bluuebunny/crossref_metadata_2025 huggingface dataset:
An independent person in action under the Children Act 1989 complaints procedure
Authors: Bridge Gillian
Published: August 2002

Under Section 26 (4) of the Children Act 1989, local authorities are obliged to appoint independent people to participate in investigations at stage two of the complaints procedure. The nature of their role and tasks were ill defined by the Department of Health Guidance (1991), and hitherto there has been little research in this area. Using the author's experiences, this discussion paper examines some of the dilemmas of undertaking this role, and raises questions about how independent people are meeting legal requirements. From the material discussed here, it appears that the system of including independent people in complaints' investigations is not meeting the intended objectives of ensuring that complaints by young people themselves benefit from impartial scrutiny. Instead, independent people are mainly engaged with investigating officers in unravelling complex situations, many with long histories of serious breakdowns in communication between parents, carers and local authority children's services. In the light of these findings, the Department of Health's recent consultation paper, Listening to People is welcome, although rather disappointing in restricting its attention largely to procedural issues. In this paper the author promotes greater attention to the growing expertise of independent people currently investigating complaints. Additionally it is recommended that a more accessible means for young people to complain should be devised. Copyright © 2001 John Wiley & Sons, Ltd.
Attitudes towards and the practice of discipline amongst parents of pre‐school children in Nottingham
Authors: Thompson Anne E , Pearce John B
Published: August 2002

This study investigates parents' attitudes towards the disciplining of young children, and compares their beliefs about discipline to their actual practice of behaviour management. Data have been collected from a sample of parents whose children are attending Nottinghamshire nursery schools using self‐report questionnaires. Only one quarter of respondents agree that smacking is the appropriate way to handle the unsafe behaviour of a three year old child, and many of the sample recognise that parents who smack their children may face repercussions from social services and the courts. However almost two thirds of the sample had smacked their pre‐school child in the past week. Parents who endorse the use of non‐coercive management techniques smack their children as well. These results suggest that initiatives to promote positive discipline may not be sufficient in themselves to reduce the physical punishment of children. Copyright © 2000 John Wiley & Sons, Ltd.
Stereoselective binding and degradation of sulbenicillin in the presence of human serum albumin
Authors: Tsuda Yasuyuki , Tsunoi Tomoko , Watanabe Naoko , Ishida Mariko , Yamada Hideo , Itoh Tomoo
Published: August 2002

Binding of sulbenicillin (SBPC) isomers to human serum albumin (HSA) was stereoselective. There were at least two classes of binding sites on HSA for SBPC isomers. At the stereoselective high affinity site, binding was in favor of R‐SBPC, the binding constant of R‐SBPC being approximately 2.3‐fold greater than that of S‐SBPC. By using site marker ligands, it was revealed that the stereoselective site was Site I (warfarin binding site). Affinity for the low affinity (nonstereoselective) site was similar for the diastereomers, approximately 7–30‐fold lower than for the stereoselective site. R‐SBPC and S‐SBPC appeared to displace each other competitively at both binding sites. On the other hand, R‐SBPC was degraded much faster than S‐SBPC in the presence of HSA, with a degradation rate constant approximately 7‐fold greater for R‐SBPC than for S‐SBPC. The degradation of R‐SBPC was inhibited in the presence of warfarin and dependent on the concentration of R‐SBPC bound to Site I. The results demonstrate that Site I is responsible for the stereoselective degradation. Chirality 13:236–243, 2001. © 2001 Wiley‐Liss, Inc.
Discrimination in resolving systems. VI. Comparison of the diastereomers of deoxyephedrinium and ephedrinium 4′‐fluoromandelates
Authors: Valente Edward J. , Smith Tyler N. , Harris Marcus E.
Published: August 2002

(−)‐(R)‐Deoxyephedrine forms poorly discriminating diastereomeric salts with 4′‐fluoromandelic acid from 95% ethanol. Both less‐soluble (L) (S)‐4′‐fluoromandelate and more‐soluble (M) (R)‐4′‐fluoromandelate phases are monoclinic and unsolvated. Their solubility ratio (M/L) in 95% ethanol is only 1.2, which correlates with the similarity and small differences in their respective heats of fusion and fusion temperatures. The (R)‐deoxyephedrinium and the related (1R;2S)‐ephedrinium 4′‐fluoromandelate systems show L‐salts with higher ion‐pair volumes and lower densities than their M‐salts. (R)‐Deoxyephedrinium salts have higher volumes than the comparable (1R;2S)‐ephedrinium salts even though the resolving base (R)‐deoxyephedrine lacks the benzylic hydroxy. In the solids, bilayered structures segregate polar and nonpolar molecular regions. The principle interionic interactions are hydrogen bonds between protonated secondary ammonium ions and carboxylates forming infinite chains with a six‐atom repeating unit H‐N+‐H···O‐C−‐O [C22(6)]. These are buttressed by mandelate hydroxy to carboxylate hydrogen bonds. Differing interactions between phenyl and 4′‐fluorophenyl rings in the nonpolar layers of the salts correlate with the density and stability inversion. Chirality 13:244–250, 2001. © 2001 Wiley‐Liss, Inc.
Enantiomers of 2‐[(Acylamino)ethyl]‐1,4‐benzodiazepines, Potent ligands of κ‐opioid receptor: Chiral chromatographic resolution, configurational assignment, and biological activity
Authors: Azzolina O. , Collina S. , Linati L. , Anzini M. , Cappelli A. , Scheideler M.A. , Sbacchi M.
Published: August 2002

