bluuebunny/crossref_metadata_2025 huggingface dataset:
An exploratory study of Malaysian publication productivity in computer science and information technology
Authors: Gu Yinian
Published: October 2002

Explores the Malaysian computer science and information technology publication productivity. A total of 547 unique Malaysian authors, affiliated to 52 organizations in Malaysia, contributed 461 publications between 1990 and 1999 as indicated by data collected from three Web‐based databases. The majority (378 or 69.1%) of authors wrote one publication. The productive authors and the number of their papers as well as the position of their names in the articles are listed to indicate their productivity and degree of involvement in their research publications. Researchers from the universities contribute about 428 (92.8%) publications. The three most productive institutions together account for a total of 258 (56.0%) publications. The composition of the publications are 197 (42.7%) journal articles, 263 (57.1%) conference papers, and 1 (0.2%) monograph chapters. The results indicate that the scholars published in a few core proceedings but contributed to a wide variety of journals. Thirty‐nine fields of research undertaken by the scholars are also revealed. The possible reasons for the amount and pattern of contributions are related to the size of researcher population in the country, the availability of refereed scholarly journals, and the total expenditure allocated to information, computers, and communication technology (ICCT) research in Malaysia.
Statistical concepts of capability of detection
Authors: Wilrich Peter‐Th.
Published: October 2002

The minimum detectable value of a measurement system is the smallest true value of the measurand X that can be detected as distinct from the true value x = 0 with a specified probability 1−β. If the measurand X is measured indirectly and the directly measurable variable Y is linearly related to X, the minimum detectable value depends on the design of the measurement system, i.e. the calibration experiment for the estimation of the linear relationship and the number of repeated measurements of the sample. In this paper a design is derived that assures the minimum detectable value to be equal to a specified value. Copyright © 2002 John Wiley & Sons, Ltd.
The outstanding metabolic stability of a 14C‐labeled β‐nonapeptide in rats – in vitro and in vivo pharmacokinetic studies
Authors: Wiegand Hansjörg , Wirz Bernard , Schweitzer Alain , Camenisch Gian P. , Rodriguez Perez Maria I. , Gross Gerhard , Woessner Ralph , Voges Rolf , Arvidsson Per I. , Frackenpohl Jens , Seebach Dieter
Published: October 2002

In vitro studies: In CaCo‐2 cell monolayers the β‐nonapeptide H(β‐HAla‐β‐HLys‐β‐HPhe)3‐OH·4HCl (1), 14C‐labeled on both C atoms of the CH2–CO moiety of the central β‐HPhe residue, showed a low intrinsic permeability (<1%) and is subject to a prominent efflux system. The β‐peptide (1) binds to human and rat plasma protein in vitro independent of the concentration of 1 and of the species (30–36% bound fraction at 50, 500, and 5000 ng/ml), and has only low affinity for the corresponding blood cells (less than 5% of compound 1 in blood cells).

In vivo studies: The in vivo pharmacokinetic characteristics after i.v. administration of 5 mg/kg (to male rats and to bile‐duct‐operated rats) were: (i) negligible in vivo biotransformation of 1 (in urine, plasma and feces unchanged 1 represented virtually the only compound‐related molecule); (ii) rapid initial decline (0–8 h post dose) of levels of compound 1 in blood and plasma followed by a slower decline (8–96 h post dose); (iii) in non‐operated animals after 96 h only 38% of the dose was excreted and after 168 h 49% of the dose was found remaining in the carcass; elimination through the intestine wall represented the major elimination pathway in non‐operated animals while in bile‐duct‐cannulated animals biliary excretion was not found to contribute substantially to elimination (iv) quantitative whole‐body autoradioluminography (QWBAL) investigations revealed that the kidney was by far the most important target organ of distribution; other tissues with high concentrations of compound‐related radioactivity were cartilage, lymph nodes, and liver, whereas lowest levels were found in white fat and in the brain. After p.o. administration (10 mg/kg) negligible radioactivity was observed in the systemic circulation, indicating negligible absorption; essentially the entire oral dose was recovered unchanged in feces collected over a period of 96 h. Copyright © 2002 John Wiley & Sons, Ltd.
Importance of minor groove functional groups for the stability of DNA duplexes
Authors: Sun Zhenhua , Chen Dongli , Lan Tao , McLaughlin Larry W.
Published: October 2002

Eight oligonucleotide duplexes have been prepared with four pairs of selected complementary pairs of native/analogue heterocyclic bases incorporated at a selected test site. The base pairs vary in the nature of their functionality in the minor groove. Each pair has a minor groove purine amino group present or absent, and correspondingly has a minor grove pyrimidine carbonyl present or absent. Loss of duplex stability is most notable when the minor groove pyrimidine carbonyl is absent although in other respects normal Watson–Crick hydrogen bonding is maintained in these sequences. These differences in stability are discussed in terms of possible variations in minor groove hydration. © 2002 Wiley Periodicals, Inc. Biopolymers (Nucleic Acid Sci) 65: 211–217, 2002
Modified model for the regulation of the tryptophan operon in Escherichia coli
Authors: Giona Massimiliano , Adrover Alessandra
Published: October 2002

