bluuebunny/crossref_metadata_2025 huggingface dataset:
Definition of the gene content of the human genome: the need for deep experimental verification
Authors: Simpson Andrew J. G. , de Souza Sandro J. , Camargo Anamaria A. , Brentani Ricardo R.
Published: August 2002

Based on the analysis of the drafts of the human genome sequence, it is being speculated that our species may possess an unexpectedly low number of genes. The quality of the drafts, the impossibility of accurate gene prediction and the lack of sufficient transcript sequence data, however, render such speculations very premature. The complexity of human gene structure requires additional and extensive experimental verification of transcripts that may result in major revisions of these early estimates of the number ofhuman genes. Copyright © 2001 John Wiley & Sons, Ltd.
The price of a loaf of bread: some conceptions of family support*
Authors: Penn Helen , Gough David
Published: August 2002

This paper reports on a case study of one local authority, and illustrates the different definitions of the term ‘family support’ employed by the different agencies within the authority. It provides a framework to analyse the contribution of the agencies according to the assumptions they make about methods and efficacy of intervention and access to and termination of intervention. It contrasts the findings from this framework with a needs based model of ‘family support’. Social work and health services tend to operate within a narrow, historically determined range, focusing most heavily on emotional support and behavioural change; whereas users and some of the other agencies are more likely to raise matters such as income maintenance, child care, leisure and education. The findings of the case study are discussed in relation to resources for families, key issues for the implementation of family support identified during the introduction of the Children Act, 1989, and the relevance of Social Services Inspectorate inspections to these issues. Copyright © 2002 John Wiley & Sons, Ltd.
Preparation of (R)‐ and (S)‐α‐methyldopa from a chiral hydantoin containing the α‐phenylethyl group
Authors: LeóN‐Romo José Luis , Virues Claudia I. , Aviña Judit , Regla Ignacio , Juaristi Eusebio
Published: August 2002

Chiral hydantoin (S)‐1 was prepared in good yield from phenyl isocyanate and N‐[(S)‐α‐phenylethyl]glycinate, (S)‐3. Enolate (S)‐1‐Li was methylated in high yield and good diastereoselectivity. In contrast, a second alkylation reaction of methylated enolate (S)‐4‐Li proceeded with essentially no diastereoselectivity. Nevertheless, dialkylated hydantoins, (S,S)‐7 and (S,R)‐7, could be readily separated by flash chromatography and subsequent hydrolysis of either derivative afforded the desired (S)‐L‐α‐methyldopa or (R)‐D‐α‐methyldopa in good yield. Chirality 14:144–150, 2002. © 2002 Wiley‐Liss, Inc.
Atropisomerism as a probe of restrictions to motion above and below the glass transition temperature of Polymers
Authors: Park JI‐Woong , Green Mark M.
Published: August 2002

This short review and interpretation of work conducted in the authors' laboratory concerns the use of atropisomeric 1,1′‐binaphthyl derivatives to gain information about the glassy properties of polymers. Bridged binaphthyls appended with oligophenyl paddles are found to yield a series of probes whose racemization kinetics reveal new kinds of information concerning the basis of the time scale and length scale for the restrictions to motion and the heterogeneity of the polymeric glassy state. Because the time scale of the racemization is slower than all other glass probes used previously, new kinds of information were gained for the first time below the glass transition temperature. Chirality 14:209–214, 2002.© 2002 Wiley‐Liss, Inc.
Competitive intelligence and the product life cycle
Authors: Burkhardt Kimberly E.
Published: August 2002

The types of intelligence efforts used by CI professionals depend, in part, on an understanding—and appreciation—of the product life cycle. During the initial stage of market introduction, the role of CI will be to identify and monitor potential competitors. Once potential competition is identified, strategic planning will be needed to assess—and then implement—methodologies appropriate for the evolving competitive environment. During the advanced stages of growth and maturity, competitive threats will change in quantity and/or quality; these will be active transitional periods for intelligence professionals. During the seemingly inevitable decline stage of products and markets, the CI professional will need to help prolong profitability and to prevent as much market loss as possible through a variety of strategies. As a product life cycle draws to a close, CI practitioners can pull together acquired knowledge of market competition, which can then be applied to future markets. In sum, the role of the CI professional is to gather, assess, and disseminate intelligence that will aid the firm in maintaining a competitive advantage through all stages of the product life cycle. © 2001 John Wiley & Sons, Inc.
Host focal adhesion protein domains that bind to the translocated intimin receptor (Tir) of enteropathogenic Escherichia coli (EPEC)
Authors: Huang Lily , Mittal Balraj , Sanger Joseph W. , Sanger Jean M.
Published: August 2002

Enteropathogenic Escherichia coli (EPEC) attach to the plasma membrane of infected host cells and induce diarrhea in a variety of farm animals as well in humans. These bacteria inject a three‐domain protein receptor, Tir (translocated intimin receptor), that is subsequently inserted into the plasma membrane. EPEC induce the host cell to form membrane‐covered actin‐rich columns called pedestals. Focal adhesion constituents, alpha‐actinin, talin, and vinculin, are localized along the length of the pedestals and we have previously reported they bind the two cytoplasmic domains of Tir, (Tir I and Tir III) [Freeman et al., 2000: Cell Motil. Cytoskeleton 47:307–318]. In the present study, various constructs were made expressing different regions of these three focal adhesion proteins to determine which domains of the proteins bound Tir I. Three different assays were used to detect Tir I/host protein domain interactions. In co‐precipitation assays, His‐Tir I bound to the 27‐kDa region of alpha‐actinin; to four different domains of talin; and to the N‐terminal domain of the vinculin head and the vinculin tail domain. A yeast two‐hybrid analysis of Tir I and the various focal adhesion fusion proteins revealed a region near the C‐terminus of talin was the only domain to interact with Tir I. Finally, to assess direct binding interactions, biotinylated Tir I was used in overlay assays and confirmed the binding of Tir I with the 27‐kDa region of alpha‐actinin, the four regions of talin, and the vinculin tail. These binding interactions between hostfocal adhesion proteins and EPEC Tir may facilitate the adhesion of EPEC to the host cell surface. Cell Motil. Cytoskeleton 52:255–265, 2002. © 2002 Wiley‐Liss, Inc.
Irinotecan hydrochloride for the treatment of recurrent and refractory non‐Hodgkin lymphoma
Authors: Sugiyama Katsuki , Omachi Ken , Fujiwara Keiichi , Saotome Takashi , Mizunuma Nobuyuki , Takahashi Shunji , Ito Yoshinori , Aiba Keisuke , Horikoshi Noboru
Published: August 2002

