bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic lumped‐parameter models for foundations based on polynomial‐fraction approximation
Authors: Wu Wen‐Hwa , Lee Wen‐How
Published: October 2002

Based on the approximation by polynomial‐fraction, a series of systematic lumped‐parameter models are developed in this paper for efficiently representing the dynamic behaviour of unbounded soil. Concise formulation is first employed to represent the dynamic flexibility function of foundation with a ratio of two polynomials. By defining an appropriate quadratic error function, the optimal coefficients of the polynomials can be directly solved from a system of linear equations. Through performing partial‐fraction expansion on this polynomial‐fraction and designing two basic discrete‐element models corresponding to the partial fractions, systematic lumped‐parameter models can be conveniently established by connecting these basic units in series. Since the systematic lumped‐parameter models are configured without introducing any mass, the foundation input motion can be directly applied to these models for their applications to the analysis of seismic excitation. The effectiveness of these new models is strictly validated by successfully simulating a semi‐infinite bar on an elastic foundation. Subsequently, these models are applied for representing the dynamic stiffness functions for different types of foundation. Comparison of the new models with the other existing lumped‐parameter models is also made to illustrate their advantages in requiring fewer parameters and featuring a more systematic expansion. Copyright © 2002 John Wiley & Sons, Ltd.
Syntheses and odour descriptions of cyclopropanated compounds 2.1 Analogues of methyl jasmonate
Authors: Kiyota Hiromasa , Koike Takanori , Higashi Emi , Oritani Takayuki
Published: October 2002

Analogues of methyl jasmonate bearing a cyclopropane ring were synthesized and their odour characteristics were examined. Cyclopropanation of the pentenyl side chains not only increased the odour intensity, but also gave a mossy mushroom characteristic when compared with the original odour. Modification of the cyclopentanone to fix the cis ring geometry reduced both the quality and intensity of the original odour. Copyright © 2002 John Wiley & Sons, Ltd.
Approximation for convenience yield in commodity futures pricing
Authors: Heaney Richard
Published: October 2002

The pricing of commodity futures contracts is important both for professionals and academics. It is often

argued that futures prices include a convenience yield, and this article uses a simple trading strategy to

approximate the impact of convenience yields. The approximation requires only three variables—underlying

asset price volatility, futures contract price volatility, and the futures contract time to maturity. The

approximation is tested using spot and futures prices from the London Metals Exchange contracts for copper,

lead, and zinc with quarterly observations drawn from a 25‐year period from 1975 to 2000. Matching

Euro‐Market interest rates are used to estimate the risk‐free rate. The convenience yield

approximation is both statistically and economically important in explaining variation between the futures price

and the spot price after adjustment for interest rates. © 2002 Wiley Periodicals, Inc. Jrl Fut Mark

22:1005–1017, 2002
The chromosome translocation t(7;11)(p15;p15) in acute myeloid leukemia results in fusion of the NUP98 gene with a HOXA cluster gene, HOXA13, but not HOXA9
Authors: Taketani Takeshi , Taki Tomohiko , Ono Ryoichi , Kobayashi Yukio , Ida Kohmei , Hayashi Yasuhide
Published: October 2002

The nucleoporin gene NUP98 has been reported to be fused to 9 partner genes in hematologic malignancies with 11p15 translocations. The NUP98‐HOXA9 fusion gene has been identified in acute myeloid leukemia (AML) and chronic myelogenous leukemia with t(7;11)(p15;p15). We report here a novel NUP98 partner gene, HOXA13, in a patient with de novo AML having t(7;11)(p15;p15). The HOXA13 gene is part of the HOXA cluster genes and contains 2 exons, encoding a protein of 338 amino acids with a homeodomain. The NUP98‐HOXA13 fusion protein consists of the N‐terminal phenylalanine‐glycine repeat motif of NUP98 and the C‐terminal homeodomain of HOXA13, similar to the NUP98‐HOXA9 fusion protein. Reverse transcriptase–polymerase chain reaction (RT‐PCR) analysis in various leukemic cell lines showed that the HOXA13 gene was expressed significantly more frequently in acute monocytic leukemic cell lines than in other leukemic cell lines (P = 0.039). HOXA13 and three HOXA cluster genes (A9, A10, A11) located at the 5′ end of the HOXA9 gene were frequently expressed in myeloid leukemic cell lines. Our results revealed that t(7;11)(p15;p15) was not a single chromosomal abnormality at the molecular level. The protein encoded by the NUP98‐HOXA13 fusion gene is similar to that encoded by NUP98‐HOXA9, and the expression pattern of the HOXA13 gene in leukemic cell lines is similar to that of the HOXA9 gene, suggesting that the NUP98‐HOXA13 fusion protein may play a role in leukemogenesis through a mechanism similar to that of the NUP98‐HOXA9 fusion protein. © 2002 Wiley‐Liss, Inc.
A 10‐Mb paracentric inversion of chromosome arm 2p inactivates MSH2 and is responsible for hereditary nonpolyposis colorectal cancer in a North‐American kindred
Authors: Wagner Anja , van der Klift Heleen , Franken Patrick , Wijnen Juul , Breukel Cor , Bezrookove Vladimir , Smits Ron , Kinarsky Yulia , Barrows Alicia , Franklin Barbara , Lynch Jane , Lynch Henry , Fodde Riccardo
Published: October 2002