This article proposes a modification of the model developed by Sinha (1988) and Sen and Liu (1990) for the regulation dynamics of the tryptophan operon in E. coli based on a consistent overall balance of the agent repressing the mRNA transcription. The dynamics of the model are analyzed by means of continuation techniques and the influence of periodic fluctuations in the intracellular demand for tryptophan is addressed. The analysis provides deeper insight into the dynamics of this operon system and the results obtained may be a useful starting point for the optimization of tryptophan yield in bacterial cultures. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 297–304, 2002.
Modelling of the enzymatic kinetically controlled synthesis of cephalexin: Influence of diffusion limitation
Authors: Schroën C.G.P.H. , Fretz C.B. , DeBruin V.H. , Berendsen W. , Moody H.M. , Roos E.C. , VanRoon J.L. , Kroon P.J. , Strubel M. , Janssen A.E.M. , Tramper J.
Published: October 2002

In this study the influence of diffusion limitation on enzymatic kinetically controlled cephalexin synthesis from phenylglycine amide and 7‐aminodeacetoxycephalosporinic acid (7‐ADCA) was investigated systematically. It was found that if diffusion limitation occurred, both the synthesis/hydrolysis ratio (S/H ratio) and the yield decreased, resulting in lower product and higher by‐product concentrations. The effect of pH, enzyme loading, and temperature was investigated, their influence on the course of the reaction was evaluated, and eventually diffusion limitation was minimised. It was found that at pH ≥7 the effect of diffusion limitation was eminent; the difference in S/H ratio and yield between free and immobilised enzyme was considerable. At lower pH, the influence of diffusion limitation was minimal. At low temperature, high yields and S/H ratios were found for all enzymes tested because the hydrolysis reactions were suppressed and the synthesis reaction was hardly influenced by temperature. The enzyme loading influenced the S/H ratio and yield, as expected for diffusion‐limited particles. For Assemblase 3750® (the number refers to the degree of enzyme loading), it was proven that both cephalexin synthesis and hydrolysis were diffusion limited. For Assemblase 7500®, which carries double the enzyme load of Assemblase 3750®, these reactions were also proven to be diffusion limited, together with the binding‐step of the substrate phenylglycine amide to the enzyme. For an actual process, the effects of diffusion limitation should preferably be minimised. This can be achieved at low temperature, low pH, and high substrate concentrations. An optimum in S/H ratio and yield was found at pH 7.5 and low temperature, where a relatively low reaction pH can be combined with a relatively high solubility of 7‐ADCA. When comparing the different enzymes at these conditions, the free enzyme gave slightly better results than both immobilised biocatalysts, but the effect of diffusion limitation was minimal. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 331–340, 2002.
Versatile method for production and controlled polymer‐immobilization of biologically active recombinant proteins
Authors: Allard Laure , Cheynet Valérie , Oriol Guy , Mandrand Bernard , Delair Thierry , Mallet François
Published: October 2002

The immobilization of a protein by covalent attachment to a support matrix should involve only functional groups of the protein that are not essential for its biological activity. A general strategy for obtaining recombinant proteins designed for oriented covalent grafting onto copolymers was investigated. The rationale involves the definition of seven p24‐derived recombinant proteins as fused to either distant or adjacent tags comprising primary amine rich tag consisting of six contiguous lysines suitable for oriented covalent immobilization and a hexa‐histidine tag suitable for metal chelate affinity purification. High‐level expression, efficient affinity purification, and coupling yields onto maleic anhydride‐alt‐methyl vinyl ether copolymers higher than 95% were obtained for all proteins. Afterwards, an investigation of the biological features of the immobilized vs. nonimmobilized protein onto the copolymer allowed us to select one bioconjugate which was used in a diagnostic context, i.e., as a capture antigen in an ELISA format test. Sera from 107 HIV‐seropositive individuals at various stages of HIV infection, including two seroconversion panels and 104 healthy HIV‐seronegative controls, were tested using either RH24 or RK24H‐copolymer coated onto the microtiter plate. These assays showed that the use of such a protein‐copolymer bioconjugate allowed detection of lower antibody titers than the RH24 protein, illus‐ trating the potential of applications of such doubly tagged proteins. Thus, a set of expression vectors was designed containing four different combinations of hexa‐lysine and hexa‐histidine tags and a multiple cloning site, allowing the production of different recombinant fusion proteins suitable for biological reactivity conservation after immobilization. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 341–348, 2002.
Enhanced kinetic extraction of parvovirus B19 structural proteins
Authors: Sico Colleen , White Stephen , Tsao Eric , Varma Amit
Published: October 2002