BACKGROUND

Irinotecan hydrochloride (CPT‐11) has a broad range of antitumor activity and has demonstrated little cross‐resistance with doxorubicin or vincristine. In the current study, the authors investigated the efficacy and adverse effects of irinotecan in the treatment of recurrent and refractory non‐Hodgkin lymphoma, for which current therapies appear to be unsatisfactory.

METHODS

Irinotecan was administered by intravenous infusion at a dose of 40 mg/m2/day for 3 days, and this regimen was repeated 2–3 times at weekly intervals, followed by 2 weeks off therapy. The subjects were 48 patients with recurrent or refractory non‐Hodgkin lymphoma. The histologic classification (Working Formulation) was low grade in 8 patients, intermediate grade in 36 patients, high grade in 1 patient, and other (angiocentric lymphoma, Ki‐1 lymphoma, and unidentified) in 3 patients.

RESULTS

Forty‐five patients were determined to be evaluable. Therapy resulted in a complete disease remission in 2 patients and a partial remission in 15 patients. The response rate was 37.8%. The median duration of response was 64 days and the median time to disease progression was 77 days. The median survival time was 422 days. Major adverse reactions included myelosuppression and gastrointestinal toxicity. Leukopenia, anemia, and thrombocytopenia of Grade 3 or 4 (according to the National Cancer Institute Common Toxicity Criteria) was observed in 63.0%, 30.4%, and 6.5% of the patients, respectively, and Grade 3 or 4 diarrhea occurred in 30.4% of patients. Treatment was withdrawn because of diarrhea in three patients. Because of myelosuppression and diarrhea, approximately 67% of the patients required changes to the regimen, including dose reduction, prolongation of the interval between treatments, and reducing the number of days of consecutive treatment.

CONCLUSIONS

The results of the current study suggest the activity of irinotecan as salvage therapy for patients with recurrent and refractory non‐Hodgkin lymphoma. However, the optimum dosing schedule remains to be determined. Cancer 2002;94:594–600. © 2002 American Cancer Society.

DOI 10.1002/cncr.10266
Tumor vaccine for ovarian carcinoma targeting sperm protein 17
Authors: Chiriva‐Internati Maurizio , Wang Zhiqing , Salati Emanuela , Timmins Patrick , Lim Seah H.
Published: August 2002

BACKGROUND

The authors previously identified sperm protein 17 (Sp17) as being expressed in patients with multiple myeloma. The restricted expression of Sp17 in normal tissue makes it an ideal target for tumor vaccine. In the current study, the authors extended their research to include ovarian carcinoma.

METHODS

A pair of sequence specific primers was used in reverse transcriptase‐polymerase chain reaction to determine the gene expression of Sp17. A recombinant Sp17 protein was used with monocyte‐derived dendritic cells and autologous peripheral blood mononuclear cells to generate Sp17 specific cytotoxic T‐lymphocytes (CTLs). The successful generation of Sp17 specific CTLs was confirmed using standard 51chromium‐release assays.

RESULTS

Sp17 was found to be expressed in the primary tumor cells from 70% of the patients with ovarian carcinoma. Human leukocyte antigen (HLA) class I‐ restricted Sp17 specific CTLs were generated successfully from the peripheral blood of three patients with ovarian carcinoma at the time of disease presentation. These CTLs were able to lyse autologous Epstein‐Barr virus‐transformed lymphoblastoid cells in a Sp17‐dependent manner. Target lysis was HLA class I‐dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecules. The CTLs also lysed Sp17‐positive autologous tumor cells, suggesting that Sp17 is processed and presented in association with the HLA class I molecules in Sp17‐ positive tumor cells in a concentration and configuration that could be recognized by recombinant protein‐primed CTLs. Tumor cell killing by the CTLs appeared to be mediated through the perforin pathway. Flow cytometric analysis of the CTLs indicated that they predominantly were CD8 in phenotype and produced interferon‐γ and scant amounts of interleukin‐4.

CONCLUSIONS

The results of the current study suggest the potential of Sp17 as a target for immunotherapy in patients with ovarian carcinoma. Cancer 2002;94:2447–53. © 2002 American Cancer Society.

DOI 10.1002/cncr.10506
Hypoxia upregulates Bcl‐2 expression and suppresses interferon‐γ induced antiangiogenic activity in human tumor derived endothelial cells
Authors: Wang Jiang Huai , Wu Qiong Di , Bouchier‐Hayes David , Redmond H. Paul
Published: August 2002

BACKGROUND

Hypoxia in solid tumors potentially stimulates angiogenesis by promoting vascular endothelial growth factor (VEGF) production and upregulating VEGF receptor expression. However, it is unknown whether hypoxia can modulate the effect of anti‐angiogenic treatment on tumor‐derived endothelium.

