bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome profiles of familial/bilateral and sporadic testicular germ cell tumors
Authors: Kraggerud Sigrid Marie , Skotheim Rolf I. , Szymanska Jadwiga , Eknæs Mette , Fosså Sophie D. , Stenwig Anna E. , Peltomäki Päivi , Lothe Ragnhild A.
Published: August 2002

In order to investigate the genetics of testicular germ cell tumors (TGCTs), we examined 33 TGCTs, including 15 familial/bilateral and 18 sporadic tumors, using comparative genomic hybridization. The frequencies of the histological subtypes were comparable between the two groups. Gains of the whole or parts of chromosome 12 were found in 30 tumors (91%). Furthermore, increased copy number of the whole or parts of chromosomes 7, 8, 17, and X, and decreased copy number of the whole or parts of chromosomes 4, 11, 13, and 18 were observed in ≥50% of the tumors. Sixteen smallest regions of overlapping changes were delineated on 12 different chromosomes. The chromosomal copy numbers of familial/bilateral and sporadic TGCTs were comparable, suggesting similar genetic pathways to disease in both groups. However, significant differences were observed between the two main histological subgroups. Gains from 15q and 22q were associated with seminomas (P = 0.005 and P = 0.02, respectively), whereas gain of the proximal 17q (17q11.2–21) and high‐level amplification from chromosome arm 12p, and losses from 10q were associated with nonseminomas (P < 0.001, P = 0.04, and P = 0.03, respectively). © 2002 Wiley‐Liss, Inc.
Genotypic and phenotypic progression in endometrial tumorigenesis: Determining when defects in DNA mismatch repair and KRAS2 occur
Authors: Cohn David E. , Mutch David G. , Herzog Thomas J. , Rader Janet S. , Dintzis Suzanne M. , Gersell Deborah J. , Todd Christina R. , Goodfellow Paul J.
Published: August 2002

We set out to determine the relative timing of loss of DNA mismatch repair and KRAS2 mutation in endometrial tumorigenesis. We studied endometrial carcinoma (CA) and synchronous atypical endometrial hyperplasia (AEH), the premalignant precursor of endometrial cancer. Carcinoma and hyperplasia were investigated for loss of mismatch repair as evidenced by microsatellite instability (MSI) and for KRAS2 mutations. Endometrial cancers previously shown to be MSI‐positive were evaluated for KRAS2 codon 12 and 13 mutations. DNA was isolated from foci of AEH concomitant with, but physically remote from, the cancers by use of tissues prepared by laser capture microdissection (LCM). The AEH DNAs were then assessed for MSI and KRAS2 mutations. Of 210 endometrial CAs investigated, 51 (26%) were MSI‐positive, and among those, 21 (41%) arose concomitantly with AEH. Of 41 foci of AEH (mean, two foci per patient) investigated, 34 (83%) were MSI‐positive. KRAS2 mutations were seen in 5/51 (10%) MSI‐positive carcinomas. From the five patients informative for both KRAS2 mutation and MSI, 10 foci of AEH were available for investigation. All 10 AEH specimens (100%) were MSI‐positive, and six (60%) had the KRAS2 mutation present in the coexisting CA. The observation that some MSI‐positive AEH specimens lack the KRAS2 mutation seen in the coexisting CA supports a model in which loss of DNA mismatch repair precedes KRAS2 mutation. However, in addition to the absence of KRAS2 mutations in AEH, we discovered mutations in LCM hyperplasia and carcinoma specimens that were not present in the portion of the cancers originally investigated. These discordant genotypes suggest genetic heterogeneity in endometrial hyperplasia and concomitant cancer. © 2001 Wiley‐Liss, Inc.
Wnt‐6 is expressed in the ureter bud and induces kidney tubule development in vitro
Authors: Itäranta Petri , Lin Yanfeng , Peräsaari Juha , Roël Giulietta , Destrée Olivier , Vainio Seppo
Published: August 2002

Summary: The embryonic kidney is a classic developmental model system for studying inductive tissue interactions that govern organogenesis. We report here that Wnt‐6 is expressed in the ureter bud, and that cell lines expressing Wnt‐6 induce nephrogenesis in vitro. Wnt‐6 cells induce tubules with similar kinetics to spinal cord (SPC) and lead to induced expression of Pax2, Pax8, Sfrp2, and E‐cadherin genes, early markers of tubulogenesis. Moreover, Wnt‐6 signaling rescues tubulogenesis in mesenchyme separated from Wnt‐4 mutant embryos and leads to activation of Wnt‐4 transcription. Wnt‐6 also induces a secondary axis in early Xenopus embryos. We conclude that Wnt‐6 is a candidate for the ureter epithelium‐derived signal that leads to activation of kidney tubulogenesis via Wnt‐4. genesis 32:259–268, 2002. © 2002 Wiley‐Liss, Inc.
Characterization of a novel EGFP reporter mouse to monitor Cre recombination as demonstrated by a Tie2 Cre mouse line
Authors: Constien Rainer , Forde Anne , Liliensiek Birgit , Gröne Hermann‐Josef , Nawroth Peter , Hämmerling Günter , Arnold Bernd
Published: August 2002