Recombinant structural proteins (VP1 and VP2) of the human parvovirus B19 have been expressed simultaneously using the baculovirus expression system to form virus‐like particles (VLPs) that have potential use as vaccines. In this study, we report optimization of extraction conditions to recover these VLPs from cell paste. Under hypotonic conditions with neutral pH these VLPs were poorly extracted (up to 3% extraction). Addition of reducing agents, detergents, salts, and sonication did not improve the extractability. While screening for conditions to improve the extractability of the VLPs, we discovered that a combination of higher pH and elevated processing temperature significantly increased the extraction. Whereas increasing pH alone increased extractability from 3% to 6% (pH increased from 8.0 to 9.5), the effect of elevated temperature was much more substantial. At 50°C, we observed the extraction to be more than fivefold higher than that at room temperature (up to 25% extracted at pH 9.0). The kinetics of extraction at elevated temperatures showed a rapid initial rate of extraction (on the order of minutes) followed by a plateau. In addition, we compared the extraction of VP1 expressed alone. VP1 expressed alone is incapable of forming VLPs. We observed that non‐VLP VP1 was easily extractable (up to 60% extracted) under conditions in which the VP1 + VP2 VLPs were not extractable. From these studies we conclude that parvovirus B19 structural proteins expressed to form VLPs have a hindered extractability as compared with non‐VLP protein. This hindrance to extraction can be significantly reduced by processing at elevated temperatures and an increased pH, possibly due to the enhanced rates of solubilization and diffusion. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 80: 250–256, 2002.
Variations in breast carcinoma treatment in older medicare beneficiaries
Authors: Mandelblatt Jeanne S. , Kerner Jon F. , Hadley Jack , Hwang Yi‐Ting , Eggert Lynne , Johnson Lenora E. , Gold Karen ,   For the OPTIONS (Outcomes and Preferences for Treatment in Older Women Nationwide Study) Research Team
Published: October 2002

BACKGROUND

To evaluate associations between race and breast carcinoma treatment.

METHODS

Data from 984 black and 849 white Medicare beneficiaries 67 years or older with local breast carcinoma and a subset of 732 surviving women interviewed 3–4 years posttreatment were used to calculate adjusted odds of treatment, controlling for age, comorbidity, attitudes, region, and area measures of socioeconomic and health care resources.

RESULTS

Sixty‐seven percent of women received a mastectomy and 33% received breast‐conserving surgery. The odds of radiation omission were 48% higher (95% confidence interval [CI] 1.01–2.19) for blacks than for whites after considering covariates, but the absolute number of women who failed to receive this modality was small (11%). In race‐stratified models, the odds of having radiation omitted were significantly higher among blacks living greater distances from a cancer center (vs. lesser) or living in areas with high poverty (vs. low), but these factors did not affect radiation use among whites. Among those interviewed, blacks reported perceiving more ageism and racism in the health care system than whites (P = 0.001). The independent odds of receiving mastectomy (vs. breast conservation and radiation) were 2.72 times higher (95% CI 1.25–5.92) among women reporting the highest quartile of perceived ageism scores, compared with the lowest, and higher perceived ageism tended to be associated with higher odds of radiation omission (P = 0.06).

CONCLUSIONS

Older black women with localized breast carcinoma may have a different experience obtaining treatment than their white counterparts. The absolute number of women receiving nonstandard care was small and the effects were small to moderate. However, if these patterns persist, it will be important to evaluate whether such experiences contribute to within‐stage race mortality disparities. Cancer 2002;95:1401–14. © 2002 American Cancer Society.

DOI 10.1002/cncr.10825
Generation of band‐pass constant‐envelope signals with a pre‐assigned spectrum: a synthesis procedure
Authors: Callegari S.
Published: October 2002

The recent, increasing adoption of spread‐spectrum techniques, either in communications or in other fields, makes the design of band‐pass sources a topical subject. We consider the generation of constant‐envelope (i.e. constant power) band‐pass signals via a frequency modulation technique. In particular, we propose a general solution to the synthesis problem of delivering a constant envelope signal with a pre‐assigned band‐pass spectrum. Both quasi‐stationary and non‐stationary modulations are discussed and a novel optimization algorithm is proposed for the latter case. A design example concludes the presentation. Copyright © 2002 John Wiley & Sons, Ltd.
Progressive medial temporal lobe changes in Alzheimer's disease revealed by quantitative MRI: potential use for monitoring of drug‐related changes
Authors: Pantel Johannes , Schönknecht Peter , Essig Marco , Amann Michael , Eysenbach Katrin , Schad Lothar R. , Schröder Johannes
Published: October 2002

With the advent of new and more effective drugs for the treatment of Alzheimer's disease (AD), establishment of objective surrogate markers of disease progression has become an issue of high clinical relevance. In order to investigate the potential of volumetric magnetic resonance imaging (MRI) for monitoring disease progression, we investigated the progression rates of hippocampal and generalized brain atrophy in a group of AD patients with respect to rates of clinical deterioration. While AD, in comparison to healthy aging, was characterized by a rapid decline of hippocampal volumes, only a moderate decrease of whole brain volumes occurred, indicating that hippocampal atrophy was not merely a function of generalized brain atrophy. Progression of hippocampal atrophy, but not of whole brain atrophy, was significantly correlated with clinical deterioration. These findings indicate that progressive hippocampal volume reduction underlies clinical deterioration in AD and that the rate of hippocampal atrophy might be used as a morphometric index of disease progression in clinical drug trials. Drug Dev. Res. 56:51–56, 2002. © 2002 Wiley‐Liss, Inc.
Biological markers of Alzheimer's disease
Authors: Mehta Pankaj D. , Pirttilä Tuula
Published: October 2002