Genomic deletions of the MSH2 gene are a frequent cause of hereditary nonpolyposis colorectal cancer (HNPCC), a common hereditary predisposition to the development of tumors in several organs including the gastrointestinal and urinary tracts and endometrium. The mutation spectrum at the MSH2 gene is extremely heterogeneous because it includes nonsense and missense point mutations, small insertions and deletions leading to frameshifts, and larger genomic deletions, the latter representing approximately 25% of the total mutation burden. Here, we report the identification and molecular characterization of the first paracentric inversion of the MSH2 locus known to cause HNPCC. Southern blot analysis and inverse PCR showed that the centromeric and telomeric breakpoints of the paracentric inversion map within intron 7 and to a contig 10 Mb 3′ of MSH2, respectively. Pathogenicity of the paracentric inversion was demonstrated by conversion analysis. The patient's lymphocytes were employed to generate somatic cell hybrids to analyze the expression of the inverted MSH2 allele in an Msh2‐deficient rodent cellular background. The inversion was shown to abolish MSH2 expression by both northern and western analysis. This study confirms that Southern blot analysis still represents a useful and informative tool to screen for and identify complex genomic rearrangements in HNPCC. Moreover, monoallelic expression analysis represents an attractive approach to demonstrate pathogenicity of unusual mutations in autosomal dominant hereditary conditions. © 2002 Wiley‐Liss, Inc.
Chromosomal aberrations in prostate cancer xenografts detected by comparative genomic hybridization
Authors: Laitinen Sari , Karhu Ritva , Sawyers Charles L. , Vessella Robert L. , Visakorpi Tapio
Published: October 2002

A major problem in studying prostate cancer has been the lack of model systems because of the difficulties in growing prostate cancer cells in vitro. Recently, however, several human prostate cancer xenografts, grown in immune‐deficient mice, have been established. Here, we characterized 13 such xenografts (LuCaP 23.8, 23.12, 35, 41, 49, 58, 69, 70, 73, LAPC‐4AD, LAPC‐4AI, LAPC‐9AD, and LAPC‐9AI) as well as one prostate cancer cell line (22Rv1) derived from a xenograft for chromosomal alterations by comparative genomic hybridization and a modification of multicolor fluorescence in situ hybridization. On average, the xenografts contained 13 (range 5–28) aberrations, 5 (1–13) gains, and 8 (1–15) losses, per case. The chromosome arms that most often contained losses were 2q, 5q, 6q, 8p, 13q, and 18q, and gains were 7q, 8q, and Xq. The same regions were previously shown to be often altered in advanced prostate carcinomas in patients. The androgen‐dependent and corresponding androgen‐independent sublines of LAPC‐4 and LAPC‐9 shared all genetic alterations, suggesting that the transition of the growth from androgen dependency to independence does not involve major chromosomal aberrations in these two models. In conclusion, the identified genetic aberrations lay the groundwork for further detailed genetic analyses of these xenografts. © 2002 Wiley‐Liss, Inc.
Densely methylated MLH1 promoter correlates with decreased mRNA expression in sporadic colorectal cancers
Authors: Furukawa Taiji , Konishi Fumio , Masubuchi Shigehiko , Shitoh Kazuhisa , Nagai Hideo , Tsukamoto Toshihiko
Published: October 2002

It has been reported that MLH1 is silenced by promoter methylation, and that this phenomenon is associated with microsatellite instability (MSI) in sporadic colorectal cancer (CRC). To clarify the significance of MLH1 promoter methylation in sporadic CRC, we examined the correlation between methylation status over the entire promoter region and mRNA expression in cases showing high‐frequency MSI (MSI‐H). MLH1 promoter methylation was analyzed using the bisulfite modification sequencing in 48 MSI‐H cases. We also screened for somatic mutation, loss of heterozygosity, and immunohistochemical staining of MLH1. The results showed that methylation patterns could be subdivided into three types: methylation of more than 80% of the CpG sites analyzed (type 1 methylation), methylation of less than 20% (type 2 methylation), and methylation mainly in the region 500 to 921 bases upstream from the translation start site (type 3 methylation). Of the three types, only type 1 methylation correlated with decreased mRNA expression. The frequency of type 1 methylation was significantly higher in cases involving the proximal colon (66.7%, 18/27) compared to that of the distal colon and rectum (23.8%, 5/21, P = 0.004). Immunohistochemical staining of MSI‐H cases showed that decreased MLH1 was found in 77.1% (37/48). Of the cases with decreased MLH1, type 1 methylation was present in 59.5% (22/37). Overall, our data suggested that the type 1 methylation pattern may affect MLH1 mRNA expression, such that the majority of MSI‐H cases in sporadic CRC, especially proximal colon cancer, exhibited type 1 methylation. © 2002 Wiley‐Liss, Inc.
Novel Sxra ES cell line offers hope for Y chromosome gene‐targeted mice
Authors: Simpson Elizabeth M. , Johnson Kevin A. , Shirley Bobbi‐Jo , Fang Ge Y. , Bayleran Janet K. , Lerner Charles P.
Published: October 2002

Summary: A mouse targeted for a Y Chromosome gene has not been reported. Because the Y Chromosome is present in only one copy, and most of its genes are critical for germ cell development, such a mouse would likely be infertile. Thus, we describe a new reproductive strategy to enable transmission of targeted Y Chromosome genes to subsequent generations. The strategy uses two segregating copies of Y Chromosome genes to mimic the autosomal condition. To achieve this, we developed a new embryonic stem cell line from the XYSxra mouse, which carries a duplication of the gene‐rich Y Chromosome short arm. Importantly, we demonstrate germ line transmission of the YSxra chromosome and describe this significant new tool as a practical solution to enable reproduction in mice targeted for Y Chromosome genes. genesis 33:62–66, 2002. © 2002 Wiley‐Liss, Inc.
Mouse model of split hand/foot malformation type I
Authors: Merlo Giorgio R. , Paleari Laura , Mantero Stefano , Genova Francesca , Beverdam Annemiek , Palmisano Giulio L. , Barbieri Ottavia , Levi Giovanni
Published: October 2002