METHODS

Human tumor‐derived endothelial cells (HTDEC) were freshly isolated from surgically removed human colorectal tumors by collagenase/DNase digestion and Percol gradient sedimentation. Cell proliferation was assessed by measuring BrdU incorporation, and capillary tube formation was measured using Matrigel. Cell apoptosis was assessed by flow cytometry and ELISA, and Bcl‐2 expression was detected by Western blot analysis.

RESULTS

Under aerobic culture conditions (5% CO2 plus 21% O2) HTDEC expressed less Bcl‐2 and were more susceptible to IFN‐γ‐induced apoptosis with significant reductions in both cell proliferation and capillary tube formation, when compared with normal human macrovascular and microvascular EC. Following exposure of HTDEC to hypoxia (5% CO2 plus 2% O2), IFN‐γ ‐induced cell apoptosis, and antiangiogenic activity (i.e. an inhibition in cell proliferation and capillary tube formation) in HTDEC were markedly attenuated. This finding correlated with hypoxia‐induced upregulation of Bcl‐2 expression in HTDEC.

CONCLUSIONS

These results indicate that hypoxia can protect HTDEC against IFN‐γ ‐mediated cell death and antiangiogenic activity, and suggest that improvement of tumor oxygenation may potentiate the efficacy of anti‐cancer therapies specifically targeting the inhibition of tumor angiogenesis. Cancer 2002;94:2745–55. © 2002 American Cancer Society.

DOI 10.1002/cncr.10520
Neuroendocrine tumors of the sinonasal tract
Authors: Fitzek Markus M. , Thornton Allan F. , Varvares Marc , Ancukiewicz Marek , Mcintyre James , Adams Judy , Rosenthal Stanley , Joseph Michael , Amrein Philip
Published: August 2002

BACKGROUND

The authors report the results of a prospective study of patients with malignant neuroendocrine tumors of the sinonasal tract who received multimodality treatment incorporating high‐dose proton‐photon radiotherapy.

METHODS

Nineteen patients with olfactory neuroblastoma (ONB) or neuroendocrine carcinoma (NEC) were treated between 1992 and 1998 on a prospective study. Four patients had Kadish Stage B disease, and 15 patients had Kadish Stage C disease. The median patient age was 44 years. Patients received chemotherapy with 2 courses of cisplatin and etoposide followed by high‐dose proton‐photon radiotherapy to 69.2 cobalt–Gray equivalents (CGE) using 1.6–1.8 CGE per fraction twice daily in a concomitant boost schedule. Two further courses of chemotherapy were given to responders.

RESULTS

Of 19 patients, 15 patients were alive at the time of this report with a median follow‐up of 45 months (range, 20–92 months). Four patients died from disseminated disease 8–47 months after their original diagnosis. The 5‐year survival rate was 74%. There were two local recurrences, and both patients underwent salvage surgery. The 5‐year local control rate of initial treatment was 88%. Acute toxicity of chemotherapy was tolerable, with no patient sustaining more than Grade 3 hematologic toxicity. Thirteen patients showed a partial or complete response to chemotherapy. One patient developed unilateral visual loss after the first course of chemotherapy; otherwise, visual preservation was achieved in all patients. Four patients who were clinically intact developed radiation‐induced damage to the frontal or temporal lobe by magnetic resonance imaging criteria. Two patients showed soft tissue and/or bone necrosis, and one of these patients required surgical repair of a cerebrospinal fluid leak.

CONCLUSIONS

Neoadjuvant chemotherapy and high‐dose proton‐photon radiotherapy is a successful treatment approach for patients with ONB and NEC. Radical surgery is reserved for nonresponders. Due to the precision of delivery of radiation with stereotactic setup and protons, no radiation‐induced visual loss was observed. Cancer 2002;94:2623–34. © 2002 American Cancer Society.

DOI 10.1002/cncr.10537
Effects of oxygen and glucose deprivation on the expression and distribution of neuronal and inducible nitric oxide synthases and on protein nitration in rat cerebral cortex
Authors: Alonso David , Serrano Julia , Rodríguez Ignacio , Ruíz‐Cabello Jesús , Fernández Ana Patricia , Encinas Juan Manuel , Castro‐Blanco Susana , Bentura María Luisa , Santacana María , Richart Ana , Fernández‐Vizarra Paula , Uttenthal Lars Otto , Rodrigo José
Published: August 2002

Changes in the nitric oxide (NO) system of the rat cerebral cortex were investigated by immunohistochemistry, immunoblotting, NO synthase (NOS) activity assay, and magnetic resonance imaging (MRI) in an experimental model of global cerebral ischemia and reperfusion. Brains were perfused transcardially with an oxygenated plasma substitute and subjected to 30 minutes of oxygen and glucose deprivation, followed by reperfusion for up to 12 hours with oxygenated medium containing glucose. A sham group was perfused without oxygen or glucose deprivation, and a further group was treated with the NOS inhibitor Nω‐nitro‐L‐arginine methyl ester (L‐NAME) before and during perfusion. Global ischemia led to cerebrocortical injury as shown by diffusion MRI. This was accompanied by increasing morphologic changes in the large type I interneurons expressing neuronal NOS (nNOS) and the appearance of nNOS immunoreactivity in small type II neurons. The nNOS‐immunoreactive band and calcium‐dependent NOS activity showed an initial increase, followed by a fall after 6 hours of reperfusion. Inducible NOS immunoreactivity appeared in neurons, especially pyramidal cells of layers IV–V, after 4 hours of reperfusion, with corresponding changes on immunoblotting and in calcium‐independent NOS activity. Immunoreactive protein nitrotyrosine, present in the nuclear area of neurons in nonperfused controls and sham‐perfused animals, showed changes in intensity and distribution, appearing in the neuronal processes during the reperfusion period. Prior and concurrent L‐NAME administration blocked the changes on diffusion MRI and attenuated the morphologic changes, suggesting that NO and consequent peroxynitrite formation during ischemia–reperfusion contributes to cerebral injury. J. Comp. Neurol. 443:183–200, 2002. © 2002 Wiley‐Liss, Inc.
Postnatal development of connectional specificity of corticospinal terminals in the cat
Authors: Li Qun , Martin John H.
Published: August 2002

