bluuebunny/crossref_metadata_2025 huggingface dataset:
Luteinizing hormone induction of ovarian tumors: Oligogenic differences between mouse strains dictates tumor disposition
Authors: Keri Ruth A. , Lozada Kristen L. , Abdul-Karim Fadi W. , Nadeau Joseph H. , Nilson John H.
Published: July 2002

The use of fertility drugs has continued to grow since their
introduction in the 1960s. Accompanying this increase has been the
speculation that repetitive use of these drugs can cause ovarian tumors
or cancer. We recently reported that transgenic mice with chronically
elevated luteinizing hormone (LH), an analog of which is commonly used
in fertility regimens, develop granulosa cell (GC) tumors. In this
report we show that LH induction of these tumors is highly dependent on
genetic background. In CF-1 mice, chronically elevated LH invariably
causes GC tumors by 5 months of age. However, in hybrid mice generated
by crossing CF-1 males with C57BL/6, SJL, or CD-1 females, elevated
levels of this same hormone cause a completely different phenotype
resembling a luteoma of pregnancy. We also show that three genes likely
control these alternative hormonal responses. This clinical correlate
of elevated LH reveals remarkably distinct, strain-dependent, ovarian
phenotypes. In addition, these results support the rare incidence of GC
tumors in the human population, and suggest that the ability of certain
fertility drugs to cause ovarian tumors may depend on an individual's
genetic predisposition.
Behavioral alterations associated with apoptosis and down-regulation of presenilin 1 in the brains of p53-deficient mice
Authors: Amson Robert , Lassalle Jean-Michel , Halley Hélène , Prieur Sylvie , Lethrosne Florence , Roperch Jean-Pierre , Israeli David , Gendron Marie-Claude , Duyckaerts Charles , Checler Frédéric , Dausset Jean , Cohen Daniel , Oren Moshe , Telerman Adam
Published: July 2002

Presenilin 1 (PS1) expression is repressed by the p53 tumor suppressor. As shown herein, wild-type PS1 is an effective antiapoptotic molecule capable of significantly inhibiting p53-dependent and p53-independent cell death. We analyzed, at the functional and molecular levels, the brains of p53 knockout mice. Surprisingly, we found that lack of p53 expression induces apoptotic brain lesions, accompanied by learning deficiency and behavioral alterations. p53-deficient mice show an unexpected overexpression of p21
waf1
with subsequent down-regulation of PS1 in their brains. This process is progressive and age-dependent. These data indicate that the p53 pathway, besides affecting tumor suppression, may play a major role in regulating neurobehavioral function and cell survival in the brain.
Specific interaction of CCR5 amino-terminal domain peptides containing sulfotyrosines with HIV-1 envelope glycoprotein gp120
Authors: Cormier Emmanuel G. , Persuh Marjan , Thompson Daniah A. D. , Lin Steven W. , Sakmar Thomas P. , Olson William C. , Dragic Tatjana
Published: July 2002

The HIV-1 envelope glycoprotein gp120 interacts consecutively with CD4 and the CCR5 coreceptor to mediate the entry of certain HIV-1 strains into target cells. Acidic residues and sulfotyrosines in the amino-terminal domain (Nt) of CCR5 are crucial for viral fusion and entry. We tested the binding of a panel of CCR5 Nt peptides to different soluble gp120/CD4 complexes and anti-CCR5 mAbs. The tyrosine residues in the peptides were sulfated, phosphorylated, or unmodified. None of the gp120/CD4 complexes associated with peptides containing unmodified or phosphorylated tyrosines. The gp120/CD4 complexes containing envelope glycoproteins from isolates that use CCR5 as a coreceptor associated with Nt peptides containing sulfotyrosines but not with peptides containing sulfotyrosines in scrambled Nt sequences. Finally, only peptides containing sulfotyrosines inhibited the entry of an R5 isolate. Our data show that proper posttranslational modification of the CCR5 Nt is required for gp120 binding and viral entry. More importantly, the Nt domain determines the specificity of the interaction between CCR5 and gp120s from isolates that use this coreceptor.
Retinoid-related orphan receptor γ (RORγ) is essential for lymphoid organogenesis and controls apoptosis during thymopoiesis
Authors: Kurebayashi Shogo , Ueda Eiichiro , Sakaue Morito , Patel Dhavalkumar D. , Medvedev Alex , Zhang Feng , Jetten Anton M.
Published: July 2002