Alzheimer's disease (AD) is a neurodegenerative disease that affects cognition, behavior, and function. The etiology of the disease is unknown; however, the primary risk factors for AD are aging and family history. Neurofibrillary tangles (NFT) and amyloid‐bearing neuritic plaques in the limbic and cerebral cortices are the characteristic neuropathologic lesions in brains of patients with AD. The NFT is mainly composed of hyperphosphorylated tau, whereas the major component of the neuritic plaques is the amyloid beta (Aβ) protein. The clinical diagnosis of probable AD is based on history, physical examination, neuropsychological testing, laboratory studies, and neuroimaging techniques. However, there is no laboratory marker to support the diagnosis of definite AD or monitoring the progression of the disease. Several biochemical markers related to neuropathology have been identified in cerebrospinal fluid (CSF). We describe the studies of CSF or blood levels of tau protein, amyloid β protein, amyloid precursor protein isoforms, neuronal thread protein, and iron‐binding protein (p97) in patients with AD and age‐matched nondemented controls. Due to the heterogeneity and complex nature of the disease, it is highly unlikely that a single marker specific for AD will be found. However, a panel of biomarkers may help to discriminate different subgroups of AD with distinct genetic backgrounds. Drug Dev. Res. 56: 74–84, 2002. © 2002 Wiley‐Liss, Inc.
Vascular risk factors, ApoE ϵ4 allele, and gender and the risk of Alzheimer's disease: perspectives on prevention
Authors: Kivipelto Miia , Helkala Eeva‐Liisa , Nissinen Aulikki , Soininen Hilkka , Tuomilehto Jaakko
Published: October 2002

This review summarizes the main findings from our recent research within the prospective, population‐based study investigating midlife elevated blood pressure (BP) and cholesterol values as risk factors for Alzheimer's disease (AD) and mild cognitive impairment (MCI) later in life. Furthermore, we present some new data on the gender‐related differences in the risk factor profiles for AD. Our results suggest that vascular risk factors are important for the development of AD in both genders, but some gender‐related differences in the risk factors profiles for AD may exist. Our findings also suggest that different environmental factors such as antihypertensive drug treatment may modify the effect of apolipoprotein E ϵ4 allele in the development of AD. These data emphasize the importance of effective primary prevention and early treatment of hypertension and hypercholesterolemia as potential avenues for reducing the risk of AD. Drug Dev. Res. 56:85–94, 2002. © 2002 Wiley‐Liss, Inc.
Human Apolipoprotein E concentration in response to diseases and therapeutic treatments
Authors: Siest Gérard , Zaiou Mohamed , Visvikis Sophie
Published: October 2002

Apolipoprotein (Apo) E is an important circulating and tissular protein involved in cholesterol homeostasis and many other functions. The common polymorphism in the coding region of the gene, four polymorphisms in the promoter region, other additional single nucleotide polymorphisms, as well as several ApoE variants have been identified. Outside genetic polymorphism effects, ApoE concentration is modulated in human plasma and tissue through many processes: 1) transcription regulation through hormone responsive elements; 2) cytokines; 3) compartmentalization in particles or linkage to HSPG; 4) degradation after oxidation, glycation, and proteolysis; and 5) through many specific and nonspecific receptor interactions. Is the level of ApoE in tissue or plasma critical in different pathologies such as cardiovascular diseases (CVD) or Alzheimer's disease (AD)? ApoE is able to bind to Aβ, tau, to be an antioxidant, to respond to inflammation, and is involved in cholesterol delivery, uptake, and accumulation. In experimental situations ApoE injection or positive modulation decreases cholesterol and triglycerides and improves cognitive impairment. ApoE peptides are involved in immune response. It seems more and more clear that low vs. high plasma concentration should be evaluated in large epidemiological studies. Only after such studies can the question be answered: Is a low or high concentration of ApoE beneficial or dangerous? This fascinating apolipoprotein will then be an interesting marker and/or drug target. Drug Dev. Res. 56:95–110, 2002. © 2002 Wiley‐Liss, Inc.
Olfactory functional testing: sensitivity and specificity for Alzheimer's disease
Authors: Murphy Claire
Published: October 2002

The neuropathological changes of Alzheimer's disease (AD) are earliest observed in areas of the brain central to olfactory processing, suggesting the theoretical importance and potential diagnostic utility of assessment of olfactory function in these patients. Investigations conducted to assess olfaction function in both patients with AD and those at risk for the disease are reviewed. Functional testing included olfactory threshold, odor identification, odor memory, and odor fluency. Both Alzheimer's patients and those at risk for the disease showed significant impairment in olfactory function, with some measures showing more impairment than others in the early stages of the disease process. Longitudinal investigation of some measures indicated decreased function over time consonant with increasing dementia. The sensitivity and specificity of some of these olfactory assessments will be related to analogous assessments in other modalities. The results support the incorporation of olfactory measures in batteries for assessment of early AD. Drug Dev. Res. 56:123–131, 2002. © 2002 Wiley‐Liss, Inc.
Targeting intracellular Aβ42 for Alzheimer's disease drug discovery
Authors: D'Andrea Michael R. , Lee Daniel H.S. , Wang Hoau‐Yan , Nagele Robert G.
Published: October 2002