Split hand/foot malformation type I (SHFM1) disease locus maps to chromosome 7q21.3‐q22, a region that includes the distal‐less‐related (dll) genes DLX5 and DLX6. However, incomplete penetrance, variable expressivity, segregation distortion, and syndromic association with other anomalies have so far prevented the identification of the SHFM1 gene(s) in man. Here we show that the targeted double inactivation of Dlx5 and Dlx6 in the mouse causes in homozygous mutant animals bilateral ectrodactyly with a severe defect of the central ray of the hindlimbs, a malformation typical of SHFM1. This is the first evidence that the role of dll/Dlx genes in appendage development is conserved from insects to mammals and proves their involvement in SHFM1. genesis 33:97–101, 2002. © 2002 Wiley‐Liss, Inc.
Temporal Cre‐mediated recombination exclusively in endothelial cells using Tie2 regulatory elements
Authors: Forde Anne , Constien Rainer , Gröne Hermann‐Josef , Hämmerling Günter , Arnold Bernd
Published: October 2002

Summary: The versatility of the bacteriophage Cre/LoxP system is dependent on the availability of a spectrum of tissue‐specific Cre transgenic mice to address a host of biological questions. In this paper, we report on the generation of an inducible Tie2Cre transgenic mouse line that facilitates gene targeting exclusively in endothelial cells. The temporal manner of recombination is feasible through the use of a Cre‐estrogen receptor fusion protein ERT2 and was, in practical terms, achieved by feeding the animals the estrogen antagonist tamoxifen orally for 5 weeks. High efficiency of recombination was found in the vast majority of endothelial cell populations examined, as monitored by an EGFP reporter mouse line. Critically, no EGFP expression was observed in any uninduced mice. This inducible Cre line will be a very beneficial asset to investigating the role of endothelial specific genes in the adult mouse and to induce transgenes in the endothelium in an extremely efficient manner. genesis 33:191–197, 2002. © 2002 Wiley‐Liss, Inc.
Predictors of institutionalization in patients with dementia in Korea
Authors: Kim Jae‐Min , Shin Il‐Seon , Jeong Seong‐Joo , Gormley Niall , Yoon Jin‐Sang
Published: October 2002

Background

Many studies have sought to determine the predictors of institutionalization of patients with dementia. Such studies, performed in developed western societies, have come to various conclusions which may not be supported in an East Asian culture such as that found in Korea.

Objectives

This study aimed to determine the factors that predict institutionalization of patients in Korea diagnosed with dementia.

Methods

Seventy‐nine cases (37 institutionalized, 42 community‐dwelling) in the Kwangju area were evaluated for patient characteristics, severity of dementia symptoms, caregiver characteristics, burden and distress. Logistic regression was performed to determine predictors of actual institutionalization.

Results

Six predictors of institutionalization were identified. Of these, three were patient‐related factors: higher score on the Clinical Dementia Rating, higher score on the Brief Psychiatric Rating Scale, and shorter duration of dementia. The other three were caregiver‐related factors: younger age, higher education (formal schooling), and higher cost of home care.

Conclusions

As seen in previous western studies, institutionalization of dementia sufferers was influenced by both patient and caregiver factors. But, the specific predictors and their relative influences might be explained best by the particular social, cultural and economic situation in Korea. This study was the first of its kind in Korea and, as such, could serve as a reference for future intra‐cultural and cross‐cultural comparisons. Copyright © 2002 John Wiley & Sons, Ltd.
Can psychiatric liaison reduce neuroleptic use and reduce health service utilization for dementia patients residing in care facilities
Authors: Ballard Clive , Powell Ian , James Ian , Reichelt Katharina , Myint Pat , Potkins Dawn , Bannister Carol , Lana Marisa , Howard Robert , O'Brien John , Swann Alan , Robinson Damian , Shrimanker Jay , Barber Robert
Published: October 2002

Background

The quality of care and overuse of neuroleptic medication in care environments are major issues in the care of elderly people with dementia.

Method

The quality of care (Dementia Care Mapping), the severity of Behavioural and Psychological Symptoms (BPSD—Neuropsychiatric Inventory), expressive language skills (Sheffield Acquired Language Disorder scale), service utilization and use of neuroleptic drugs was compared over 9 months between six care facilities receiving a psychiatric liaison service and three facilities receiving the usual clinical support, using a single blind design.

Results

There was a significant reduction in neuroleptic usage in the facilities receiving the liaison service (McNemar test p < 0.0001), but not amongst those receiving standard clinical support (McNemar test p = 0.07). There were also significantly less GP contacts (t = 3.9 p = 0.0001) for residents in the facilities receiving the liaison service, and a three fold reduction in psychiatric in‐patient bed usage (Bed days per person 0.6 vs. 1.5). Residents in care facilities receiving the liaison service experienced significantly less deterioration in expressive language skills (t = 2.2 p = 0.03), but there were no significant differences in BPSD or wellbeing.

Conclusion

A resource efficient psychiatric liaison service can reduce neuroleptic drug use and reduce some aspects of health service utilization; but a more extensive intervention is probably required to improve the overall quality of care. Copyright © 2002 John Wiley & Sons, Ltd.
Hyponatraemia in elderly psychiatric patients treated with Selective Serotonin Reuptake Inhibitors and venlafaxine: a retrospective controlled study in an inpatient unit
Authors: Kirby Dianne , Harrigan Susan , Ames David
Published: October 2002

Objective

To determine the prevalence of hyponatraemia associated with selective serotonin reuptake inhibitor (SSRI) and venlafaxine use in elderly patients compared to that in elderly patients not prescribed these drugs, while controlling for age, sex, depression status and illnesses or prescribed medications also associated with hyponatraemia.