Compounds 2a and 3a–e are racemic 2‐[(acylamino)ethyl]‐1,4‐benzodiazepines, tifluadom analogs, with high affinity and selectivity towards the κ‐opioid receptor. We describe the enantiomeric separation of all compounds through liquid chromatography with chiral stationary phases, as well as the resolution of the enantiomers of the most interesting compounds, 2a and 3a, by the semipreparative column Chiralpak AD. The configuration of the resolved enantiomers was investigated: the comparative study of CD and 1H NMR spectra shows that compounds (−)‐2a and (−)‐3a have the same absolute configuration of (+)‐(S)‐tifluadom. A study on the stereoselective interaction with opiate receptors is reported. Chirality 13:606–612, 2001. © 2001 Wiley‐Liss, Inc.
Reflections on Lanchester strategy
Authors: Schuler John
Published: August 2002

The Lanchester strategy of sales and marketing, based on F.W. Lanchester's equations of combat (1995), has been extensively developed in Japan since the early 1960s (Taoka, 1997). The strategy is based on a rigorous mathematical analysis of military and marketing warfare that uses elements of game theory, probability, ecology, and calculus to show that the Lanchester laws are verified in theory and practice (Onoda, 1999). As this knowledge filters out into the business world (Lewis, 1997; Yano, 1996), the interest is in real‐life case studies that illustrate the application and practice of the Lanchester strategy (Skelton, 1999). However, companies are reluctant, if not paranoid, about releasing information on strategic planning, market share, and business strategies to potential competitors, as any case study of more than superficial interest will cover these areas in detail. An approach to gaining real‐world case studies is to view recent articles in business journals through the lens of Lanchester strategy. Using data taken from recent Wall Street Journal articles, we will provide sufficient market share and background information to generate a number of case studies that illustrate the Lanchester strategy, but first we provide some background on F.W. Lanchester, the strategy, and its significance. © 2001 John Wiley & Sons, Inc.
Integrating CI with strategic market planning through the use of “Channels‐To‐Market™ mapping”
Authors: Bulger Nan
Published: August 2002

Mapping distribution channels against a company's defined market segments provides a methodical way of addressing short‐term tactical and long‐term strategic decisions, and guides the user in the focused use of CI data collection. This mapping technique is called CTM™ or Channels‐To‐Market™. It is an analytical tool based on the principle that there must be a focus on events occurring at individual market segment and distribution channel intersections, and that those events support business decision‐making at tactical and strategic levels throughout and beyond an entire business life cycle. The result is the application of CI data points to business scenarios and actual corporate business decisions. This article is a brief overview discussion concentrated on the application of the CTM™ Map and methodology, and how it makes CI tangible and “actionable” by focusing and linking the organization's CI collection efforts to relevant marketing, sales, strategic planning, and other deliverables that provide direct return on investment (ROI). © 2001 John Wiley & Sons, Inc.
The japanese intelligence culture
Authors: Ikeya Nozomu (Nick) , Ishikawa Katsumi
Published: August 2002

In Japan, the relationship between the government and business has traditionally been strong due to the country's historical and cultural background. The major governmental organizations have played a critical role supporting the nation's CI activities in business and in the industrial/technology arena. Until the 1980s, the government, especially through the Ministry of Economy, Trade, and Culture (METI), directed business to facilitate the country's economic recovery following the devastation of World War II. The government not only coordinates complex issues among companies, but also provides CI support through METI, the Japan External Trade Organization (JETRO), and its embassies. Japan's economic recession and bureaucratic corruption of the 1990s suggest that its economy is now in a transitional period from its postwar industrial success. The national policy may now change focus. It is anticipated that the roles of METI and its affiliates would also have to change. Businesses and citizens are calling for the liquidation of government‐affiliated organizations whose roles are no longer relevant or appropriate. In light of this, any CI distributed by those national organizations would be somewhat, or greatly, reduced if such restructuring takes place. However, collaboration between the government and business organizations will continue. As long as Japanese companies maintain their information‐intensive culture, there will be support for CI activities regardless of whether it comes from the government or other sources. © 2001 John Wiley & Sons, Inc.
Centrosome behavior in motile HGF‐treated PtK2 cells expressing GFP‐gamma tubulin
Authors: Danowski Barbara A. , Khodjakov Alexey , Wadsworth Patricia
Published: August 2002

In response to locomotory cues, many motile cells have been shown to reposition their centrosome to a location in front of the nucleus, towards the direction of cell migration. We examined centrosome position in PtK2 epithelial cells treated with hepatocyte growth factor (HGF), which stimulates motility but, unlike chemotactic agents or wounding of a monolayer, provides no directional cues. To observe centrosome movement directly, a plasmid encoding human gamma tubulin fused to the green fluorescent protein was expressed in HGF‐treated cells. In cells whose movements were unconstrained by neighboring cells, we found that the position of the centrosome was not correlated with the direction of cell locomotion. Further, in cells where the direction of locomotion changed during the observation period, the centrosome did not reorient toward the new direction of locomotion. Analysis of centrosome and nuclear movement showed that motion of the centrosome often lagged behind that of the nucleus. Analysis of 249 fixed cells stained with an antibody to gamma tubulin confirmed our observations in live cells: 69% of the cells had centrosomes behind the nucleus, away from the direction of locomotion. Of these, 41% had their centrosome in the retraction tail. Confocal microscopy showed that the microtubule array in HGF treated PtK2 cells was predominantly non‐centrosomal. Because microtubules are required for efficient cellular locomotion, we propose that non‐centrosomal microtubules stabilize the direction of locomotion without a requirement for reorientation of the centrosome. Cell Motil. Cytoskeleton 50:59–68, 2001. © 2001 Wiley‐Liss, Inc.
NMR of peptides and proteins in oriented membranes
Authors: Marassi Francesca M.
Published: August 2002

