bluuebunny/crossref_metadata_2025 huggingface dataset:
Nerve growth factor signaling of p75 induces differentiation and ceramide‐mediated apoptosis in Schwann cells cultured from degenerating nerves
Authors: Hirata Hitoshi , Hibasami Hiroshige , Yoshida Toshimichi , Ogawa Masaru , Matsumoto Mamoru , Morita Akimasa , Uchida Atsumasa
Published: August 2002

In peripheral nerve regeneration or remyelination, immature Schwann cells expressing p75NTR play cardinal roles in the support and regeneration of axons (Griffin JW, Hoffman PN. Peripheral Neuropathy 361–376, 1993). Only one of four to six Schwann cells participate in remyelination of damaged or regenerating axons. The rest of the cells, or supernumerary Schwann cells, show severe atrophy and gradually decrease in number, reestablishing a 1:1 axon–Schwann cell relationship (Said G, Duckett S. Acta Neuropathol (Berl) 53:173–179, 1981). Recent reports demonstrated that severely atrophied supernumerary Schwann cells are eliminated by apoptosis during axonal regeneration or remyelination (Hirata H, Hibasami H. Apoptosis 3:353–360, 1998; Berciano MT, Calle E. Acta Neuropathol (Berl) 95:269–279, 1998). The mechanism to induce selective death of supernumerary Schwann cells without causing any damage to axon‐associated Schwann cells or axons remains to be determined. In this article, we report that p75NTR, the low‐affinity receptor for all members of neurotrophins, signals both cell differentiation and apoptosis through intracellular ceramide elevation. The final response is dependent on the intracellular ceramide level and Schwann cells modulate their response by changing expression level of p75NTR. This effect was selective for nerve growth factor (NGF). Taken together, the present study suggests that NGF contributes both to phenotypic regulation and to elimination of the dedifferentiated Schwann cells, while supporting survival or regeneration of certain types of axons during peripheral nerve repair or regeneration. GLIA 36:245–258, 2001. © 2001 Wiley‐Liss, Inc.
Differential expression of costimulatory molecules B7‐1 and B7‐2 on microglial cells induced by Th1 and Th2 cells in organotypic brain tissue
Authors: Wolf Susanne A. , Gimsa Ulrike , Bechmann Ingo , Nitsch Robert
Published: August 2002

Autoreactive T‐cells are involved in demyelination, neurodegeneration, and the recruitment of peripheral macrophages and nonspecific activated T‐cells in autoimmune diseases such as multiple sclerosis (MS). The ligation of costimulatory B7 molecules on microglia with CD28/CTLA‐4 on T‐cells is thought to be crucial to the onset and course of MS and its rodent model experimental autoimmune encephalomyelitis (EAE). It is currently unclear as to how far the nature of infiltrating T‐cells has an impact on the expression of the B7 molecules on microglia, the resident antigen‐presenting cells (APCs) of the brain. We studied the expression of B7‐1 and B7‐2 on microglia after encounter with preactivated Th1 and Th2 cells from transgenic mice whose T‐cells express a receptor (TCR) either specific to myelin basic protein (MBP) or ovalbumin (OVA) using murine organotypic entorhinal‐hippocampal slice cultures (OEHSC). Our main finding was that Th1 cells downregulate the constitutive expression of B7‐2 and induce B7‐1 expression while Th2 cells do not induce this B7‐1 upregulation. The main difference between MBP‐ and OVA‐specific cells was seen in experiments were Th1 cells had direct contact to APCs but not to brain tissue. In contrast to MBP‐specific Th1 cells, OVA‐specific Th1 cells required the addition of antigen to upregulate B7‐1 and downregulate B7‐2. When the cells were allowed to have contact to brain tissue, no difference was seen in the pattern of B7 regulation between OVA‐ and MBP‐specific T‐cells. Our data suggest that T‐cells are able to modulate B7 expression on microglial cells in the brain independent of antigen presentation through TCR/MHC‐II ligation but presumably by soluble mediators. GLIA 36:414–420, 2001. © 2001 Wiley‐Liss, Inc.
Persecutory symptoms and perceptual disturbance in a community sample of older people: the Islington study
Authors: Livingston G. , Kitchen G. , Manela M. , Katona C. , Copeland J.
Published: August 2002

Background

While there are extensive studies of paranoid symptoms and perceptual disturbance (PPD) in younger adults, relatively little is known about older adults with similar symptoms.

Method

This study took place in Islington, an inner London borough. Enumeration Districts were randomised to provide a sampling frame. Residents aged 65 or over were interviewed at home. The Short‐CARE was used to elicit psychiatric symptoms and diagnosis. Sociodemographic particulars were elicited using the Client Sociodemographic and Service Receipt Inventory. Questions were asked regarding sight and hearing. We used subsections of the geriatric mental scale to identify people who had PPD symptoms. Medications taken were recorded. We asked ‘Do you have any health problems?’ as a screening question for subjective health problems.

Results

We interviewed 720 people. Twenty‐eight (3.9%) participants scored positively on the PPD sub‐scales of the GMS. A forward logistic regression analysis for independent predictors of PPD found the significant independent predictors were dementia (p = 0.0000; odds ratio 6.8), drinking alcohol in last 6 months (p < 0.03; odds ratio 0.3), drinking alcohol to help sleep (p < 0.005; odds ratio 9.6), subjective memory loss (p < 0.007; odds ratio 3.3) and uncorrected visual impairment (p < 0.02; odds ratio 2.8).