Design and setting

Retrospective controlled analysis in a 36‐bed inpatient unit for elderly psychiatric patients in Melbourne.

Patients

Inpatients (199) with a mean age of 74.2 years of whom 74 were prescribed an SSRI or venlafaxine.

Results

Patients on SSRIs or venlafaxine were 5.6 times as likely as patients not so treated to have hyponatraemia. Thirty‐nine percent of patients on an SSRI or venlafaxine had hyponatraemia compared with 10% of controls. Ten of the 14 patients on venlafaxine were hyponatraemic. Controlling for thiazide status did not reduce the odds of these patients having hyponatraemia and taking an SSRI or venlafaxine was still strongly associated with hyponatraemia after also controlling for age, sex, and depression status, consumption of other drugs potentially causative of hyponatraemia and medical illness severity (Odds Ratio (OR) 3.5, p = 0.008).

Conclusions

SSRI and venlafaxine use is strongly associated with the presence of hyponatraemia in a population of elderly psychiatric inpatients and the association is not due to confounding by age, sex, depression status, medical illness severity or consumption of other drugs. Elderly patients on SSRIs or venlfaxine should have sodium levels checked before and after commencement of antidepressant treatment. Copyright © 2002 John Wiley & Sons, Ltd.
Development and inter‐rater reliability of a standardized verbal instruction manual for the Chinese Geriatric Depression Scale—short form
Authors: Wong M. T. P. , Ho T. P. , Ho M. Y. , Yu C. S. , Wong Y. H. , Lee S. Y.
Published: October 2002

The Geriatric Depression Scale (GDS) is a common screening tool for elderly depression in Hong Kong. This study aimed at (1) developing a standardized manual for the verbal administration and scoring of the GDS‐SF, and (2) comparing the inter‐rater reliability between the standardized and non‐standardized verbal administration of GDS‐SF. Two studies were reported. In Study 1, the process of developing the manual was described. In Study 2, we compared the inter‐rater reliabilities of GDS‐SF scores using the standardized verbal instructions and the traditional non‐standardized administration. Results of Study 2 indicated that the standardized procedure in verbal administration and scoring improved the inter‐rater reliabilities of GDS‐SF. Copyright © 2002 John Wiley & Sons, Ltd.
Functional anatomy of syntactic and semantic processing in language comprehension
Authors: Luke Kang‐Kwong , Liu Ho‐Ling , Wai Yo‐Yo , Wan Yung‐Liang , Tan Li Hai
Published: October 2002

A functional magnetic resonance imaging (fMRI) study was conducted to map syntactic and semantic processes onto the brain. Chinese‐English bilingual subjects performed two experimental tasks: a syntactic plausibility judgment task in which they decided whether a viewed verb phrase was syntactically legal, and a semantic plausibility judgment task in which they decided whether a viewed phrase was semantically acceptable. A font size judgment task was used as baseline. It is found that a large‐scale distributed neural network covering the left mid‐inferior frontal and mid‐superior temporal cortices was responsible for the processing of Chinese phrases. The right homologue areas of these left cortical sites were also active, although the brain activity was obviously left‐lateralized. Unlike previous research with monolingual English speakers that showed that distinct brain regions mediate syntactic and semantic processing of English, the cortical sites contributing to syntactic analysis of Chinese phrases coincided with the cortical sites relevant to semantic analysis. Stronger brain activity, however, was seen in the left middle frontal cortex for syntactic processing (relative to semantic processing), whereas for semantic processing stronger cortical activations were shown in the left inferior prefrontal cortex and the left mid‐superior temporal gyri. The overall pattern of results indicates that syntactic processing is less independent in reading Chinese. This is attributable to the linguistic nature of the Chinese language that semantics and syntax are not always clearly demarcated. Equally interesting, we discovered that when our bilingual subjects performed syntactic and semantic acceptability judgments of English phrases, they applied the cerebral systems underlying Chinese reading to the processing of English. Hum. Brain Mapping 16:133–145, 2002. © 2002 Wiley‐Liss, Inc.
Odorant differentiated pattern of cerebral activation: Comparison of acetone and vanillin
Authors: Savic Ivanka , Gulyás Balázs , Berglund Hans
Published: October 2002

Whether different odorous compounds (odorants) are processed by different cerebral circuits is presently unknown. A first step to address this complicated issue is to investigate how the cerebral regions mediating signals from olfactory (i.e., unimodal) odorants, differ from those mediating the olfactory + trigeminal (i.e., bimodal) odorants. [15O]‐H2O‐PET scans were conducted in 12 healthy females during three separate conditions: birhinal, passive smelling of: 1) the unimodal odorant vanillin; 2) the bimodal odorant acetone; and 3) odorless air. Significant activations were calculated contrasting vanillin to air, acetone to air, and deactivations, running these contrasts in the opposite direction. Smelling of vanillin activated bilaterally the amygdala and piriform cortex. These regions were only engaged slightly by acetone. Instead, strong activations were found in the anterior and central insula and claustrum, the posterior portion of anterior cingulate, the somatosensory cortex (SI for face), cerebellum, ventral medial (VMPo) and dorsal medial (MDvc) thalamus, the lateral hypothalamus, and pons/medulla. In parallel, the somatosensory (SI, below central representation of face), secondary visual and auditory cortices, as well as the supplementary motor area and the parahippocampal gyri were deactivated. No deactivations were observed with vanillin, although the odor components of acetone and vanillin were rated similarly intense (75 ± 17 mm vs. 61 ± 22 mm, NS). The differentiated pattern of cerebral activation during odorant perception seems to be dependent on the signal transducing cranial nerves involved. In contrast to vanillin, which solely activates the olfactory cortex, acetone engages predominantly trigeminal projections from the nasal mucosa. Acetone's limited activation of the olfactory cortex may result from a cross‐modal interaction, with inhibition of acetone's odor component by its trigeminal component. Hum. Brain Mapping 17:17–27, 2002. © 2002 Wiley‐Liss, Inc.
Applications of chiral sulfoxides in enantioselective synthesis of diols and total synthesis of natural products
Authors: Solladie Guy
Published: October 2002

