bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Structure–Property Relationships of Amphiphilic Organogelators
Authors: Mohmeyer Nils , Schmidt Hans‐Werner
Published: March 2007

A series of low‐molecular‐weight amphiphilic molecules was synthesized and investigated for their ability to gel organic solvents. These amphiphilic molecules are composed of a head‐group moiety capable of forming intermolecular associations through hydrogen bonds and n‐alkyl chains of various lengths. This paper describes the continuation of recently published work, in which this class of gelators was presented for the first time. Here, the focus addresses systematically three different structural variations of the head‐group moiety: 1) the rigidity, 2) the type and strength of the hydrogen‐bond‐forming units, and 3) the reduction of the intermolecular interaction by incorporating a lateral substituent. The gelation behavior was investigated in p‐xylene and in several polar solvents. The aim was to establish structure–property relationships and to provide organogelators capable of forming gels at low concentrations with adjustable sol–gel transition temperatures and good optical quality. For some individual compounds of the series this property profile was achieved. For the investigated solvents, with particular compounds, sol–gel transition temperatures above 100 °C with a reasonable concentration of gelator are obtainable.
Experimental and Theoretical Investigations of Structural Isomers of Dichalcogenoimidodiphosphinate Dimers: Dichalcogenides or Spirocyclic Contact Ion Pairs?
Authors: Ritch Jamie S. , Chivers Tristram , Eisler Dana J. , Tuononen Heikki M.
Published: March 2007

A synthetic protocol for the tert‐butyl‐substituted dichalcogenoimidodiphosphinates [Na(tmeda){(EPtBu2)2N}] (3 a, E=S; 3 b, E=Se; 3 c, E=Te) has been developed. The one‐electron oxidation of the sodium complexes [Na(tmeda){(EPR2)2N}] with iodine produces a series of neutral dimers (EPR2NPR2E)2 (4 b, E=Se, R=iPr; 4 c, E=Te, R=iPr; 5 a, E=S, R=tBu; 5 b, E=Se, R=tBu; 5 c, E=Te, R=tBu). Attempts to prepare 4 a (E=S, R=iPr) in a similar manner produced a mixture including HN(SPiPr2). Compounds 4 b, 4 c and 5 a–c were characterised by multinuclear NMR spectra and by X‐ray crystallography, which revealed two alternative structures for these dimeric molecules. The derivatives 4 b, 4 c, 5 a and 5 b exhibit acyclic structures with a central chalcogen–chalcogen linkage that is elongated by approximately 2 % (E=S), 6 % (E=Se) and 8 % (E=Te) compared to typical single‐bond values. By contrast, 5 c adopts an unique spirocyclic contact ion‐pair structure in which a [(TePtBu2)2N]− ion is Te,Te′ chelated to an incipient [(TePtBu2)2N]+ cyclic ion. DFT calculations of the relative energies of the two structural isomers indicate a trend towards increasing stability for the contact ion pair relative to the corresponding dichalcogenide on going from S to Se to Te for both the isopropyl and tert‐butyl series. The two‐electron oxidation of [Na(tmeda){(EPtBu2)2N}] (E=S, Se, Te) with iodine produced the salts [(EPtBu2)2N]+X− (7 a, E=S, X=I3; 7 b, E=Se, X=I; 7 c, E=Te, X=I), which were characterised by X‐ray crystallography. Compound 7 a exists as a monomeric, ion‐separated complex with [d(SS)=2.084(2) Å]; 7 b and 7 c are dimeric [d(SeSe)=2.502(1) Å; d(TeTe)=2.884(1) Å].
Monitoring plasma voriconazole levels may be necessary to avoid subtherapeutic levels in hematopoietic stem cell transplant recipients
Authors: Trifilio Steve , Pennick Gennethel , Pi Judy , Zook Jennifer , Golf Mary , Kaniecki Kimberley , Singhal Seema , Williams Stephanie , Winter Jane , Tallman Martin , Gordon Leo , Frankfurt Olga , Evens Andrew , Mehta Jayesh
Published: March 2007

BACKGROUND.

Low voriconazole levels have been associated with a higher failure rate in patients with confirmed fungal infections.

METHODS.

Steady‐state plasma trough voriconazole levels were measured after at least 5 days of therapy in 87 patients with hematologic malignancies on 201 separate occasions (1–5 levels per patient; median, 2). Most patients (90%) had undergone allogeneic hematopoietic stem cell transplantation. The daily voriconazole dose, administered in 2 divided doses, was 200 mg (n = 4), 400 mg (n = 151), 500 mg (n = 20), 600 mg (n = 18), and 800 mg (n = 8); corresponding to 2.0–16.3 (median, 5.4) mg/kg. Plasma voriconazole levels were 0–12.5 μg/mL (median, 1.2). Voriconazole was undetectable (<0.2 μg/mL) in 15%.

RESULTS.

The correlation between dose and levels was weak (r = 0.14; P = .045). The median absolute daily drug dose (400 mg) was identical in groups of patients with levels of 0, 0.2 to 0.5, >0.5 to 2.0, >2.0 to 5.0, and >5.0. Whereas the daily drug dose in mg/kg was significantly higher when the levels were >5.0 μg/mL, there was no consistent relation between dose and level below that threshold. In adult patients getting standard doses of voriconazole orally, the drug levels are highly variable. Based on limited available data, between a quarter and two‐thirds of these levels could potentially be associated with a lower likelihood of response or a higher likelihood of failure.

CONCLUSIONS.