Conclusion

There is a relatively high prevalence of PPD in older people living in the community. This is not associated with higher use of services despite the increased needs. Further studies should consider interventions to meet this unmet need. Copyright © 2001 John Wiley & Sons, Ltd
Recurrent falls are associated with increased length of stay in elderly psychiatric inpatients
Authors: Greene Elaine , Cunningham Conal J. , Eustace Andrew , Kidd Nick , Clare Anthony W. , Lawlor Brian A.
Published: August 2002

Objectives

To identify factors which may contribute to prolonged length of stay in an elderly psychiatric inpatient setting.

Design

Retrospective case note study.

Methods

A list of all patients over the age of 65 discharged from a private psychiatric hospital over a three‐year period excluding those with a length of stay of over 365 days was obtained (n = 1147). A random sample of 150 patients was selected from the study population. A case note study was then performed looking at a number of variables which have been postulated to affect length of stay. The resulting data was analysed using multivariate statistics.

Results

There was no statistically significant association found between baseline factors (including age, gender, cognitive impairment, marital status, order of admission and preadmission living arrangement) and length of stay. Having recurrent falls whilst an inpatient was associated with prolonged hospital stay (p = 0.0006).

Conclusion

Experiencing recurrent falls whilst an inpatient is associated with prolonged length of stay. Recurrent falls in the elderly may be associated with both physical illness and the use of psychotropic medications. A prospective study examining factors contributing to falls would be important in decreasing fall risk and reducing length of stay. Copyright © 2001 John Wiley & Sons, Ltd.
Syntheses and structural characterization of water‐soluble selenium reagents for the redox control of protein disulfide bonds
Authors: Iwaoka Michio , Takahashi Taro , Tomoda Shuji
Published: August 2002

A new class of water‐soluble redox reagents (1–4) that contain selenium as the active site was developed for the purpose of the redox control of protein structures. The X‐ray crystallographic analyses revealed that trans‐3,4‐dihydroxy‐1‐selenolane (DHSred) (1) and its Se‐oxide (DHSox) (2) have two axial hydroxy groups on the selenolane five‐membered ring, whereas trans‐1,2‐diselenane‐4,5‐diol (DSTox) (3), a selenium analog of oxidized dithiothreitol (DTTox), has two equatorial hydroxy groups on the diselenane six‐membered ring. According to the vicinal3JHHcoupling constants observed for1–3, it was suggested that they adopt similar structures in solution to those in the solid state. Diselenothreitol (DSTred) (4), a selenium analog of dithiothreitol (DTTred), was also synthesized, but it was too air sensitive to be isolated. The reactions of1–4with DTToxand DTTredindicated that the oxidizing power of DHSox(2) exceeds by far that of DTTox, while the reducing power of DSTred(4) exceeds that of DTTred. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:293–299, 2001
Measuring the social importance of concentration or dispersion of individual health benefits
Authors: Rodríguez‐Míguez Eva , Pinto‐Prades José‐Luis
Published: August 2002

In this paper we address the importance of distributive preferences in the social valuation of quality‐adjusted life years (QALYs). We propose a social welfare function that generalises the functions traditionally used in the health economic literature. The novelty is that, depending on the individual health gains, this function can represent either preferences for concentrating or preferences for spreading total gain or both together, an issue which has not been addressed until now. Based on an experiment, we observe that this generalisation provides a suitable approximation to the sampled social preferences. Copyright © 2001 John Wiley & Sons, Ltd.
Carcinoma of the skin of the head and neck with perineural invasion
Authors: Mendenhall William M. , Amdur Robert J. , Williams Lorna Sohn , Mancuso Anthony A. , Stringer Scott P. , Mendenhall Nancy Price
Published: August 2002

Background

Perineural invasion is observed in a small subset of patients with carcinomas of the skin of the head and neck.

Methods

Review of the patient literature highlighting the University of Florida experience.

Results

Patients with early perineural invasion are asymptomatic, and the phenomenon is discovered only on pathologic examination of the excised lesion. These patients are defined as having “incidental” perineural invasion, and treatment with surgery followed by postoperative irradiation results in a cure rate of approximately 80%. Undiagnosed, the perineural carcinoma slowly progresses and eventually results in symptoms, usually facial weakness or numbness. The disease eventually extends to the skull base and becomes incompletely resectable. Symptomatic patients are defined as having “clinical” perineural invasion, and aggressive treatment results in a cure rate of approximately 45%.

Conclusions

Perineural invasion is an uncommon spread pattern observed in patients with skin cancer and is associated with a relatively poor prognosis. The likelihood of cure is inversely related to the proximal extent of the cancer and is lower for symptomatic compared with asymptomatic patients. © 2002 John Wiley & Sons, Inc. Head Neck 24: 78–83, 2002.
Inducible nitric oxide synthase expression in laryngeal neoplasia: Correlation with angiogenesis
Authors: Franchi Alessandro , Gallo Oreste , Paglierani Milena , Sardi Iacopo , Magnelli Lucia , Masini Emanuela , Santucci Marco
Published: August 2002

Background

The nitric oxide (NO) pathway plays a relevant role in angiogenesis and tumor progression in squamous cell carcinoma (SCC) of the head and neck. The aim of this study was to assess whether the NO pathway may be correlated with angiogenesis in the transition from laryngeal dysplasia to invasive carcinoma.