The sulfoxide mediated enantioselective reduction of carbonyl compounds was extended to the synthesis of enantiomerically pure syn and anti diols, including C2 symmetric diols. Several applications related to the syntheses of natural products are described. Finally, this sulfoxide mediated enantioselective synthesis was extended to the transformation of ethyl oxalate or other oxalic acid derivatives to enantiomerically pure syn and anti 1,2‐diols. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:443–452, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10079
Desmoplastic melanoma of the lip
Authors: Hessel Amy C. , Byers Robert M.
Published: October 2002

Background

This retrospective study looks at the prognosis of desmoplastic melanoma of the lip, correlating it with the clinical course, treatment, and patterns of failure.

Method

Twenty‐two patients with desmoplastic melanoma of the lip were seen at the University of Texas M. D. Anderson Cancer Center from 1965 to 1998.

Results

Three disease groups: (I) untreated tumor (3 patients), (II) excisional scar (10 patients), and (III) locoregional recurrence (9 patients). Group I had two cures and one failure. In group II six had no recurrences, and there were four failures. In group III, all patients failed. Ten patients (45%) had no evidence of disease, of which three (30%) had an initial misdiagnosis. Twelve patients (55%) died of disease or were living with disease, of which eight (67%) had an initial misdiagnosis.

Conclusions

Desmoplastic melanoma of the lip is often misdiagnosed and, therefore, inappropriately treated with multiple recurrences and poor prognosis. Accurate diagnosis and combined treatment may improve local control and survival. © 2002 Wiley Periodicals, Inc. Head Neck 24: 605–608, 2002
Expression of glutathione s‐transferase π in benign mucosa, Barrett's metaplasia, and adenocarcinoma of the esophagus
Authors: Chandra Rakesh K. , Bentz Brandon G. , Haines G. Kenneth , Robinson Alan M. , Radosevich James A.
Published: October 2002

Background

Glutathione s‐transferase π (GSTπ) is an enzyme that provides cellular protection against redox‐mediated damage by free radicals, which have been implicated in carcinogenesis.

Methods

Forty‐three consecutive specimens from 19 patients were reviewed to identify samples of squamous mucosa, Barrett's metaplasia, adenocarcinoma, and peritumoral inflammation. Serial sections were stained with an anti‐GSTπ polyclonal antibody, and GSTπ expression was quantified for each histologic group.

Results

GSTπ expression was diminished in peritumoral mononuclear inflammatory cells (p < .001) compared with squamous epithelium, Barrett's metaplasia, or adenocarcinoma. Barrett's metaplasia exhibited decreased GSTπ expression compared with squamous mucosa (p = .045). GSTπ expression by >50% of adenocarcinoma cells was associated with an increased risk (2.25×) of disease at last follow‐up.

Conclusions

GSTπ is prominently expressed in esophageal squamous mucosa and adenocarcinoma. Mononuclear cells may be susceptible to oxidative damage secondary to weak GSTπ production. GSTπ may protect the tumor cells themselves from the cytotoxic effects of free radicals. The biochemical role of GSTπ expression in malignant transformation deserves further investigation. © 2002 Wiley Periodicals, Inc. Head Neck 24: 575–581, 2002
A multicenter phase II study of tgDCC‐E1A for the intratumoral treatment of patients with recurrent head and neck squamous cell carcinoma
Authors: Villaret Doug , Glisson Bonnie , Kenady Daniel , Hanna Ehab , Carey Mary , Gleich Lyon , Yoo George H. , Futran Neal , Hung Mien‐Chie , Anklesaria Pervin , Heald Alison E.
Published: October 2002

Background

The anti‐cancer gene, E1A, can be complexed to a lipid carrier, DC‐Cholesterol:DOPE, to form tgDCC‐E1A, which can be injected directly into tumors.

Methods

Twenty‐four patients with recurrent, unresectable, head and neck cancer were treated with intratumoral injections of tgDCC‐E1A over 8 weeks. Tumor response was assessed using CT scans. Time to progression and overall survival were calculated.

Results

Intratumoral tgDCC‐E1A was well tolerated in all patients. No significant toxicities related to tgDCC‐E1A were reported. One patient (4.2%) had a complete response, two patients (8.3%) had minor response, and seven patients (29.2%) had stable disease by two‐dimensional cross‐products on blinded CT scans. The median time to progression was 8.6 weeks (range, 3.3–43.7 weeks), and median survival was 4.6 months (range, 1.3–15.6 months).