Future voriconazole studies should incorporate prospective therapeutic drug monitoring and consideration should be given to checking levels in patients receiving the drug for confirmed, life‐threatening fungal infections. Cancer 2007. © 2007 American Cancer Society.
Ciliated hepatic foregut cyst: Report of a case on fine‐needle aspiration
Authors: Kaplan Keith J. , Escobar Maura , Alonzo Marc , Berlin Jonathan W.
Published: March 2007

Ciliated hepatic foregut cyst (CHFC) is a rare, benign, solitary cyst consisting of ciliated columnar epithelium. They are lined by a layer of ciliated columnar cells and contain mucoid material and debris. It is the ciliated epithelium that distinguishes them from other hepatic cysts. The cyst is generally found incidentally on radiologic imaging or during surgical exploration. There has been an increase in the number of reports of CHFC during the past 15 years in the surgical pathology literature, presumably because of increased availability of various radiologic imaging modalities. Although it is rare, CHFC should be included in the differential diagnosis of cystic lesions of the liver and is important to consider in aspirates obtained for the evaluation of possible neoplastic disease. We report a case diagnosed by fine‐needle aspiration for a liver cyst discovered incidentally during the evaluation of acute pancreatitis. Diagn. Cytopathol. 2007;35:245–249. © 2007 Wiley‐Liss, Inc.
Immunocytochemistry for hepatocyte nuclear factor‐1β (HNF‐1β): A marker for ovarian clear cell carcinoma
Authors: Kato Noriko , Toukairin Michiko , Asanuma Izumi , Motoyama Teiichi
Published: March 2007

Recent microarray studies have shown that the expression of hepatocyte nuclear factor‐1β (HNF‐1β) was significantly up‐regulated in clear cell carcinoma (CCC) of the ovary. HNF‐1β may be a useful marker for CCC in peritoneal fluid cytology. We designed an experimental study using three CCC cell lines to evaluate the influence of alcohol fixation or air drying on immunocytochemistry for HNF‐1β. Each cell line was cultured on chamber slides or transplanted into the abdominal cavity of nude mice, then the slides or ascites smears of nude mice were immunostained with or without microwave‐mediated epitope retrieval. Immunoreactivity with HNF‐1β, which was either alcohol‐fixed or air‐dried, was noticeably improved after microwave heating. In contrast, two serous adenocarcinoma cell lines never showed immunoreactivity. Based on these results, 21 archival Papanicolaou‐stained slides of peritoneal fluid (5 CCCs, 12 serous, 2 mucinous, and 2 endometrioid adenocarcinomas) were decolorized and immunostained under heating pretreatment. Five of 5 CCCs were distinctively positive for HNF‐1β, whereas all non‐CCC ovarian cancers were negative for this protein. The present study clearly demonstrated that heating epitope retrieval improved the immunoreactivity for a nuclear protein in alcohol‐fixed or air‐dried cytology specimens. HNF‐1β is likely to be helpful for the diagnosis of CCC in the peritoneal fluid. Diagn. Cytopathol. 2007;35:193–197. © 2007 Wiley‐Liss, Inc.
Mucinous carcinoma of breast with abundant psammoma bodies in fine‐needle aspiration cytology: A case report
Authors: Raveendran Pillai K. , Jayasree K. , Jayalal K. S. , Mani K. S. , Abraham Elizabeth K.
Published: March 2007

Fine‐needle aspiration (FNA) cytology plays an important role in the diagnosis of various pathologic conditions in the breast. Microcalcification can be observed in benign and malignant breast lesions, but psammoma bodies (PBs) are rarely reported in breast lesions and are a feature of papillary neoplasms. However, we have observed PBs in large numbers in a mucinous carcinoma of breast, which is not previously reported in FNA of breast lesions. A 65‐yr‐old postmenopausal woman underwent FNA of a palpable mass. The aspirate revealed mucinous carcinoma cells associated with plenty of PBs. This case report of mucinous carcinoma of the breast with abundant PBs highlights the cytodiagnostic pattern of the lesion and formation of PBs. Diagn. Cytopathol. 2007;35:230–233. © 2007 Wiley‐Liss, Inc.
Molecular detection of Chlamydia trachomatis and HPV infections in cervical samples with normal and abnormal cytopathological findings
Authors: de Paula Francisco Danilo Ferreira , Fernandes Ana Paula , Carmo Bianca Bianco do , Vieira Daniela Cristina Duarte , Dutra Miriam Santos , Santos Caleb Guedes Miranda dos , Souza Maria do Carmo M. , Andrade Túlio César Alvim , Vago Annamaria Ravara , Fernandes Paula Ávila
Published: March 2007

It has been suggested that Chlamydia trachomatis (CT) and human papillomaviruses (HPV) co‐infection could contribute to development of intraepithelial lesions. In this study, HPV and CT‐DNA were investigated in 250 cervicovaginal samples of patients from Minas Gerais, Brazil. The cytological analysis revealed that 70% of samples (175) were negative, 5.2% (13) presented atypical squamous or glandular cells of undetermined significance (ASCUS/AGUS), 12.4% (31) presented low‐grade squamous intraepithelial lesion (LSIL), 10.8% (27) high‐grade squamous intraepithelial lesion (HSIL), and 1.6% (4) invasive carcinoma. HPV‐DNA and HPV/CT co‐infection was observed in 40% (100/250) and in 5.2% (13/250) of samples, respectively. Among the positive cytological samples, HPV‐DNA was detected in 73.3% and CT‐DNA in 9.33% and in 13%, if only the HPV positive samples were considered. The highest co‐infection rate (15.4%) was observed among ASCUS/AGUS samples. Although a significant association was found for HPV infection and the precursor lesions of cervical cancer, it was not possible to establish a significant association between these lesions and CT or HPV/CT co‐infection. Diagn. Cytopathol. 2007;35:198–202. © 2007 Wiley‐Liss, Inc.
Mycobacterial heat‐shock proteins as carrier molecules
Authors: Lussow Alexander R. , Barrios Christy , van Embden Jan , Van Der Zee Ruur , Verdini Antonio S. , Pessi Antonello , Louis Jacques A. , Lambert Paul‐Henri , Giudice Giuseppe Del
Published: March 2007

