bluuebunny/crossref_metadata_2025_split huggingface dataset:
Numerical analysis of 1.55‐µm wavelength optical deflector using arrayed waveguide with staircase‐like refractive index distribution
Authors: Miki Kazunori , Kawakita Yasumasa , Kihara Tatsuya , Shimomura Kazuhiko 
Published: March 2003

AbstractThis paper proposes an optical deflector using an arrayed waveguide with a staircase‐like refractive index profile. This device is an optical deflector using an array waveguide with the refractive index different in each of the component waveguides. Optical deflection is accomplished by application of a voltage. In order to study the deflection properties, a theoretical analysis of the structure, device parameters, deflection angle, and number of resolution points is carried out. As a method of realizing an arrayed waveguide with built‐in refractive index steps, selective organometallic vapor phase epitaxial growth is used for fabrication of an array waveguide with multiple quantum well structures. Initial experimental results are reported here. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(4): 1–9, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10103
Photodynamic therapy with Pd‐bacteriopheophorbide (TOOKAD): Successful in vivo treatment of human prostatic small cell carcinoma xenografts
Authors: Koudinova Natalia V. , Pinthus Jehonathan H. , Brandis Alexander , Brenner Ori , Bendel Peter , Ramon Jacob , Eshhar Zelig , Scherz Avigdor , Salomon Yoram 
Published: March 2003

AbstractSmall cell carcinoma of the prostate (SCCP), although relatively rare, is the most aggressive variant of prostate cancer, currently with no successful treatment. It was therefore tempting to evaluate the response of this violent malignancy and its bone lesions to Pd‐Bacteriopheophorbide (TOOKAD)‐based photodynamic therapy (PDT), already proven by us to efficiently eradicate other aggressive non‐epithelial solid tumors. TOOKAD is a novel bacteriochlorophyll‐derived, second‐generation photosensitizer recently, developed by us for the treatment of bulky tumors. This photosensitizer is endowed with strong light absorbance (ϵ0 ∼ 105 mol−1 cm−1) in the near infrared region (λ=763nm), allowing deep tissue penetration. The TOOKAD‐PDT protocol targets the tumor vasculature leading to inflammation, hypoxia, necrosis and tumor eradication. The sensitizer clears rapidly from the circulation within a few hours and does not accumulate in tissues, which is compatible with the treatment of localized tumor and isolated metastases. Briefly, male CD1‐nude mice were grafted with the human SCCP (WISH‐PC2) in 3 relevant anatomic locations: subcutaneous (representing tumor mass), intraosseous (representing bone metastases) and orthotopically within the murine prostate microenvironment. The PDT protocol consisted of i.v. administration of TOOKAD (4 mg/kg), followed by immediate illumination (650–800 nm) from a xenon light source or a diode laser emitting at 770 nm. Controls included untreated animals or animals treated with light or TOOKAD alone. Tumor volume, human plasma chromogranin A levels, animal well being and survival were used as end points. In addition, histopathology and immunohistochemistry were used to define the tumor response. Subcutaneous tumors exhibited complete healing within 28–40 days, reaching an overall long‐term cure rate of 69%, followed for 90 days after PDT. Intratibial WISH‐PC2 lesions responded with complete tumor elimination in 50% of the treated mice at 70–90 days after PDT as documented histologically. The response of the orthotopic model was also analyzed histologically with similar results. The study with this model suggests that TOOKAD‐based PDT can reach large tumors and is a feasible, efficient and well‐tolerated approach for minimally invasive treatment of local and disseminated SCCP. © 2003 Wiley‐Liss, Inc.
Analysis of chromosomal instability in pulmonary or liver metastases and matched primary hepatocellular carcinoma after orthotopic liver transplantation
Authors: Gross‐Goupil Marine , Riou Philippe , Emile Jean‐François , Saffroy Raphaël , Azoulay Daniel , Lacherade Isabelle , Receveur Aline , Piatier‐Tonneau Dominique , Castaing Denis , Debuire Brigitte , Lemoine Antoinette 
Published: March 2003