Conclusions

Intratumoral injections of tgDCC‐E1A were safe and well tolerated. Modest tumor response was observed. Further development of tgDCC‐E1A is warranted in combination with other treatment modalities. © 2002 Wiley Periodicals, Inc.
Stereotactic radiosurgery for locally recurrent nasopharyngeal carcinoma
Authors: Pai Ping‐Ching , Chuang Chi‐Cheng , Wei Kuo‐Chen , Tsang Ngan‐Ming , Tseng Chen‐Kan , Chang Chen‐Nen
Published: October 2002

Background

Stereotactic radiosurgery has been used to treat intracranial tumors. Recently, it has also been used for the treatment of head and neck tumors involving the base of skull, including recurrent NPC.

Methods

From October 1994 to April 1999, 36 patients with recurrent NPC, were retreated by stereotactic radiosurgery. These patients received radiosurgery as a boost treatment after reirradiation for recurrence. The external RT dose ranged from 20 to 60 Gy. The tumor volume ranged from 3.58 to 24.6 cc. The target surface dose ranged from 8 to 20 Gy. The median follow‐up was 22.1 months.

Results

The 3‐year local control rate was 56%. The 5‐year overall survival was 49%. Persistence after radiosurgery had a worse survival than those who had secondary recurrence. Age and gender were marginally significant. No patient had new severe complications after retreatment. Four patients (11%) had nasopharyngeal necrosis after radiosurgery, none had nasal bleeding or headache, but a foul odor was present in one patient.

Conclusions

Conformal radiotherapy and stereotactic radiotherapy provide good local control and survival without severe complications for patients with recurrent NPC. © 2002 Wiley Periodicals, Inc. Head Neck 24: 748–753, 2002
Nuclear and cytoplasmic p53 expression in pharyngeal squamous cell carcinoma: Prognostic implications
Authors: Pukkila Matti J. , Kumpulainen Eero J. , Virtaniemi Jukka A. , Johansson Risto T. , Halonen Pirjo M. , Kellokoski Jari K. , Kosunen Ari S. T. , Nuutinen Juhani , Kosma Veli‐Matti
Published: October 2002

Background

The role of p53 expression in human neoplasms is still controversial, and it has been associated with both favorable and unfavorable outcome of the patients. Also cytoplasmic expression of p53 protein has been reported to affect survival in some cancers. Furthermore, an association between p53 and β‐catenin expression has been demonstrated. We studied the expression of p53 in a large group of oropharyngeal and hypopharyngeal squamous cell carcinomas and its relation to catenin expression, histologic differentiation, clinical data, and prognosis.

Methods

Primary tumors for analyses were obtained from 123 patients diagnosed with squamous cell carcinoma of the oropharynx or hypopharynx between 1975 and 1998 in Eastern Finland. Immunohistochemistry was used to evaluate the expression of p53 as well as α‐, β‐, and γ‐catenins.

Results

In the primary tumors (n = 123), the nuclear p53 expression index was low in 42 (34%), intermediate in 38 (31%), and high in 43 (35%) cases. Cytoplasmic p53 expression was present in 56 (46%) and absent in 67 (54%) tumors. In univariate analyses (Kaplan‐Meier), hypopharyngeal primary site (p = .02), high T class (p < .0005), presence of distant metastases (p = .02), low Karnofsky performance index (p < .0005), high nuclear p53 expression index (p = .01), and positive cytoplasmic p53 expression (p = .04) predicted poorer overall survival (OS). In Cox proportional hazards model, only T class (p = .0005), Karnofsky performance index (p = .005), and nuclear β‐catenin expression (p = .038) predicted poorer OS.

Conclusion

Positive cytoplasmic p53 expression and nuclear p53 overexpression seem to relate to more aggressive features and unfavorable outcome in pharyngeal squamous cell carcinoma (PSCC). However, unlike more traditional variables, p53 expression is not an independent predictor of disease outcome in PSCC. © 2002 Wiley Periodicals, Inc. Head Neck 24: 784–791, 2002
Establishment of a non‐governmental regional approach to La Plata River Basin integrated watershed management promoted throughout three international workshops supported by UN and Japanese agencies, led by ILEC
Authors: Calcagno Alberto , Yamashiki Yosuke , Mugetti Ana
Published: October 2002

The La Plata River Basin is one of the largest international river basins in the world, with an area of about 3 million km2. It spreads across five countries (Argentina, Bolivia, Brazil, Paraguay and Uruguay), and its water resources are essential for their economic development. Together with reservoir development, extensive deforestation, intensive agriculture practices and large urban developments took place in the Paraná, Paraguay and Uruguay basins, affecting environmental conditions and raising important issues concerning water resources use and conservation. Therefore, the need to promote participatory and cooperative efforts among water resources stakeholders, as well as the systematic exchange of information and experiences on common regional problems among organizations and experts from throughout the basin who are devoted to water resources use and management, was reported by researchers and managers gathered at the First and Second International Workshops on Regional Approaches for Reservoir Development and Management in the La Plata River Basin (held in 1991 and 1994). As a concrete response to this need, the efforts of a number of organizations from various countries within the basin, with the support of international and national governmental organizations, resulted in the foundation of La Plata River Basin Environmental Research and Management Network (RIGA) in March 2001. This was within the framework of the Third International Workshop, which was precisely one of the short‐term activities included in the RIGA Action Plan. During the preparatory processes for the RIGA Network, the presence of Japanese cooperation supporting the La Plata River Basin Workshops through a non‐governmental international organization (ILEC) played an important role in stimulating such an organization‐based joint approach in the basin. This outcome, although not originally planned, constituted a welcomed byproduct of its main specific interest in the region, which was the establishment of international sustainable management guidelines for lake and reservoir management. Copyright © 2002 John Wiley & Sons, Ltd.
Investigation of submarine groundwater discharge
Authors: Taniguchi Makoto , Burnett William C. , Cable Jaye E. , Turner Jeffrey V.
Published: October 2002