To identify the physiological functions of the retinoid-related orphan receptor γ (RORγ), a member of the nuclear receptor superfamily, mice deficient in RORγ function were generated by targeted disruption. RORγ−/−mice lack peripheral and mesenteric lymph nodes and Peyer's patches, indicating that RORγ expression is indispensable for lymph node organogenesis. Although the spleen is enlarged, its architecture is normal. The number of peripheral blood CD3+and CD4+lymphocytes is reduced 6- and 10-fold, respectively, whereas the number of circulating B cells is normal. The thymus of RORγ−/−mice contains 74.4% ± 8.9% fewer thymocytes than that of wild-type mice. Flow cytometric analysis showed a decrease in the CD4+CD8+subpopulation. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining demonstrated a 4-fold increase in apoptotic cells in the cortex of the thymus of RORγ−/−mice. The latter was supported by the observed increase in annexin V-positive cells. RORγ−/−thymocytes placed in culture exhibit a dramatic increase in the rate of “spontaneous” apoptosis. This increase is largely associated with CD4+CD8+thymocytes and may, at least in part, be related to the greatly reduced level of expression of the anti-apoptotic gene Bcl-XL. Flow cytometric analysis demonstrated a 6-fold rise in the percentage of cells in the S phase of the cell cycle among thymocytes from RORγ−/−mice. Our observations indicate that RORγ is essential for lymphoid organogenesis and plays an important regulatory role in thymopoiesis. Our findings support a model in which RORγ negatively controls apoptosis in thymocytes.
Complex promoter and coding region β
2
-adrenergic receptor haplotypes alter receptor expression and predict
in vivo
responsiveness
Authors: Drysdale Connie M. , McGraw Dennis W. , Stack Catharine B. , Stephens J. Claiborne , Judson Richard S. , Nandabalan Krishnan , Arnold Kevin , Ruano Gualberto , Liggett Stephen B.
Published: July 2002

The human β
2
-adrenergic receptor gene has multiple single-nucleotide polymorphisms (SNPs), but the relevance of chromosomally phased SNPs (haplotypes) is not known. The phylogeny and the
in vitro
and
in vivo
consequences of variations in the 5′ upstream and ORF were delineated in a multiethnic reference population and an asthmatic cohort. Thirteen SNPs were found organized into 12 haplotypes out of the theoretically possible 8,192 combinations. Deep divergence in the distribution of some haplotypes was noted in Caucasian, African-American, Asian, and Hispanic-Latino ethnic groups with >20-fold differences among the frequencies of the four major haplotypes. The relevance of the five most common β
2
-adrenergic receptor haplotype pairs was determined
in vivo
by assessing the bronchodilator response to β agonist in asthmatics. Mean responses by haplotype pair varied by >2-fold, and response was significantly related to the haplotype pair (
P
= 0.007) but not to individual SNPs. Expression vectors representing two of the haplotypes differing at eight of the SNP loci and associated with divergent
in vivo
responsiveness to agonist were used to transfect HEK293 cells. β
2
-adrenergic receptor mRNA levels and receptor density in cells transfected with the haplotype associated with the greater physiologic response were ≈50% greater than those transfected with the lower response haplotype. The results indicate that the unique interactions of multiple SNPs within a haplotype ultimately can affect biologic and therapeutic phenotype and that individual SNPs may have poor predictive power as pharmacogenetic loci.
Auditory neuroscience: Development, transduction, and integration
Authors: Hudspeth A. J. , Konishi Masakazu
Published: July 2002

Hearing underlies our ability to locate sound sources in the
environment, our appreciation of music, and our ability to communicate.
Participants in the National Academy of Sciences colloquium on Auditory
Neuroscience: Development, Transduction, and Integration presented
research results bearing on four key issues in auditory research. How
does the complex inner ear develop? How does the cochlea transduce
sounds into electrical signals? How does the brain's ability to
compute the location of a sound source develop? How does the forebrain
analyze complex sounds, particularly species-specific communications?
This article provides an introduction to the papers stemming from the
meeting.
Notch signaling in the development of the inner ear: Lessons from
Drosophila
Authors: Eddison Mark , Le Roux Isabelle , Lewis Julian
Published: July 2002

The sensory patches in the ear of a vertebrate can be compared with
the mechanosensory bristles of a fly. This comparison has led to the
discovery that lateral inhibition mediated by the Notch cell–cell
signaling pathway, first characterized in
Drosophila
and
crucial for bristle development, also has a key role in controlling the
pattern of sensory hair cells and supporting cells in the ear. We
review the arguments for considering the sensory patches of the
vertebrate ear and bristles of the insect to be homologous structures,
evolved from a common ancestral mechanosensory organ, and we examine
more closely the role of Notch signaling in each system. Using viral
vectors to misexpress components of the Notch pathway in the chick ear,
we show that a simple lateral-inhibition model based on feedback
regulation of the Notch ligand Delta is inadequate for the ear just as
it is for the fly bristle. The Notch ligand Serrate1, expressed in
supporting cells in the ear, is regulated by lateral induction, not
lateral inhibition; commitment to become a hair cell is not simply
controlled by levels of expression of the Notch ligands Delta1,
Serrate1, and Serrate2 in the neighbors of the nascent hair cell; and
at least one factor, Numb, capable of blocking reception of lateral
inhibition is concentrated in hair cells. These findings reinforce the
parallels between the vertebrate ear and the fly bristle and show how
study of the insect system can help us understand the vertebrate.
A membrane-associated progesterone-binding protein, 25-Dx, is regulated by progesterone in brain regions involved in female reproductive behaviors
Authors: Krebs Christopher J. , Jarvis Erich D. , Chan Johnny , Lydon John P. , Ogawa Sonoko , Pfaff Donald W.
Published: July 2002