The purpose of this study was to examine postnatal development of connectional specificity of corticospinal terminals. We labeled a small population of primary motor cortex neurons with the anterograde tracer biotinylated dextran amine. We reconstructed individual corticospinal segmental axon terminals in the spinal gray matter in cats of varying postnatal ages and adults. We found that at days 25 and 35 the segmental termination field of reconstructed axons was large, estimated to cover more than half of the contralateral gray matter. Branches and varicosities were sparse and had a relatively uniform distribution. When we examined the terminal fields of multiple axons, reconstructed over the same set of spinal sections (120–200 μm), we found that there was extensive overlap. By day 55, the morphology and termination fields had changed remarkably. There were many short branches, organized into discrete clusters, and varicosities were preferentially located within these clusters. The termination field of individual axons was substantially reduced compared with that of younger animals, and there was minimal overlap between the terminals of neighboring corticospinal neurons. In adults, a further reduction was seen in the spatial extent of terminals, branching, and varicosity density. Termination overlap was not substantially different from that in PD 55 animals. Development of spatially restricted clusters of short terminal branches and dense axonal varicosities occurred just prior to development of the motor map in primary motor cortex and may be necessary for ensuring that the corticospinal system can exert a dominant influence on skilled limb movement control in maturity. J. Comp. Neurol. 447:57–71, 2002. © 2002 Wiley‐Liss, Inc.
Motor neurons rapidly accumulate DNA single‐strand breaks after in vitro exposure to nitric oxide and peroxynitrite and in vivo axotomy
Authors: Liu Zhiping , Martin Lee J.
Published: August 2002

The mechanisms of neuronal degeneration in motor neuron disease are not fully understood. We tested the hypothesis that oxidative stress in vitro and axotomy in vivo induce single‐strand breaks (SSB) in DNA, a form of early DNA damage, in adult motor neurons early during their degeneration. We developed and characterized a novel cell suspension system enriched in motor neurons from adult rat spinal cord ventral horn. This cell system is ∼84% neurons, with ∼86% of these neurons being motor neurons; ∼72% of these motor neurons are α‐motor neurons. Motor neuron viability in suspension is ∼100% immediately after isolation and ∼61% after 12 hours of incubation. During incubation, isolated motor neurons generate high levels of superoxide. We used single‐cell gel electrophoresis (comet assay) to detect DNA‐SSB in motor neurons. Exposure of motor neurons to nitric oxide (NO) donors (sodium nitroprusside or NONOate), H2O2, or NO donor plus H2O2 rapidly induces DNA‐SSB and causes motor neuron degeneration, the occurrence of which is dose and time related, as represented by comet formation and cell loss. Motor neuron toxicity is potentiated by cotreatment with NO donor and H2O2 (at nontoxic concentrations alone). Peroxynitrite causes DNA‐SSB in motor neurons. The DNA damage profiles (shown by the comet morphology and moment) of NO donors, NO donor plus H2O2, and peroxynitrite are similar. In an in vivo model of motor neuron apoptosis, DNA‐SSB accumulate slowly in avulsed motor neurons before apoptotic nuclear features emerge, and the comet fingerprint is similar to NO toxicity. We conclude that motor neurons challenged by oxidative stress and axotomy accumulate DNA‐SSB early in their degeneration and that the formation of peroxynitrite is involved in the mechanisms. J. Comp. Neurol. 432:35–60, 2001. © 2001 Wiley‐Liss, Inc.
Distribution and development of FMRFamide‐like immunoreactive neuronal systems in the brain of the brown trout, Salmo trutta fario
Authors: Castro Antonio , Becerra Manuela , Anadón Ramón , Manso María Jesús
Published: August 2002

The distribution of Phe‐Met‐Arg‐Phe‐amide (FMRFamide) peptide‐immunoreactive (FMRF‐ir) cells and fibers in the terminal nerve and central nervous system was investigated in developing stages and adults of the brown trout, Salmo trutta fario. The first FMRF‐ir neurons appeared in the terminal nerve system of 8‐mm embryos in and below the olfactory placode. In the brain, FMRF‐ir neurons were first observed in the rostral hypothalamus, primordial hypothalamic lobe, mesencephalic laminar nucleus, and locus coeruleus of 12‐ to 13 ‐m embryos. After hatching, FMRF‐ir cells appeared in the lateral part of the ventral telencephalic area and the anterior tuberal nucleus. In adult trout, FMRF‐ir cells were observed in all these areas. The number of FMRF‐ir neurons increased markedly in some of these populations during development. Dense innervation by FMRF‐ir fibers was observed in the dorsal and lateral parts of the dorsal telencephalic area, and in the ventral telencephalic area, the lateral preoptic area, the medial hypothalamic and posterior tubercle regions, midbrain tegmentum and rhombencephalic reticular areas, the central gray, the superior raphe nucleus, the secondary visceral nucleus, the vagal nuclei, and the area postrema. Fairly rich FMRF‐ir innervation was also observed in the optic tectum and some parts of the torus semicircularis. The saccus vasculosus and hypophysis received a moderate amount of FMRF‐ir fibers. Innervation of most of these regions appeared either in late alevins or fry, although FMRF‐ir fibers in the preoptic area, hypothalamus, and reticular areas appeared in embryos. Comparative analysis of the complex innervation pattern observed in the brain of trout suggests that FMRF is involved in a variety of functions, like the FMRF family of peptides in mammals. J. Comp. Neurol. 440:43–64, 2001. © 2001 Wiley‐Liss, Inc.
Neuroectodermal origin of brain pericytes and vascular smooth muscle cells
Authors: Korn Johannes , Christ Bodo , Kurz Haymo
Published: August 2002