Coastal hydrogeologists and oceanographers now recognize the potentially significant contribution that submarine groundwater discharge (SGD) could make to the coastal ocean. SGD may be both volumetrically and chemically important to coastal water and chemical budgets. A worldwide compilation of observed SGD shows that groundwater seepage from the land to the ocean occurs in many environments along the world's continental margins. Further, SGD has a significant influence on the environmental condition of many nearshore marine environments and provides a strong motivation for improved assessments. Our review reveals a critical lack of data from coastal zones of almost all parts of the world, especially in South America, Africa and parts of Asia, making a comprehensive compilation incomplete. SGD should be paid more attention with regard to water and dissolved material budgets at the local and global scales. SGD intercomparison experiments and coastal typologies (classification) may enable evaluation of the accuracy of the SGD estimates and up‐scaling of SGD to a global scale. Copyright © 2002 John Wiley & Sons, Ltd.
Measurement of surface water runoff from plots of two different sizes
Authors: Joel Abraham , Messing Ingmar , Seguel Oscar , Casanova Manuel
Published: October 2002

Intensities and amounts of water infiltration and runoff on sloping land are governed by the rainfall pattern and soil hydraulic conductivity, as well as by the microtopography and soil surface conditions. These components are closely interrelated and occur simultaneously, and their particular contribution may change during a rainfall event, or their effects may vary at different field scales. The scale effect on the process of infiltration/runoff was studied under natural field and rainfall conditions for two plot sizes: small plots of 0·25 m2 and large plots of 50 m2. The measurements were carried out in the central region of Chile in a piedmont most recently used as natural pastureland. Three blocks, each having one large plot and five small plots, were established. Cumulative rainfall and runoff quantities were sampled every 5 min. Significant variations in runoff responses to rainfall rates were found for the two plot sizes. On average, large plots yielded only 40% of runoff quantities produced on small plots per unit area. This difference between plot sizes was observed even during periods of continuous runoff. Copyright © 2002 John Wiley & Sons, Ltd.
Aberrant methylation of the CDKN2a/p16INK4a gene promoter region in preinvasive bronchial lesions: A prospective study in high‐risk patients without invasive cancer.
Authors: Lamy Aude , Sesboüé Richard , Bourguignon Jeannette , Dautréaux Brigitte , Métayer Josette , Frébourg Thierry , Thiberville Luc
Published: October 2002

Among the identified factors involved in malignant transformation, abnormal methylation of the CDKN2A/p16INK4a gene promoter has been described as an early event, particularly in bronchial cell cancerization. Precancerous bronchial lesions (n = 70) prospectively sampled during fluorescence endoscopy in a series of 37 patients at high risk for lung cancer were studied with respect to the methylation status of the CDKN2A gene. Methylation‐specific polymerase chain reaction was performed on DNA extracted from pure bronchial cell populations derived from biopsies and detection of p16 protein was studied by immunohistochemistry on contiguous parallel biopsies. Aberrant methylation of the CDKN2A gene promoter was found in 19% of preinvasive lesions and its frequency increased with the histologic grade of the lesions. Methylation in at least 1 bronchial site was significantly more frequent in patients with cancer history, although there was no difference in the outcome of patients with or without methylation in bronchial epithelium. The other risk factors studied (tobacco and asbestos exposure) did not influence the methylation status. There was no relationship between CDKN2A methylation and the evolutionary character of the lesions. Our results confirm that abnormal methylation of the CDKN2A gene promoter is an early event in bronchial cell cancerization, which can persist for several years after carcinogen exposure cessation, and show that this epigenetic alteration cannot predict the evolution of precancerous lesions within a 2‐year follow‐up. © 2002 Wiley‐Liss, Inc.
Prognostic value of P53 mutations in rectal carcinoma
Authors: Rebischung Christine , Gérard Jean‐Pierre , Gayet Jacqueline , Thomas Gilles , Hamelin Richard , Laurent‐Puig Pierre
Published: October 2002

The influence of p53 mutations on the response to ionizing radiation and survival was retrospectively evaluated in patients treated with preoperative radiotherapy for rectal carcinoma. From 1989 to 1991, 86 rectal cancer patients treated by preoperative radiotherapy were included in this series. For all patients, endorectal sonography (to define ultrasonography TNM [uTNM]) was performed before treatment; 19 patients were classified as stage 1, 27 as stage 2 and 40 as stage 3. Response to radiotherapy (39 Gy in 13 fractions delivered in 17 days) was assessed by comparing the uT and the T obtained by histologic examination of the resected specimen (TNM classification). A rectal cancer biopsy was performed before treatment and enabled the search for p53 mutations by denaturing gradient gel electrophoresis (DGGE) and sequencing. The status of the p53 gene was correlated with the response to radiotherapy and survival. Forty‐nine percent of the tumors presented abnormal DGGE profiles. The prevalence of p53 mutations was significantly higher in patients who did not respond to radiotherapy (63%) than in those who did respond (34%) (p < 0.01). Presence of a p53 mutation was associated with significantly shorter 5‐year survival compared to patients without mutations (p < 0.02). In a multivariate analysis, p53 mutation status remained a prognostic factor independent of tumor posttreatment staging (p < 0.05). p53 status is an independent prognostic factor of response to radiotherapy and survival in rectal carcinoma. © 2002 Wiley‐Liss, Inc.
Non‐competitive steroid inhibition of oestrogen receptor functions
Authors: Puddefoot John R. , Barker Stewart , Glover Hilary R. , Malouitre Sylvanie D.M. , Vinson Gavin P.
Published: October 2002