We have previously shown that the priming of mice with live Mycobacterium tuberculosis var. bovis (Bacillus Calmette‐Guérin, BCG) and immunization with the repetitive malaria synthetic peptide (NANP)40 conjugated to purified protein derivative (PPD), led to the induction of high and long‐lasting titers of anti‐peptide IgG antibodies, overcoming the requirement of adjuvants and the genetic restriction of the antibody response to the peptide (Lussow et al., Proc. Natl. Acad. Sci. USA 1990. 87: 2960). This initial work led us to the following observations. BCG had to be live for priming to lead to the induction of anti‐peptide antibodies. Surprisingly, priming with other living microorganisms which chronically infect the macrophage (e.g. Salmonella typhimurium and Leishmania major) also induced anti‐peptide antibodies in mice immunized with PPD‐(NANP)40 conjugate. It was, thus, hypothesized that molecules expressed during active infection and also known to be highly conserved between species, namely the heat‐shock proteins (hsp), could mediate the T cell sensitization required for the production of anti‐peptide antibodies. In fact, when the PPD portion of the conjugate was replaced by a highly purified recombinant protein corresponding to the 65‐kDa (GroEL‐type) hsp of M. bovis, this resulted in the production of anti‐(NANP) IgG antibodies in BCG‐primed mice, irrespective of the major histocompatibility complex‐controlled responsiveness to the (NANP) sequence itself. Further, similar induction of anti‐peptide antibody response was also obtained with a recombinant 70‐kDa (DnaK‐type) hsp of M. tuberculosis, but not with a small molecular mass (18 kDa) of M. leprae. Finally, an adjuvant‐free carrier effect for anti‐peptide IgG antibody production in BCG‐primed mice, was also exerted by the GroEL hsp of Escherichia coli. This finding that hsp can act as carrier molecules without requiring conventional adjuvants is of potential importance in the development of vaccine strategies.
Interleukin 6 inhibits delayed‐type hypersensitivity and the development of adjuvant arthritis
Authors: Mihara Masahiko , Ikuta Makoto , Koishihara Yasuo , Ohsugi Yoshiyuki
Published: March 2007

We studied the effect of interleukin 6 (IL 6) on the delayed‐type hypersensitivity (DTH). In mice immunized with sheep red blood cells (SRBC), a DTH response was evoked by antigen challenge into the hind paw 5 days after immunization. The magnitude of the response was assessed by footpad swelling measured 24 h after antigen challenge. IL 6 significantly suppressed the DTH in its induction phase in a dose‐dependent manner when administered s.c. into the back at a dose of > 2.5 μg twice a day (5 μg/day) for 5 consecutive days from the day of immunization (day 0) to 1 day before antigen challenge (day 4). Heat‐inactivated IL 6 did not suppress the DTH response. Furthermore, the suppressive activity of IL 6 was completely abolished by affinity chromatography on an anti‐IL 6 antibody. This suppression was also obtained when IL 6 was administered only on day 0 and day 1, but not on days 3 and 4. This indicates that IL 6 acts on the early part of the induction phase of DTH development. Furthermore, footpad swelling was suppressed even by the administration of IL 6 after antigen challenge. These results show that IL 6 suppresses both the induction and effector phases of DTH. To confirm further this inhibitory effect of IL 6, we examined its effect on the development of adjuvant arthritis in rats. Administration of IL 6 also significantly suppressed the development of adjuvant arthritis.
Heterogeneous expression of CD23 epitopes by eosinophils from patients. Relationships with IgE‐mediated functions
Authors: Capron Monique , Truong Marie‐José , Aldebert Delphine , Gruart Valérie , Suemura Masaki , Delespesse Guy , Tourvieille Béatrice , Capron André
Published: March 2007

The receptor for IgE (FcϵRII) on human eosinophils presents some common characteristics with CD23, a differentiation marker of B cells. We have used flow cytometry for evaluating the expression of various epitopes of CD23 on purified eosinophils from patients with eosinophilia. A correlation was found between the binding of myeloma IgE protein and the binding of a monoclonal antibody (mAb 135), directed against the IgE‐binding site of B cell CD23. Using two additional anti‐CD23 mAb, directed (8‐30) or not (3‐5) against the IgE‐binding site, a low expression of these CD23 epitopes was observed on eosinophils from different eosinophilic patients. Northern blot analysis of eosinophil RNA with the cDNA probe of CD23 revealed a low‐abundancy transcript in three of the six patients expressing membrane CD23. The inhibition by all anti‐CD23 mAb of IgE‐mediated cytotoxicity and IgE binding to eosinophils clearly indicated the participation of a CD23‐related molecule in IgE‐dependent eosinophil functions.
Differential expression of VLA‐4 integrin by resident and peripheral blood B lymphocytes. Acquisition of functionally active α4β1‐fibronectin receptors upon B cell activation
Authors: Postigo Antonio A. , Pulido Rafael , Campanero Miguel R. , Acevedo Agustín , García‐Pardo Angeles , Corbi Angel L. , Sanchez‐Madrid Francisco , De Landazuri Manuel O.
Published: March 2007