Summary: The use of the Cre/loxP system has greatly empowered the field of gene targeting. Here we describe the successful establishment of a novel knock‐in EGFP reporter mouse line to monitor Cre‐induced recombination in the vast majority of cell types. The value of this reporter mouse line is demonstrated by the use of a novel Tie2Cre transgenic mouse line that facilitates gene targeting in endothelial and hematopoietic cells. High efficiency of recombination was found in all endothelial cells and in the majority of hematopoietic cells but was absent in other tissues. Furthermore, in the second generation, the Tie2Cre mouse can be used to get 100% recombination of one allele, whilst allowing tissue specific in the second, therefore offering excellent efficiency. genesis 30:36–44, 2001. © 2001 Wiley‐Liss, Inc.
Modeling of HLA class II susceptibility to Type I diabetes reveals an effect associated with DPB1
Authors: Valdes Ana M. , Noble Janelle A. , Génin Emmanuelle , Clerget‐Darpoux Françoise , Erlich Henry A. , Thomson Glenys
Published: August 2002

In this report, we present evidence that the HLA class II DPB1 locus (or a locus with alleles in linkage disequilibrium with DPB1) contributes to Type I diabetes (IDDM) susceptibility in addition to the contribution of the HLA DR and DQ loci. The marker association segregation chi‐square (MASC) method, which fits both genotype frequency and affected sib‐pair identity‐by‐descent (IBD) distributions, was applied to 257 sib pairs affected with IDDM. Fitting DR‐DQ as the sole HLA susceptibility loci was strongly rejected. Next, we considered the DPB1 contribution to disease susceptibility. Published reports indicate a predisposing role for alleles DPB1*0301 and DPB1*0202, including our previous stratification analyses of association data on this sample. IDDM probands were stratified into those not carrying the alleles DPB1*0301 and DPB1*0202 (group DPB1‐A), and those carrying at least one copy of either allele (group DPB1‐B). Both groups of probands have almost identical frequencies of DR and DQ haplotypes but significantly different IBD distributions in the subset of families with probands who do not carry the highly predisposing DR3/DR4 genotype. In these data, DPB1 (or a locus in linkage disequilibrium), in addition to DR‐DQ, is involved in IDDM susceptibility and affects IBD in the HLA region. Addition of DPB1 in a genetic model of IDDM gives a better fit to the data than consideration of DR‐DQ alone. Our results are consistent with previous reports implicating DPB1 in IDDM susceptibility. Genet. Epidemiol. 21:212–223, 2001. © 2001 Wiley‐Liss, Inc.
Bayesian oligogenic analysis of quantitative and qualitative traits in general pedigrees
Authors: Uimari Pekka , Sillanpää Mikko J.
Published: August 2002

A Bayesian method for multipoint oligogenic analysis of quantitative and qualitative traits is presented. This method can be applied to general pedigrees, which do not necessarily have to be “peelable” and can have large numbers of markers. The number of quantitative/qualitative trait loci (QTL), their map positions in the genome, and phenotypic effects (mode of inheritances) are all estimated simultaneously within the same framework. The summaries of the estimated parameters are based on the marginal posterior distributions that are obtained through Markov chain Monte Carlo (MCMC) methods. The method uses founder alleles together with segregation indicators in order to determine the genotypes of the trait loci of all individuals in the pedigree. To improve mixing properties of the sampler, we propose (1) joint sampling of map position and segregation indicators, (2) omitting data augmentation for untyped or uninformative markers (homozygous parent), and (3) updating several markers jointly within a single block. The performance of the method was tested with two replicate GAW10 data sets (considering two levels of available marker information). The results were concordant and similar to those presented earlier with other methods. These analyses clearly illustrate the utility and wide applicability of the method. Genet. Epidemiol. 21:224–242, 2001. © 2001 Wiley‐Liss, Inc.
Polyphase evolution and reaction sequence of compositional domains in metabasalt: a model based on local chemical equilibrium and metamorphic differentiation
Authors: Toóth T. M. , Grandjean V. , Engi M.
Published: August 2002

Eclogitic garnet amphibolite samples from the Southern Steep Belt of the Central Alps show evidence of several stages of metamorphic evolution and exhumation. A method for unravelling this evolution is presented and applied to these samples. It involves a combination of detailed petrographic analysis and microchemical characterization with quantitative models of the thermodynamically stable phase relations for specific compositional domains of each sample. Preserved mineral relics and textural evidence are compared to model predictions to identify the important irreversible reactions. The interpretation of the exhumation history is thus based on the consistency of a wide spectrum of observations with predicted phase diagrams, leading to robust reconstruction of a pressure–temperature (P–T) path even where the mineralogical relics in samples are insufficient, due to retrogression, to warrant application of multi‐equilibrium thermobarometric techniques.

The formation of compositionally different domains in the metabasalt samples studied is attributed to prograde growth of porphyroblasts (e.g. garnet, plagioclase, zoisite) in the matrix, implying substantial metamorphic differentiation at the scale of a few millimetres. Chemical interaction among different domains during the subsequent P–T evolution is shown to have been very limited. This led to different reaction sequences during exhumation, in which relics preserved in different domains reflect a range of continually changing P–T conditions. For samples from a single outcrop, we deduce a Barrovian prograde path to eclogite facies (23 ± 3 kbar, 750 ± 50°C), followed by (rapid) decompression to 8 ± 1 kbar and 675 ± 25°C, and a final heating phase at similar pressures reaching 750 ± 40°C. This evolution is attributed to the Alpine cycle involving subduction→collision and slab breakoff→extrusion of tectonic fragments that make up the Southern Steep Belt of the Central Alps. Copyright © 2000 John Wiley & Sons, Ltd.
Expression of glial fibrillary acidic protein and glutamine synthetase by Müller cells after optic nerve damage and intravitreal application of brain‐derived neurotrophic factor
Authors: Chen Hao , Weber Arthur J.
Published: August 2002