AbstractTo investigate the genetic mechanism of metastatic spread in hepatocellular carcinoma (HCC), we analyzed genomic changes in lung or liver metastases and the corresponding primary tumors (83 tumor samples) in 18 patients who underwent orthotopic liver transplantation. We studied the incidence of microsatellite instability (MSI) and loss of heterozygosity (LOH) involving 8 highly polymorphic microsatellite markers and the polyA tract, Bat26. We also sought alterations of p53 and β‐catenin gene mutations. High MSI (>30–40% of the loci analyzed) was found only in primary tumors (11%), whereas LOH was observed in 50% of primary and in 39% of recurrent tumors. p53 mutations were found in 2 cases of primary HCC but not in the corresponding metastases. P53 was overexpressed in 4 primary HCC (22%) and 7 metastases (39%). The percentage of β‐catenin gene mutations was low (6%). Lung metastases retained the D16S402 microsatellite abnormalities observed in the primary tumors, whereas recurrent liver tumor did not (p = 0.02). In conclusion, LOH and P53 protein overexpression, rather than mutations in the p53 or β‐catenin genes or MSI, seem to be involved in the spreading of HCC, suggesting the presence of metastasis suppressor genes in the vicinity of the chromosomal loci in question. © 2003 Wiley‐Liss, Inc.
Refined mapping of 1q32 amplicons in malignant gliomas confirms MDM4 as the main amplification target
Authors: Riemenschneider Markus J. , Knobbe Christiane B. , Reifenberger Guido 
Published: March 2003

AbstractWe previously reported on the amplification and overexpression of the mouse double minute 4 homolog gene (MDM4) from 1q32 in a subset of malignant gliomas (Riemenschneider et al., Cancer Res 1999;59:6091–6). More recently, amplification and overexpression of the neighboring contactin 2 gene (CNTN2) was reported in individual malignant gliomas without MDM4 amplification (Rickman et al., Cancer Res 2001;61:2162–8). To address the question of whether 1q32 carries 2 independent amplification targets or a common target other than MDM4 and CNTN2, we analyzed primary malignant gliomas for amplification and overexpression of 17 different genes from this region. Our results indicate a single region of amplification that comprises the genes MDM4, GAC1, PIK3C2B and PEPP3, with only MDM4 amplification being invariably associated with overexpression. CNTN2 was found to be coamplified with MDM4 in 3 malignant gliomas but overexpressed in only 1 of these tumors. No CNTN2 amplification was detected in any of 102 malignant gliomas without MDM4 amplification. Our data therefore corroborate the notion that MDM4 is the main amplification target on 1q32 in malignant gliomas. However, coamplification and overexpression of adjacent genes may provide an additional growth advantage in some malignant gliomas with MDM4 amplification. © 2003 Wiley‐Liss, Inc.
Identification, sequencing and serology of HLA‐B*3527
Authors: Guttridge M.G. , Thompson J. , Street J. , Darke C. 
Published: March 2003

Abstract:We describe a variant HLA‐B*35 allele (B*3527) that was detected by the polymerase chain reaction using sequence‐specific primers (PCR‐SSP) in an individual on the Welsh Bone Marrow Donor registry. B*3527 differs from B*3501 by a single base (G/A) at position 302 that encodes an amino acid change of Ser to Asn at position 77 in the Bw6 epitope. Serological studies using 38 B35‐, 4 Bw6‐ and 7 Bw4‐reactive sera indicated that the B*3527 product was indistinguishable from the B35 specificity, and that the substitution did not significantly affect the Bw6 epitope. A family study determined the B*3527 bearing haplotype as: HLA‐A*29, B*3527, Cw*0401, DRB1*0404, DRB4*0101/0103, DQA1*03, DQB1*0302, BFS, C4A3, C4B1. The phenotype and gene frequencies in the local Welsh population were<0.01% and <0.00005%, respectivelyNote.
Interleukin‐10 (IL‐10) genotypes in inflammatory bowel disease
Authors: Tagore A. , Gonsalkorale W.M. , Pravica V. , Hajeer A.H. , McMahon R. , Whorwell P.J. , Sinnott P.J. , Hutchinson I.V. 
Published: March 2003

Abstract:Interleukin‐10 (IL‐10) is an anti‐inflammatory cytokine. Its production in humans is under genetic control, and genotype defines high or low producers of this cytokine. This study addresses the hypothesis that idiopathic inflammatory bowel disease (IBD) patients are more likely to have the low IL‐10 producer genotype and phenotype. DNA was extracted from blood cells of patients with Crohn’s disease (CD) or with ulcerative colitis (UC) for IL‐10 genotyping. The frequency of the high IL‐10 producer allele (−1082*G) was decreased in the whole IBD group (41% vs. 51%, P=0.03) and in the UC patients compared with normal controls (37% vs. 51%; P=0.04). Hence, there appears to be an association between the IL‐10 genotypes and IBD. This suggests that individuals genetically predisposed to produce less IL‐10 are at a higher risk of developing IBD, in particular, UC.
Molecular modeling of the minor histocompatibility antigen HA‐1 peptides binding to HLA‐A alleles
Authors: Ren E.C. , Kangueane P. , Kolatkar P. , Lin M.T. , Tseng L.H. , Hansen J.A. 
Published: March 2003