The origin of vascular pericytes (PCs) and smooth muscle cells (vSMCs) in the brain has hitherto remained an open question. In the present study, we used the quail‐chick chimerization technique to elucidate the lineage of cranial PCs/vSMCs. We transplanted complete halves of brain anlagen, or dorsal (presumptive neural crest [NC]) or ventral cranial neural tube. Additional experiments included transplantations of neuroectoderm into limb mesenchyme, and of head mesoderm or limb mesenchyme into paraxial head mesoderm. After interspecific transplantation of quail brain rudiment, graft‐derived vSMCs were found in the vessel walls of the grafted brain. Notably, transplanted ventral neural tube also gave rise to vSMCs. After grafting of quail head mesoderm, quail endothelial cells were found in the host brain, but no vSMCs of donor origin. Grafting of quail whole or ventral neural tube into the limb bud led to endowment of graft and host vessels with graft‐derived vSMCs. Quail limb bud mesenchyme contributed to vSMCs in the ectopic neural graft, but, when transplanted into paraxial head mesenchyme, it did not form intraneural vSMCs. After orthotopic transplantation of cranial NC, graft‐derived vSMCs were not only found in meninges and brain of the operated side, but also on the contralateral side. Our results show that 1) avian cranial neuroectoderm is able to differentiate into vSMCs of the brain; 2) this potential is not restricted to the prospective NC; and 3) neither cranial mesoderm nor cranially transplanted limb bud mesoderm can give rise to brain vSMC. J. Comp. Neurol. 442:78–88, 2002. © 2002 Wiley‐Liss, Inc.
On the theory of a Cosserat point and shear locking in thin beams
Authors: Rubin M. B.
Published: August 2002

It is well known that with the assumption of constant strain elements, the Galerkin approach yields a numerical solution of the equilibrium equations of a beam with shear deformation which exhibits the unphysical feature of shear locking. Here, it is shown that the numerical solution that is based on the theory of a Cosserat point converges to the exact solution of the beam theory even when the kinematics are consistent with the constant strain assumption and the beam thickness approaches zero. The main difference between these two numerical approaches is the way they each determine the constitutive equations (or stiffnesses) of the elements. The Galerkin approach determines the stiffnesses of each element by integrating the constitutive equations for the beam assuming that the kinematic approximation is valid pointwise. In contrast, the constitutive equations of the Cosserat point are related to derivatives of a strain energy function and the constitutive constants are determined using a physical approach which matches the responses to simple shear and pure bending. The results indicate that the Cosserat approach takes full advantage of the reduced number of degrees of freedom used to describe the beam. Copyright © 2001 John Wiley & Sons, Ltd.
Visual perception of texture of textiles
Authors: Lee Wonjoung , Sato Masako
Published: August 2002

The mechanism of visual texture perception was investigated by measuring visual evaluation values. Textile samples of different surface structures were examined, along with corresponding image samples rendered on paper. The relation between physical properties of textiles and light reflected from the textiles, and the relation between the reflected light stimulating the eyes of the subject and the psychological perception of texture are discussed. © 2001 John Wiley & Sons, Inc. Col Res Appl, 26, 469–477, 2001
Scalars convected by a two‐dimensional incompressible flow
Authors: Cordoba Diego , Fefferman Charles
Published: August 2002

We provide a test for numerical simulations, for several two dimensional incompressible flows, that appear to develop sharp fronts. We show that in order to have a front the velocity has to have uncontrolled velocity growth. © 2001 John Wiley & Sons, Inc.
The Virtual Service Grid: an architecture for delivering high‐end network services
Authors: Weissman Jon B. , Lee Byoung‐Dai
Published: August 2002

This paper presents the design of a new system architecture, Virtual Service Grid (VSG), for delivering high‐performance network services. The VSG is based on the concept of the virtual service which provides location, replication, and fault transparency to clients accessing remotely deployed high‐end services. One of the novel features of the virtual service is the ability to self‐scale in response to client demand. The VSG exploits network and service information to make adaptive dynamic replica selection, creation, and deletion decisions. We describe the VSG architecture, middleware, and replica management policies. We have deployed the VSG on a wide‐area Internet testbed to evaluate its performance. The results indicate that the VSG can deliver efficient performance for a wide range of client workloads, both in terms of reduced response time and in the utilization of system resources. Copyright © 2002 John Wiley & Sons, Ltd.
Kinetics of HL‐60 cell entry to apoptosis during treatment with TNF‐α or camptothecin assayed by the stathmo‐apoptosis method
Authors: Smolewski Piotr , Grabarek Jerzy , Lee Brian W. , Johnson Gary L. , Darzynkiewicz Zbigniew
Published: August 2002

Background

Duration of apoptosis, from onset to final disintegration of the cell, is often short and variable. The apoptotic index (AI), as a snapshot of a transient event of variable length, does not truly represent incidence of apoptosis in the studied cell population. We recently proposed to estimate the cumulative apoptotic index (CAI) by inducing stathmo‐apoptosis. A fluorescent inhibitor of caspases (FLICA) FAM‐VAD‐FMK is used to arrest the process of apoptosis and thereby prevent cell disintegration. Simultaneously, the arrested/apoptotic cells become FLICA‐labeled. In the present study, this approach was applied to measure kinetics of HL‐60 cell entrance into apoptosis induced via cell surface death receptor or a mitochondria‐initiated pathway.