For years, extracellular deposition of the “pathologic” β‐amyloid1–42 (Aβ42) in the brain has been considered as the major cause of the appearance of neuritic plaques that are subsequently responsible for neuronal death in Alzheimer's disease (AD). However, recent work has shown that significant amounts of β‐amyloid, especially Aβ42, are being sequestered within the perikaryon of affected pyramidal neurons prior to the appearance of plaques. This has led us to challenge the prevailing theory and suggest that at least some of the amyloid plaques, specifically the dense‐core plaques in the cerebrum and hippocampus, may derive from the lysis of those neurons that are overburdened with intracellular Aβ42. We discuss the possible role of intracellular Aβ42 accumulation in the development of AD pathology and review an alternate hypothesis, where Aβ42 is first accumulated inside the neurons and later released out to the brain parenchyma via neuronal lysis finally forming a dense‐core plaque (“Inside‐Out” hypothesis). We describe a mechanism for Aβ42 internalization into neurons that involves the high affinity interaction between Aβ42 and the alpha7 nicotinic acetylcholine receptor (α7nAChR) and the internalization and intracellular accumulation of the Aβ42/α7nAChR complex. This alternative hypothesis can account for many of the well‐known features of AD pathology, including specific cholinergic and cholinoceptive neuronal and synaptic loss that affects cognitive and memory functions, the distribution, morphology and composition of dense‐core plaques, and their association with inflammation. More importantly, it provides the scientific rationale for targeting the mechanisms that lead to the intraneuronal Aβ42 as a novel strategy for AD drug discovery. Drug Dev. Res 56:194–200, 2002. © 2002 Wiley‐Liss, Inc.
A Lagrangian–Eulerian model of particle dispersion in a turbulent plane mixing layer
Authors: Oliveira L.A. , Costa V. A. F. , Baliga B. R.
Published: October 2002

A Lagrangian–Eulerian model for the dispersion of solid particles in a two‐dimensional, incompressible, turbulent flow is reported and validated. Prediction of the continuous phase is done by solving an Eulerian model using a control‐volume finite element method (CVFEM). A Lagrangian model is also applied, using a Runge–Kutta method to obtain the particle trajectories. The effect of fluid turbulence upon particle dispersion is taken into consideration through a simple stochastic approach. Validation tests are performed by comparing predictions for both phases in a particle‐laden, plane mixing layer airflow with corresponding measurements formerly reported by other authors. Even though some limitations are detected in the calculation of particle dispersion, on the whole the validation results are rather successful. Copyright © 2002 John Wiley & Sons, Ltd.
Hand grip strength: A phenotype suitable for identifying genetic variants affecting mid‐ and late‐life physical functioning
Authors: Frederiksen Henrik , Gaist David , Christian Petersen Hans , Hjelmborg Jacob , McGue Matt , Vaupel James W. , Christensen Kaare
Published: October 2002

Physical functioning late in life has been shown to be affected by genetic factors. Only a few genetic variants have been suggested to be associated with physical functioning, and this only in selected populations (e.g., young healthy males and elite athletes). Declining physical functioning late in life is a major problem in terms of prevalence, morbidity, functional limitations, and quality of life. It is therefore of interest to find a phenotype reflecting physical functioning which has a relatively high heritability and which can be measured in large samples. Hand grip strength is known to be associated with muscular functioning in other muscle groups and with activities of daily living (ADL) functioning, and it predicts incident disability. We studied 1,757 Danish twin pairs aged 45–96 years, and found that this phenotype has a heritability of 52% (95% confidence interval (CI), 48–55%). A powerful design to detect genes associated with a phenotype is obtained using the extreme discordant and concordant sib pairs, of whom 28 and 77 dizygotic twin pairs, respectively, were found in this study. Hence grip strength is a suitable phenotype for identifying genetic variants of importance to mid‐ and late‐life physical functioning. Genet. Epidemiol. 23:110–122, 2002. © 2002 Wiley‐Liss, Inc.
Combined hearing and visual impairment and depression in a population aged 75 years and older
Authors: Lupsakko Taina , Mäntyjärvi Maija , Kautiainen Hannu , Sulkava Raimo
Published: October 2002

Background

Depression is associated with both visual and hearing impairment. Little is known about the relationship between combined hearing and visual impairment and mood in this age group. The aim of this population‐based study was to investigate the association between functional sensory impairment, especially combined sensory impairment and depressive symptoms and depression diagnosed according to the DSM‐IV criteria.

Method

The study group consisted of 470 adults, population‐based sample, aged 75 years or older. We used the Snellen eye charts with E‐letters and reading charts to evaluate the functional visual acuity. The ability to conduct a face‐to‐face conversation, the hearing aid use and the self‐reported hearing problems were used to assess the functional hearing acuity. Depression was identified with two different methods. A geriatrician interviewed the subjects and the DSM‐IV checklist was used to determine whether they met the criteria for major depression. The Zung Depression Status Inventory (DSI) was used to identify depressive symptoms. The cut off points of 40/80 and 48/80 in the DSI‐score was used.

Results

Seventy‐two persons (15%) of the study population had depression diagnosed according to the DSM‐IV criteria. Twelve per cent of subjects in the Functional Hearing Impairment (FHI) group, twenty per cent in the Functional Visual Impairment (FVI) group, eighteen per cent in the Combined Sensory Impairment (CSI) group and fifteen per cent in the Adequate Sensory Function (ASF) group suffered major depression. The differences between these groups were insignificant. The occurrence rates of the DSI score equal or over 40 points was 50% in the FHI group, 53% in the FVI group, 70% in the CSI group and 45% in the ASF group. The difference between the ASF group and sensory impairment group including FHI, FVI and CSI groups was statistically significant (p = 0.03).