The ventromedial hypothalamus (VMH) plays a central role in the regulation of the female reproductive behavior lordosis, a behavior dependent upon the sequential activation of receptors for the ovarian steroid hormones estradiol (E) and progesterone (P). These receptors function as transcription factors to alter the expression of target genes. To discover behaviorally relevant genes targeted by E and P in the VMH, we used the differential display PCR to identify messenger RNAs that are differentially expressed in the hypothalamus of ovariectomized (ovx) rats treated with E alone compared with ovariectomized rats treated with E and P. We show here that one interesting mRNA within the hypothalamus that is repressed by P after E priming encodes the protein 25-Dx, the rat homolog of the human membrane-associated P-binding protein Hpr6.6. Neurons in the brain containing the highest levels of 25-Dx are located in several nuclei of the basal forebrain, including the VMH. 25-Dx expression is also higher in the hypothalamus of female P receptor “knockout” mice than in their wild-type littermates. These findings suggest a mechanism in which the activation of nuclear P receptor represses expression of a membrane P receptor, 25-Dx, during lordosis facilitation.
Stepwise assembly of initiation proteins at budding yeast replication origins
in vitro
Authors: Seki Takashi , Diffley John F. X.
Published: July 2002

The initiation of DNA replication in the budding yeast
Saccharomyces cerevisiae
occurs in two sequential and
mutually exclusive steps. Prereplicative complexes (pre-RCs) containing
origin recognition complex (ORC), Cdc6p, and the MCM2–7 proteins
assemble only under conditions of low cyclin-dependent kinase (Cdk)
activity during G
1
, whereas origin activation is driven by
the increase in Cdk activity at the end of G
1
. As a first
step toward the reconstitution of this two-step process
in
vitro
, we describe a system in which extracts prepared from
G
1
-arrested cells promote sequential assembly of ORC,
Cdc6p, and MCM2–7 proteins onto exogenously added origin-containing
DNA. This reaction requires an intact ARS consensus sequence and
requires ATP for two distinct steps. Extracts from cells arrested in
mitosis also can support the binding of ORC but are unable to load
either Cdc6p or MCM2–7 proteins. This system should be useful for
studying the mechanism and regulation of pre-RC assembly.
Archaeal adaptation to higher temperatures revealed by genomic sequence of
Thermoplasma volcanium
Authors: Kawashima Tsuyoshi , Amano Naoki , Koike Hideaki , Makino Shin-ichi , Higuchi Sadaharu , Kawashima-Ohya Yoshie , Watanabe Koji , Yamazaki Masaaki , Kanehori Keiichi , Kawamoto Takeshi , Nunoshiba Tatsuo , Yamamoto Yoshihiro , Aramaki Hironori , Makino Kozo , Suzuki Masashi
Published: July 2002

The complete genomic sequence of the archaeon
Thermoplasma
volcanium
, possessing optimum growth temperature (OGT) of
60°C, is reported. By systematically comparing this genomic sequence
with the other known genomic sequences of archaea, all possessing
higher OGT, a number of strong correlations have been identified
between characteristics of genomic organization and the OGT. With
increasing OGT, in the genomic DNA, frequency of clustering purines and
pyrimidines into separate dinucleotides rises (e.g., by often forming
AA and TT, whereas avoiding TA and AT). Proteins coded in a genome are
divided into two distinct subpopulations possessing isoelectric points
in different ranges (i.e., acidic and basic), and with increasing OGT
the size of the basic subpopulation becomes larger. At the metabolic
level, genes coding for enzymes mediating pathways for synthesizing
some coenzymes, such as heme, start missing. These findings provide
insights into the design of individual genomic components, as well as
principles for coordinating changes in these designs for the adaptation
to new environments.
Expression of reelin in adult mammalian blood, liver, pituitary pars intermedia, and adrenal chromaffin cells
Authors: Smalheiser Neil R. , Costa Erminio , Guidotti Alessandro , Impagnatiello Francesco , Auta James , Lacor Pascale , Kriho Virginia , Pappas George D.
Published: July 2002

Reelin regulates telencephalic and cerebellar lamination during
mammalian development and is expressed in several structures of the
adult brain; however, only traces of reelin were believed to be in
peripheral tissues. Because reelin structurally resembles extracellular
matrix proteins, and because many of these proteins are expressed in
blood, we hypothesized that reelin also might be detectable in the
circulation. Reelin (420 kDa) and two reelin-like immunoreactive bands
(310 and 160 kDa) are expressed in serum and platelet-poor plasma of
rats, mice, and humans, but these three bands were not detectable in
serum of homozygous
reeler
(
rl
/
rl
) mice. Reelin plasma levels in
heterozygous (
rl
/+) mice were half of those in
wild-type littermates. Western blotting and immunocytochemistry using
antireelin mAbs indicated that reelin-like immunoreactivity was
expressed in a subset of chromaffin cells within the rat adrenal
medulla and in a subset of cells coexpressing
α-melanocyte-stimulating hormone within the pituitary pars
intermedia. However, surgical removal of adrenal or pituitary failed to
decrease the amount of reelin (420-kDa band) expressed in serum. Adult
liver expressed one-third of the reelin mRNA concentration expressed in
adult mouse cerebral cortex. Full-length reelin protein was detectable
in liver extracts
in situ
; acutely isolated liver cells
also secreted full-length reelin
in vitro
. Liver appears
to be a prime candidate to produce and maintain the circulating reelin
pool. It now becomes relevant to ask whether circulating reelin has a
physiologic role on one or more peripheral target tissues.
Mutants of
Arabidopsis thaliana
defective in the acquisition of tolerance to high temperature stress
Authors: Hong Suk-Whan , Vierling Elizabeth
Published: July 2002