Very‐late antigen (VLA)‐4 (CD49d/CD29) constitutes the only member of the β1 integrin family that plays a role in the interaction of lymphoid cells with both extracellular matrix and endothelial cells through two identified ligands: fibronectin (FN) and VCAM‐1, respectively. The expression and functional activity of VLA‐4 has been studied in different maturation and activation stages of B cells from several cellular compartments. Resident B lymphocytes of different lymphoid organs were almost negative for VLA‐4 as detected by both immunoperoxidase staining and flow cytometry analysis. However, a high expression of both chains of this heterodimer was observed when tonsillar B cells were activated in vitro with different stimuli, such as phorbol esters or Staphylococcus aureus Cowan I (SAC). Both nonactivated and in vitro activated B cells from peripheral blood constitutively expressed high levels of this surface antigen. The induced expression of VLA‐4 after activation of tonsillar B lymphocytes was accompanied by the acquisition of the capacity to bind to a 38‐kDa proteolytic fragment, containing the connecting segment I domain, of FN. Interestingly, nonactivated peripheral blood B cells were unable to attach to this FN fragment, in spite of their constitutive expression of VLA‐4, and only acquired this functional capacity after cell activation with phorbol esters and SAC. This FN‐binding acquisition was not affected by preincubation with inhibitors of protein and RNA synthesis. These results underline that the FN‐binding activity of VLA‐4 is dependent on processes affecting cellular activation as described for other members of the integrin family. By contrast, VLA‐4‐mediated homotypic aggregation of peripheral blood B cells could be triggered by anti‐α4 monoclonal antibodies independently of the cell activation state.
Use of variable human Vδ genes to create functional T cell receptor α chain transcripts
Authors: Sottini Alessandra , Imberti Luisa , Fiordalisi Gianfranco , Primi Daniele
Published: March 2007

Previous studies of the human T cell receptor δ genes identified five commonly used Vδ segments distinct from any of the known Vα genes. To define better the relationship between the T cell receptor δ and α repertoires we amplified cDNA obtained by polyclonally activated lymphocytes with a common 3′ antisense Cα‐specific primer and with five different 5′ sense Vδ family‐specific primers. Amplified products were detected in staphylococcal enterotoxin C2, staphylococcal enterotoxin E, phytohemagglutinin, concanavalin A, anti‐CD3 and anti‐Vβ8‐activated cells, although each cell population expressed a selective pattern of Vδ genes. Sequence analysis revealed that each of the known Vδ genes can productively rearrange to Jα segments to produce functional Vδ‐Jα‐Cα transcripts. These results argue strongly against the notion that the human Vα repertoires are distinct. They further suggest that the restricted δ repertoire observed in many γ/δ clones results from selection rather than from controlled rearrangements at the T cell receptor α/δ locus.
Self‐nonself discrimination and repertoire selection of human T cells differentiated in an HLA‐semiallogeneic environment following bone marrow transplantation for severe combined immunodeficiency
Authors: Knobloch Christian , Goldmann Shraga F. , Friedrich Wilhelm
Published: March 2007

We have analyzed allorecognition, HLA restriction and T cell receptor (TcR) diversity in an HLA‐heterozygous (HLA‐DRw6,7) severe combined immunodeficiency (SCID) patient whose T cell system had been repopulated by HLA‐homozygous (HLA‐DRw6) paternal T cells following T cell‐depleted bone marrow transplantation (BMT). Donor origin of T cells and host origin of antigen‐presenting cells (APC) in peripheral blood and BM is shown by HLA typing of separated cell populations and two‐color immunofluorescence using an anti‐HLA monoclonal antibody (mAb). Peripheral blood lymphocytes (PBL) from the chimeric patient proliferate normally against PHA, anti‐TcR/CD3 mAb, pooled allogeneic PBL, and also against the recall antigen (Ag) tetanus toxoid and purified protein derivative of tuberculin (PPD) following immunization, suggesting recognition by donor (DRw6) T cells of Ag presented by host (DRw6,7) APC. PPD‐specific cytotoxic T lymphocytes generated in vitro from patient PBL post‐BMT display specific cytotoxicity against targets expressing DRw6 and DR7, but not against DR‐mismatched targets, suggesting that HLA restriction of Ag recognition may occur through determinants expressed by the host and not by the donor. Donor T cells differentiated in the HLA‐semiallogeneic host show specific proliferative and cytotoxic responses against HLA‐mismatched stimulators, but not against stimulators taken from the host, expressing the host‐specific HLA‐haplotype, or expressing the host‐specific HLA‐DR7 antigens. Compared to T cells directly taken from the donor, differentiation of donor T cells in the host is associated with a significant decrease of T cells expressing TcR Vβ5 and Vα2 determinants, while no differences in the abundance of of TcR Vβ6, Vβ8 and Vβ12 subsets were noticed. We conclude that allorecognition, major histocompatibility complex (MHC) restriction and TcR diversity generation of human T cells can be modulated through differentiation in an MHC‐different environment, as had been previously shown to be the case in murine model systems.
CD4 and CD8 accessory molecules function through interactions with major histocompatibility complex molecules which are not directly associated with the T cell receptor‐antigen complex
Authors: Lustgarten Joseph , Waks Tova , Eshhar Zelig
Published: March 2007

Both the subset‐specific, CD4 and CD8 T cell accessory molecules and the antigen‐specific T cell receptor (TcR) interact with major histocompatibility complex (MHC) class I and class II molecules on the surface of antigen‐presenting cells. We analyzed whether the CD4/CD8 molecules exert their accessory function through binding with the same MHC molecules which participate in the TcR‐antigen‐MHC complex. We utilized a CD4−, CD8−, class I‐allospecific T cell hybridoma which functionally manifests both cytotoxic T lymphocyte (CTL) and T helperl (Th1) phenotypes, and rendered it bispecific by transfecting it with genes encoding either a class II‐restricted, 2,4,6‐trinitrohenyl (TNP)‐I‐Ad‐specific TcR or a non‐MHC‐restricted chimeric TcR. composed of a variable part of an anti‐TNP antibody. Expression of either CD4 or CD8 transgenes in these hybridomas enhanced and augmented their reactivity towards the appropriate target cells regardless of the type of TcR‐MHC interaction. Thus, class I‐specific responses could be enhanced through CD4‐class II interactions, and class II‐restricted responses could be augmented through CD8‐class I interactions. Furthermore, these accessory molecules also potentiated TNP‐specific responses by the chimeric TcR which is MHC unrestricted. The accessory molecules facilitated both interleukin 2 (IL 2) production and cytolytic activity by shortening the activation time and rendering the cells responsive to lower antigenic stimuli. The degree of activity of the T cell hybridomas correlated with the level of accessory molecule expression and was not related to the effector function mediated by the cells. Anti‐CD4 or ‐CD8 antibodies completely inhibited the activity of transfectants expressing the corresponding accessory molecule, regardless of the MHC type of the TcR interaction. Such antibodies blocked direct TcR stimulation provided by either anti‐T3/Ti antibodies or lectins. but could not inhibit the activation through agents that bypass the TcR such as phorbol 12‐myristate 13‐acetate plus ionophore. Taken together, these studies demonstrate that the CD8/CD4 molecules can exert their accessory function through interactions with MHC molecules which are not directly associated with the TcR‐Ag‐MHC complex, and that this accessory effect is associated with TcR‐mediated triggering at an early stage of the signaling process and is not related to the effector mechanism assigned to the CD4 and CD8 T cell subsets.
Induction of nitric oxide synthase in rat peritoneal neutrophils and its inhibition by dexamethasone
Authors: McCall Thérèse B. , Palmer Richard M. J. , Moncada Salvador
Published: March 2007