Solid‐state NMR spectroscopy is used to determine the structures of membrane peptides and proteins in lipid bilayers. The methodology for membrane protein structure determination using solid‐state NMR of oriented lipid bilayer samples is outlined. Recent developments in recombinant bacterial expression systems for the preparation of isotopically labeled membrane proteins, pulse sequences for high‐resolution spectroscopy, and structural indices that guide the structure assembly process greatly extend the capabilities of the technique. © 2002 Wiley Periodicals, Inc. Concepts in Magn Reson 14, 212–224, 2002.
Predictive model of axillary lymph node involvement in women with small invasive breast carcinoma
Authors: Martin Caroline , Cutuli Bruno , Velten Michel
Published: August 2002

BACKGROUND

Axillary lymph node involvement (ALNI) remains the most accurate predictive factor for recurrence risk and survival in patients with invasive breast carcinoma (IBC) and is an essential element in therapeutic decisions. However, axillary dissection (AD) is responsible for several side effects and is now discussed in small IBC. The objective of this study was to define a predictive model of ALNI by using clinical and histologic variables available before surgery.

METHODS

The authors studied 795 cases of IBC (T0, T1, T2 ≤ 4 cm; N0; M0) treated between 1980 and 1997 by conservative surgery and radiation therapy. All cases had axillary dissection with at least 10 lymph nodes removed. A stepwise logistic regression analysis was performed to build a predictive model of ALNI. The authors then used the jackknife resampling technique to produce unbiased estimates of the probabilities of ALNI along with their confidence intervals.

RESULTS

The global ALNI rate was 25.7%. The final predictive model included clinical tumor size, location, and histologic subtype and grade as variables independently associated with ALNI. The estimated probability of ALNI varied from 6% to 45%, according to case characteristics for these variables.

CONCLUSIONS

These results show that the omission of AD in surgical procedures for these tumors is debatable. Even when ALNI rates were low, the superior bounds of the confidence intervals could be high. Consequently, we do not recommend to omit AD in women whose estimated risks are higher than 25%. Women with a risk of ALNI lower than 25% could benefit from the sentinel lymph node procedure with, likewise, a limited risk of false‐negative. Cancer 2002;94:314–22. © 2002 American Cancer Society.
Alternative bimonthly cycles of doxorubicin, cyclophosphamide, and etoposide, cisplatin with hematopoietic growth factor support in patients with carcinoma of unknown primary site
Authors: Culine Stéphane , Fabbro Michel , Ychou Marc , Romieu Gilles , Cupissol Didier , Pinguet Frédéric
Published: August 2002

BACKGROUND

Because carcinomas of unknown primary origin are highly malignant tumors with a bad prognosis (median survival, 6–12 months) and no current optimal therapy, the authors designed a prospective dose‐dense chemotherapy regimen with the objective of improving the results observed in patients who receive conventional treatment.

METHODS

Eighty‐two patients received alternative bimonthly cycles of doxorubicin 50 mg/m2 with cyclophosphamide 1000 mg/m2 (AC) and etoposide 300 mg/m2 with cisplatin 100 mg/m2 (EP). Cycles were given at 2‐week intervals with granulocyte‐macrophage–stimulating factor support (5 μg/kg per day) from Day 4 to Day 10. Patients without measurable lesions were included, because the major end point was survival.

RESULTS

The median number of alternative cycles of AC and EP was 4 cycles (range, 1–12 cycles). An objective response was observed in 24 of 62 patients (39%; 95% confidence interval, 30–48%) with measurable lesions, including 6 patients who achieved a complete response. Among 20 patients with nonmeasurable disease, 9 patients (45%) had no evidence of progressive disease at the end of chemotherapy. The overall median survival of 82 patients was 10 months, with 5 patients surviving clinically disease free at 17 months, 29 months, 45 months, 64 months, and 70 months after the end of treatment. Myelosuppression was the most common toxicity. Two toxic deaths occurred.

CONCLUSIONS

Using these doses and schedules, a dose‐dense chemotherapy regimen did not appear to improve the outcome of patients with carcinoma of unknown primary site. Alternative studies dealing with news drugs will be required. Cancer 2002;94:840–6. © 2002 American Cancer Society.

DOI 10.1002/cncr.10264
Expression of CD95 (Fas) in sun‐exposed human skin and cutaneous carcinomas
Authors: Filipowicz Ewa , Adegboyega P. , Sanchez R. L. , Gatalica Zoran
Published: August 2002

BACKGROUND

Carcinomas of the skin are by far the most common human malignancies. Continuous exposure to ultraviolet (UV) light facilitates the development of precancerous lesions (actinic keratosis [AK]) that may progress to invasive squamous carcinomas. Apoptosis, triggered by the activation of CD95 (Fas), is one of the most important defense mechanisms against UV light–induced carcinogenesis in experimental models, but the dynamics of CD95 expression in patients with sun‐induced lesions are largely unknown.

METHODS

The authors studied the expression of CD95 (Fas) in biopsy samples of normal skin (not exposed to sun) and compared it with chronically sun‐exposed skin (as evidenced by solar elastosis), AK, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), and keratoacanthomas (KA).