Abstract:Mismatch of the minor histocompatibility antigen HA‐1 has been shown to correlate with graft‐versus‐host disease in HLA‐matched sibling marrow transplants. The HA‐1H peptide (VLHDDLLEA) that generates this response is known to be presented by HLA‐A*0201. In order to understand the interaction of HA‐1 peptides with other HLA‐A alleles, we have used the LOOK interface to construct molecular models of both HA‐1H peptide (VLHDDLLEA) and HA‐1R peptide (VLRDDLLEA) binding with 103 HLA‐A alleles. The results show that in addition to A*0201, 21/103 other HLA‐A alleles should be able to bind HA‐1H peptide but not HA‐1R peptide. Based on the modeled predictions, HLA alleles can be categorised into 4 groups with respect to their interaction with HA‐1 peptides: Group 1 – bind HA‐1H peptide but not HA‐1R peptide; Group 2 – bind HA‐1R peptide but not HA‐1H peptide; Group 3 – bind both HA‐1H and HA‐1R peptides; Group 4 – bind neither peptide. These predicted binding patterns of HA‐1 peptides will be useful as an aid for defining a wider pool of HLA‐A alleles in which HA‐1 disparities among donor‐recipient pairs can be investigated.
DPB1*8501, a novel DPB1 variant in the US Black population
Authors: Rozemuller E.H. , Van Der Zwan A.W. , Voorter C.E.M. , Tilanus M.G.J. 
Published: March 2003

Abstract:We describe a new DPB1 allele, DPB1*8501, which was identified by sequencing‐based typing (SBT) in the UCLA exchange. DPB1*8501 is similar to DPB1*2701 with a difference at position 272, (G to A). This difference leads to an amino‐acid change of codon 91 from arginine (CGC) to histidine (CAC). Until now this position has been considered conserved. This substitution is located at the 3′ site of exon 2, and may interfere with typing strategies using primers or probes located in this region ( Note).
Synthesis and biological evaluation of destruxin A and related analogs
Authors: Ast T. , Schmidt M. , Germeroth L. , Wenschuh H. , Barron E. , Kinne L. , Simmons K. 
Published: March 2003

Abstract:This report describes the development of an efficient solid‐phase synthesis protocol and adaptation of reported solution phase procedures for the synthesis of the cyclic depsihexapeptide destruxin A and related analogs. The solid‐phase method described is based on standard Fmoc peptide chemistry, including a new synthetic method for the assembly of the depsi bond‐containing unit. In order to select analogs of destruxin A for synthesis and evaluation of insecticidal activity, the work of Hellberget al., describing a set ofZ‐descriptors for amino acid side‐chains comparing their physicochemical properties, was utilized. Destruxin A and 27 different analogs with structural variations in four residues were synthesized and insecticidal activity was evaluated via injections into tobacco budworm (Heliothis virescens) larvae. Several destruxin A analogs were found to be at least as potent as the native compound.
Environmental control of flowering time in Antirrhinum majus
Authors: Cremer F. , Havelange A. , Saedler H. , Huijser P. 
Published: March 2003

The effect of different environmental conditions on flowering time and the number of leaves produced before the first flower is formed has been investigated in Antirrhinum majus L. The effect of light quality has been tested by decreasing the red/far‐red ratio, generally resulting in a reduced flowering time and leaf number. Furthermore, it could be shown that photoperiod, temperature and light intensity are inversely correlated with flowering time and leaf number. However, lowering the temperature from 15 to 12°C resulted in a reduction of flowering time. This observation shows that Antirrhinum can be vernalised.Using defined combinations of the four environmental factors we have been able to reduce flowering time to only 42 days or to delay flowering for at least 2 years. The results obtained allow an optimisation of the screening conditions for identifying flowering time mutants in Antirrhinum.
Inhibition of platelet aggregation in baboons: therapeutic implications for xenotransplantation
Authors: Alwayn Ian P. J. , Appel James Z. , Goepfert Christian , Buhler Leo , Cooper David K. C. , Robson Simon C. 
Published: March 2003