The ability of organisms to acquire thermotolerance to normally lethal high temperatures is an ancient and conserved adaptive response. However, knowledge of cellular factors essential to this response is limited. Acquisition of thermotolerance is likely to be of particular importance to plants that experience daily temperature fluctuations and are unable to escape to more favorable environments. We developed a screen, based on hypocotyl elongation, for mutants of
Arabidopsis thaliana
that are unable to acquire thermotolerance to high-temperature stress and have defined four separate genetic loci,
hot1–4
, required for this process.
hot1
was found to have a mutation in the heat shock protein 101 (Hsp101) gene, converting a conserved Glu residue in the second ATP-binding domain to a Lys residue, a mutation that is predicted to compromise Hsp101 ATPase activity. In addition to exhibiting a thermotolerance defect as assayed by hypocotyl elongation, 10-day-old
hot1
seedlings were also unable to acquire thermotolerance, and
hot1
seeds had greatly reduced basal thermotolerance. Complementation of
hot1
plants by transformation with wild-type Hsp101 genomic DNA restored
hot1
plants to the wild-type phenotype. The
hot
mutants are the first mutants defective in thermotolerance that have been isolated in a higher eukaryote, and
hot1
represents the first mutation in an Hsp in any higher plant. The phenotype of
hot1
also provides direct evidence that Hsp101, which is required for thermotolerance in bacteria and yeast, is also essential for thermotolerance in a complex eukaryote.
Wnt/Shh interactions regulate ectodermal boundary formation during mammalian tooth development
Authors: Sarkar Lena , Cobourne Martyn , Naylor Stuart , Smalley Matthew , Dale Trevor , Sharpe Paul T.
Published: July 2002

Interactions between the Wnt (wingless) and hedgehog signaling pathways were first described as playing a role in establishing boundaries between ectodermal cells in
Drosophila
segmentation. During the initiation of mammalian tooth development, boundaries that distinguish oral from dental ectoderm must be formed to correctly position the sites of tooth formation. We describe a reciprocal relationship between the expression of
Wnt-7b
in presumptive oral ectoderm and
Shh
in presumptive dental ectoderm in mouse embryos that mark boundaries between these cells with different developmental fates. By using a murine retrovirus to ectopically express Wnt-7b in presumptive dental ectoderm in mandibular arch explants, we show that
Shh
expression in the ectoderm and
Ptc
expression in the underlying ectomesenchyme are down-regulated, and tooth development is subsequently arrested. This suggests that Wnt-7b acts to repress
Shh
expression in oral ectoderm, thus maintaining the boundaries between oral and dental ectodermal cells. Implantation of beads soaked in Shh protein into Wnt-7b-infected explants resulted in complete rescue of tooth development, confirming that the repressive action of Wnt-7b specifically affects Shh signaling.
How reliable are human phylogenetic hypotheses?
Authors: Collard Mark , Wood Bernard
Published: July 2002

Cladistic analysis of cranial and dental evidence has been widely used to generate phylogenetic hypotheses about humans and their fossil relatives. However, the reliability of these hypotheses has never been subjected to external validation. To rectify this, we applied identical methods to equivalent evidence from two groups of extant higher primates for whom reliable molecular phylogenies are available, the hominoids and papionins. We found that the phylogenetic hypotheses based on the craniodental data were incompatible with the molecular phylogenies for the groups. Given the robustness of the molecular phylogenies, these results indicate that little confidence can be placed in phylogenies generated solely from higher primate craniodental evidence. The corollary of this is that existing phylogenetic hypotheses about human evolution are unlikely to be reliable. Accordingly, new approaches are required to address the problem of hominin phylogeny.
Nodes of Ranvier form in association with ezrin-radixin-moesin (ERM)-positive Schwann cell processes
Authors: Melendez-Vasquez Carmen V. , Rios Jose C. , Zanazzi George , Lambert Stephen , Bretscher Anthony , Salzer James L.
Published: July 2002

In the adult peripheral nerve, microvillous processes of
myelinating Schwann cells project to the nodes of Ranvier; their
composition and physiologic function have not been established. As the
ezrin-radixin-moesin (ERM) proteins are expressed in the microvilli of
many epithelial cells, we have examined the expression and distribution
of these proteins in Schwann cells and neurons
in vitro
and
in vivo
. Cultured Schwann cells express high levels
of all three proteins and the ezrin-binding protein 50, whereas neurons
express much lower, although detectable, levels of radixin and moesin.
Ezrin is specific for Schwann cells. All three ERM proteins are
expressed predominantly at the membrane of cultured Schwann cells,
notably in their microvilli.
In vivo
, the ERM proteins
are concentrated strikingly in the nodal processes of myelinating
Schwann cells. Because these processes are devoid of myelin proteins,
they represent a unique compartment of the myelinating Schwann cell.
During development, the ERM proteins become concentrated at the ends of
Schwann cells before myelin basic protein expression, demonstrating
that Schwann cells are polarized longitudinally at the onset of
myelination. ERM-positive Schwann cell processes overlie and are
associated closely with nascent nodes of Ranvier, identified by
clusters of ankyrin G. Ankyrin accumulation at the node precedes that
of Caspr at the paranodes and therefore does not depend on the presence
of mature paranodal junctions. These results demonstrate that nodes of
Ranvier in the peripheral nervous system form in contact with
specialized processes of myelinating Schwann cells that are highly
enriched in ERM proteins.
Dynamic regulation of the tryptophan operon: A modeling study and comparison with experimental data
Authors: Santillán Moisés , Mackey Michael C.
Published: July 2002