RESULTS

Normal skin keratinocytes expressed CD95 in cytoplasmic membranes and intercellular bridges in the basal layer. In chronically sun‐exposed keratinocytes (solar elastosis, no evidence of dysplasia), CD95 expression was up‐regulated and was observed throughout the entire thickness of the epidermis. However, in actinic keratosis there was a complete absence of Fas in approximately two‐thirds of the cases (8 of 12). In invasive SCC, CD95 was expressed focally and weakly only at the sites of contact with stromal lymphocytes. Keratoacanthomas consistently expressed CD95 at the interface with the inflammatory cells. No staining was observed in BCC.

CONCLUSIONS

CD95 (Fas) up‐regulation in chronically sun‐exposed keratinocytes indicates an important role in the control of sun‐induced damage. Further sun exposure results, however, in significant down‐regulation of this defense mechanism, proportional to the degree of dysplasia. Cancer 2002;94:814–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10277
Frequent impairment of the spindle assembly checkpoint in hepatocellular carcinoma
Authors: Saeki Ayuko , Tamura Shinji , Ito Nobuyuki , Kiso Shinichi , Matsuda Yasuo , Yabuuchi Iwao , Kawata Sumio , Matsuzawa Yuji
Published: August 2002

BACKGROUND

Chromosomal instability (CI) leading to aneuploidy is one form of genetic instability, a characteristic feature of various types of cancers. Recent work has suggested that CI can be induced by a spindle assembly checkpoint defect. The aim of the current study was to determine the frequency of a defect of the checkpoint in hepatocellular carcinoma (HCC) and to establish whether alterations of genes encoding the checkpoint were associated with CI in HCC.

METHODS

Aneuploidy and the function of the spindle assembly checkpoint were examined using DNA flow cytometry and morphologic analysis with microtubule disrupting drugs. To explore the molecular basis, the authors examined the expression and alterations of the mitotic checkpoint gene, BUB1, using Northern hybridization and direct sequencing in 8 HCC cell lines and 50 HCC specimens. Furthermore, the authors examined the alterations of other mitotic checkpoint genes, BUBR1, BUB3, MAD2B, and CDC20, using direct sequencing in HCC cell lines with aneuploidy.

RESULTS

An impaired spindle assembly checkpoint was found in five (62.5%) of the eight aneuploid cell lines. Transcriptional expressions of the BUB1 gene appeared in all cell lines. While some polymorphic base changes were noted in BUB1, BUBR1, and CDC20, no mutations responsible for impairment of the mitotic checkpoint were found in either the HCC cell lines or HCC specimens, which suggests that these genes did not seem to be involved in tumor development in HCC.

CONCLUSIONS

The loss of spindle assembly checkpoint occurred with a high frequency in HCC with CI. However, other mechanisms might also contribute to CI in HCC. Cancer 2002;94:2047–54. © 2002 American Cancer Society.

DOI 10.1002/cncr.10448
A Phase II trial of intravenous gemcitabine and 5‐fluorouracil with subcutaneous interleukin‐2 and interferon‐α in patients with metastatic renal cell carcinoma
Authors: Ryan Christopher W. , Vogelzang Nicholas J. , Stadler Walter M.
Published: August 2002

BACKGROUND

The objective of this study was to determine the response rate and toxicity of gemcitabine and continuous‐infusion 5‐fluorouracil (5‐FU) in combination with subcutaneous interleukin‐2 (IL2) and interferon‐α (IFNA) in patients with metastatic renal cell carcinoma.

METHODS

Forty‐one patients were treated with gemcitabine 600 mg/m2 on Days 1, 8, and 15 and continuous‐infusion 5‐FU on Days 1–21. The dose of 5‐FU was 200 mg/m2 per day for the initial 8 patients but was reduced to 150 mg/m2 per day for all remaining patients due to toxicity. Starting on Day 15, IL2 and IFNA were administered for 4 weeks. IL2 was administered at a dose of 11 × 106 IU subcutaneously (sc) 4 days per week and IFNA was administered at a dose of 10.0 × 106 IU sc 2 days per week.

RESULTS

Of 41 patients enrolled in the study, there was 1 complete response (CR), and there were 5 partial responses (PR), for an overall response rate of 14.6% (90% confidence interval [90%CI], 6.6–26.9%). The median time to disease progression was 6.6 months (90%CI, 3.9–7.5 months), and the median overall survival was 20.6 months (90%CI, 9.6–23.3 months). Toxicity was moderate to severe, with fatigue, fever, anorexia, or nausea experienced by 75–90% of patients. Mucositis and neutropenia, likely due to the gemcitabine and 5‐FU, were experienced by a majority of patients.