Materials and Methods

Cultures of HL‐60 cells were treated with either TNF‐α or camptothecin (CPT) in the absence or constant presence of 10–50 μM FLICA. The CAI was measured at different time points for up to 48 h by flow cytometry. Bivariate analysis of DNA content and cell labeling with FLICA was used to correlate apoptosis with the cell‐cycle position.

Results

Selective loss of apoptotic cells seen in HL‐60 cell cultures exposed to either TNF‐α or CPT alone was prevented in cultures containing FLICA. Addition of FLICA alone had no effect on cell viability. The percentage of FLICA‐labeled cells was plotted as a function of time after addition of TNF‐α or CPT. The rate of cell entry to apop‐ tosis was subsequently estimated from the slopes of the stathmo‐apoptotic plot. The slopes revealed that the TNF‐α or CPT‐treated cells asynchronously underwent apoptosis with a stochastic‐like kinetics and at two different rates. About 50% of cells in the TNF‐α‐treated cultures underwent apoptosis during the initial 6 h at a rate of ∼8% of cells per hour; the remaining cells were undergoing apoptosis at a rate of ∼2.5% of cells per hour for up to 24 h. Also, about 50% of the CPT‐treated cells, predominantly those in S phase of the cell cycle, underwent apoptosis within the initial 8 h of CPT exposure, at a rate of ∼7% of cells per hour. Remaining cells were undergoing apoptosis at a rate of ∼1% of cells per hour during up to 48 h exposure to CPT. Spontaneous apoptosis in the untreated cultures occurred at a rate of 0.2% of cells per hour.

Conclusions

This approach provides a means for measuring the kinetics of cell entrance to apoptosis (caspase activation) in large populations of cells in relation to the cell‐cycle position. Cytometry 47:143–149, 2002. © 2002 Wiley‐Liss, Inc.
Fine‐needle aspiration cytology of umbilical nodules: “Sister Joseph's nodule”
Authors: Sahai Kavita , Kapila Kusum , Verma Kusum
Published: August 2002

Metastatic tumor deposits in the umbilicus are not uncommon. Fine‐needle aspiration cytology is an important, simple, cost‐effective diagnostic tool for delineating the value of umbilical nodules. However, only a few reviews and case reports of diagnosis of umbilical metastases by fine‐needle aspiration cytology are available. A review of 52 cases of umbilical nodule aspirates over a 16‐yr period forms the basis of this brief report. Diagn. Cytopathol. 25:309–310, 2001. © 2001 Wiley‐Liss, Inc.
Permeability and single‐channel properties of mesenteric, basilar, and septal (coronary) artery smooth‐muscle P2X receptors
Authors: Lewis Carolyn J. , Davies Noel W. , Evans Richard J.
Published: August 2002

P2X1 receptors for ATP are expressed in vascular smooth muscle and are thought to underlie the native artery smooth muscle rapidly desensitising α,β‐methylene ATP (α,β‐meATP) sensitive P2X receptor phenotype. We have characterised the ionic permeability and single‐channel conductance from rat mesenteric, basilar, and septal (coronary) arteries. The relative permeabilities (PX/PNa) to methylamine, dimethylamine, and Tris were essentially the same for all three arteries and give an estimate of the minimum diameter of the ionic pore as 0.8 nm. The P2X receptor channels in arteries had a high calcium permeability (PCa2+/PNa ∼3.5). In outside‐out patches, α,β‐meATP evoked transient currents with a single‐channel conductance of ∼12 pS (in physiological solution with 2.5 mM Ca2+ and 1 mM Mg2+). The single‐channel conductance was increased to ∼17 pS with a 0.1 mM Ca2+‐ and nominally Mg2+‐free physiological solution. These properties for artery P2X receptors are essentially the same as for recombinant P2X1 receptors and confirm that homomeric P2X1 receptors underlie the native P2X receptor current phenotype in these arteries. Drug Dev. Res. 52:164–169, 2001. © 2001 Wiley‐Liss, Inc.
Regulation of biliary secretion by extracellular nucleotides
Authors: Feranchak Andrew P. , Fitz J. Gregory
Published: August 2002

Bile formation is an essential function of the liver and depends upon complimentary actions of hepatocytes and intrahepatic bile duct cells, or cholangiocytes. Cholangiocytes contribute importantly to the volume and composition of bile secreted by the liver through absorption and secretion of fluid and electrolytes. Biophysical measurements suggest that increases in Cl– permeability at the apical membrane of cholangiocytes represent an important cellular site for regulation of secretion. Recent evidence suggests that extracellular ATP may serve as a signal modifying cholangiocyte secretion through the regulation of membrane Cl– permeability. Through activation of P2Y2 receptors in the apical (luminal) membrane of cholangiocytes, ATP functions as a local autocrine/paracrine regulatory factor that modulates biliary secretion. Consequently, the purpose of this review is to describe the cellular mechanisms thought to contribute to ATP release and review the evidence supporting a role for ATP in the regulation of cholangiocyte Cl– secretion and bile formation. Characterization of the factors that regulate local nucleotide concentrations and purinergic signaling may represent therapeutic targets for the pharmacologic modulation of bile composition and flow. Drug Dev. Res. 52:232–238, 2001. © 2001 Wiley‐Liss, Inc.
Purine nucleosides protect injured neurons and stimulate neuronal regeneration by intracellular and membrane receptor‐mediated mechanisms
Authors: Di Iorio Patrizia , Caciagli Francesco , Giuliani Patricia , Ballerini Patrizia , Ciccarelli Renata , Sperling Oded , Zoref‐Shani Esther , Benowitz Larry , Traversa Ugo , Bombi Giulia , Florio Tulio , Virgilio Antonella , Andrew Craig M. , Crocker Candice E. , Werstiuk Eva S. , Middlemiss Pamela J. , Rathbone Michel P.
Published: August 2002