A mathematical model for regulation of the tryptophan operon is
presented. This model takes into account repression, feedback enzyme
inhibition, and transcriptional attenuation. Special attention is given
to model parameter estimation based on experimental data. The model's
system of delay differential equations is numerically solved, and the
results are compared with experimental data on the temporal evolution
of enzyme activity in cultures of
Escherichia coli
after a
nutritional shift (minimal + tryptophan medium to minimal medium).
Good agreement is obtained between the numeric simulations and the
experimental results for wild-type
E. coli
, as well as for
two different mutant strains.
Dynamic modeling of gene expression data
Authors: Holter Neal S. , Maritan Amos , Cieplak Marek , Fedoroff Nina V. , Banavar Jayanth R.
Published: July 2002

We describe the time evolution of gene expression levels by using a
time translational matrix to predict future expression levels of genes
based on their expression levels at some initial time. We deduce the
time translational matrix for previously published DNA microarray gene
expression data sets by modeling them within a linear framework by
using the characteristic modes obtained by singular value
decomposition. The resulting time translation matrix provides a measure
of the relationships among the modes and governs their time evolution.
We show that a truncated matrix linking just a few modes is a good
approximation of the full time translation matrix. This finding
suggests that the number of essential connections among the genes is
small.
The effects of aging on gene expression in the hypothalamus and cortex of mice
Authors: Jiang Cecilia H. , Tsien Joe Z. , Schultz Peter G. , Hu Yinghe
Published: July 2002

A better understanding of the molecular effects of aging in the
brain may help to reveal important aspects of organismal aging, as well
as processes that lead to age-related brain dysfunction. In this study,
we have examined differences in gene expression in the hypothalamus and
cortex of young and aged mice by using high-density oligonucleotide
arrays. A number of key genes involved in neuronal structure and
signaling are differentially expressed in both the aged hypothalamus
and cortex, including synaptotagmin I, cAMP-dependent protein kinase C
β, apolipoprotein E, protein phosphatase 2A, and prostaglandin D.
Misregulation of these proteins may contribute to age-related memory
deficits and neurodegenerative diseases. In addition, many proteases
that play essential roles in regulating neuropeptide metabolism,
amyloid precursor protein processing, and neuronal apoptosis
are up-regulated in the aged brain and likely contribute significantly
to brain aging. Finally, a subset of these genes whose expression is
affected by aging are oppositely affected by exposure of mice to an
enriched environment, suggesting that these genes may play important
roles in learning and memory.
Immigrant Settlement Patterns in Metropolitan Chicago
Authors: Newbold K. Bruce , Spindler John
Published: July 2002

The distribution of the immigrant population reflects a dynamic system that evolves over time and differs by arrival cohort and national origin. Government policies, new information, employment opportunities, housing, racism or other cultural effects may be responsible for subsequent migrations and changes in the population distribution of the foreign-born. Using data from the 5 per cent Public Use Microdata Sample, 1990, this paper compares settlement patterns of immigrant arrival cohorts within metropolitan Chicago, filtered through the lens of Zelinksy and Lee's heterolocalism framework. Cohorts are defined based on period of arrival in the US and by age. The spatial geography associated with each arrival cohort is constructed with respect to areas of relative concentration within the metropolitan area.
Full Circle or Spiralling Out of Control? State Violence and the Control of Urbanisation in Papua New Guinea
Authors: Koczberski Gina , Curry George N. , Connell John
Published: July 2002

There is an administrative reluctance to recognise the permanency of urban settlement in Papua New Guinea. This reluctance, evident since the 1960s, has been characteristic of both the colonial and post-colonial administrations. Opposition to some facets of urbanisation continues today, despite growing population and land pressures in most rural areas and real problems of landlessness emerging in particular rural areas. Colonial control of urban populations has been replicated in contemporary times, often in more draconian form. Eviction of urban settlers has been tied to issues of crime and urban respectability, and lingering perceptions that Melanesians should be rural residents. The growth of informal settlements and urbanisation are not seen as issues of urban planning, nor is the context of urban migration linked to socioeconomic inequality, hence other forms of urban policy are largely absent. Strengthening alliances between land-owners and the state (especially police and provincial administrations) have thus emphasised intraurban inequality and hampered national development.
Berlin: Towards a Global City?
Authors: Kratke Stefan
Published: July 2002

Since 1990, the debate on urban restructuring in the new German capital city Berlin has frequently raised the question of whether Berlin is developing towards a global city type of urban region. Many European metropoles would like to be classified as global cities in order to enhance their reputation in the framework of interurban competition. The vision of Berlin as an upcoming global city had become part of the urban government's programme of innovation and technology development by 1999. This article provides a critical assessment of the global city vision of Berlin. The paper concentrates on two important aspects of the global city's economy: supraregional economic control capacity and the concentration of high-level business services. The findings are based on an empirical analysis of Berlin's interregional capital links and of the urban economy's functional structure, comparing Berlin, Hamburg and Paris. The conclusion is that Berlin hardly has a chance of becoming a 'true' global city in terms of a strategic economic centre with internationally extending control capacities like London and Paris.
A Quantitative Analysis of Investment in New Housing in Greece
Authors: Donatos George
Published: July 2002