CONCLUSIONS

The addition of gemcitabine and 5‐FU to subcutaneous IL2 and IFNA results in a similar response rate to what was observed in previous studies of IL2‐based therapy. The toxicity of this four‐drug combination is significant, and the regimen is not recommended for further development. Cancer 2002;94:2602–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10528
Subcellular distribution of high‐voltage‐activated calcium channel subtypes in rat globus pallidus neurons
Authors: Hanson Jesse E. , Smith Yoland
Published: August 2002

Globus pallidus (GP) neurons receive dense inhibitory synaptic inputs interspersed with sparse excitatory inputs distributed across the entire extent of their somata and dendrites. Yet, despite this predominance of inhibitory influence, GP neurons fire at a high tonic rate, suggesting that intrinsic properties play an important role in determining the physiological characteristics of these neurons. High‐voltage‐activated (HVA) calcium channels represent an important class of conductances that plays roles in controlling neurotransmitter release, postsynaptic excitability, and intracellular calcium signaling. To better understand the intrinsic properties of GP neurons, we examined the subcellular localization of HVA calcium channels by using immunocytochemistry at the electron microscopic level. Peroxidase labeling with antibodies against P/Q‐, N‐, and R‐type HVA calcium channels demonstrated the presence of these channels in both proximal and distal dendrites of GP neurons. P/Q‐, N‐, and R‐type channels were also found in presynaptic terminals, whereas L‐type channels were found exclusively postsynaptically in neuronal elements. Immunogold labeling demonstrated that, although the density of intracellular L‐type calcium channel labeling remains constant throughout the proximal‐distal extent of the dendritic tree of GP neurons, the density of plasma membrane‐bound channels is greater in distal dendrites. The finding of HVA calcium channels distributed throughout the whole dendritic tree of GP neurons indicates that these channels may interact with synaptic inputs to allow rich processing possibilities for GP neuron dendrites. Furthermore, the finding of a greater density of plasma membrane‐bound L‐type channels in distal dendrites expands the view that L‐type channels are important only in somatic and proximal locations. J. Comp. Neurol. 442:89–98, 2002. © 2002 Wiley‐Liss, Inc.
Intratelencephalic connections of the hippocampus in pigeons (Columba livia)
Authors: Atoji Yasuro , Wild J. Martin , Yamamoto Yoshio , Suzuki Yoshitaka
Published: August 2002

Behavioral experiments using ablation of the hippocampus are increasingly being used to address the hypothesis that the avian hippocampus plays a role in memory, as in mammals. However, the morphological basis of the avian hippocampus has been poorly understood. In the present study, the afferent and efferent connections of the hippocampus in the pigeon telencephalon were defined by injections, at various rostrocaudal sites, of neuronal tracers mainly into the triangular part located between its V‐shaped layer of densely packed neurons. The major results obtained in the present study were as follows. 1) A topographical organization of the commissural projections was confirmed. These projections had two courses that projected to the contralateral side, one traveling through the fiber wall of the ventromedial telencephalon, which was the main path from neurons in the caudal hippocampus, and the other running down through the septohippocampal junction, which was the main path from neurons in the middle to rostral hippocampus. Both courses passed through the pallial commissure. 2) The hippocampus projected bilaterally to the septum, parahippocampal area (APH), and dorsolateral cortical area (CDL). These projections were also distributed topographically, with contralateral efferents crossing through the pallial commissure. 3) The hippocampus had ipsilateral reciprocal connections with APH, CDL, and the dorsal hyperstriatum. Septal afferents to the ipsilateral hippocampus were very small. 4) Intrinsic connections were found between the triangular part of the hippocampus and the lateral limb of the V‐shaped layer of neurons. 5) The hippocampus projected ipsilaterally to the ventral basal ganglia and the fasciculus diagonalis Brocae. In sum, these connections of the hippocampus may form a neuronal circuit for the processing of spatial memory in pigeons. J. Comp. Neurol. 447:177–199, 2002. © 2002 Wiley‐Liss, Inc.
Local differences in vagal afferent innervation of the rat esophagus are reflected by neurochemical differences at the level of the sensory ganglia and by different brainstem projections
Authors: Wank Michael , Neuhuber Winfried L.
Published: August 2002

The objective of the present study was to characterize further the vagal afferent fibers in the rat esophagus, particularly those in its uppermost part, their cell bodies in vagal sensory ganglia, and their central projections. We applied immunohistochemistry for calretinin, calbindin, and calcitonin gene‐related peptide (CGRP); retrograde tracing with FluoroGold; and transganglionic tracing with wheat germ agglutinin‐horseradish peroxidase in combination with neurectomies. Vagal terminal structures in the muscularis propria of the whole esophagus consisted of calretinin‐immunoreactive intraganglionic laminar endings that were linked to cervical vagal and recurrent laryngeal nerve pathways. The mucosa of the uppermost esophagus was innervated by a very dense net of longitudinally arranged, calretinin‐positive fibers that were depleted by section of the superior laryngeal nerve. Distal to this area, the mucosa was virtually devoid of calretinin‐immunoreactive vagal afferents. Calretinin‐positive mucosal fibers in the upper cervical esophagus were classified into four types. One type, the finger‐like endings, was sometimes immunoreactive also for CGRP. About one‐third of cell bodies in vagal sensory ganglia retrogradely labeled from the upper cervical esophagus expressed CGRP, whereas two‐thirds coexpressed calretinin and calbindin but not CGRP. In addition to the central subnucleus of the nucleus of the solitary tract, vagal afferents from the upper cervical esophagus also projected heavily to the interstitial subnucleus. This additional projection was attributed to mucosal afferents traveling through the superior laryngeal nerve. The present study provides a possible morphological basis for bronchopulmonary and aversive reflexes elicited upon stimulation of the esophagus. J. Comp. Neurol. 435:41–59, 2001. © 2001 Wiley‐Liss, Inc.
Anatomical and functional connections among cell groups in the gerbil brain that are activated with ejaculation
Authors: Heeb Michaela M. , Yahr Pauline
Published: August 2002