Like adenine‐based purines, extracellular nonadenine‐based purines have a multitude of trophic effects on the growth, differentiation, and survival of target cells. The nonadenine‐based purines, which include guanosine, inosine, and GTP, apparently exert their trophic effects by interacting with both intercellular targets as well as those on the cell surface. Specifically, guanosine and inosine target the protein kinase N‐kinase, in promoting remarkable nerve process extension, even in long tracts of the central nervous system after injury. In contrast, GTP may exert its effects via a cell surface receptor coupled to the release of calcium from internal stores. In other cases trophic effects may be mediated by the enhancement of release of adenine‐based purines by guanosine. Additionally, evidence is presented for the existence of a high‐affinity binding site for guanosine with receptor‐like characteristics on the plasma membranes of astrocytes and brain tissue. This site may be G‐protein‐coupled and exert its effects through activation of the MAP kinase cascade. One effect apparently mediated through this mechanism is the production and release by astrocytes of trophic protein growth factors such as NGF and TGFβ. These have substantial neuroprotective effects. Additionally, this pathway is apparently involved in modulating the expression of P2Y1 and P2Y2 receptors in response to extracellular guanosine. Extracellular nonadenine‐based purines can interact with other growth factors, but these interactions are not always synergistic. For example, combinations of guanosine and FGF are antagonistic and reduce the growth of microvascular cells in vitro. Some of the properties of the nonadenine‐based purines likely derive from their unique intracellular metabolism in which conversion of guanine to xanthine is the final catabolic step. This step is catalyzed by guanase, the activity of which varies markedly in different brain regions, raising the possibility that guanine or guanosine are involved in neurotransmission. Together these data suggest several potentially useful pharmacological approaches involving nonadenine‐based purines to modulate trophic effects in the central nervous system. Drug Dev. Res. 52:303–315, 2001. © 2001 Wiley‐Liss, Inc.
New insights into adenosine receptor modulation of myocardial ischemia‐reperfusion injury
Authors: Lasley Robert D. , Narayan Prakash , Mentzer Robert M.
Published: August 2002

The cardioprotective effects of adenosine in numerous experimental models have been well described and there is evidence that adenosine is beneficial in the clinical setting. However, the exact mechanism by which adenosine exerts its beneficial effects in reversibly and irreversibly injured myocardium has not been determined. In addition, with the exception of the A1 receptor, there is not universal agreement on the involvement of adenosine receptor subtypes. This review summarizes recent findings in our laboratory on the role of the A3 and A2a receptors in adenosine cardioprotection and compartmentation of cardiomyocyte adenosine receptor signaling. Drug Dev. Res. 52:357–365, 2001. © 2001 Wiley‐Liss, Inc.
Adenosine mediates the antiinflammatory effects of methotrexate as well as its toxicities
Authors: Cronstein Bruce N. , Montesinos M. Carmen , Chan Edwin
Published: August 2002

Methotrexate remains the mainstay of therapy for rheumatoid arthritis yet its mechanism of action remains unclear. Recent work from our laboratory indicates that methotrexate promotes increased adenosine release from cells and tissues and that the anti‐inflammatory actions of methotrexate are mediated by adenosine, acting at its receptors on inflammatory and other cells. Similarly, evidence from our laboratory suggests that such toxicities as methotrexate‐accelerated nodulosis and methotrexate‐induced hepatic fibrosis are mediated by adenosine acting at its receptors. Drug Dev. Res. 52:394–396, 2001. © 2001 Wiley‐Liss, Inc.
Convergence of psychological and biological development
Authors: Posner Michael I.
Published: August 2002

The special issue provides an opportunity to assess the degree of integration that has been achieved between studies of psychological and biological development. This commentary uses the material in the special issue to address integration of the two fields and to suggest some future developments. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 339–343, 2002. DOI 10.1002/dev.10037
Autoantibodies to GAD, IA‐2 and insulin in ICA‐positive first‐degree relatives of children with type 1 diabetes: a comparison between parents and siblings
Authors: Korhonen Sari , Knip Maria M. , Kulmala Petri , Savola Kaisa , Åkerblom Hans K. , Knip Mikael ,   The Finnish Study Group for ICA Screening
Published: August 2002

Background

Islet cell antibodies (ICA) represent a heterogenous group of autoantibodies to diabetes‐associated antigens, including glutamic acid decarboxylase (GAD) and the IA‐2 protein. The objectives of the present study were to compare the prevalence of autoantibodies to known biochemically characterized autoantigens between ICA‐positive non‐diabetic parents and siblings of children with type 1 diabetes and to evaluate how such antibodies explain ICA reactivity.

Methods

The presence and levels of GAD antibodies (GADA), IA‐2 antibodies (IA‐2A) and insulin autoantibodies (IAA) were analyzed in the sera of 184 ICA‐positive first‐degree relatives (79 parents and 105 siblings).

Results

The prevalences of GADA (61.9% in siblings vs 32.9% in parents), IA‐2A (55.2% vs 15.2%) and IAA (41.0% vs 0%) were increased among ICA‐positive siblings relative to ICA‐positive parents (p<0.001). The siblings had higher ICA titers (p<0.001) than the parents but tended to have lower GADA levels (p=0.12). IA‐2A levels did not differ between the two groups. IA‐2A levels explained a higher proportion of the ICA reactivity in the siblings than in the parents (44% vs 12%, p=0.004), and GADA levels had the same tendency (27% vs 10%, p=0.11). In a multiple regression analysis, GADA and IA‐2A were found to explain together 16% of the ICA reactivity in parents and 49% in siblings (p=0.003 for the difference).