Müller glia play an important role in maintaining retinal homeostasis, and brain‐derived neurotrophic factor (BDNF) has proven to be an effective retinal ganglion cell (RGC) neuroprotectant following optic nerve injury. The goal of these studies was to investigate the relation between optic nerve injury and Müller cell activation, and to determine the extent to which BDNF affects the injury response of Müller cells. Using immunocytochemistry and Western blot analysis, temporal changes in the expression of glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) were examined in rats after optic nerve crush alone, or in conjunction with an intravitreal injection of BDNF (5 μg). GFAP protein levels were normal at 1 day post‐crush, but increased ∼9‐fold by day 3 and remained elevated over the 2‐week period studied. Müller cell GS expression remained stable after optic nerve crush, but the protein showed a transient shift in its cellular distribution; during the initial 24‐h period post‐crush the GS protein appeared to translocate from the cell body to the inner and outer glial processes, and particularly to the basal endfeet located in the ganglion cell layer. BDNF alone, or in combination with optic nerve crush, did not have a significant effect on the expression of either GFAP or GS compared with the normal retina, or after optic nerve crush alone, respectively. The data indicate that although BDNF is a potent neuroprotectant in the vertebrate retina, it does not appear to have a significant influence on Müller cell expression of either GS or GFAP in response to optic nerve injury. GLIA 38:115–125, 2002. © 2002 Wiley‐Liss, Inc.
Long‐term modulation of glucose utilization by IL‐1α and TNF‐α in astrocytes: Na+ pump activity as a potential target via distinct signaling mechanisms
Authors: Véga Céline , Pellerin Luc , Dantzer Robert , Magistretti Pierre J.
Published: August 2002

Interleukin‐1α (IL‐1α) and tumor necrosis factor‐α (TNF‐α) markedly stimulate glucose utilization in primary cultures of mouse cortical astrocytes. The mechanism that gives rise to this effect, which takes place several hours after application of cytokine, has remained unclear. Experiments were conducted to identify the major signaling cascades involved in the metabolic action of cytokine. First, the selective IL‐1 receptor antagonist (IL‐1ra) prevents the effect of IL‐1α on glucose utilization in a concentration‐dependent manner, whereas it has no effect on the action of TNF‐α. Then, using inhibitors of three classical signaling cascades known to be activated by cytokines, it appears that the PI3 kinase is essential for the effect of both IL‐1α and TNF‐α, whereas the action of IL‐1α also requires activation of the MAP kinase pathway. Participation of a phospholipase C‐dependent pathway does not appear critical for both IL‐1α and TNF‐α. Inhibition of NO synthase by L‐NAME did not prevent the metabolic response to both IL‐1α and TNF‐α, indicating that nitric oxide is probably not involved. In contrast, the Na+/K+ ATPase inhibitor ouabain prevents the IL‐1α‐ and TNF‐α‐stimulated 2‐deoxyglucose (2DG) uptake. When treatment of astrocytes with a cytokine was followed 24 h later by an acute application of glutamate, a synergistic enhancement in glucose utilization was observed. This effect was greatly reduced by ouabain. These data suggest that Na+ pump activity is a common target for both the long‐term metabolic action of cytokines promoted by the activation of distinct signaling pathways and the enhanced metabolic response to glutamate. GLIA 39:10–18, 2002. © 2002 Wiley‐Liss, Inc.
Distribution of P2X receptors on astrocytes in juvenile rat hippocampus
Authors: Kukley Maria , Barden Julian A. , Steinhäuser Christian , Jabs Ronald
Published: August 2002

Recent evidence suggested that ATP acting via ionotropic (P2X) and metabotropic (P2Y) purinergic receptors might be involved in signaling between glial cells and within glial–neuronal networks. In contrast to their neuronal counterpart, the identity of P2X receptors in CNS glial cells is largely unknown. In the present study, antibodies recognizing the subunits P2X1–P2X7 were applied together with the astroglial marker S100β and nuclear labeling with Hoechst 33342 to investigate semiquantitatively the distribution of the whole set of P2X receptors in astrocytes of the juvenile rat hippocampus. Expression of P2X1–P2X4, P2X6, and P2X7 subunits was observed in astrocytes of various hippocampal subregions, but the cells were completely devoid of P2X5 protein. S100β‐positive cells expressing subunits P2X3–P2X7 occurred evenly in the different subfields, while P2X1‐ and P2X2‐positive astrocytes were distributed more heterogeneously. The staining pattern of P2X subunits also differed at the subcellular level. Antibodies against P2X2 and P2X4 labeled both astroglial cell bodies and processes. Immunoreactivity for P2X1 and P2X6 was mainly confined to somatic areas of S100β‐positive cells, whereas the subunit P2X3 was primarily localized along astroglial processes. Knowledge of the distribution of P2X receptors might provide a basis for a better understanding of their specific role in cell–cell signaling. GLIA 36:11–21, 2001. © 2001 Wiley‐Liss, Inc.
Bupropion SR in the naturalistic treatment of elderly patients with major depression
Authors: Steffens David C. , Doraiswamy P. Murali , McQuoid Douglas R.
Published: August 2002

Introduction

Bupropion immediate release (IR) and bupropion sustained release (SR) are frequently used to treat geriatric depression, as they have few cardiovascular, gastrointestinal and sexual adverse effects. We sought to examine the efficacy and dosing patterns of bupropion in a naturalistic cohort of elderly subjects with major depression (MD).