This paper analyses empirically investment in housing in Greece using aggregate data for the period 1958-89 and a version of the flexible accelerator model of investment demand. Housing production is undertaken mainly by households aiming at private home ownership and is subject to significant fluctuations which were more pronounced in the 1980s. The estimation of the model shows that traditional determinants of housing demand, such as income and population, influence significantly investment decisions. Moreover, the dynamic specification adopted seems to have traced well the dynamic adjustment of the housing stock. Finance variables, on the other hand, were not found to affect significantly housing investment. Tests of stability indicated that estimated equations are reasonably stable over the sample period.
Health Levels Influenced by Urban Residential Conditions in a Megacity—Tokyo
Authors: Tanaka Atsuko , Takano Takehito , Nakamura Keiko , Takeuchi Sachiko
Published: July 2002

Influences of residential conditions in a megacity on the health levels of residents were investigated. Correlations between mortalities and specified residential-condition indicators in study areas randomly selected from the megacity Tokyo were examined. Indicators representing housing and city planning were significantly correlated with mortalities after adjusting for socio-economic differences between the communities. Urbanisation to a certain level seems to have been associated with good health; however, the most densely developed artificial urban environment seems to be associated with negative health outcomes. Coping skills with regard to health problems are discussed in relation to health levels. A survey elucidated that the coping attitude of the elderly is related with their educational level, family structure, frequency of receiving health information and contact with a family doctor.
The University in the Metropolitan Arena: Impacts and Public Policy Implications
Authors: Felsenstein Daniel
Published: July 2002

This paper estimates some of the impacts associated with a metropolitan university. The impact of the university in the metropolitan arena is conceptualised as a series of backward (expenditure) and forward (knowledge-related) linkages. These relationships can be both positive and negative and can operate in both the short and long terms. Their correct identification requires that the counter-factual situation of the area without the university be adequately specified. On the basis of a case study of the impacts associated with Northwestern University on the Chicago metropolitan area, some of these issues are highlighted. The results emphasise the magnitude of the university expenditure links with the metropolitan economy and the importance of scale when comparing these with more localised negative impacts. The paper concludes with some public policy implications relating to the role of the university as a non-profit organisation competing with local businesses and as an export base sector in the metropolitan economy.
Gendering the Polarisation Debate: A Comment on Hamnett's 'Social Polarisation, Economic Restructuring and Welfare State Regimes'
Authors: Bruegel Irene
Published: July 2002

This note looks at the juxtaposition of a polarising income distribution and a 'professionalising' occupational structure as an account of recent trends in London. It suggests that Hamnett may read too much occupational upgrading from the data and that he does not tackle adequately the question of earned income polarisation. While welfare systems always mediate the relationship between the global and the local, Esping-Anderson's welfare state categorisations do not help to explain differences between New York and London. Gender relations are seen to underpin occupational and income trends in metropolitan areas.
Poverty and Progress? Reflections on Housing and Urban Policies in Developing Countries, 1976-96
Authors: Pugh Cedric
Published: July 2002

The Habitat II conference in June 1996 was more determined by retrospect and prospect than by the discussions during the several days in Istanbul. The policy outcomes were fashioned by reforms and research in the mid 1980s leading to the 'new urban agenda', the Global Strategy for Shelter, and the environmentalism from the Rio de Janeiro Earth Summit in 1992. At Istanbul, much of this was endorsed and converted into 'action plans'. To the extent that 'action plans' are compatible with national political and institutional conditions, they may influence a prospective future. Policy has become much more comprehensive and complex than in the Habitat I forerunner at Vancouver in 1976. The complexities were not fully acknowledged in Istanbul. They range from the inherent political conflicts in policy-based advice and financial support to the uncertainties of markets and macroeconomic events in a liberalised international economy. This paper evaluates widely in retrospect, in prospect and in the circumstances of post-1986 reforms. It is written from the perspectives of political science, economics (both orthodox and heterodox), and the social science of institutions. On-location work in east Asia, south-east Asia, south Asia, east Africa and Mexico have also influenced ways of thinking. Library work was undertaken in India, Kenya, Mexico, Sri Lanka, Singapore, Australia, Britain and in the archives of the Ford Foundation.
Land Tenure Issues in Economic Development
Authors: Dale Peter
Published: July 2002

Land, property and construction are reckoned to account for around 20 per cent of the gross domestic product of many nations. The relationship between people and the land is complex and differs between nations depending on their history, culture and legal system. Many countries, especially those in transition from command to market-driven economies, are re-engineering their cadastral and land registration systems in order to provide cheaper, faster and more secure ways of transacting land. This paper focuses on the importance of land tenure arrangements and the need to manage information about land and property in support of land markets and sustainable development.
Ten Years of the Urban Programme 1981-91: The Impact and Implications of its Assistance to Small Businesses
Authors: Baldock Robert Owen
Published: July 2002

