I Ghunaim, B Maher, S Weinberg, M Marazita
Aim –
The aim of the study was to ascertain some epidemiological factors such as sex and consanguinity that may be associated with cleft lip with or without cleft palate (CL ± CP) in Kuwait as well as to conduct genetic segregation analysis of these families.
Setting and sample population –
A total of 113 families ascertained through 121 CL ± CP and CP surgical probands in Kuwait. The frequencies of cleft types and the epidemiological variables were calculated using SPSS version 5.0 software. Chi‐square for goodness‐of‐fit test was used to test the significance of the associated epidemiological variables to facial clefts. Genetic segregation analysis was performed on 76 families with extended pedigrees and included only those with non‐syndromic CL ± CP (NS CL ± CP). Major locus segregation analysis was used to fit models to the observed family patterns under Class A regressive models as implemented by REGD routine in S.A.G.E. release 4.0. A test for heterogeneity was also conducted to complete data set in addition to two subsets: Arabs and nomads.
Results –
Of the 121 patients, 34(28.1%) had CP, 30(24.8%) had CL and 57 (47.1%) had CL + CP. The male to female ratio was 0.89 for CP, 1.14 for CL, 1.35 for CL + CP and 1.2 for all the clefts. The percentage of consanguineous families among those with a positive family history (60%) was not significantly different from that of the general population (54.3%), whereas for all the families with clefts the percent consanguineous was significantly lower (38%). No evidence of heterogeneity in the results between the Arab and nomad subsets was observed. The results for the major locus segregation analysis were inconclusive.
Conclusion –
No definite association was observed between consanguinity and the occurrence of facial clefts in Kuwait. General transmission models in the full data set showed no evidence of heterogeneity in the results between the Arab and nomad subsets.