Methods: Drugs tested in these experiments were aurintricarboxylic acid (ATA, von Willebrand Factor‐GPIb inhibitor), fucoidin (a selectin‐inhibitor), 1‐benzylimidazole (1‐BI, thromboxane synthase antagonist), prostacyclin (PGI2, endothelial stabilizer), heparin (thrombin antagonist), nitroprusside sodium or nicotinamide (NPN or NA, both NO‐donors), and eptifibatide (EFT, GPIIb/IIIa receptor antagonist). These were infused intravenously to nine baboons. Coagulation parameters and platelet counts were monitored and baboons were observed for adverse side‐effects. The efficacy of these agents in inhibiting platelet aggregation was assayed in a platelet aggregometer. Results: Treatment with ATA and fucoidin resulted in complete inhibition of platelet aggregation but also in major perturbation of coagulation parameters. 1‐BI and PGI2 had no effect when administered alone, but in combination resulted in moderate inhibition of aggregation without disturbance in PT or PTT. NPN and NA had no substantive effects on platelet aggregation. Heparin resulted in specific inhibition of thrombin‐induced platelet aggregation and, as anticipated, was associated with moderate prolongation of PTT. Importantly, EFT caused complete inhibition of platelet aggregation without changes in coagulation. Platelet counts, fibrinogen levels, and fibrinogen degradation products remained within the normal ranges in all experiments. Conclusions: Although excellent inhibition of platelet activation was obtained with ATA and fucoidin, clinical use may be precluded by concomitant disturbances of coagulation. Combinations of heparin and EFT may prove beneficial in preventing the thrombotic disorders associated with xenograft rejection while maintaining adequate hemostatic responses. These agents are to be evaluated in our pig‐to‐primate xenotransplantation models.
Rejection of porcine islet xenografts mediated by CD4+ T cells activated through the indirect antigen recognition pathway
Authors: Olack Barbara J. , Jaramillo Andrés , Benshoff Nicholas D. , Kaleem Zahid , Swanson Carol J. , Lowell Jeffrey A. , Mohanakumar T. 
Published: March 2003

Olack BJ, Jaramillo A, Benshoff ND, Kaleem Z, Swanson CJ, Lowell JA, Mohanakumar T. Rejection of porcine islet xenografts mediated by CD4+ T cells activated through the indirect antigen recognition pathway. Xenotransplantation 2002; 9: 393–401. © Blackwell Munksgaard, 2002We have previously demonstrated that human T cells responding to porcine islets are primarily CD4+ and recognized porcine major histocompatibility complex class I molecules through the indirect pathway of antigen presentation. To determine whether this mechanism is responsible for rejection of adult porcine islets xenografts, porcine islets from adult pigs were transplanted under the kidney capsule of streptozotocin‐treated CD4‐knockout (KO), CD8‐KO, Ig‐KO and normal C57BL/6 mice. Islet xenografts were acutely rejected with similar kinetics when transplanted into normal C57BL/6 (MST=17.6 ± 3.5 days) and Ig‐KO (MST=19.0 ± 1.7 days) mice. Interestingly, islet xenografts were rejected significantly earlier when transplanted into CD8‐KO mice as compared with normal C57BL/6 (MST=7.0 ± 0.01 days, P=2 × 10−4). Histopathological analysis revealed classical acute cellular rejection with severe diffuse interstitial cellular infiltrates in all rejected islet xenografts. In contrast, islet xenografts were not rejected when transplanted into CD4‐KO mice (MST ≥ 100 days, P=1 × 10−9). Histopathological analysis revealed no cellular infiltrates and intact islet xenografts. CD4+ T cells from both normal C57BL/6 and CD8‐KO xenograft recipients showed detectable proliferative responses to porcine islets in the presence but not in the absence of syngeneic antigen‐presenting cells. In addition, the anti‐islet proliferative responses observed in normal C57BL/6 mice were significantly lower than those observed in CD8‐KO mice. IgG anti‐porcine antibodies were readily detected in C57BL/6 and CD8‐KO xenograft recipients but not in Ig‐KO or CD4‐KO recipients. These results indicate that indirectly activated CD4+ T cells mediate acute rejection of adult porcine islet xenografts and that xenoreactive CD8+ T cells and antibodies are not necessary in this process.
Spatiotemporal expression of NGFR during pre‐natal human tooth development
Authors: Becktor KB , Hansen BF , Nolting D , Kjær I 
Published: March 2003

Structured AbstractAuthors– Becktor KB, Hansen BF, Nolting D, Kjær I.Objectives– The relation between nerve growth factor receptor (NGFR) in the human pre‐natal tooth buds and the dental follicle was investigated. In particular, we sought to determine if there is a specific pattern of p75NGFR expression in developing human tooth buds and their surrounding tissue.Setting and Sample Population– The Department of Orthodontics at Copenhagen University, Denmark. Histological sections from 11 fetuses, aged 11–21 gestational weeks.Method– The sections were studied by conventional immunohistochemistry.Results– Specific spatiotemporal patterns of p75NGFR reactions were observed in the tooth buds and dental follicle: Before matrix production by the ameloblasts, the entire inner enamel epithelium and the entire dental follicle display p75NGFR immunoreactivity; after matrix production is initiated, the immunoreactivity of the matrix producing cells is lost, as is that of the dental follicle adjacent to these matrix‐producing cells.Conclusion– A unique spatiotemporal distribution of NGFR in the pre‐eruptive human tooth bud was demonstrated.
The genomic context of natural killer receptor extended gene families
Authors: Trowsdale John , Barten Roland , Haude Anja , Stewart C. Andrew , Beck Stephan , Wilson Michael J. 
Published: March 2003