Based on Fos expression, four areas of the gerbil brain are activated with ejaculation, i.e., the posterodorsal preoptic nucleus (PdPN), the lateral part of the posterodorsal medial amygdala (MeApd), the medial cell group of the sexually dimorphic preoptic area (medial SDA), and the parvicellular part of the subparafascicular thalamus (SPFp). The SPFp and medial SDA also express Fos earlier in the context of mating. To study connections among these areas, we injected one with FluoroGold and assessed the colocalization of FluoroGold and mating‐induced Fos in the others. To determine if any of these areas activates the others, we lesioned one unilaterally and measured mating‐induced Fos ipsilaterally and contralaterally in the others. Half of the SPFp cells projecting to the medial SDA, PdPN, and MeApd were activated with mating. SPFp lesions also decreased Fos expression in those areas. However, those areas do not project to the SPFp or affect its Fos expression with mating. Projections from the lateral MeApd to the medial SDA and PdPN, and from the medial SDA to the lateral MeApd, were also activated with mating, but lesions in these areas did not affect Fos expression in the others. Because 32–50% of the mating‐activated cells in the SPFp participated in each SPFp projection identified, projections may have been identified for all of the mating‐activated cells in the SPFp. In contrast, most of the mating‐activated cells in the lateral MeApd, PdPN, and medial SDA do not participate in any projection studied, suggesting that they are either interneurons or project elsewhere. J. Comp. Neurol. 439:248–258, 2001. © 2001 Wiley‐Liss, Inc.
Restoration of mitochondrial function reverses developmental neuronal death in vitro
Authors: Pena Carlos , Zhou Yinong , Lust David , Pilar Guillermo
Published: August 2002

In a previous study characterizing morphological and functional features of cell death in trophically deprived chick ciliary ganglion neurons (Pena and Pilar [2000] J. Comp. Neurol. 424:377–396), we hypothesized that early cell death events might be targets for reversal, allowing for rescue of dying neurons. To test this hypothesis, ciliary ganglion (CG) neurons were cultured with or without trophic support (choroid, iris, and pigment epithelium soluble extract [CIPE]), or without trophic support for 11 or 18 hours and then exposed to trophic support. Prior to and at the onset of cell death commitment (11 hours) CIPE‐deprived neurons exhibited increased membrane permeability, blebbing, cytoplasmic vacuolization, swollen mitochondria, low adenosine triphosphate levels, and release of cytochrome c from mitochondria. CIPE readdition at 11 hours reversed these changes. Between 11 and 18 hours, irreversible DNA fragmentation increased in CIPE‐deprived neurons. Cyclosporin A and bongkrekic acid (inhibitors of mitochondrial transition permeability pores) prevented membrane permeability increases and delayed the progression to death in trophically deprived neurons by 12 hours; however, by 48 hours all neurons had died. BOC‐Asp‐CH2F (BAF), a pan‐caspase inhibitor, did not prevent early events of cell death including increased membrane permeability and Cyto c release, but it inhibited DNA fragmentation and prolonged neuronal survival to 48 hours. We conclude that mitochondria changes occur early, prior to commitment and that the suppression of these changes can prevent all the downstream events of death, whereas caspase inhibitors have no effect on the early mitochondria/plasma membrane changes. Mitochondria thus play a critical role in the transition from reversible to irreversible commitment to developmental neuronal death. Furthermore, neuronal death is brought about by activation of one of two distinct pathways, one localized in mitochondria and the other dependent on activation of caspases. J. Comp. Neurol. 440:156–176, 2001. © 2001 Wiley‐Liss, Inc.
Occurrence of glutamate receptor subunit 1–containing aggresome‐like structures during normal development of rat spinal cord interneurons
Authors: Serrando Maite , Casanovas Anna , Esquerda Josep E.
Published: August 2002

During a developmental study of the expression of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) ‐type glutamate receptor subunits in rat spinal cord, we observed the existence of cytoplasmic inclusion bodies with positive immunoreactivity to glutamate receptor subunit 1 (GluR1) but not to other glutamate receptor subunits. GluR1‐positive bodies have a diameter of between 1 and 3 μm and can be seen widely distributed throughout spinal cord gray matter, with the exception of the ventral horn region. They transiently appear within a definite developmental time‐period between embryonic day 19 and postnatal day 17 and are only associated with neuronal cells. Ultrastructural analysis revealed that these inclusions were located adjacent to the nucleus and consisted of amorphous material without any limiting membrane. Immunocytochemical analysis revealed that the inclusions displayed positive immunoreactivity to ubiquitin, HSP70, and 20S proteasome. All these data indicate that GluR1‐containing inclusions display all the ultrastructural and immunocytochemical characteristics of the recently described structure, which have been given the name aggresomes. Further studies are needed to determine the biological significance of these normally occurring aggresome‐like inclusions, because aggresomes are usually considered in a pathologic context. J. Comp. Neurol. 442:23–34, 2002. © 2002 Wiley‐Liss, Inc.
A new algorithm of time stepping in the non‐linear dynamic analysis
Authors: Haitian Yang , Qiang Gao , Xinglin Guo , Chengwei Wu
Published: August 2002

This paper presents a new scheme of time stepping for solving non‐linear dynamic problems. By expanding variables in a discretized time interval, FEM‐based recurrent formulae are derived leading to a self‐adaptive algorithm for different sizes of time steps. There will be no requirement of iteration for the non‐linear solutions. Numerical validation shows satisfactory results. Copyright © 2001 John Wiley & Sons, Ltd.
CBS versus GLS stabilization of the incompressible Navier–Stokes equations and the role of the time step as stabilization parameter
Authors: Codina R. , Zienkiewicz O. C.
Published: August 2002