Conclusions

Depressive symptoms, but not major depression, were common if elderly persons had combined sensory impairment. Copyright © 2002 John Wiley & Sons, Ltd.
The role of the science dean
Authors: Gentile James M.
Published: October 2002

Leadership at the divisional level helps to form and frame a sense of community that breaks down disciplinary boundaries, encourages the joint pursuit of a research‐rich learning environment, and fosters the scholarly career of each member of the faculty in the context of serving broader institutional goals.
Spindle epithelial tumor with thymus‐like differentiation (SETTLE) of the thyroid
Authors: Iwasa Kazunori , Imai Miwa Akasofu , Noguchi Masakuni , Tanaka Shigehiro , Sasaki Tadashi , Katsuda Shogo , Kawahara Ei , Mizukami Yuji
Published: October 2002

Background

Tumors of the so‐called intrathyroidal epithelial thymoma type are a rare group of thyroid neoplasm tumors. Of this type of tumor, spindle epithelial tumor with thymuslike differentiation (SETTLE) has been reported only 17 times in English literature.

Methods

An 18‐year‐old woman was initially seen with a 6‐cm left thyroid mass that was resected with a left thyroidectomy. Histopathologic features of the excised left thyroid tumor together with an immunohistochemistry and electron microscopy led us to a diagnosis of SETTLE.

Results

Most of the specimen was composed of highly cellular spindle cells that formed intersecting and streaming fascicles. The spindle cells showed both vimentin immunoreactivity and cytokeratin immunoreactivity but no immunoreactivity for thyroglobulin or calcitonin. Electron microscopic examination of the spindle cells demonstrated prominent cytoplasmic tonofilaments, desmosomes, and basal lamina consistent with epithelial cell origin. DNA content analysis by flow cytometry revealed DNA diploidy.

Conclusions

SETTLE of thyroid gland is an extremely rare entity. A review of the literature reveals that SETTLE has distinctive morphologic features and an immunohistochemical profile. © 2002 Wiley Periodicals, Inc. Head Neck 24: 888–893, 2002
Copper‐transporting P‐type adenosine triphosphatase (ATP7B) as a cisplatin based chemoresistance marker in ovarian carcinoma: Comparative analysis with expression of MDR1, MRP1, MRP2, LRP and BCRP
Authors: Nakayama Kentaro , Kanzaki Atsuko , Ogawa Kenji , Miyazaki Kohji , Neamati Nouri , Takebayashi Yuji
Published: October 2002

Intrinsic or acquired resistance to chemotherapy is the major obstacle to overcome in the treatment of patients with solid carcinoma. Cisplatin is one of the most effective chemotherapeutic agents for treating ovarian carcinoma. Recently, copper‐transporting P‐type adenosine triphosphatase (ATP7B) has been demonstrated as one of the genes responsible for cisplatin resistance in vitro. We hypothesized that the expression of ATP7B gene increases resistance to cisplatin in ovarian carcinoma and a priori knowledge of its expression is important for the choice of therapy. The aim of our study was to assess the role of ATP7B gene in ovarian carcinoma and compare its expression with those of multidrug resistance‐related transporters such as MDR1, MRP1, MRP2, LRP and BCRP genes. The transporters' gene expression profiles from 82 patients treated with cisplatin‐based chemotherapy after surgery were assessed by RT‐PCR. We did not observe any significant correlation between ATP7B gene expression and those of MDR1, MRP1, MRP2, LRP or BCRP. The expression level of ATP7B gene was significantly increased (p < 0.05) in patients with moderately‐/poorly‐differentiated ovarian carcinomas treated with cisplatin‐based chemotherapy, thus ATP7B may serve as an independent prognostic factor in these patients. In contrast, the expression level of MDR1, MRP1, MRP2, LRP and BCRP genes were not prognostic indicators of disease. These findings suggest that ATP7B gene may be considered as a novel chemoresistance marker and that inhibitor(s) of ATP7B might be useful, in patients with ovarian carcinoma treated with cisplatin‐based chemotherapy. © 2002 Wiley‐Liss, Inc.
The density of melanocytic nevi correlates with constitutional variables and history of sunburns: A prevalence study among Italian schoolchildren
Authors: Carli Paolo , Naldi Luigi , Lovati Silvia , Vecchia Carlo La ,   Oncology Cooperative Group of the Italian Group for Epidemiologic Research in Dermatology (GISED)
Published: October 2002

In several studies from northern Europe, north America and Australia, melanocytic nevi are correlated with pigmentary traits and with intense sun exposure in a way similar to malignant melanoma. However, it is unclear if these data can be extrapolated to populations in other geographic locations and with different prevalent phenotypes. Our study was conducted among schoolchildren aged 13–14 years in 16 Italian cities. The parents of 3,127 children of a total of 3,160 (99%) consented to our study. A structured questionnaire was used to collect information about sun exposure and lifetime history of sunburns. Children were also examined by trained dermatologists to assess pigmentary traits and to make a count of melanocytic nevi. The median nevus density was higher among boys than girls. Areas that are usually chronically exposed to the sun exhibited a higher density of nevi compared to intermittently and rarely exposed areas. A higher density of nevi was found in children with lighter skin, blond hair and blue eyes. Red‐haired children had a remarkably lower nevus density compared to the other color categories. The density of nevi increased with an increased number of reported episodes of sunburns. The results concerning nevi ≥6 mm in diameter paralleled those obtained for the total nevus density. However, at variance with total nevus density, a significant relation was also observed between larger nevi and freckling. Our study confirms that, in Italian schoolchildren, there is a relation between pigmentary traits, history of sunburns and the density of melanocytic nevi. Melanocytic nevi and malignant melanoma share a similar risk factor profile. © 2002 Wiley‐Liss, Inc.
The SSX gene family: Characterization of 9 complete genes
Authors: Güre Ali O. , Wei Isaac J. , Old Lloyd J. , Chen Yao‐Tseng
Published: October 2002