Rat peritoneal polymorphonuclear leukocytes (PMN) elicited with oyster glycogen contain a Ca2+‐independent nitric oxide (NO) synthase which is induced in vivo in a time‐dependent manner. When washed PMN containing low levels of enzyme activity were cultured ex vivo further expression of NO synthase was observed. This was inhibited by cycloheximide indicating that de novo synthesis of the enzyme occurred during the ex vivo incubation. Enzyme activity was enhanced by interferon (IFN)‐γ, but not by tumor necrosis factor (TNF)‐α when added ex vivo. However, IFN‐γ and TNF‐α synergized to increase further the expression of NO synthase.

Treatment of rats with dexamethasone inhibited the induction of NO synthase in elicited PMN. This treatment reduced the accumulation of PMN by approximately 30%, without affecting cell viability. Dexamethasone also inhibited the induction of the NO synthase ex vivo in a concentration‐dependent manner. Furthermore, the enhanced enzyme activity following treatment of PMN with cytokines was also inhibited by dexamethasone. Once induced, dexamethasone did not affect enzyme activity. These data indicate that PMN elicited in the rat peritoneum with oyster glycogen express an NO synthase in vivo and ex vivo. The induction of the enzyme can be further stimulated ex vivo with IFN‐γ and TNF‐α and inhibited by dexamethasone. The inhibition of the induction of NO synthase in the PMN by dexamethasone may contribute to the anti‐inflammatory activity of this and other glucocorticoids.
Ontogeny of T cell maturation in LEC mutant rats which bear a congenital arrest of maturation from CD4+CD8+ to CD4+CD8− thymocytes
Authors: Agui Takashi , Sakai Tohru , Matsumoto Kozo
Published: March 2007

LEC rats bear a congenital deficiency in CD4+CD8− thymocytes and peripheral CD4+ T cells, and consequently a deficiency in Th cell functions. Ontogeny of T cell maturation in normal and LEC mutant rats was, therefore, investigated. Prenatal development of thymocytes in normal rat strains, with respect to the expression of CD4/CD8 and TcR antigens, was similar to that of mice except that its kinetics was delayed by approximately 24 h. The kinetics of T cell maturation in LEC rats was comparable with that of normal rats up to day 19 of gestation, at which stage double‐negative thymocytes (CD4−CD8−) developed into double positives (CD4+CD8+) through immature CD4−CD8+ subset. At day 19 of gestation in LEC as well as normal rats, double positives occupied ∼80% of the total thymocytes, half of which were TcR‐dull positive, indicating that TcR was normally rearranged and then expressed in LEC rat thymocytes. These data indicate that double negatives normally mature into at least double positives in LEC rats. Both single positives appeared after day 19 of gestation in normal rats. while in LEC rats CD4+CD8− cells did not appear, suggesting that the deficiency in CD4+CD8− cells is due to a congenital arrest of maturation from CD4+CD8+ to CD4+CD8− cells, but not due to a postnatal deletion.
Is there really a “lack of natural tolerance to allotypic γ‐globulins in rabbits”?
Authors: Meier Daniel , Kelus Andrew S.
Published: March 2007

We present data of extended studies on the possibility of maternally derived allotype Ig inducing a state of natural immunological tolerance to a non‐inherited allotype in the offspring. Rabbits homozygous at the a locus, encoding allotypes in the variable region of immunoglobulin heavy chains, and rabbits homozygous at the unliked b locus, encoding allotypes of the constant region of x1 light chains, were immunized at the age of 2 months against the non‐inherited allotype of their heterozygous mothers to which they had been exposed in utero and in early life. As control, we immunized rabbits of the same Ig phenotype but born to homozygous mothers, and therefore not exposed to that allotype. Immunization was done in a3/a3 offspring of either a1/a3 or a3/a3 mothers, by injecting al IgG, and in b6/b6 offspring of b4/b6 or b6/b6 mothers, by injecting b4 IgG. The IgG was injected either in a soluble form or emulsified in adjuvant. Injection of soluble IgG elicited only a low response, if any, revealing no differences between the various groups. All rabbits responded upon immunization with IgG in adjuvant.

We have not found any good evidence for natural tolerance to a non‐inherited allotype, although progeny of a1/a3 mothers had slightly decreased responses to al. On the contrary, progeny of b4/b6 mothers responded even better than offspring of b6/b6 mothers, upon such immunization with b4.

To induce tolerance experimentally, we injected newborn rabbits, either from heterozygous a1/a3 or from homozygous a3/a3 mothers, with a1 serum or IgG. Newborn of heterozygous b4/b6 or of homozygous b6/b6 mothers were injected with b4 serum or IgG in the same way. Such treatment resulted in partial tolerance to each allotype.