Methods

31 elderly ( > 60 years) patients with unipolar MD (DSM‐IV) who were enrolled in Duke's Mental Health Clinical Research Center for the Study of Depression in Later Life were prescribed bupropion SR or IR, alone or in combination with other antidepressant agents, for 12 weeks. Montgomery–Asberg depression rating scale (MADRS) scores and clinical global impression (CGI) severity scores were used to define response.

Results

74% (23/31) of the sample were responders (MADRS < 15) and 53% (16/30) achieved a partial (CGI = 2) or complete (CGI = 1) remission of MD at week 12. Among patients treated with bupropion SR monotherapy, the mean (range) maximal daily dose achieved was 240 mg (150–400 mg). Among those treated with bupropion IR, the mean (range) maximum daily dose achieved was 258 mg (150–450 mg). In subjects on monotherapy, 67% (10/15) of MD subjects were responders (MADRS < 15) and 50% (7/14) achieved full or partial remission. Response rates did not differ statistically among those with high and low medical comorbidity.

Conclusions

In this naturalistic 12‐week study, geriatric MD patients with high and low medical comorbidity responded well to bupropion and bupropion SR. In elderly patients, four to eight week acute treatment periods may be insufficient. Our findings suggest that nearly 50% of elderly depressed subjects at a tertiary center may need combination therapy over the course of their illness. Controlled randomized studies to establish the long‐term efficacy and optimal dose of the newer antidepressants in geriatric depression are urgently needed. Copyright © 2001 John Wiley & Sons, Ltd.
Neural basis for sentence comprehension: Grammatical and short‐term memory components
Authors: Cooke Ayanna , Zurif Edgar B. , DeVita Christian , Alsop David , Koenig Phyllis , Detre John , Gee James , Pinãngo Maria , Balogh Jennifer , Grossman Murray
Published: August 2002

We monitored regional cerebral activity with BOLD fMRI while subjects were presented written sentences differing in their grammatical structure (subject‐relative or object‐relative center‐embedded clauses) and their short‐term memory demands (short or long antecedent‐gap linkages). A core region of left posterior superior temporal cortex was recruited during all sentence conditions in comparison to a pseudofont baseline, suggesting that this area plays a central role in sustaining comprehension that is common to all sentences. Right posterior superior temporal cortex was recruited during sentences with long compared to short antecedent‐gap linkages regardless of grammatical structure, suggesting that this brain region supports passive short‐term memory during sentence comprehension. Recruitment of left inferior frontal cortex was most clearly associated with sentences that featured both an object‐relative clause and a long antecedent‐gap linkage, suggesting that this region supports the cognitive resources required to maintain long‐distance syntactic dependencies during the comprehension of grammatically complex sentences. Hum. Brain Mapping 15:80–94, 2001. © 2001 Wiley‐Liss, Inc.
2‐Polyfluoroacylcycloalkanones in reactions with selected phosphorus(III) compounds
Authors: Sevenard Dmitri V. , Lork Enno , Pashkevich Kazimir I. , Röschenthaler Gerd‐Volker
Published: August 2002

The reactivity of 2‐polyfluoroacylcycloalkanones and their O‐silylated derivatives towards phosphites and tris(trimethylsilyl)aminoiminophosphine has been investigated. From α‐polyfluoroalkyl substituted phosphonates, generated from tris(trimethylsilyl) phosphite and 1,3‐diketones, the respective phosphonic acids and their salts have been obtained. In one case, upon warming, a phosphonic acid underwent a ring closure to yield an oxaphospholene. 2‐Trifluoroacetylcycloalkanones and diethyl isocyanatophosphite furnished phosphoranes diastereospecifically, via addition of phosphorus at the trifluoroacetyl group and two additional heterocyclizations. Tris(trimethylsilyl)aminoiminophosphine formed very reactive trimethylsilylimino‐1,2λ5σ4‐phospholenes, which added hexafluoroacetone to give spirocyclic 1,3,2λ5σ5‐oxazaphosphetanes. The structures of the new compounds were determined by NMR spectroscopy and X‐ray single crystal analysis. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:97–107, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10001
Aminodiphenylphosphanes: Isotope‐induced chemical shifts 1Δ14/15N(31P), coupling constants 1J(31P,15N), and chemical shifts δ15N and δ31P
Authors: Contreras Rosalinda , Grevy Jean Michel , García‐Hernández Zureima , Göizado‐Rodriguez Marisol , Wrackmeyer Bernd
Published: August 2002

A series of aminodiphenylphosphanes 1 [Ph2P‐N(H)tBu (a), ‐NEt2 (b), ‐NiPr2 (c)], 2 [Ph2P‐NHPh (a), ‐NH‐2‐pyridine (b), ‐NH‐3‐pyridine (c), ‐NH‐4‐pyridine (d), NH‐pyrimidine (e), NH‐2,6‐Me2‐C6H3 (f), NH‐3‐Me‐2‐pyridine (g)], 3 [Ph2P‐N(Me)Ph (a), ‐NPh2 (b)], and N‐pyrrolyldiphenylphosphane 4 (Ph2P‐NC4H4) was prepared and studied by NMR (1H, 13C, 31P, 15N NMR) spectroscopy. The isotope‐induced chemical shifts 1Δ14/15N(31P) were determined at natural abundance of 15N by using HEED INEPT experiments. A dependence of 1Δ14/15N(31P) on the substituents at nitrogen was found (alkyl < H < aryl; increasingly negative values). The magnitude and sign of the coupling constants 1J(31P,15N) (positive sign) are dominated by the presence of the lone pair of electrons at the phosphorus atom. The X‐ray structural analysis of 2b is reported, showing the presence of dimers owing to intermolecular hydrogen bridges in the solid state. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:542–550, 2001
Individual differences in spatial memory among aged rats are related to hippocampal PKCγ immunoreactivity
Authors: Colombo Paul J. , Gallagher Michela
Published: August 2002