Human SSX genes comprise a gene family with 6 known members. SSX1, 2 and 4 have been found to be involved in the t(X;18) translocation characteristically found in all synovial sarcomas. Four (SSX1, 2, 4 and 5) are known to be expressed in a subset of tumors and testis, and anti‐SSX antibodies have been found in sera from cancer patients. SSX antigens are thus typical cancer‐testis (CT) antigens. To identify additional SSX family members, we isolated and characterized human genomic clones homologous to a prototype SSX cDNA. We also searched public databases for sequences similar to SSX. This identified 3 additional SSX genes, SSX7, 8, 9, and also completed the sequence of the formerly partially defined SSX6 gene. In addition to these novel SSX genes, several SSX pseudogenes were identified. With the exception of 1 pseudogene, all SSX genomic SSX sequences map to chromosome X. Among normal tissues, SSX7 mRNA was present only in testis, whereas SSX6, 8 and 9 were not detected in any normal tissue. SSX6 and 7 were expressed in 1 of 9 melanoma cell lines tested, whereas SSX8 and 9 expression was not detected in any tumor tissue or cell lines tested. SSX1, 2, 4 and 5 mRNA expression can be induced in cell lines by 5‐aza‐2‐deoxycytidine or Trichostatin A. These agents also induce SSX6, but not SSX3, 7, 8 or 9 in the tumor cell lines tested, indicating that mechanisms other than methylation or histone acetylation may be responsible for the repressed state of some SSX genes. © 2002 Wiley‐Liss, Inc.
Cigarette smoking, alcohol consumption and subsequent gastric cancer risk by subsite and histologic type
Authors: Sasazuki Shizuka , Sasaki Satoshi , Tsugane Shoichiro ,   Japanese Public Health Center Study Group
Published: October 2002

The effect of cigarette smoking or alcohol consumption on the risk of gastric cancer has not been clarified. We investigated this relationship, considering the anatomic subsite and histologic type of gastric cancer. A total of 19,657 men (aged 40–59 years at baseline), who responded to the baseline questionnaire and reported no serious illness at that time, were followed for 10 years, from January 1990 to December 1999. Gastric cancer was confirmed histologically in 293 men. Smoking was associated with an increased risk of the differentiated type of distal gastric cancer; compared to the group who never smoked, the adjusted rate ratios (RRs) of gastric cancer for past and current smokers were 2.0 (95% CI 1.1–3.7) and 2.1 (95% CI 1.2–3.6), respectively. No association was observed between cigarette smoking and risk of the undifferentiated type of distal gastric cancer except for a suggestive association with cardia cancer. For alcohol consumption, elevated risk was suggested only for cardia cancer of all histologic types, though the relationship failed to reach significance. Among those who drank alcohol at least once per week, RRs for ethanol intake of 2.7–161.0, 162.0–322.0 and 322.5+ g/week compared to those who drank 0–3 times/month were 2.5 (95% CI 0.7–9.5), 3.3 (0.9–11.6) and 3.0 (0.8–11.1), respectively (ptrend = 0.66). In conclusion, our results confirm that smoking is related to gastric cancer of the differentiated type. Further studies with more cases are needed to detect a positive association between cigarette smoking or alcohol consumption and cardia cancer. © 2002 Wiley‐Liss, Inc.
Calibrated histochemistry applied to oxygen supply and demand in hypertrophied rat myocardium
Authors: Des Tombe A.L. , Van Beek‐Harmsen B.J. , Lee‐De Groot M.B.E. , Van Der Laarse W.J.
Published: October 2002

Oxygen supply and demand of individual cardiomyocytes during the development of myocardial hypertrophy is studied using calibrated histochemical methods. An oxygen diffusion model is used to calculate the critical extracellular oxygen tension (PO2,crit) required by cardiomyocytes to prevent hypoxia during hypertrophic growth, and determinants of PO2,crit are estimated using calibrated histochemical methods for succinate dehydrogenase activity, cardiomyocyte cross‐sectional area, and myoglobin concentration. The model calculation demonstrates that it is essential to calibrate the histochemical methods, so that absolute values for the relevant parameters are obtained. The succinate dehydrogenase activity, which is proportional to the maximum rate of oxygen consumption, and the myoglobin concentration hardly change while the cardiomyocytes grow. The cross‐sectional area of the cardiomyocytes, which increases up to threefold in the right ventricular wall due to pulmonary hypertension in monocrotaline‐treated rats, is the most important determinant of PO2,crit in this model of myocardial hypertrophy. The relationship between oxygen supply and demand at the level of the cardiomyocyte can be investigated using paired determinations of spatially integrated succinate dehydrogenase activity and capillary density. Hypoxia‐inducible factor 1α can be demonstrated by immunohistochemistry in cardiomyocytes with high PO2,crit and increased spatially integrated succinate dehydrogenase activity, indicating that limited oxygen supply affects gene expression in these cells. We conclude that a mismatch of oxygen supply and demand may develop during hypertrophic growth, which can play a role in the transition from myocardial hypertrophy to heart failure. Microsc. Res. Tech. 58:412–420, 2002. © 2002 Wiley‐Liss, Inc.
Cell death and differentiation in the development of the endocardial cushion of the embryonic heart
Authors: Abdelwahid Eltyeb , Pelliniemi Lauri J. , Jokinen Eero
Published: October 2002