Summary: The two sets of inhibitory and activating natural killer (NK) receptor genes belong either to the Ig or to the C‐type lectin superfamilies. Both are extensive and diverse, comprising genes of varying degrees of relatedness, indicative of a process of iterative duplication. We have constructed gene maps to help understand how and when NK receptor genes developed and the nature of their polymorphism. A cluster of over 15 C‐type lectin genes, the natural killer complex is located on human chromosome 12p13.1, syntenic with a region in mouse that borders multiple Ly49 loci. The equivalent locus in man is occupied by a single pseudogene, LY49L. The immunoglobulin superfamily of loci, the leukocyte receptor complex (LRC), on chromosome 19q13.4, contains many polymorphic killer cell immunoglobulin‐like receptor (KIR) genes as well as multiple related sequences. These include immunoglobulin‐like transcript (ILT) (or leukocyte immunoglobulin‐like receptor genes), leukocyte‐associated inhibitory receptor genes (LAIR), NKp46, FcαR and the platelet glycoprotein receptor VI locus, which encodes a collagen‐binding molecule. KIRs are expressed mostly on NK cells and some T cells. The other LRC loci are more widely expressed. Further centromeric of the LRC are sets of additional loci with weak sequence similarity to the KIRs, including the extensive CD66(CEA) and Siglec families. The LRC‐syntenic region in mice contains no orthologues of KIRs. Some of the KIR genes are highly polymorphic in terms of sequence as well as for presence/absence of genes on different haplotypes. Some anchor loci, such as KIR2DL4, are present on most haplotypes. A few ILT loci, such as ILT5 and ILT8, are polymorphic, but only ILT6 exhibits presence/absence variation. This knowledge of the genomic organisation of the extensive NK superfamilies underpins efforts to understand the functions of the encoded NK receptor molecules. It leads to the conclusion that the functional homology of human KIR and mouse Ly49 genes arose by convergent evolution. NK receptor immunogenetics has interesting parallels with the major histocompatibility complex (MHC) in which some of the polymorphic genes are ligands for NK molecules. There are hints of an ancient genetic relationship between NK receptor genes and MHC‐paralogous regions on chromosomes 1, 9 and 19. The picture that emerges from both complexes is of eternal evolutionary restlessness, presumably in response to resistance to disease.This work was funded by the Wellcome Trust and the MRC
The UL16‐binding proteins, a novel family of MHC class I‐related ligands for NKG2D, activate natural killer cell functions
Authors: Sutherland Claire L. , Chalupny N. Jan , Cosman David 
Published: March 2003

Summary: The UL16‐binding proteins (ULBPs) are a novel family of MHC class I‐related molecules (MICs) that were identified based on their ability to bind to the human cytomegalovirus (HCMV) glycoprotein UL16. UL16 also binds to a member of another family of MHC class I‐like molecules, MICB. The ULBPs and MICs are ligands for NKG2D/DAP10, an activating receptor expressed by natural killer (NK) cells and other immune effector cells, and this interaction can be blocked by UL16. Engagement of NKG2D/DAP10 by ULBPs or MICs expressed on a target cell can overcome an inhibitory signal generated by NK‐cell recognition of MHC class I molecules and trigger NK cytotoxicity. ULBPs elicit their effects on NK cells by activating the janus kinase 2, signal transducer and activator of transcription 5, extracellular‐signal‐regulated kinase mitogen‐activated protein kinase and Akt/protein kinase B signal transduction pathways. Although ULBPs alone activate multiple signaling pathways and induce modest cytokine production, ULBPs synergize strongly with interleukin‐12 for production of interferon‐γ by NK cells. This finding is consistent with reports in T cells that NKG2D/DAP10 can act as a co‐stimulatory receptor in a similar manner as CD28. The possible roles of ULBPs in mediating immune responses to viruses and tumors and the potential mechanisms by which UL16 may allow HCMV to evade immune detection are areas of active investigation.We thank Gary Carlton for assistance with figures and Anne Aumell for editorial assistance.