We reported previously that the extent of spatial memory impairment among aged rats was correlated positively with levels of protein kinase Cγ in hippocampal homogenates measured by quantitative Western blotting (Colombo et al., 1997). In the current study, immunocytochemistry was used to test whether the relationship between elevated PKCγ and memory impairment among aged rats could be localized further within regions of the hippocampus. Six‐ and 24‐month‐old male Long‐Evans rats were first trained in the water maze on a standard place‐learning task and then trained 2 weeks later on a transfer task designed for rapid acquisition. In comparison with young rats, aged rats with impaired spatial memory had increased PKCγ‐immunoreactivity (PKCγ‐ir) in CA1 of the hippocampus, but not the dentate gyrus. In addition, PKCγ‐ir in CA1 was correlated positively with spatial memory impairment among aged rats on the standard place‐learning and the transfer training tasks. The current results are consistent with our previous report of PKCγ in hippocampal homogenates, and show further that the relationships between PKCγ‐ir and memory impairments among aged rats are most evident in area CA1. Thus age‐related impairments of spatial memory, as well as deficits in the flexible use of previously acquired information, may result from dysregulation of PKCγ. Hippocampus 2002;12:285–289. © 2002 Wiley‐Liss, Inc.
Chronic psychosocial stress regulates the expression of both GR and MR mRNA in the hippocampal formation of tree shrews
Authors: Meyer Ute , van Kampen Marja , Isovich Eleonora , Flügge Gabriele , Fuchs Eberhard
Published: August 2002

A persistent hyperactivity of the hypothalamic‐pituitary‐adrenal axis and thus elevated glucocorticoid levels are main neuroendocrine features of depressive symptomatology in humans. The broad range of effects that are set off by glucocorticoids is mediated by glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs), which themselves are subject to autoregulation. In order to investigate the impact of long‐lasting psychological stress on corticosteroid receptor mRNA expression in the hippocampal formation, we employed the psychosocial stress paradigm in male tree shrews (Tupaia belangeri). By in situ hybridization studies and semiquantitative evaluation of stress‐induced changes of GR and MR mRNA expression at the single‐cell level, brain tissue from subordinate animals which were exposed to 27 days (1 h/day) of social confrontation was compared to that of nonstressed animals. Four weeks of stress exposure resulted in a downregulation of GR mRNA in the dentate gyrus and hippocampal subfields CA1 and CA3 of subordinate male tree shrews compared to controls. The MR mRNA content in these subfields of the anterior hippocampus was also clearly reduced. On the contrary, in a more posterior location on the longitudinal axis of the tree shrew hippocampus, the MR message was increased in subfields CA1 and CA3 and in the dentate gyrus. These results suggest a relevance of the stress‐induced regulation of both corticosteroid receptor subtype mRNAs in a naturalistic challenging situation. Moreover, the differential regulation of MR mRNA along the rostrocaudal axis of the hippocampus adds another feature to the heterogenous composition of this structure. Hippocampus 2001;11:329–336. © 2001 Wiley‐Liss, Inc.
Prescription practices of public and private health care providers in Attock District of Pakistan
Authors: Siddiqi S. , Hamid S. , Rafique G. , Chaudhry S. A. , Ali N. , Shahab S. , Sauerborn R.
Published: August 2002

The irrational use of drugs is a major problem of present day medical practice and its consequences include the development of resistance to antibiotics, ineffective treatment, adverse effects and an economic burden on the patient and society. A study from Attock District of Pakistan assessed this problem in the formal allopathic health sector and compared prescribing practices of health care providers in the public and private sector. WHO recommended drug use indicators were used to study prescription practices.

Prescriptions were collected from 60 public and 48 private health facilities. The mean (± SE) number of drugs per prescription was 4.1 ± 0.06 for private and 2.7 ± 0.04 for public providers ( p < 0.0001). General practitioners (GPs) who represent the private sector prescribed at least one antibiotic in 62% of prescriptions compared with 54% for public sector providers. Over 48% of GP prescriptions had at least one injectable drug compared with 22.0% by public providers ( p < 0.0001). Thirteen percent of GP prescriptions had two or more injections. More than 11% of GP prescriptions had an intravenous infusion compared with 1% for public providers ( p < 0.001). GPs prescribed three or more oral drugs in 70% of prescriptions compared with 44% for public providers ( p < 0.0001).

Prescription practices were analysed for four health problems, acute respiratory infection (ARI), childhood diarrhoea (CD), fever in children and fever in adults. For these disorders, both groups prescribed antibiotics generously, however, GPs prescribed them more frequently in ARI, CD and fever in children ( p < 0.01). GPs prescribed steroids more frequently, however, it was significantly higher in ARI cases ( p < 0.001). For all the four health problems studied, GPs prescribed injections more frequently than public providers ( p < 0.001). In CD cases GPs prescribed oral rehydration salt (ORS) less frequently (33.3%) than public providers (57.7%). GPs prescribed intravenous infusion in 12.3% cases of fever in adults compared with none by public providers ( p < 0.001).