The transformation of the endocardial cushion into valves and septa is a critical step in cardiac morphogenesis as it initiates the development of the four‐chambered heart. This transformation results from a region‐specific balance between cellular proliferation, apoptosis, and differentiation. The development of the form and structure of the endocardial cushion is accompanied by precise patterns of abundant cell death having the morphological features of programmed cell death (apoptosis), which plays an important role in the elimination of redundant cells and in changes of phenotypic composition during histogenesis. Apoptosis is an essential process in morphogenesis as it balances mitosis in renewing tissues. It is controlled by one or more genetic programs that kill the targeted cell. However, the causes, role, and regulation of apoptosis in the developing endocardial cushion still remain to be determined. The clarification of the role of the apoptosis regulatory genes constitutes a major task in future studies of cell death in the developing heart. This new molecular histology of heart development awaits further experiments to clarify the interactive mechanisms that act to ensure the sculpting of the endocardial cushion into valves and septa by determining the size of the cushion cell populations. The relation between the expression of different factors and the modifications of the cushion region during cardiac development are reviewed. In addition, we review and summarize information on molecules identified in our experiments that imply the activity of a number of essential genes coinciding with the key steps in generating the overall architecture of the heart. We correlate their temporal and spatial expression with their proposed roles. Microsc. Res. Tech. 58:395–403, 2002. © 2002 Wiley‐Liss, Inc.
Production of helper‐dependent adenovirus vector relies on helper virus structure and complementing
Authors: Zhou Heshan Sam , Zhao Tiejun , Rao X. Mei , Beaudet Arthur L.
Published: October 2002

Background

The helper‐dependent (HD) adenoviral (Ad) vector relies on a helper virus to provide viral proteins for vector amplification. HD‐Ad vectors can significantly increase therapeutic gene expression and improve safety. However, the yield of an HD‐Ad vector is generally lower than that of an E1‐deleted first‐generation vector, likely due to the alterations in viral E3 or packaging regions of a helper virus that attenuate its replication and complementing for an HD‐Ad vector.

Methods

To study this question and improve HD‐Ad vector production, we have generated four different helper viruses with a wild‐type or deleted E3 region, and with a relocated loxP. We have also constructed a first‐generation vector with a wild‐type E3 region and without the loxP site. We compared the replication of these viruses in Cre‐positive and ‐negative cells and studied their complementing for HD‐Ad vector production.

Results

Viruses with deleted E3 formed smaller plaques and produced lower titer compared with viruses containing the E3 region. The site where a loxP is inserted can also affect virus replication. Higher yield of HD‐Ad vector was obtained when a helper virus with wild‐type E3 was used. We also showed that deletion of the packaging signal in a helper virus through loxP/Cre interaction decreased the viral DNA complementing ability.

Conclusions

Although the E3 region is not essential for adenovirus replication in vivo, deletion of this region attenuates virus replication. Production of HD‐Ad vector can be further improved by modifications in helper virus structure. Copyright © 2002 John Wiley & Sons, Ltd.
Diamond laser scalpel vs. steel scalpel: A side by side comparison of cutaneous wound healing
Authors: Keel Douglas M. , Goldman Mitchel P. , Fitzpatrick Richard E. , Butterwick Kimberly J.
Published: October 2002

Background and Objectives

To compare the cutaneous wound healing using the diamond laser scalpel with wound healing using a steel scalpel and electrocoagulation for hemostasis.

Study Design/Materials and Methods

A prospective and randomized, comparative trial was conducted on eighteen patients. Fusiform excisions were performed using the diamond laser scalpel on one half of each excision and a steel scalpel with electrocoagulation for hemostasis on the other half. The Clinicon SureBlade diamond laser scalpel was used with the Luxar CO2 attachment at the 6–8‐W settings. Blinded assessment of adverse events and photographs were taken at 1 day, 7–10 days, 4 weeks, and 8–12 weeks. The final scar was evaluated at 8–12 weeks for cosmetic outcome and three physicians blinded to the method of excision evaluated photographs of the wounds. Histologic evaluation was performed on all excisions for collateral thermal damage.

Results

Investigator assessment showed no statistically significant differences between the diamond laser scalpel side and the steel scalpel side with respect to bleeding, bruising, swelling, pain, dehiscence, or final scar appearance. The mean residual thermal damage was 350.3 μm (95% CI ± 37 μm, P < 0.001). The diamond laser scalpel scored higher on intra‐operative coagulation (P = 0.20) although these differences were not statistically significant.

Conclusions

The cosmetic outcomes of cutaneous excisions performed with the diamond laser scalpel are equivalent to excisions performed with steel scalpels with electrocoagulation for hemostasis. Lasers Surg. Med. 31:41–44, 2002. © 2002 Wiley‐Liss, Inc.