This paper presents the findings of a comparative study of small business land and premises support schemes operating under the Urban Program me (UP) in the London boroughs of Wandsworth and Haringey. The results of this study are used to evaluate whether politics makes a difference to policy outcomes in local areas. The article indicates that there are crucial differences in the policies of the two boroughs studied and that several key elements of the two boroughs' different approaches to small business support were particularly successful, such as low business rates and the targeting of niche market businesses. However, both boroughs failed to integrate effectively their UP policies within a wider economic development strategy. Given that the type of small business support policies examined here continue to form an important part of contemporary local economic policy, the author argues that these findings offer important lessons. It is recommended that this issue of co-ordination must be addressed by all bodies administering local economic support policies in the future.
Residential Desegregation in Two South African Cities: A Comparative Study of Bloemfontein and Pietersburg
Authors: Kotze N.J. , Donaldson S.E.
Published: July 2002

The abolition of the Group Areas Act in 1991 has, in the space of five years, contributed to major changes in the former apartheid cities of South Africa. However, the socio-political transformation that has taken place has been experienced differently-as can be seen, for example, in Bloemfontein and Pietersburg, the capitals of the Free State and the Northern Province respectively. Historic factors, locations and the new-found status of the two cities have influenced the desegregation process that has occurred. The spatial lay-out of Bloemfontein, a city with its own black township, differs sharply from that of Pietersburg, a city without a township during the apartheid era. This paper assesses desegregation in these two provincial capitals in post-apartheid South Africa and investigates residential desegregation patterns, grass-roots political changes (the outcomes of the local elections held in November 1994), and property values as a further indication of the differences that exist between these two cities.
Tenant-Landlord Relations, the Anti-apartheid Struggle and Physical Decline in Hillbrow, an Inner-city Neighbourhood in Johannesburg
Authors: Morris Alan
Published: July 2002

This paper examines the role of tenant-landlord relations in the physical decline of apartment blocks in an inner-city neighbourhood in Johannesburg that had undergone a racial transition during the height of the anti- apartheid struggle. It is argued that apartment blocks owned in their entirety by small landlords were most likely to be characterised by inadequate maintenance, decline and tenant resistance. Tenant resistance, however, rather than stabilising apartment blocks, often had the effect of intensifying the spiral of decline in the apartment blocks affected. The strategies adopted by tenants to resist landlords perceived as exploitative were influenced by the anti-apartheid struggle during the period.
The Inner-city Apartment versus the Suburb: Housing Sub-markets in a New Zealand City
Authors: Morrison Philip S. , McMurray Scott
Published: July 2002

This paper addresses a new phenomenon in New Zealand—the growing demand for residence within the central business district. The construction of inner-city apartments has seen a ready response by local authorities keen to rejuvenate a demand for downtown services, by developers facing a slow-down in suburban growth and by absentee owners as well as owner-occupiers seeking to broaden their residential portfolios. The paper argues that, although we are witness to the emergence of a new and different housing sub-market, the inner-city apartment is in fact a natural extension of an existing demand for residence close to the city; its recent appearance as inner-city apartments is simply a reflection of the competition for inner-city land rather than the revealed preference of buyers for a wholly different type of housing. Far from turning their back on the single-dwelling unit, most apartment buyers seek dwelling attributes similar to those of their single-unit, suburban counterparts. What is unique to this new sub-market therefore is its location. The inner-city apartment is primarily a geographical reaction to the marked physical separation of residence, paid work and live entertainment which characterises the suburb rather than a switch of preference for a wholly new residential form. Although these are quite distinct housing forms, there remain strong market connections between the inner-city apartment and detached, single-unit dwellings in the suburbs. Fashionable though these new apartment units are, New Zealand housing continues to be dominated by low-density, suburban, single-unit dwellings.
The Development of Inductive Reasoning: Cross-sectional Assessments in an Educational Context
Authors: Csapó Beno
Published: July 2002

This paper links two research paradigms, one that studies attributes and mechanisms of inductive reasoning and one that tries to make school learning more meaningful and knowledge better understood and more easily applied, by examining how inductive reasoning develops during a significant age range of schooling and how it relates to certain other cognitive functions. Six tests of inductive reasoning (number analogies, verbal analogies, number series, verbal series, coding, exclusion) were devised and administered to 3rd, 5th, 7th, 9th, and 11th grade students ( N 2000). Data were also collected on students’ school achievement, and a test of applied science knowledge was administered to the two oldest samples. The comparison of age groups indicated that the fastest development of inductive reasoning took place between the 5th and 9th grades; a major development was detected before the 5th grade, and only modest changes were found after the 9th grade. Regression analysis models indicated that inductive reasoning accounted for around twice as large a proportion of the results of the test that measured the applied science knowledge in everyday situations as did school knowledge (represented by school grades).
Northern Ireland: the Development Context
Authors: Gaffikin Frank , McEldowney Malachy , Morrissey Mike , Sterrett Ken
Published: July 2002

This article provides a con textual framework for the new agenda for development, represented in the economic strategy known as Strategy 2010, and the regional spatial plan known as Shaping Our Future. These are considered in the following two articles. This article begins by setting a perspective on the political economy of Northern Ireland an d follows with an outline of the spatial planning process. In conclusion, it raises the key challenges facing attempts to renew the region.
Somatostatin in inflammatory bowel disease
Authors: Van Bergeijk J. D. , Wilson J. H. P.
Published: July 2002