In this work we compare two apparently different stabilization procedures for the finite element approximation of the incompressible Navier–Stokes equations. The first is the characteristic‐based split (CBS). It combines the characteristic Galerkin method to deal with convection dominated flows with a classical splitting technique, which in some cases allows us to use equal velocity–pressure interpolations. The second approach is the Galerkin‐least‐squares (GLS) method, in which a least‐squares form of the element residual is added to the basic Galerkin equations. It is shown that both formulations display similar stabilization mechanisms, provided the stabilization parameter of the GLS method is identified with the time step of the CBS approach. This identification can be understood from a formal Fourier analysis of the linearized problem. Copyright © 2001 John Wiley & Sons, Ltd.
Reduction of variation in T‐cell subset enumeration among 55 laboratories using single‐platform, three or four‐color flow cytometry based on CD45 and SSC‐based gating of lymphocytes
Authors: Gratama Jan W. , Kraan Jaco , Keeney Mike , Granger Viv , Barnett David
Published: August 2002

BACKGROUND

Enumeration of CD4+ and CD8+ T‐cell subsets provides relevant information for diagnosis and monitoring of patients with cellular immunodeficiencies. As a result, an external quality assurance scheme was implemented in Belgium, The Netherlands, and Luxemburg in 1995. A workshop was held to train the participants in state‐of‐the art technology for assessment of absolute T‐cell subset counts (i.e., a three or four‐color, single‐platform assay with lymphocyte gating based on CD45 and sideward light scatter) with the aim to achieve between‐site coefficients of variation (CVs) <10% and within‐site CVs <5% for ≥75% of the participants. Methods: Three send‐outs of stabilized blood from a healthy donor were distributed to 55 laboratories, each with the request to perform the standard assay on three occasions. For comparison, each laboratory performed its local technique in parallel. Results: With the standard technique, between‐site CVs of ∼8% (CD3+ T cells), ∼9% (CD4+ T cells), and ∼10% (CD8+ T cells) were achieved. Within‐site CVs were <5% for 82% (CD3+ T cells) and ∼70% (CD4+ and CD8+ subsets) of the participants. Local techniques yielded between‐site CVs of 13%–17% for CD3+, CD4+, and CD8+ T cells. Conclusions: The state‐of‐the‐art technology for T‐cell subset enumeration was implemented successfully among 55 Belgian‐Dutch laboratories and resulted in significant reductions of between‐site variation of absolute CD3+, CD4+, and CD8+ T‐cell counts. Cytometry (Clin. Cytometry) 50:92–101, 2002. © 2002 Wiley‐Liss, Inc.
On optimal cell planning: Case study for a DCS 1800 system
Authors: Bouzouki Stavroula , Kotsopoulos Stavros , Karagiannidis George , Chassomeris Kostas , Lymberopoulos Dimitris
Published: August 2002

Micro and pico cell planning strategies are adopted in personal communication systems (PCS) in order to increase their capacity. The usage of the upper UHF band in combination with greater bandwidth is already proposed by telecom engineers in order to achieve the promised service quality and data rates. These strategies are characterized by an increased number of cells in specific geographical areas with the corresponding operating base transceiving stations (BTS) located at relatively low heights above the street level. In this case, the cell planning procedure in linear streets under line‐of‐sight (LOS) conditions needs further study concerning the technical characteristics of the PCS.

In this paper, the propagation characteristics of a DCS 1800 system are investigated on a theoretical and experimental basis in a specific geographical area (center of Patras City in Northern Pelloponesse). An improved RF propagation model is proposed in order to determine the propagation path losses occurring under certain multipath fading conditions. Hence an optimum determination of a system's cellular area can be achieved. Copyright © 2001 John Wiley & Sons, Ltd.
Reproducibility of cervicovaginal ThinPrep® cellularity assessment
Authors: Haroon Shamsa , Samayoa Luis , Witzke Donald , Davey Diane
Published: August 2002

Criteria for judging the squamous cellularity adequacy of cervicovaginal ThinPreps® using cell counts in representative fields have been proposed. We compared the interobserver reproducibility in the designation of ThinPreps® as satisfactory (SAT), satisfactory but limited by (SBLB), or unsatisfactory (UNS) for interpretation. Three reviewers independently assessed 145 cervicovaginal ThinPreps accessioned from 1997–1999 at the University of Kentucky cytopathology laboratory. Scant specimens were retrieved by computer search and more cellular specimens were added to make 145. Adjacent fields on a diameter including center at 10× and 40× were counted for sufficiently preserved and unobscured cells. A specimen was designated UNS if four or more fields at 10× had less than 10 squamous cells, and SBLB if four or more fields at 40× had less than five squamous cells. All three observers agreed on the adequacy designation in 76% of cases and the overall kappa was 0.73 (near excellent). Complete interobserver agreement was present in 86% (63/73) of UNS cases, 79% (33/42) of SAT, but only 47% (14/30) of SBLB slides. When SBLB and UNS categories were combined, the discrimination from the SAT category was excellent (kappa = 0.87) with pairwise k‐values of 0.94–0.97. In conclusion, adjacent field cell count methods to judge ThinPrep cellularity provide near excellent interobserver reproducibility. While we have designated both UNS and SBLB adequacy categories, criteria could easily be revised to set one threshold to separate SAT and UNS ThinPreps. Diagn. Cytopathol. 2002;26:19–21. © 2002 Wiley‐Liss, Inc.
Pulmonary parenchymal splenosis
Authors: Sarda Rakesh , Sproat Ian , Kurtycz Daniel F. , Hafez Reza
Published: August 2002