Conclusions

These results indicate that the increased frequency of additional diabetes‐associated autoantibodies in ICA‐positive siblings when compared to their ICA‐positive parents may reflect the increased risk of progression to clinical type 1 diabetes previously reported in young ICA‐positive relatives. We conclude that ICA immunofluorescence is not only due to GADA and IA‐2A, but there are other additional antigens contributing to the ICA reactivity. Antibodies to such antigens appear to be more common among adults than in children. Copyright © 2002 John Wiley & Sons, Ltd.
Green fluorescent protein expression in germ‐line transmitted transgenic zebrafish under a stratified epithelial promoter from Keratin8
Authors: Gong Zhiyuan , Ju Bensheng , Wang Xukun , He Jiangyan , Wan Haiyan , Sudha Putter Mudumana , Yan Tie
Published: August 2002

A zebrafish cDNA encoding a novel keratin protein was characterized and named keratin8, or krt8. krt8 expression was initiated at 4.5 hr postfertilization, immediately after the time of zygotic genome activation. The expression is limited to a single layer of envelope cells on the surface of embryos and, in later stages, it also appears in the innermost epithelial layer of the anterior‐ and posteriormost portions of the digestive tract. In adult, its expression was limited to the surface layer of stratified epithelial tissues, including skin epidermis and epithelia of mouth, pharynx, esophagus, and rectum but not in the gastral and intestinal epithelia. By using a 2.2‐kb promoter from krt8, several stable green fluorescent protein (gfp) transgenic zebrafish lines were established. All of these transgenic lines displayed GFP expression in tissues mentioned above except for the rectum; therefore, the pattern of transgenic GFP expression is essentially identical to that of the endogenous krt8 mRNAs. krt8‐GFP fusion protein was also expressed in zebrafish embryos under a ubiquitous promoter, and the fusion protein was capable of assembling into intermediate filaments only in the epithelia that normally expressed krt8 mRNAs, indicating the specificity of keratin assembly in vivo. © 2002 Wiley‐Liss, Inc.
Constructing the hindbrain: Insights from the zebrafish
Authors: Moens Cecilia B. , Prince Victoria E.
Published: August 2002

The hindbrain is responsible for controlling essential functions such as respiration and heart beat that we literally do not think about most of the time. In addition, cranial nerves projecting from the hindbrain control muscles in the jaw, eye, and face, and receive sensory input from these same areas. In all vertebrates that have been studied, the hindbrain passes through a segmented phase shortly after the neural tube has formed, with a series of seven bulges—the rhombomeres—forming along the anterior‐posterior extent of the neural tube. Our current understanding of vertebrate hindbrain development comes from integrating data from several model systems. Work on the chick has helped us to understand the cell biology of the rhombomeres, whereas the power of mouse molecular genetics has allowed investigation of the molecular mechanisms underlying their development. This review focuses on the special insights that the zebrafish system has provided to our understanding of hindbrain development. As we will discuss, work in the zebrafish has elucidated inductive events that specify the presumptive hindbrain domain and has identified genes required for hindbrain segmentation and the specification of segment identities. © 2002 Wiley‐Liss, Inc.
Induction of ureter branching as a response to Wnt‐2b signaling during early kidney organogenesis
Authors: Lin Yanfeng , Liu Aiping , Zhang Shaobing , Ruusunen Tarja , Kreidberg Jordan A. , Peltoketo Hellevi , Drummond Iain , Vainio Seppo
Published: August 2002

Epithelial–mesenchymal tissue interactions play a central role in vertebrate organogenesis, but the molecular mediators and mechanisms of these morphogenetic interactions are still not well characterized. We report here on the expression pattern of Wnt‐2b during mouse organogenesis and on tests of its function in epithelial– mesenchymal interactions during kidney development. Wnt‐2b is expressed in numerous developing organs in the mouse embryo, including the kidney, lung, salivary gland, gut, pancreas, adrenal gland, and genital tubercle. Additional sites of expression include the branchial arches and craniofacial placodes such as the eye and ear. The data suggest that the expression of Wnt‐2b is associated with organs regulated by epithelial–mesenchymal interactions. It is typically localized in the capsular epithelium or peripheral mesenchymal cells of organ rudiments, e.g., the perinephric mesenchymal cells in the region of the presumptive renal stroma in the developing kidney at E11.5. Functional studies of the kidney demonstrate that cells expressing Wnt‐2b are not capable of inducing tubule formation but instead stimulate ureter development. Incubation of isolated ureteric buds on such cells supports bud growth and branching. In addition, recombination of Wnt‐2b‐pretreated ureteric bud tissue with isolated nephrogenic mesenchyme results in a recovery of organogenesis and the expression of epithelial genes within the reconstituted organ explant. Lithium, a known activator of Wnt signaling (Hedgepeth et al. [1997] Dev Biol 185:82–91), is also sufficient to promote ureter branching in the reconstituted kidney in a comparable manner to Wnt‐2b signaling, whereas Wnt‐4, which induces tubules, neither supports the growth of a ureteric bud nor leads to reconstitution of the ureteric bud with the kidney mesenchyme. We conclude that Wnt‐2b may act in the mouse kidney as an early mesenchymal signal controlling morphogenesis of epithelial tissue, and that the Wnt pathway may regulate ureter branching directly. In addition, Wnt signals in the kidney differ qualitatively and are specific to either the epithelial ureteric bud or the kidney mesenchyme. © 2001 Wiley‐Liss, Inc.