Currently available antioestrogens, such as tamoxifen, are competitive inhibitors that bind to the ligand binding sites of oestrogen receptors, ERα and ERβ. The search for alternative anti‐hormone therapies is prompted by the need for drugs that are effective when tumours become tamoxifen resistant. The existence of different receptor isoforms also raise the possibility of improving selectivity. Earlier use of the 3β‐hydroxysteroid dehydrogenase inhibitor, trilostane (4α,5‐ epoxy‐17β‐hydroxy‐3‐oxo‐5α‐androstane‐2α‐carbonitrile), suggested that it had beneficial actions in breast cancer that were only partially attributable to inhibition of steroidogenesis. The present studies on the interactions of trilostane with oestrogen receptors show that it (i) inhibits oestrogen‐stimulated proliferation in MCF‐7 breast cancer cells, (ii) enhances the affinity of oestradiol binding to ER in rat uteri and specifically increases oestradiol binding to an ERβ‐like isoform, (iii) inhibits ERα and ERβ binding to the classical vitellogenin gene oestrogen response element (ERE) and (iv) inhibits oestrogen‐stimulated gene transcription in ERE‐linked reporter systems in MCF‐7 cells. The results demonstrate a novel, presumably allosteric, mode of antioestrogen action. The beneficial actions of trilostane in breast cancer may be attributed to the combination of this antioestrogen effect with its well documented suppression of steroidogenesis. © 2002 Wiley‐Liss, Inc.
Inhibitory effect of the peptide epitalon on the development of spontaneous mammary tumors in HER‐2/neu transgenic mice
Authors: Anisimov Vladimir N. , Khavinson Vladimir KH. , Provinciali Mauro , Alimova Irina N. , Baturin Dmitri A. , Popovich Irina G. , Zabezhinski Mark A. , Imyanitov Eugeni N. , Mancini Romina , Franceschi Claudio
Published: October 2002

Female FVB/N HER‐2/neu transgenic mice from the age of 2 months were subcutaneously injected with saline, the peptide Epitalon® (Ala‐Glu‐Asp‐Gly) or with the peptide Vilon® (Lys‐Glu) in a single dose of 1 μg/mouse for 5 consecutive days every month. Epitalon treatment reduced the cumulative number and the maximum size of tumors (p < 0.05). Furthermore, the number of mice bearing 1 mammary tumor was increased, whereas the number of mice bearing 2 or more mammary tumors was reduced in Epitalon‐treated in comparison to saline‐treated animals (p < 0.05). The size but not the number of lung metastases was reduced in Epitalon‐treated compared to saline‐treated mice (p < 0.05). The treatment with Vilon produced significant negative effects when compared to the control group, with an increased incidence of mammary cancer development (p < 0.05), a shorter mean latent period of tumors (p < 0.05) and an increased cumulative number of tumors (p < 0.05). A 3.7‐fold reduction in the expression of HER‐2/neu mRNA was found in mammary tumors from HER‐2/neu transgenic mice treated with Epitalon compared to control animals. The expression of mRNA for HER‐2/neu was also partially reduced in Vilon‐treated mice, but it remained significantly higher in Vilon‐ than in Epitalon‐treated animals (1.9‐fold increase). The data demonstrate the inhibitory effect of Epitalon in the development of spontaneous mammary tumors in HER‐2/neu mice, suggesting that a downregulation of HER‐2/neu gene expression in mammary adenocarcinoma may be responsible, at least in part, for the antitumor effect of the peptide. © 2002 Wiley‐Liss, Inc.
Response of normal female human osteoblasts (NHOst) to 17β‐estradiol is modulated by implant surface morphology
Authors: Lohmann C. H. , Tandy E. M. , Sylvia V. L. , Hell‐Vocke A. K. , Cochran D. L. , Dean D. D. , Boyan B. D. , Schwartz Z.
Published: October 2002

Titanium (Ti) surfaces with rough microtopographies enhance osteogenic differentiation, local factor production, and response to osteogenic agents in vitro and increase pullout strength of dental implants in vivo. Estrogens regulate bone formation, resorption, and remodeling in females and may be important in implant success. Here, we tested the hypothesis that estrogen modulates osteoblast response to implant surface morphology. Primary female human osteoblasts were cultured to confluence on three Ti surfaces (pretreatment, PT ‐ Ra 0.60 μm; sandblasted and acid‐etched, SLA ‐ Ra 3.97 μm; and Ti plasma‐sprayed, TPS ‐ Ra 5.21 μm) and treated for 24 h with 10−7 or 10−8 M 17β‐estradiol (E2). Cell number decreased with increasing surface roughness, but was not sensitive to E2. Alkaline phosphatase specific activity of isolated cells and cell layer lysates was lower on rough surfaces. E2 increased both parameters on smooth surfaces, whereas on rough surfaces, the stimulatory effect of E2 on alkaline phosphatase was evident only when measuring cell layer lysates. Osteocalcin levels were higher in the conditioned media of cells grown on rough surfaces; E2 had no effect in cultures on the plastic surfaces, but increased osteocalcin production on all Ti surfaces. TGF‐β1 and PGE2 production was increased on rough surfaces, and E2 augmented this effect in a synergistic manner; on smooth surfaces, there was no change in production with E2. The response of osteoblasts to surface topography was modulated by E2. On smooth surfaces, E2 affected only alkaline phosphatase, but on rough surfaces, E2 increased levels of osteocalcin, TGF‐β1, and PGE2. These results show that normal adult human female osteoblasts are sensitive to surface microtopography and that E2 can alter this response. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 204–213, 2002