Methods

We investigated the expression of the inducible NO synthase (iNOS) in 26 laryngeal precancerous lesions and 35 squamous cell carcinomas with respect to microvessel density. In addition, we determined iNOS activity and cGMP levels in specimens from SCCs.

Results

There was a significant increase of iNOS levels detected immunohistochemically passing from hyperplastic/mild dysplastic to moderate/severe dysplastic lesions to SCC (p = .04). Accordingly, Northern and Western analyses demonstrated higher iNOS mRNA and protein levels in SCCs than dysplastic mucosa. iNOS expression was significantly correlated with microvessel counts both in the group of preneoplastic lesions (p = .02) and in the group of SCCs (p = .01). In addition, iNOS activity was correlated with iNOS immunohistochemical expression (p = .1) and was significantly associated with increased vascularization (p = .03) in SCCs. Similarly, iNOS expression was significantly correlated with cGMP levels in SCC (p = .02) and increased tumor vascularization correlated with higher cGMP levels (rs = .4; p = .01).

Conclusions

Our data indicate that the NO pathway may play a relevant role in the angiogenesis associated with the progression from laryngeal dysplasia to laryngeal SCC. © 2002 John Wiley & Sons, Inc. Head Neck 24: 16–23, 2002.
Internal jugular vein versus external jugular vein anastamosis: Implications for successful free tissue transfer
Authors: Chalian Ara A. , Anderson Timothy D. , Weinstein Gregory S. , Weber Randal S.
Published: August 2002

Background

Microvascular free flaps are becoming the reconstructive option of choice for many head and neck defects. Many previous studies have examined factors predicting free flap survival. No study has compared differences in free flap survival when anastomosed to the internal or external jugular systems.

Methods

Retrospective review of all free flaps performed at an academic medical center by a single head and neck microvascular surgeon during the period July 1995 to December 1999. Flaps were closely monitored postoperatively and taken back to the operating room urgently for arterial insufficiency or venous congestion.

Results

On hundred fifty‐six free flaps were performed during this time period. Sixty‐five free flaps were anastomosed to the external jugular (EJ) vein and 86 to the IJ system (62 to the proximal common facial vein, 17 end‐side on the IJ, and 7 to other branches). Five had either two venous anastomoses or were anastomosed to other veins and were excluded from statistical analysis. Six (4%) vascular thromboses occurred; 5 were venous and 1 arterial. Success by group was 99% for IJ anastomosis (1 arterial thrombosis) and 92% for EJ anastomosis (5 venous thromboses, p = .03). Urgent anastomotic revision and reperfusion salvaged 5 of the 6 flaps (overall success 99%).

Conclusions

Although the overall success rate (96% success with 99% success with salvage) is comparable to other large series, microvascular free flaps anastomosed to the external jugular vein failed at a significantly higher rate than those anastomosed to the IJ system. This suggests that the IJ system should be used as a recipient vessel when feasible. © 2001 John Wiley & Sons, Inc. Head Neck 23: 475–478, 2001
Use of excitotoxins to lesion the hippocampus: Update
Authors: Jarrard Leonard E.
Published: August 2002

Although many of the problems associated with the use of conventional lesion techniques (aspiration, electrolytic, radiofrequency) can be avoided by employing focal injections of excitotoxins, experience gained over the past 12 years has shown that considerable care must be exercised with this newer method, to limit the cell loss to the intended area or structure. Of the toxins that have been used most often to selectively destroy the cells that comprise the hippocampus, ibotenic acid (IBO) and N‐methyl‐D‐aspartate (NMDA) have proved to be nonspecific in their effects on different cell types and these toxins do not cause seizures. In contrast, focal injections of kainate (KA) and quisqualate result in damage that centers primarily in the CA3 pyramidal cell field and hilar cells in the dentate gyrus. In addition, there are obvious seizures and secondary distant damage involving a number of structures and areas associated with mediating seizure activity. Intrahippocampal injections of the toxin colchicine result in a preferential destruction of dentate granule cells but usually also lead to additional cell loss in adjacent areas. Attempts to limit cell loss to specific hippocampal subfields, using different toxins, have met with mixed success. Both the dosage of the agent and the volume injected are important in determining the extent of cell loss, but the volume of the toxin injected has been shown to be especially important in limiting the damage to the intended area. With the development of newer procedures (e.g., immunotoxins, gene knockouts, antisense) that permit more selective cell loss, it should be possible in the future to achieve a level of lesion control that has been lacking in the past. As with the use of excitotoxins, these newer approaches will require special care to limit the damage to the intended area and interpret the results obtained properly. Hippocampus 2002;12:405–414. © 2002 Wiley‐Liss, Inc.
Laminar film condensation heat transfer of hydrogen and nitrogen inside a vertical tube
Authors: Ohira Katsuhide
Published: August 2002

There have been a number of experimental investigations on condensing heat transfer to cryogenic fluids. The investigations with nitrogen and oxygen have shown reasonable agreement between experimental data and those predicted by Nusselt's theory. On the other hand, in the previous investigations with much colder fluids, such as hydrogen, deuterium, and helium, the experimental condensing heat transfer coefficients are smaller than those predicted by Nusselt's theory, and these differences become much larger when the film Reynolds number or decreasing temperature difference across the condensate film is decreased. In the present investigation, hydrogen and nitrogen were condensed inside a vertical tube (d = 15 mm, L = 30 mm) under steady‐state conditions, respectively, and condensing heat transfer coefficients were precisely measured. From the experimental results, the condensing heat transfer coefficients for saturated hydrogen and nitrogen vapors agree with those predicted by Nusselt's theory within ±20%. The results of the present study suggest that deuterium and helium might also behave as predicted by Nusselt's theory. © 2001 Scripta Technica, Heat Trans Asian Res 30(7): 542–560, 2001
Heat transfer in an inclined enclosure with an inner rotating plate
Authors: Kimura Teruo , Takeuchi Masanori , Nagai Niroh , Yoshida Tetsuya
Published: August 2002