A combination of non‐regulatory and regulatory interventions, directed at providers as well as consumers, would need to be implemented to improve prescription practices of health care providers. Regulation alone would be ineffective unless it is supported by a well‐established institutional mechanism which ensures effective implementation. The Federal Ministry of Health and the Provincial Departments of Health have to play a critical role in this respect, while the role of the Pakistan Medical Association in self‐regulation of prescription practices can not be overemphasized. Improper prescription practices will not improve without consumer targeted interventions that educate and empower communities regarding the hazards of inappropriate drug use. Copyright © 2002 John Wiley & Sons, Ltd.
Analysis of stress due to shrinkage in a hardening process of liquid epoxy resin
Authors: Nishimura Tetsuro , Nakagawa Yasutada
Published: August 2002

At present, epoxy resin is applied during the manufacturing of more compact and thinner components for the packaging of electronic and other devices. Epoxy resin has superior properties in terms of heat resistance, insulation, and strength; however, defects such as deformations and cracks often occur because of stress concentration. It is important to determine the inner stress of resin solidification for molding processes. Through a combination of numerical analyses of heat generated due to chemical reactions and experiments on shrinkage and strain that occur during hardening of epoxy resin, it becomes possible to analyze the stress generated due to hardening shrinkage. The developed analytical method can contribute to the realization of highly reliable components made of epoxy resin. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(3): 194–211, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10028
Natural convection heat transfer along a vertical flat plate with a projection in the turbulent region
Authors: Komori Katsuo , Kito Shunsuke , Inagaki Terumi , Mizoguchi Norio
Published: August 2002

In the present study, the heat transfer coefficients occurring with a projection in the turbulent region of a vertical flat plate were measured experimentally for various projection heights in the range of 0 to 20 mm. The wall temperature and fluid flow fields were also visualized using a liquid crystal sheet and nylon 12 powder, respectively. The average and local Nusselt numbers reach 1.07 to 1.22 and 1.2 to 1.7 times those for pure turbulent natural convection, respectively. The maximum enhancement rates of heat transfer are attained at a position of 2.3 to 3.3 times the projection height from the upper projection surface toward the downstream, and these positions are in good agreement with those of the reattachment of the fluid flow and with centers of dark red regions in the liquid crystal. On the other hand, the heat transfer coefficients in the just upstream and downstream regions of the projection are small compared with those for no projection. By introducing the nondimensional parameter R, the present experimental results are rearranged quantitatively and effectively. © 2001 Scripta Technica, Heat Trans Asian Res, 30(3): 222–233, 2001
Production by microphytobenthos in the Swan–Canning Estuary
Authors: Masini R. J. , McComb Arthur J.
Published: August 2002

Intact sediment cores containing microphytobenthos, dominated by episammic diatoms, were collected from shallow sand flats of the Swan–Canning Estuary, Perth, southwestern Australia, and their photosynthesis–light relations deduced from changes in oxygen (17 cores) or pH (13 cores). The theoretical saturating light intensity Ik determined from O2 was 107 µE m−2 s−1, and the light intensity at which photosynthesis is saturated, Isat, was about 1100 µE m−2 s−1. Mean gross production and respiration increased with temperature. Infaunal contributions to total respiration were measured for two cores at about 30%.

The sediment photic zone was estimated as 0·5 mm in fine sediments of the upper estuary and 3·5 mm in coarse sediments of the lower estuary. Microalgae from below the photic zone photosynthesized on exposure to light. Biomass (measured as chlorophyll a) decreased down the sediment profile and was linearly correlated with net and gross maximum photosynthesis. Relative photosynthetic efficiencies were high, and light compensation increased with increasing depth in the sediment.

Q10 values estimated from both net oxygen and carbon dioxide flux decreased with increasing temperature. Highest and lowest Q10 values were for respiration and net production derived from pH measurements. Copyright © 2001 John Wiley & Sons, Ltd.
Under‐ice movement of cohesive sediments before river‐ice breakup
Authors: Milburn D. , Prowse T. D.
Published: August 2002

A significant body of research exists on river hydraulics and sediment transport during open‐water conditions, and to a lesser extent during the period of ice‐cover. Most of the ice‐related studies, however, are based on controlled laboratory experiments or field studies conducted under stable ice‐cover conditions. They have largely ignored the most dynamic periods, such as breakup, when hydraulic conditions are most rapidly changing and energy levels are maximized. Moreover, the entire pre‐breakup to ice‐clearance period is virtually devoid of even standard hydrometric measurements of suspended sediment, largely because of safety and logistic problems. Some recent work has pointed to the formation of a sediment plume comprising fine‐grained sediments that develops before the main breakup fracturing of the ice cover. This plume has been noted as being particularly ecologically significant because it can contain the winter‐long deposition of contaminants that preferentially attach to fine‐grained material. Unfortunately, however, because measurements of the critical parameters affecting sediment transport during these periods are rarely taken, much uncertainty remains about the hydraulic forces that resuspend and transport sediments under an ice cover, and particularly for cohesive fine‐grained sediments. This paper describes a field experiment designed to broaden our understanding of sediment transport during this critical pre‐breakup period. Detailed measurements of river stage, ice elevations, flow velocity profiles and suspended sediment were taken over a 17‐day period just before the 1998 river‐ice breakup at Hay River, Northwest Territories, Canada. Results indicated that just before breakup, the shear stress, which governs the beginning of sediment motion, increases dramatically and drives the development of the under‐ice sediment plume of very fine‐grained, cohesive sediments. The shear stress in this case became critical at a mean under‐ice velocity of 0·4 m/s. Copyright © 2002 John Wiley & Sons, Ltd.
Temporal and spatial rainfall analysis across a humid tropical catchment
Authors: Campling P. , Gobin A. , Feyen J.
Published: August 2002