In an attempt to amplify the tolerizing effect of the maternal al Ig, we injected newborn rabbits of a1/a3 mothers with the serum of their mother. The response upon subsequent immunization with a1 allotype of another individual did not differ significantly from the response of control rabbits.

The response was much poorer when rabbits were injected with nonmaternal tolerogen at birth, and when the same Ig preparation was used as immunogen.

In a control experiment, neonatal injection of xenogeneic proteins, human IgG or bovine serum albumin, clearly resulted in tolerance. We speculate that tolerance to allotypes is established in the T cell repertoire only but bypassed by recognition of idiotypic determinants on antigen molecules by helper T cells, which trigger anti‐allotype antibody formation by allotype‐specific B cells. The end result of it is a lack of natural tolerance.
Interferon‐γ inhibits serotonin release from mouse peritoneal mast cells
Authors: Coleman John W. , Buckley Mark G. , Holliday Mark R. , Morris Alan G.
Published: March 2007

Conditioned medium (CM) from concanavalin A‐activated mouse spleen cells inhibits antigen‐induced 5‐hydroxytryptamine (5‐HT) release from mouse peritoneal mast cells when added for 24 or 48 h to cell cultures containing monoclonal IgE sensitizing antibody. We present the following evidence that the spleen cell‐derived inhibitory factor is interferon‐γ (IFN‐γ): (a) CM from Con A‐activated spleen cells and from Chinese hamster ovary (CHO) cells transfected with the murine (Mu)IFN‐γ gene both produced a graded inhibition of 5‐HT release when added to peritoneal cell cultures containing IgE and subsequently challenged with antigen; (b) the relative inhibitory potency of the two preparations corresponded to their relative IFN content as determined by antiviral bioassay; (c) the inhibitory activity of spleen cell CM and of CM from IFN‐γ gene‐transfected CHO cells was abolished by treatment with a rat monoclonal MuIFN‐γ‐neutralizing antibody, i.e. 5‐HT release returned to control levels, and (d) a highly immunopurified preparation of recombinant MuIFN‐γ retained the inhibitory activity, and was active at concentrations as low as 2 U/ml. The inhibitory activity of IFN‐γ appeared to be a direct effect of the cytokine on mast cells, since CM generated for different time periods from unfractionated peritoneal cells treated with purified recombinant MuIFN‐γ contained no inhibitory activity other than IFN‐γ itself, as demonstrated by neutralization of the cytokine with monoclonal antibody. Furthermore, purified recombinant MuIFN‐γ was equally active on mast cells enriched by density centrifugation up to 95% purity as on unfractionated peritoneal cells (1%–2% mast cells). Purified recombinant MuIFN‐γ inhibited 5‐HT release induced by a range of different cell activators, namely antigen, anti‐IgE, compound 48/80 and calcium ionophore A23187. Hence inhibition is not specific to IgE‐dependent activation of mast cells, but seems to be directed more generally at the secretory process of these cells.
Rat “first‐wave” mature thymocytes: Cycling lymphoblasts that are sensitive to activation‐induced cell death but rescued by interleukin 2
Authors: Lawetzky Alexandra , Kubbies Manfred , Hünig Thomas
Published: March 2007

The sequential appearance of thymocyte subsets in rat ontogeny was studied using the surface markers CD4, CD8, and the α/β T cell receptor (here referred to as TcR). It was noted that the first TcRhigh thymocytes, appearing around birth, are not resting lymphocytes but cycling blast cells. These “first wave” TcRhigh cells are medullary in location and predominantly of the CD4/CD8 “single‐positive” phenotype. Only about 5% express the light chain of the interleukin (IL)2 receptor, indicating that binding of IL 2 to high‐affinity receptors is not driving proliferation of these blasts.

Newborn TcR high blast cells were purified and analyzed in vitro. When cultured without further additions, they rapidly stopped cycling. Stimulation with cross‐linked anti‐TcR monoclonal antibody plus IL 2 resulted in vigorous and rapid proliferation that exhibited accelerated kinetics as compared to peripheral resting T cells. In contrast, TcR cross‐linking without exogenous IL 2 induced cell death. This TcR‐induced cell death involved fragmentation of DNA characteristic of apoptosis that was readily detectable within 18 h of culture. Addition of IL 2 to these short‐term cultures prevented TcR‐induced DNA fragmentation. Together, these results suggest that in newly formed TcRhigh thymocytes, TcR engagement results in clonal deletion if the IL 2 receptor remains unoccupied but allows clonal expansion if IL 2 is provided. This mechanism may be operative in the establishment of self‐tolerance during T cell development.
Enhancement of IgG production elicited in mice by treatment with anti‐CD8 antibody
Authors: Coutelier Jean‐Paul
Published: March 2007

Injection of an anti‐CD8 monoclonal antibody into mice was followed by an increase in the production of immunoglobulins of the IgG1, IgG2a, and IgG2b, but neither the IgG3 nor the IgM isotypes. A maximal effect was observed 6 days after administration of 10μg antibody. However, no modification of spleen cell proliferation was elicited by the anti‐CD8 treatment. Virally induced IgG2a and IgG2b secretion remained unchanged in mice infected with lactate dehydrogen‐ase‐elevating virus that received a concomitant injection of anti‐CD8 antibody, whereas an enhancement of IgG1 was observed. Simultaneous treatment with an anti‐CD4 antibody abrogated the immunoglobulin secretion triggered by anti‐CD8. These results suggest that immunoglobulin production in unmanipulated mice is controlled by CD8+ lymphocytes.
Thymic epithelial cell‐derived supernatants sustain the maturation of human prothymocytes: Involvement of interleukin 1 and CD23
Authors: Dalloul Ali H. , Fourcade Christine , Debré Patrice , Mossalayi M. Djavad
Published: March 2007