The effects of an inner rotating plate on the heat transfer in a differentially heated inclined enclosure were investigated experimentally. The aspect ratio of the enclosure (height/width) was 1 throughout the experiments. An acrylic plate with a small thermal conductivity was installed horizontally at the center of the square enclosure, and was rotated at various speeds by using a motor attached outside of the enclosure. The inclination angle of the enclosure was varied from –90° to 90°. Purified water was used for the working fluid. The flow pattern was sketched by a visualization experiment using aluminum powder. The heat transfer enhancement can be clearly seen for the inclined enclosure with the hot wall downward facing. The rotating plate used here is useful for the regulation of a wide‐ranging heat transfer rate. © 2001 Scripta Technica, Heat Trans Asian Res, 30(4): 331–340, 2001
A comparative study of venlafaxine with a focused education and psychotherapy program versus venlafaxine alone in the treatment of depression in general practice
Authors: Judd F. K. , Piterman L. , Cockram A. M. , McCall L. , Weissman M. M.
Published: August 2002

The efficacy of a focused education and psychotherapy program (FEPP) plus antidepressant was compared with that of usual psychosocial treatment and antidepressant in a general practice setting. The FEPP comprised interpersonal counselling (IPC) delivered in a modified way to suit the general practice setting, together with patient education and selected cognitive behavioural techniques. All patients were treated with venlafaxine‐XR. Thirty‐one patients entered the study, three withdrawing before completion of the 12 week trial. Both treatments produced a statistically significant reduction in BDI and POMS scores from baseline, with greater improvement evident in the FEPP plus antidepressant group. Copyright © 2001 John Wiley & Sons, Ltd.
The role of seepage in erodibility
Authors: Owoputi L. O. , Stolte W. J.
Published: August 2002

This paper describes a laboratory experimental study to examine the role of seepage in the soil‐water erosion process. The study utilized a laboratory flume, which was subjected to both seepage and rainfall in order to determine the exact character of the influence of seepage on erosion rates. The results from the experimental tests performed on sand and sandy clay till are reported.

The experimental results show that seepage, by itself, has little effect on erosion rates. However, the erosion caused by rainfall is increased when seepage is present. The increased erosion was not caused by an increase in the total runoff from the seepage. It was found that seepage has an effect on the erodibility of the sand and sandy clay till. The results also show that the impact of seepage on the erodibility of the sand is greater than that of the sandy clay till. Copyright © 2001 John Wiley & Sons, Ltd.
Applying the scientific method to small catchment studies: a review of the Panola Mountain experience
Authors: Hooper Richard P.
Published: August 2002

A hallmark of the scientific method is its iterative application to a problem to increase and refine the understanding of the underlying processes controlling it. A successful iterative application of the scientific method to catchment science (including the fields of hillslope hydrology and biogeochemistry) has been hindered by two factors. First, the scale at which controlled experiments can be performed is much smaller than the scale of the phenomenon of interest. Second, computer simulation models generally have not been used as hypothesis‐testing tools as rigorously as they might have been. Model evaluation often has gone only so far as evaluation of goodness of fit, rather than a full structural analysis, which is more useful when treating the model as a hypothesis. An iterative application of a simple mixing model to the Panola Mountain Research Watershed is reviewed to illustrate the increase in understanding gained by this approach and to discern general principles that may be applicable to other studies. The lessons learned include the need for an explicitly stated conceptual model of the catchment, the definition of objective measures of its applicability, and a clear linkage between the scale of observations and the scale of predictions. Published in 2001 by John Wiley & Sons, Ltd.
Trends in total phosphorus and total nitrogen concentrations of tributaries to the Swan–Canning Estuary, 1987 to 1998
Authors: Donohue Robert , Davidson W. Angus , Peters Norman E. , Nelson Samuel , Jakowyna Brad
Published: August 2002

Temporal wet‐season trends from 1987 to 1998 of total N and total P concentrations (TN and TP, respectively) in 14 tributaries to the Swan–Canning Estuary in Western Australia were evaluated using the Mann–Kendall or Seasonal kendall tests. Six of the catchments drained clay soils primarily on the Darling Plateau, which borders the sandy coastal plain on the east; two rural catchments drained the coastal plain; and six urban catchments drained the coastal plain. Generally, TN and TP were lower in tributaries draining clay soils than in tributaries draining siliceous sandy soils. Annual median TN and TP were relatively constant and no trends were detected in tributaries draining clay soils. TN and TP were higher (median TN = 1·6 and TP = 0·1 mg l−1) and more variable temporally in tributaries draining the coastal plain. Statistically significant (α < 0·01) TN trends were detected in 50% of the urban coastal plain tributaries and most were decreasing (−0·07 to +0·53 mg l−1 year−1). Decreasing TP trends were detected at the two rural coastal plain tributaries and two of the urban drains (−0·01 to 0·15 mg l−1 year−1 over periods from 5 to 12 years). Flow adjustment of TN and TP was responsible for removing trends in the raw data at some sites. The inter‐annual variability of TN and TP of coastal plain tributaries was also related to the proximity of the water table to the land surface, which in turn was related to the annual precipitation. Fixed‐interval sampling may be able to detect TN and TP changes associated with the implementation of management strategies in sandy coastal plain catchments. Tributary sampling during rainstorms and continuous monitoring of discharge are needed to better define processes controlling nutrient flux and concentration variability, and to detect trends in the urban catchments and the clay soil catchments, primarily those draining the Darling Plateau. Copyright © 2001 John Wiley & Sons, Ltd.
Chinese cross‐border insolvencies: current issues and future developments*
Authors: Shi Jingxia
Published: August 2002