We describe the cytologic findings of a case of pulmonary parenchymal splenosis, a rare condition that follows lacerating trauma to the spleen, and may masquerade as a metastatic neoplasm. Approximately 24 cases of thoracic splenosis have so far been reported, the vast majority presenting as pleural‐based nodules, and the cytological features of only two cases, both belonging to the latter group, have been described. We believe our case report to be the first to describe the cytological features of an intrapulmonary splenosis, and its features differ from the prior cases by having a mixed inflammatory cell infiltrate, with a predominance of lymphocytes, plus pulmonary macrophages and occasional endothelial cells. This condition has variable cytological features, but the correct diagnosis can be made in the presence of appropriate history and radiographic findings. Confirmation may require biopsy or radionucleide imaging. Diagn. Cytopathol. 24:352–355, 2001. © 2001 Wiley‐Liss, Inc.
Pitfalls in TRAP assay in routine detection of malignancy in effusions
Authors: Braunschweig Richard , Guilleret Isabelle , Delacrétaz Françoise , Bosman Fred T. , Mihaescu Anca , Benhattar Jean
Published: August 2002

Telomerase has been found to be reactivated in a majority of cancers but is inactive in most somatic cells. Our principal goal was to determine the potential use of the telomeric repeat amplification protocol (TRAP) assay as marker for malignancy in cytological effusions. The simple selection criterion was the cytological diagnosis, and routine samples were classified into malignant (58 samples) and nonmalignant (233 samples). Of the malignant samples, 44/58 (76%) were positive by TRAP assay. Of the 14 telomerase‐negative cytology‐positive samples, RNA integrity was poor in 9, indicating suboptimal sample conservation for molecular analysis. In 3 of the remaining 5 samples with a negative TRAP assay, a high number of malignant cells was observed, and these cells might have been telomerase‐negative. Thus, the sensitivity of TRAP assay for the presence of malignant cells was about 76%. In the cytologically nonmalignant effusions, the presence of telomerase activity was observed in 24% (55/233). Of these, 6% were highly suspicious for malignancy, 9% were doubtful, and 9% were cytologically nonmalignant effusions confirmed by a follow‐up of 12 mo or more. According to these data, the specificity of the TRAP assay to detect tumor cells in effusions ranged only between 82–91%. Our results indicate that, although the TRAP assay is positive in 6–15% of putative malignant effusions, the relatively high number of TRAP false‐negative and false‐positive cases renders this test unsuitable for routine diagnostic purposes. Diagn. Cytopathol. 25:225–230, 2001. © 2001 Wiley‐Liss, Inc.
Cytological diagnosis of primary leiomyosarcoma of bone: Case report
Authors: Cohen Isaac , Loberant Norman , Goldfeld Moshe , Volpin Gershon
Published: August 2002

We report on a case of primary leiomyosarcoma of the bone in a 77‐yr‐old man. The patient presented with a painful, enlarging mass in the left shoulder of 6 mo duration. Radiography and computed tomography (CT) revealed a large destructive intramedullary lesion of the proximal humerus, with massive extension into the surrounding soft tissues. CT‐guided fine‐needle aspiration biopsies (FNAB) of both the bony and soft‐tissue lesions were performed. Cytological examination showed a neoplastic process composed of spindle cells mixed with pleomorphic cells. The smooth muscle origin of the neoplastic cells was confirmed by immunocytochemical analysis. We describe the cytological features of this rare primary tumor of bone, and consider the differential diagnosis of spindle‐cell neoplasms. Diagn. Cytopathol. 25:239–243, 2001. © 2001 Wiley‐Liss, Inc.
Effect of lignans isolated from Hernandia nymphaeifolia on reactive oxygen species generation and calcium mobilization in human neutrophils
Authors: Chao Yu‐Ying , Jan Chung‐Ren , Ko Ying‐Chin , Chen Jih‐Jung , Chen Ih‐Sheng
Published: August 2002

The effect of five lignans isolated from Hernandia nymphaeifolia on the reactive oxygen species (ROS) generation (O2– and H2O2) and Ca2+ mobilization in human neutrophils was investigated. The five lignans were epi‐yangambin, epi‐magnolin, epi‐aschantin, deoxypodophyllotoxin, and yatein. All five lignans (25–200 μM) suppressed the ROS generation induced by 20 μM N‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) and 1 μM phorbol myristate acetate (PMA) without altering the ROS generation induced by 0.1 μM arachidonic acid. In Ca2+‐containing medium, the lignans (50–100 μM) inhibited 20 μM fMLP‐ and 0.1 μM arachidonic acid‐induced increases in the intracellular free Ca2+ levels ([Ca2+]i). In Ca2+‐free medium, the lignans (50–100 μM) inhibited 0.1 μM arachidonic acid‐induced [Ca2+]i increase without changing 20 μM fMLP‐induced [Ca2+]i increase. In Ca2+‐free medium, after depleting intracellular Ca2+ stores with fMLP and arachidonic acid, addition of 3 mM Ca2+ induced Ca2+ influx. However, the lignans inhibited fMLP‐ and arachidonic acid‐induced Ca2+ influx. Collectively, this study shows that the lignans alter ROS generation and Ca2+ signaling in human neutrophils in a multiple manner. Drug Dev. Res. 55:118–126, 2002. © 2002 Wiley‐Liss, Inc.