During their development, human CD7+ lymphoid stem cells migrate into the thymus where, following intimate contact with thymic tissue, they proliferate and differentiate into functionally mature T lymphocytes. In this study, we investigated the effect of thymic epithelial cell‐derived supernatants (TEC‐SN) on early CD7+CD2−CD3− thymocytes. Our results indicate that TEC‐SN are able to promote CD2 and CD3/TcR α/β expression by CD7+ precursors. This activity correlated with soluble CD23 and interleukin 1 levels in TEC‐SN. Furthermore, monoclonal antibodies to these cytokines decreased in vitro maturation of prothymocytes. Thus, in addition to cell‐cell interactions, human TEC produce cytokines able to support early steps of thymocyte differentiation.
Opposing effects of protein tyrosine kinase inhibitors on the monoclonal antibody induced internalization of CD3 and CD4 antigens
Authors: Thuillier Laure , Pérignon Jean‐Louis , Selz Françoise , Griscelli Claude , Fischer Alain
Published: March 2007

We have previously demonstrated that the monoclonal antibody (mAb)‐induced moduiation of CD3 and CD4 antigens from the surface of human peripheral blood lymphocytes is not dependent from protein kinase C activity (Thuillier et al., Eur. J. Immunol. 1990. 20: 1197). In the present report we study the effect of genistein and of herbimycin A, two potent inhibitors of protein tyrosine kinases (PTK), on the mAb‐induced modulation of CD3 and CD4 surface antigens. Both genistein and herbimycin inhibited the mAb‐induced internalization of CD3 and, in contrast, facilitated that of CD4 antigen. These results indicate that the mAb‐induced modulation of CD3 is essentially dependent on the PTK pathway, whereas PTK appear to negatively regulate the mAb‐induced modulation of CD4.
Glucocorticoids suppress the production of interleukin 4 by human lymphocytes
Authors: Wu Chang You , Fargeas Christine , Nakajima Toshiharu , Delespesse Guy
Published: March 2007

Given that glucocorticoids (GCS) were reported to increase the production of interleukin 4 (IL4) by mouse T cells and that GCS are widely used to treat allergic diseases it was important to examine the effect of these agents on IL4 production by human lymphocytes. We here demonstrate that the production of IL4 by human lymphocytes is markedly inhibited by small concentrations of hydrocortisone. The suppression is observed at the protein and at the mRNA levels and it is not secondary to the GCS‐induced inhibition of IL2 production.
Supramolecular Chemistry and Anion Binding in Palladium(II) and Silver(I) Complexes Containing N,N′‐Dipyridylxanthene‐4,5‐dicarboxamide Ligands
Authors: Yue Nancy L. S. , Jennings Michael C. , Puddephatt Richard J.
Published: March 2007

Two new ligands, 2,7‐di‐tert‐butyl‐9,9‐dimethyl‐N,N′‐di(3‐pyridyl)‐ (1) and ‐N,N′‐bis[(3‐pyridyl)methyl]xanthene‐4,5‐dicarboxamide (2), and their complexes with palladium(II) and silver(I) are reported. Intramolecular hydrogen bonding orients the ligands so as to favour formation of macrocyclic complexes, and the structures of [Pd2X4(μ‐1)2] (3a), X = Cl; (3b) X = Br, and [Ag2(μ‐2)2](CF3SO3)2 (5a) are reported. Intermolecular hydrogen bonding can also occur and can lead to supramolecular self‐assembly to give sheet 3a or ribbon 5a structures, or serve to bind anions or solvent molecules. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Reactivity of Ruthenium(II) and Copper(I) Complexes that Possess Anionic Heteroatomic Ligands: Synthetic Exploitation of Nucleophilicity and Basicity of Amido, Hydroxo, Alkoxo, and Aryloxo Ligands for the Activation of Substrates that Possess Polar Bonds as well as Nonpolar C–H and H–H Bonds (Eur. J. Inorg. Chem. 9/2007)
Authors: Gunnoe T. Brent
Published: March 2007

The cover picture shows the disruption of amido‐ and alkoxo‐to‐metal π‐donation because of a filled dπ manifold, which occurs for metal centers in low oxidation states and which renders the anionic amido, alkoxo and related ligands highly reactive. The low oxidation states decrease the predilection toward metal‐center reduction and, as a result, tend to promote “even‐electron” chemistry over odd‐electron radical chemistry that is based on net single‐electron reduction of the metal. For RuII and CuI complexes, evidence for the enhanced reactivity of the heteroatomic ligands is derived from acid/base reactions as well as from nucleophilic additions. The combination of a Lewis acid metal center and a basic/nucleophilic heteroatomic ligand (amido, hydroxo, alkoxo, etc.) can be exploited for the activation of substrates that possess polar and nonpolar bonds, for example for metal‐mediated C–H activation and for catalytic hydroamination and hydroalkoxylation of activated olefins. Details are presented in the Microreview by T. B. Gunnoe on p. 1185 ff.
Efficient One‐Pot Synthesis of Enantiomerically Pure 2‐(Hydroxymethyl)morpholines
Authors: Breuning Matthias , Winnacker Malte , Steiner Melanie
Published: March 2007

An efficient and convenient one‐pot procedure for the synthesis of enantiomerically pure 2‐(hydroxymethyl)morpholines with a widely variable substitution pattern was developed. Addition of chiral β‐amino alcohols to (S)‐ or (R)‐epichlorohydrin in the presence of LiClO4 afforded the corresponding chloro alcohols, which were treated with NaOMe to give the epoxides and, by subsequent intramolecular cyclization, the target compounds in good yields (57–77 %). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
On‐line coupling of SPE and CE‐MS for peptide analysis
Authors: Tempels F. W. Alexander , Underberg Willy J. M. , Somsen Govert W. , de Jong Gerhardus J.
Published: March 2007