This article deals with several problems pertaining to cross‐border insolvency, an important but ignored area in China. In this article, the current status of Chinese bankruptcy laws has been firstly addressed, with a focus on its legal blank on cross‐border insolvency and unsatisfactory judicial practice. Thereafter, the influential Guargdong International Trust and Investment company case has been analysed, which further highlights the inadequacy of Chinese bankruptcy legislation and crying needs for its reform. Basing on the essential principles embodied in the United Nations Commission on International Trade Law Model Law and European Union Regulation, the gaps between Chinese bankruptcy laws and international practice have been made clear. Accordingly, the developments of Chinese cross‐border insolvency have been proposed in order to provide helpful references for the future legislation. Copyright © 2001 John Wiley & Sons, Ltd.
Impact of the American anti‐smoking campaign on lung cancer mortality
Authors: Rodu Brad , Cole Philip
Published: August 2002

Customary statistics on smoking practices are limited because they do not correlate well with the frequency of smoking‐related diseases. Our study developed outcome measures based on lung cancer mortality and used them to assess the anti‐smoking campaign. Changes in mortality from lung cancer were used to assess significant smoking among 5‐year birth cohorts of white men born from 1901 to 1942. We used each cohort's lung cancer mortality rate at ages 40–44 to indicate its earlier smoking. A lung cancer mortality ratio was developed to describe each cohort's continued smoking from ages 40–44 to 55–59. These ratios were then compared with the durations of the cohorts' exposure to the anti‐smoking campaign that began in 1965. Lung cancer mortality in white men ages 40–44 peaked in 1970 and declined continuously thereafter, indicating that the anti‐smoking campaign promptly reduced significant smoking among younger men. However, the lung cancer mortality ratio indicates that only half of smokers in the specified birth cohorts were able to quit by ages 55–59, despite receiving ever more intense anti‐smoking messages. The anti‐smoking campaign produced moderate benefits among younger white male smokers but fewer benefits among older smokers because of the existence of a large number of inveterate smokers. © 2001 Wiley‐Liss, Inc.
Identification and characterization of genes involved in the carcinogenesis of human squamous cell cervical carcinoma
Authors: Cheng Qing , Lau Wen Min , Tay S.K. , Chew S.H. , Ho T.H. , Hui Kam M.
Published: August 2002

We utilized RT‐PCR differential display and cDNA microarrays to identify cellular genes involved in the multi‐step carcinogenesis of squamous cell cervical carcinoma. Thirty‐eight cervical cancer patients in various stages of the disease and 5 non‐cervical cancer patients were studied. Twenty‐five cDNA clones were identified and these were subsequently demonstrated to be consistently over‐expressed in squamous cell cervical carcinoma biopsies of various FIGO stages. To further evaluate the possible role that these genes may play in the progression of disease, we performed Northern blot analysis and RNA‐RNA in situ hybridization studies using cervical cancer biopsies of various FIGO stages. Of particular interest are the 2 clones G32C4B and G30CC that have been identified to be the NADH dehydrogenase 4 gene and the gene that encodes ribosomal protein S12 respectively when compared to sequences available in the GenBank database. Increased expression of these 2 genes were detected in the matched normal tissues collected together with the late FIGO stages of cervical cancer biopsies. In comparison, upregulation of these 2 genes was not detected in cervical squamous epithelium collected from patients admitted for surgery for non‐malignant conditions, suggesting that expression of these 2 genes may have altered in the adjacent histopathologically “normal” cervical squamous epithelial tissue from cervical cancer patients. The ribosomal protein S12 and the NADH dehydrogenase 4 genes may therefore be potentially useful as early pre‐transformation diagnostic markers for human cervical cancer. © 2002 Wiley‐Liss, Inc.
Manganese superoxide dismutase‐plasmid/liposome (MnSOD‐PL) administration protects mice from esophagitis associated with fractionated radiation
Authors: Epperly Michael W. , Kagan Valerian E. , Sikora Christine A. , Gretton Joan E. , Defilippi Stacy J. , Bar‐Sagi Dapha , Greenberger Joel S.
Published: August 2002