Temporal and spatial rainfall patterns were analysed to describe the distribution of daily rainfall across a medium‐sized (379km2) tropical catchment. Investigations were carried out to assess whether a climatological variogram model was appropriate for mapping rainfall taking into consideration the changing rainfall characteristics through the wet season. Exploratory, frequency and moving average analyses of 30 years' daily precipitation data were used to describe the reliability and structure of the rainfall regime. Four phases in the wet season were distinguished, with the peak period (mid‐August to mid‐September) representing the wettest period. A low‐cost rain gauge network of 36 plastic gauges with overflow reservoirs was installed and monitored to obtain spatially distributed rainfall data. Geostatistical techniques were used to develop global and wet season phase climatological variograms. The unscaled climatological variograms were cross‐validated and compared using a range of rainfall events. Ordinary Kriging was used as the interpolation method. The global climatological variogram $\gamma^{*} = 1{\cdot}2 \left[1 - \exp - {h\over 18 \hbox{ km}}\right]$ performed better, and was used to optimize the number and location of rain gauges in the network. The research showed that although distinct wet season phases could be established based on the temporal analysis of daily rainfall characteristics, the interpolation of daily rainfall across a medium‐sized catchment based on spatial analysis was better served by using the global rather than the wet season phase climatological variogram model. Copyright © 2001 John Wiley & Sons, Ltd.
The embedding of the self in early interaction
Authors: Forrester Michael A.
Published: August 2002

Presupposed in the earliest discourses we experience are implicit concepts concerning the nature of the self and identity. This paper examines the idea that through exposure to, and participation in, talk, the young infant is provided with appropriate discourses regarding what constitutes self and identity. Arguably, engaging in conversation entails entering into the co‐construction of participant stories, folk‐beliefs and everyday narratives concerning the nature and status of the self. The young child learns that he/she is required to display different versions of him/herself depending on the nature of the context. This study of the development of the discursive self begins by examining the discourse genres of the self made available to the child, that is, versions of the self presupposed in the caregivers' talk. Employing conversation analytic methods, a micro‐analysis of the talk of a parent–child dyad forms the basis of the study. The infant and parent (father) were video‐taped during mealtimes from when the infant was 18 months to 28 months old. The nature of the discourses informing ideas of the developing self are highlighted through considering examples in the parent's talk throughout this period. The findings are discussed in light of contemporary theories of the self in developmental psychology. Copyright © 2001 John Wiley & Sons, Ltd.
Lipopeptide‐based melanoma cancer vaccine induced a strong MART‐27‐35‐cytotoxic T lymphocyte response in a preclinal study
Authors: Le Gal Frédérique‐Anne , Prevost‐Blondel Armelle , Lengagne Renée , Bossus Marc , Farace Françoise , Chaboissier Aude , Gras‐Masse Hélène , Engelhard Victor H. , Guillet Jean‐Gérard , Gahéry‐Ségard Hanne
Published: August 2002

Identification of tumor antigens and their optimal antigenic peptides raised hopes for the development of peptide‐based immunotherapeutic vaccine strategies for human melanoma, however. Synthetic peptides alone are not immunogenic enough, and adequate formulation is critical for elaboration of peptide vaccines. To improve formulation, we evaluated 2 lipopeptide constructs, both including HLA‐A2‐restricted MART 27‐35‐CD8+ T lymphocyte (CTL) epitope covalently linked to universal tetanus toxoid (TT) 830‐843 helper T lymphocyte (HTL) epitope, in HLA‐A2 transgenic mouse models that mimic human CTL responses in vivo. These 2 constructs only differed in the formulation of their lipid tail. We showed that lipopeptide constructs were strongly recognized, in vitro, by human MART 27‐35 cytotoxic T cells derived from tumor‐infiltrating lymphocytes. The transgenic Mice immunized with these 2 MART lipopeptide formulations containing covalently linked HTL‐CTL epitopes induced strong MART 27‐35 cytotoxic T cells. This CTL induction was critically dependant on the presence of the helper T lymphocyte epitope. These results also showed that a single palmitoyl‐lysine chain is enough to assure immunogenicity of a given peptide and that the presence of a lipid tail bypass the need for adjuvant. These results support the selection of MART‐lipopeptide melanoma vaccine for evaluation in a clinical trial. © 2001 Wiley‐Liss, Inc.
Sporadic breast cancer in young women: Prevalence of loss of heterozygosity at p53, BRCA1 and BRCA2
Authors: Johnson Suzanne M. , Shaw Jacqueline A. , Walker Rosemary A.
Published: August 2002

Previous studies have shown that breast cancers have more aggressive pathologic features in young women. In order to examine genetic alterations associated with early‐onset breast cancer, 31 patients with no known family history, aged 26–35 years at diagnosis, were examined for loss of heterozygosity (LOH) at 3 key chromosomal intervals: 17p (p53), 17q 21 (BRCA1) and 13q12‐13 (BRCA2) using polymerase chain reaction analysis of polymorphic microsatellite markers. These were compared with 31 patients aged 55–72 years that were matched for size, type and grade. All young breast cancer cases exhibited LOH for at least 1 marker and 20 cases (64.5%) exhibited LOH at 1 or more markers from each interval. The frequency of LOH detected for each of the markers was as follows 17p: p534N (33.3%), D17S796 (36.7%), D17S799 (63.3%) and D17S513 (59.3%); 17q: D17S855 (64.5%), THRA1 (46.7%) and D17S579 (33.3%); and 13q: D13S260 (74.2%), D13S171 (47.6%) and D13S267 (40.0%). These frequencies are higher than those observed at the 3 markers studied in the matched postmenopausal patients: D17S799 (41.4%), D17S855 (35.5%), D13S260 (30.0%). These differences in frequency of LOH were statistically significant for the D17S855 and D13S260 markers (p < 0.025 and p < 0.001 respectively). Although there were more grade III carcinomas (21 of 31 cases), there was no correlation between number of alterations and high grade in younger cases. These data suggest that LOH at these regions could be related to early‐onset sporadic breast cancer. © 2001 Wiley‐Liss, Inc.
Cyclopentenyl cytosine increases the phosphorylation and incorporation into DNA of 1‐β‐D‐arabinofuranosyl cytosine in a human T‐lymphoblastic cell line
Authors: Verschuur Arnauld C. , Van Gennip Albert H. , Leen René , Voûte P.A. , Brinkman Josanne , Van Kuilenburg André B.P.
Published: August 2002