An on‐line SPE‐CE‐MS system has been developed for the analysis of peptides. Analytes are preconcentrated using a C18 microcolumn (5×0.5 mm id), and then introduced into the CE system via a valve interface. The CE system with a Polybrene‐poly(vinylsulfonate) bilayer coated capillary is combined with an ion‐trap mass spectrometer via ESI using a coaxial sheath‐liquid sprayer. The on‐line coupling of the SPE and CE step by the valve interface is advantageous because it allows an independent functioning of the system parts. Optimization of the SPE‐CE system was performed using UV detection. Subsequently, the SPE‐CE system has been coupled to the ion‐trap mass spectrometer. Test solutions with enkephalin peptides (50 ng/mL) were used for evaluation of system performance. Repeatability of effective mobility and peak area ratio of the two enkephalins were within 1.2% and 9% RSD, respectively. The analysis of 1:1 v/v diluted cerebrospinal fluid samples spiked with enkephalin peptides showed detection limits (S/N = 3) in the range of 1.5–3 ng/mL (around 5 nM), which were similar to those obtained for enkephalin test solutions. Moreover, the potential of the on‐line SPE‐CE‐MS system was demonstrated by the analysis of a cytochrome C digest. Some hydrophilic peptides did not show sufficient retention on the SPE column, and were lost during preconcentration. Nonetheless, positive identification of the protein was achieved, indicating the feasibility of the system for proteomics.
Identification of a novel human papillomavirus (HPV97) related to HPV18 and HPV45
Authors: Chen Zigui , Fu Leiping , Herrero Rolando , Schiffman Mark , Burk Robert D.
Published: March 2007

Human papillomavirus (HPV) type 97 was identified and the genome was cloned from cervicovaginal cells of a Costa Rican woman with a normal Pap smear. The HPV97 L1 open reading frame (ORF) was most closely related to HPV45 (84% identity) and HPV18 (79% identity), placing it into the high‐risk α7 species. Ectopic expression of the HPV97 E6 and E7 proteins significantly decreased steady state p53 and pRb levels using an in vitro cotransfection assay, respectively. These data suggest that HPV97 shares a most recent common ancestor with HPV18 and HPV45 and should be evaluated in cancer specimens from different geographic populations. © 2007 Wiley‐Liss, Inc.
Cell exfoliation in the human colon: Myth, reality and implications for colorectal cancer screening
Authors: Loktionov Alexandre
Published: March 2007

Colonocyte exfoliation in the human colon constitutes a unique mechanism of cell population control that can undergo significant changes under different physiological and pathological conditions. Being closely related to the apoptosis and anoikis, cell exfoliation from colonic epithelium appears to be a relatively rare event in normal conditions, but its rate dramatically increases in neoplasia, when cell removal by apoptosis in situ does not function properly. Several studies show that significant numbers of exfoliated colonocytes are not lost in the faecal contents of the gut, but retained in the mucocellular layer overlying colonic mucosa. Recent observations allow hypothesizing that the mucocellular layer containing exfoliated colonocytes may gradually migrate distally, eventually leading to the accumulation of the cells exfoliated from malignant colorectal tumours on the surface of the rectal mucosa. Implications of exfoliated colonocyte analysis to colorectal cancer screening and early diagnosis are discussed. © 2007 Wiley‐Liss, Inc.
No evidence for association of NOD2 R702W and G908R with colorectal cancer
Authors: Tuupanen Sari , Alhopuro Pia , Mecklin Jukka‐Pekka , Järvinen Heikki , Aaltonen Lauri A.
Published: March 2007

Polymorphisms in nucleotide oligomerization domain 2 gene (NOD2) have been associated with increased susceptibility to Crohn's disease. Recently, possible association of the NOD2 variants R702W, G908R and 3020insC with colorectal cancer (CRC) has been studied among Polish, Greek, Finnish and New Zealand Caucasian CRC patients, but the results have been controversial. In the Polish study, 3020insC alone, and in the Greek study all the 3 variants, showed association with CRC. In a study from New Zealand, R702W appeared to increase CRC risk. In addition, the combined frequencies of the 3 variants were significantly elevated in CRC patients compared with healthy controls. We have previously shown that NOD2 3020insC is not associated with increased CRC risk in Finland. In the current study, we have genotyped the R702W and G908R in a population‐based series of 1,042 CRC patients and in 508 healthy controls to study the possible contribution of these variants to CRC predisposition. Of the CRC patients, 953 were successfully analyzed. R702W and G908R were equally, frequently seen in CRC patients and controls (R702W: 2.2% vs. 2.1%; G908R: 0.3% vs. 0.2%). No associations between NOD2 variants and clinical characteristics were observed. Our results indicate that NOD2 variants R702W, G908R and 3020insC do not predispose to CRC in Finland. Environmental or additional genetic factors may play a role in CRC development in NOD2 variant carriers. Further work is necessary to establish the possible role of NOD2 variants in CRC predisposition. © 2007 Wiley‐Liss, Inc.
The advantage of tying one's hands: revisited
Authors: Soffritti Mirco , Zanetti Francesco
Published: March 2007

Fixing the exchange rate is often seen as an appealing strategy to gain credibility and keep inflation under control. But what is the impact of this policy on welfare? We answer this question using a microfounded, New Keynesian monetary model for a small open economy, to study the outcome of three alternative strategies for a central bank that targets both output and inflation: a policy of pure commitment; a discretionary policy where the exchange rate is free to fluctuate; and a strategy that pegs the nominal exchange rate. We first compare their impact on the policymaker's rule‐of‐thumb, quadratic objective and then on the agent's utility. In contrast to previous work, in which the policymaker maximizes a rule‐of‐thumb function, time‐consistent monetary policy leads to a lower loss than a policy that ties the policymaker's hands by stabilizing the exchange rate. However, the strategy that fixes the exchange rate is ranked first when the policymaker maximizes the agent's utility. Copyright © 2007 John Wiley & Sons, Ltd.