Intraesophageal administration of manganese superoxide dismutase‐plasmid/liposome (MnSOD‐PL) prior to single fraction radiation has been shown to protect mice from lethal esophagitis. In our study, C3H/HeNsd mice received fractionated radiation in two protocols: (i) 18 Gy daily for four days with MnSOD‐PL administration 24 hr prior to the first and third fraction, or (ii) 12 Gy daily for six days with MnSOD‐PL 24 hr prior to the first, third, and fifth fraction. Control radiated mice received either no liposomes only or LacZ (bacterial β‐galactosidase gene)‐plasmid/liposome (LacZ‐PL) by the same schedules. We measured thiol depletion and lipid peroxidation (LP) in whole esophagus and tested the effectiveness of a new plasmid, hemagglutinin (HA) epitope‐tagged MnSOD (HA‐MnSOD). In fractionation protocols, mice receiving MnSOD‐PL, but not LacZ‐PL (200 μl of plasmid/liposomes containing 200 μg of plasmid DNA), showed a significant reduction in morbidity, decreased weight loss, and improved survival. Four and seven days after 37 Gy single fraction radiation, the esophagus demonstrated a significant increase in peroxidized lipids and reduction in overall antioxidant levels, reduced thiols, and decreased glutathione (GSH). These reductions were modulated by MnSOD‐PL administration. The HA‐MnSOD plasmid product was detected in the basal layers of the esophageal epithelium 24 hr after administration and provided significant radiation protection compared to glutathione peroxidase‐plasmid/liposome (GPX‐PL), or liposomes containing MnSOD protein, vitamin E, co‐enzyme Q10, or 21‐aminosteroid. Thus, MnSOD‐PL administration significantly improved tolerance to fractionated radiation and modulated radiation effects on levels of GSH and lipid peroxidation (LP). These studies provide further support for translation of MnSOD‐PL treatment into human esophageal radiation protection. © 2001 Wiley‐Liss, Inc.
High BRCA2 mRNA expression predicts poor prognosis in breast cancer patients
Authors: Egawa Chiyomi , Miyoshi Yasuo , Taguchi Tetsuya , Tamaki Yasuhiro , Noguchi Shinzaburo
Published: August 2002

The prognostic significance of BRCA2 mRNA levels in tumor tissues was studied in sporadic breast cancer patients. BRCA2 mRNA levels were determined by real‐time PCR. Histologic grade III tumors showed significantly (p = 0.001) higher BRCA2 mRNA levels (0.828 ± 0.102 BRCA2/β‐glucuronidase mRNA ratio, mean ± SE) than histologic grade I and II tumors (0.438 ± 0.055) and estrogen receptor (ER)‐negative tumors (0.773 ± 0.102) showed a nonsignificant (p = 0.072) trend toward an increase in BRCA2 mRNA levels compared to ER‐positive tumors (0.541 ± 0.079). Other clinicopathologic parameters, such as menopausal status, lymph node status and tumor size, were not significantly associated with BRCA2 mRNA levels. Patients with high BRCA2 mRNA levels showed a significantly (p = 0.006) lower 5‐year disease free survival rate (63%) than those with low levels (94%). Lymph node metastases, ER negativity and high histologic grade were also significantly (p < 0.05) associated with poor prognosis. Multivariate analysis revealed that BRCA2 mRNA levels were a significant prognostic factor, being independent of the other conventional prognostic factors. Our results suggest that BRCA2 mRNA levels might serve as a clinically useful prognostic factor in breast cancer patients. © 2002 Wiley‐Liss, Inc.
Distinct chromosomal imbalances in pleomorphic and in high‐grade dedifferentiated liposarcomas
Authors: Rieker Ralf J. , Joos Stefan , Bartsch Christine , Willeke Frank , Schwarzbach Matthias , Otaño‐Joos Marta , Ohl Sybille , Högel Josef , Lehnert Thomas , Lichter Peter , Otto Herwart F. , Mechtersheimer Gunhild
Published: August 2002

Using comparative genomic hybridization, DNA copy number changes were studied in 14 pleomorphic liposarcomas and compared to those detected in high‐grade areas of 9 dedifferentiated liposarcomas. A total of 251 gains and 84 losses were detected. The most frequent gains involved subregions of chromosomal arms 12q and 20q (70% each), 5p (57%), 6q and 9q (52% each), 1q, 7p and 17p (48% each), 1p (43%), 6p and 17q (39% each), 20p and 22q (35% each) as well as 7q and 12p (30% each). The same subregions were also affected by 30 high level amplifications. The most frequent losses were found in subregions of chromosomal arms 13q (35%) as well as 11q and 12p (30% each). Overall, gains of chromosomal material were more frequent than losses (p < 0.001). There were significant differences in the frequency and distribution of recurrent chromosomal imbalances between pleomorphic liposarcomas and the dedifferentiated areas of dedifferentiated liposarcomas. Gains of chromosomal material detected predominantly in pleomorphic liposarcomas involved subbands 5p13–p15 (p < 0.010), 1p21 (p < 0.019), 1q21–q22 (p < 0.040) and 7q22 (p < 0.049). Conversely, high level amplifications within chromosomal subregion 12q13–q21 were only found in the dedifferentiated components of dedifferentiated liposarcomas (p < 0.001). Overall, both gains and the less pronounced losses of chromosomal material were more frequent in pleomorphic than in dedifferentiated liposarcomas (p < 0.001 and p < 0.025, respectively). These results show that pleomorphic liposarcomas display a considerable number of recurrent chromosomal imbalances that are essentially different from those present in high‐grade areas of dedifferentiated liposarcomas. Therefore, genetic data are considered as a helpful diagnostic adjunct for the discrimination between these 2 types of liposarcoma. The overall higher frequency of chromosomal imbalances in pleomorphic as compared to dedifferentiated liposarcomas could account for the more aggressive biological behavior of pleomorphic relative to dedifferentiated liposarcoma types. © 2002 Wiley‐Liss, Inc.
History of allergies and autoimmune diseases and risk of brain tumors in adults
Authors: Brenner Alina V. , Linet Martha S. , Fine Howard A. , Shapiro William R. , Selker Robert G. , Black Peter M. , Inskip Peter D.
Published: August 2002