Intestinal inflammation is controlled by various immunomodulating cells, interacting by molecular mediators. Neuropeptides, released by enteric nerve cells and neuroendocrine mucosa cells, are able to affect several aspects of the general and intestinal immune system, with both pro‐ as well as anti‐inflammatory activities. In inflammatory bowel disease (IBD) there is both morphological as well as experimental evidence for involvement of neuropeptides in the pathogenesis. Somatostatin is the main inhibitory peptide in inflammatory processes, and its possible role in IBD is discussed.
Toxicity Studies of Microbial Insecticide Bacillus thuringiensis var. kenyae in Rats, Rabbits, and Fish
Authors: Meher S. M. , Bodhankar S. L. , Kumar Arun , Dhuley J. N. , Khodape D. J. , Naik S. R.
Published: July 2002

Bacillus thuringiensis var. kenyae (B.t.k.) is a microbial insecticide effective against lepidopteran pest species. Acute oral toxicity in rats and acute dermal toxicity, ocular irritation, skin irritation in rabbits were studied for the wettable powder formulation of B.t.k. In addition, toxicity of the wettable powder formulation was also studied in fresh water fish ( Gambussia affinis). The results of these studies indicate that this wettable powder formulation of B.t.k. is nontoxic and nonirritant to rats, rabbits, and fish.
The Intergroup Rhabdomyosarcoma Study Group (IRSG): Major Lessons From the IRS‐I Through IRS‐IV Studies as Background for the Current IRS‐V Treatment Protocols
Authors: Raney R. Beverly , Maurer Harold M. , Anderson James R. , Andrassy Richard J. , Donaldson Sarah S. , Qualman Stephen J. , Wharam Moody D. , Wiener Eugene S. , Crist William M.
Published: July 2002

Purpose. To enumerate lessons from studying 4292 patients with rhabdomyosarcoma (RMS) in the Intergroup Rhabdomyosarcoma Study Group (IRSG, 1972–1997).

Patients. Untreated patients < 21 years of age at diagnosis received systemic chemotherapy, with or without irradiation (XRT) and/or surgical removal of the tumor.

Methods. Pathologic materials and treatment were reviewed to ascertain compliance and to confirm response and relapse status.

Results. Survival at 5 years increased from 55 to 71% over the period. Important lessons include the fact that extent of disease at diagnosis affects prognosis. Re‐excising an incompletely removed tumor is worthwhile if acceptable form and function can
be preserved. The eye, vagina, and bladder can usually be saved. XRT is not necessary for children with localized, completely excised embryonal RMS. Hyperfractionated XRT has thus far not produced superior local control rates compared with conventional, once‐daily XRT. Patients with non‐metastatic cranial parameningeal sarcoma can usually be cured with localized
XRT and systemic chemotherapy, without whole‐brain XRT and intrathecal drugs. Adding doxorubicin, cisplatin, etoposide, and ifosfamide has not significantly improved survival of patients with gross residual or metastatic disease beyond that achieved with VAC (vincristine, actinomycin D, cyclophosphamide) and XRT. Most patients with alveolar RMS have a
tumor‐specific translocation. Mature rhabdomyoblasts after treatment of patients with bladder rhabdomyosarcoma are not necessarily malignant, provided that the tumor has shrunk and malignant cells have disappeared.

Discussion. Current IRSG‐V protocols, summarized herein, incorporate recommendations for risk‐based management. Two new agents, topotecan and irinotecan, are under investigation for patients who have an intermediate or high risk of recurrence.
Demographic and epidemiological analysis of patients referred to speech and language therapy at eleven centres 1987‐95
Authors: Petheram Brian , Enderby Pam
Published: July 2002

This retrospective study analyses data collected on an information system developed specifically for the use of speech and language therapists and the management of their services. The age, gender, medical diagnoses, and speech and language therapy diagnoses associated with the referral of >73 000 clients to 11 speech and language therapy providers between 1987 and 1995 are reviewed. In 1987, 34.8% of the patients referred to speech and language therapy did not have a formal medical diagnosis and this was commonly associated with children with speech and language delay or disorders. However, by 1995, the group not having a formal medical diagnosis had fallen to 17.2% of referrals. Whereas in 1987, 22.7% of the referrals with a medical diagnosis to speech and language therapy were associated with stroke, this has increased in 1995 to 32.0%. Dysphagia represented 0.94% of the referrals in 1987 but 20.6% of referrals in 1995. The gender balance of referrals has remained remarkably constant over the period of study: 60% of referrals were male and 40% female. Whilst nearly half of all referrals were aged under 5 years, the proportion of all referrals represented by this age group has fallen slightly over these years. This has been matched by an increase in the proportion of the caseload aged over 70.
Antagonistic Effects of Hydrogen Peroxide and Glutathione on Acclimation to Excess Excitation Energy in Arabidopsis
Authors: Karpinska Barbara , Wingsle Gunnar , Karpinski Stanislaw
Published: July 2002

The redox status of the quinone B (QB) and plastoquinone (PQ) pools plays a key role in the cellular and systemic signalling processes that control acclimatory responses in plants. In this study, we demonstrate the effects of hydrogen peroxide and glutathione on acclimatory responses controlled by redox events in the proximity of the QB‐PQ pools. Our results suggest that the chloroplast is a sink for H2O2 and that, paradoxically, high concentrations of H2O2 in the chloroplast protect the photosynthetic apparatus and the plant cell from photoinhibition and photooxidative damage. Excess glutathione, however, caused an effect antagonistic to that observed for high H2O2. An explanation of this apparent paradox and a hypothetical redox‐signalling model are suggested.