The cytotoxic effect of 1‐β‐D‐arabinofuranosyl cytosine (araC) depends on the intracellular phosphorylation into its active compound araCTP, on the degree of degradation of araCTP and on the incorporation of araCTP into DNA. Deoxycytidine triphosphate (dCTP) inhibits the phosphorylation of araC (by feedback inhibition of the enzyme deoxycytidine kinase) and the incorporation of araCTP into DNA (by competition for DNA polymerase). In a T‐lymphoblastic cell line, we studied whether the cytotoxicity of araC (2 nM–50 μM) could be enhanced by decreasing the concentration of dCTP, using the nucleoside‐analogue cyclopentenyl cytosine (CPEC), an inhibitor of the enzyme CTP synthetase. Preincubation of the cells with CPEC (100–1,600 nM) for 2 hr increased the concentrations of araCMP 1.6–9.5‐fold, which was significant for each concentration of CPEC used. The concentration of araCDP remained low, whereas the concentration of araCTP changed depending on the concentration of araC used. With 2–15 μM of araC and a preincubation with 400 nM of CPEC, the araCTP concentration increased by 4–15% (not significant), and the total amount of araC nucleotides increased significantly by 21–45%. When using a concentration of araC of 2 nM after a preincubation with CPEC of 100 nM, the concentration of araCMP increased by 60% (p = 0.015), whereas that of araCTP decreased by 10% (p = 0.008). This was compensated by an increase of 41% (p = 0.005) of araCTP incorporation into DNA, which represented 43% of all araC metabolites. Moreover, by performing pulse/chase experiments with 400 nM of CPEC and 2μM of araC, the retention of cytosolic araCTP and the incorporated amount of araCTP into DNA were increased by CPEC. The modulation by CPEC of araC metabolism was accompanied by a synergistic increase of araC‐induced apoptosis and by an additive effect on the araC‐induced growth inhibition. © 2002 Wiley‐Liss, Inc.
Expression of cyclooxygenase‐2 in the subserosal layer correlates with postsurgical prognosis of pathological tumor stage 2 carcinoma of the gallbladder
Authors: Kawamoto Toru , Shoda Junichi , Asano Toru , Ueda Tetsuya , Furukawa Masato , Koike Naoto , Tanaka Naomi , Todoroki Takeshi , Miwa Masanao
Published: August 2002

Postsurgical recurrence at distant sites frequently occurs in pathological tumor stage 2 (pT2) carcinoma of the gallbladder even though the carcinoma is limited to the gallbladder wall. Little is known, however, about the molecular events leading to its development and progression. A large body of evidence suggests that cyclooxygenase‐2 (COX‐2) is up‐regulated in carcinoma tissues and plays roles in promoting cell‐proliferation, growth and metastasis of carcinoma cells. In the present study, immunohistochemistry was performed to determine the expression levels of COX‐2 in the subserosal layer of 33 cases of pT2 gallbladder carcinoma in which curative resections had been performed and to determine the correlations of the expression levels of COX‐2 with mode of recurrence and postsurgical survival. Immunostaining of COX‐2 in the epithelia was recognized in more than 80% of normal epithelia, noncancerous pathological lesions of the gallbladder except for intestinal metaplasia and pT1–4 carcinoma specimens. Intense staining was observed in large percentages of hyperplastic lesions (65%), pT2 carcinoma specimens (76%) and pT3 and pT4 carcinoma specimens (64%) compared to the percentages of normal epithelia and other pathological lesions (0–25%). Intense staining was also observed in the adjacent stroma in pT2 carcinoma specimens (33%) and in those in pT3 and pT4 carcinoma specimens (43%) but only in small percentages of the stroma adjacent to normal epithelia and pathological lesions (0–8%). In situ hybridization confirmed the existence of COX‐2 mRNA in both the cancerous epithelia and adjacent stroma of pT2‐pT4 carcinomas. In 33 cases of pT2 carcinoma, distant recurrence, i.e., liver metastasis, was seen in 3 of 9 cases of pT2 carcinoma (33%, P<0.05) with intense stromal staining in the subserosal layer and in 1 of 24 cases (4%) without intense staining, whereas no significant correlation was found between parameters of pathological malignancies (histological grade, lymphatic permeation, venous permeation and lymph node metastasis) and the intensity of stromal staining in the subserosal layer. The postsurgical survival outcome was significantly poorer in the former than in the latter (p = 0.010). In pT2 gallbladder carcinoma, upregulation of COX‐2 in the stroma adjacent to the cancerous epithelia in the subserosal layer correlates with the aggressiveness of the disease, such as the tendency to form distant recurrences. This phenotype may serve as a unique biological feature associated with the malignant behavior of pT2 gallbladder carcinoma. © 2002 Wiley‐Liss, Inc.