To explore a possible influence of the immune system in the development of brain tumors, we evaluated the relationship between history of allergies and autoimmune diseases and risk of brain tumors within a large, hospital‐based case‐control study. Cases (n = 782) were patients recently diagnosed with glioma (n = 489), meningioma (n = 197) or acoustic neuroma (n = 96) at hospitals in Boston, Phoenix and Pittsburgh (USA). Controls (n =799) were patients hospitalized for a variety of nonmalignant conditions and frequency‐matched to cases by hospital, age, sex, race/ethnicity and distance of residence from hospital. Research nurses collected data by personal interview of patients. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. There was a significant inverse association between glioma and history of any allergies (OR = 0.67, 95% CI = 0.52–0.86) or autoimmune diseases (OR = 0.49, 95% CI = 0.35–0.69). No significant associations were evident for meningioma or acoustic neuroma with history of any allergies. An inverse association was observed between meningioma and history of autoimmune diseases (OR = 0.59, 95% CI = 0.38–0.92). There was a suggestion of interaction between allergies and autoimmune diseases on risk of glioma (p = 0.06), with subjects having both conditions being at lowest risk (OR = 0.24, 95% CI = 0.14–0.42). Among the specific conditions, asthma and diabetes showed the most consistent associations (OR = 0.63, 95% CI = 0.43–0.92 and OR = 0.44, 95% CI = 0.27–0.70, respectively). Our results add to evidence that persons with allergies or autoimmune diseases are at reduced risk of glioma. The basis of the associations is not clear, but they might imply a role of immunologic factors in the development of brain tumors. Published 2002 Wiley‐Liss, Inc.
The MEK/ERK pathway mediates COX‐2‐selective NSAID‐induced apoptosis and induced COX‐2 protein expression in colorectal carcinoma cells
Authors: Elder Douglas J.E. , Halton Dawn E. , Playle Laura C. , Paraskeva Christos
Published: August 2002

Nonsteroidal antiinflammatory drugs (NSAIDs) can prevent colorectal tumorigenesis in humans and in rodents. In vitro and in vivo studies indicate that one of their principal antineoplastic avenues is the induction of apoptosis. We have shown previously that NS‐398, which selectively inhibits cyclooxygenase‐2 (COX‐2) over cyclooxygenase‐1, induces apoptosis of colorectal tumour cells and elevates COX‐2 protein expression. Here, we have determined that the extracellular signal‐regulated kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK) pathway mediates these effects of NS‐398. Treatment of HT29 colorectal carcinoma cells with 75 μM NS‐398 caused activation of ERK‐1/‐2 but not of the p38 and c‐Jun N‐terminal kinase (JNK) mitogen‐activated protein kinases. This was apparent at 24 hr and maintained at 72 hr. U0126, a specific inhibitor of the ERK‐activating kinases MEK‐1/‐2, prevented the activation of ERK induced by NS‐398 and blocked the increase in COX‐2 protein expression seen when HT29 cells were treated with NS‐398 alone. The activation of ERK by NS‐398 preceded and accompanied a decrease in attached cell yield and an increase in apoptosis. U0126 dose‐dependently protected HT29 cells from these antiproliferative effects of NS‐398, indicating an antiproliferative role for sustained ERK‐1/‐2 activation in response to this NSAID. These results point to a key role for the MEK/ERK signalling pathway in mediating the effects of a COX‐2‐selective NSAID on colorectal carcinoma cells. © 2002 Wiley‐Liss, Inc.
Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC‐3
Authors: Suzuki Kazuhiro , Koike Hidekazu , Matsui Hiroshi , Ono Yoshihiro , Hasumi Masaru , Nakazato Haruki , Okugi Hironobu , Sekine Yoshitaka , Oki Kazuya , Ito Kazuto , Yamamoto Takumi , Fukabori Yoshitatsu , Kurokawa Kohei , Yamanaka Hidetoshi
Published: August 2002

Genistein is a major component of soybean isoflavone and has multiple functions resulting in antitumor effects. Prostate cancer is 1 of the targets for the preventive role of genistein. We examined the effect of genistein on human prostate cancer (LNCaP and PC‐3) cells. Proliferation of both cell lines was inhibited by genistein treatment in a dose‐dependent manner. To obtain the gene expression profile of genistein in LNCaP cells, we performed cDNA microarray analysis. The expression of many genes, including apoptosis inhibitor (survivin), DNA topoisomerase II, cell division cycle 6 (CDC6) and mitogen‐activated protein kinase 6 (MAPK 6), was downregulated. Expression levels were increased more than 2‐fold in only 4 genes. The glutathione peroxidase (GPx)‐1 gene expression level was the most upregulated. Quantitative real‐time polymerase chain reaction revealed significant elevation of transcript levels of GPx‐1 in both LNCaP and PC‐3 cells. Upregulation of gene expression levels accompanied elevation of GPx enzyme activities. In contrast, no significant changes were observed in the gene expression levels and enzyme activities of the other antioxidant enzymes, superoxide dismutase and catalase. GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells. © 2002 Wiley‐Liss, Inc.
Tumor production of angiostatin is enhanced after exposure to TNF‐α
Authors: Mauceri Helena J. , Seetharam Saraswathy , Beckett Michael A. , Lee John Y. , Gupta Vinay K. , Gately Stephen , Stack M. Sharon , Brown Charles K. , Swedberg Kirsten , Kufe Donald W. , Weichselbaum Ralph R.
Published: August 2002

Infection of tumors with an adenoviral vector expressing a chimeric gene composed of the CArG elements of the Egr‐1 promoter and a cDNA encoding TNF‐α (Ad.Egr‐TNF) has previously been shown to result in the production of high intratumoral levels of TNF‐α and thereby tumor regression. The antitumor effects of TNF‐α were ascribed to vascular thrombosis. We and others, have reported that inhibition of tumor vessel thrombosis using anticoagulation therapy does not abrogate the antitumor effects after TNF‐α treatment. To investigate the potential antiangiogenic effects of TNF‐α, we studied the generation of angiostatin after intratumoral injection of Ad.Egr‐TNF. We report an increase in plasma angiostatin levels both during and after treatment with Ad.Egr‐TNF that parallel tumor regression. We also report that TNF‐α enhances angiostatin production by inducing the activity of plasminogen activator and the release of MMP‐9 by tumor cells. These studies support a model in which the antiangiogenic effects of TNF‐α on the tumor microvasculature are mediated by generation of angiostatin. © 2002 Wiley‐Liss, Inc.
Clinical role of MMP‐2/TIMP‐2 imbalance in hepatocellular carcinoma
Authors: Giannelli Gianluigi , Bergamini Carlo , Marinosci Felice , Fransvea Emilia , Quaranta Michele , Lupo Luigi , Schiraldi Oronzo , Antonaci Salvatore
Published: August 2002

An imbalance between the proteolytic activity of matrix metalloproteinase‐2 (MMP‐2) and the tissue inhibitor of MMP‐2 (TIMP‐2) is responsible for degradation of extracellular matrix (ECM) components and plays a critical role in tumor invasion and in metastasis formation. The occurrence of intra‐hepatic metastasis, which severely affects prognosis and long‐term survival, is commonly observed in the course of hepatocellular carcinoma (HCC). We investigated the expression of MT1‐MMP in tissues, whereas both MMP‐2 and TIMP‐2 were evaluated in the sera and tissues (primary and metastatic nodules) of HCC patients with and without metastasis, whose clinical outcome was followed over a 2‐year period. MT1‐MMP expression was similar among primary nodule tissues of patients with and without metastasis. Serum and tissue levels of MMP‐2 were not statistically different between patients with and without metastasis, but MMP‐2 was concentrated at the invasive edge of the metastatic tissue. On the contrary, serum and tissue levels of TIMP‐2 were significantly higher in HCC patients without metastasis than in those with. This situation was not only observed in the primary HCC tissues, but also in the metastatic nodules. These results correlate with the clinical outcome, because more than 90% of the patients with high levels of TIMP‐2 were still alive after 2 years, whereas less than 30% with low levels of TIMP‐2 had survived. Furthermore, we found a strict correlation between tissue and serum levels of TIMP‐2, this suggesting that a MMP‐2/TIMP‐2 imbalance and in particular TIMP‐2 levels, could represent an important prognostic factor in patients with HCC. © 2001 Wiley‐Liss, Inc.
Macroeconomic factors and share returns: an analysis using emerging market data
Authors: Fifield S.G.M. , Power D.M. , Sinclair C.D.
Published: August 2002

This paper investigates the extent to which global and local economic factors explain returns in emerging stock markets (ESMs). The economic factors are determined using principal components analysis. The results suggest that the local economic variables included in this study can be summarized by GDP, inflation, money and interest rates, while the selected global variables can be sufficiently characterized by world industrial production and world inflation. These components are then used as inputs into a regression analysis in order to explain the index returns of 13 ESMs over the period 1987–96. The analysis indicates that while world factors are significant in explaining ESM returns, local factors may also play a crucial role. Copyright © 2002 John Wiley & Sons, Ltd.
Poland: between geopolitical shifts and emerging migratory patterns
Authors: Iglicka Krystyna
Published: August 2002

This paper describes trends and mechanisms in population mobility in Poland which are gradually transforming this major sending country in the Central and Eastern European region into a country of net immigration and transit. Emphasis is placed on the migration into Poland from the former USSR countries since 1989, in the context of the recent geopolitical shifts in the CEE region: collapse of communist rule and forthcoming European Union enlargement. Although stress has been put on ongoing changes in migratory patterns and mechanisms that began after the collapse of the political regime, it is also emphasised here that one should not analyse trends that occurred after 1989 without understanding the history and mechanism of migration prior to that date. Therefore, trends and mechanisms of migration into Poland observed during the transition period are examined from the perspective of the migration system approach. Copyright © 2002 John Wiley & Sons, Ltd.
Infant temperament, pleasure in parenting, and marital happiness in adoptive families
Authors: Leve Leslie D. , Scaramella Laura V. , Fagot Beverly I.
Published: August 2002

Temperamental characteristics have been related to later externalizing and internalizing behavioral outcomes. To assess the relationship between temperament and the early family environment, we measured infant temperament, pleasure in parenting, and marital happiness via parent report in 99 families with a nonrelative adoptive infant. Perceptions of child temperament were assessed using two subscales of the Infant Behavior Questionnaire (IBQ; Rothbart, 1981). Mothers and fathers who rated their adoptive child as showing more Distress to Limitations (on the IBQ) reported less pleasure in routine parenting activities; this effect was mediated by marital happiness for fathers. Mothers reported less pleasure in parenting with infants perceived to be more temperamentally fearful (on the IBQ). The bidirectional relationship between temperamental characteristics and pleasure in parenting is discussed. © 2001 Michigan Association for Infant Mental Health.