bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolation of Intermediate Filaments
Authors: Leung Conrad L. , Liem Ronald K.H.
Published: July 2006

Intermediate filaments (IFs) are found in most eukaryotic cells and are made up of various IF proteins. IFs are highly insoluble in conventional extraction buffers and are therefore commonly purified under denaturing condition. Purified IF proteins can be reassembled into filaments by dialysis. At least 65 IF proteins are found in humans, and the procedures for the purification of each subunit vary somewhat, although many basic steps are similar. To illustrate the isolation of IFs, a detailed protocol is described for purifying neurofilament proteins (NFL, NFM, and NFH subunits) from bovine spinal cord. These three proteins form the predominant IF network in mature neurons. An alternative method for the purification of NFL from a prokaryotic expression system is also included. The isolation of recombinant proteins from bacteria is quite straightforward and may therefore be the method of choice for producing and purifying IFs. Finally, there is a discussion of the purification methods of other IF proteins.
Using Dali for Structural Comparison of Proteins
Authors: Holm Liisa , Kääriäinen Sakari , Wilton Chris , Plewczynski Dariusz
Published: July 2006

The Dali program is widely used for carrying out automatic comparisons of protein structures determined by X‐ray crystallography or NMR. The most familiar version is the Dali server, which performs a database search comparing a query structure supplied by the user against the database of known structures (PDB) and returns the list of structural neighbors by e‐mail. The more recently introduced DaliLite server compares two structures against each other and visualizes the result interactively. The Dali database is a structural classification based on precomputed all‐against‐all structural similarities within the PDB. The resulting hierarchical classification can be browsed on the Web and is linked to protein sequence classification resources. All Dali resources use an identical algorithm for structure comparison. Users may run Dali using the Web, or the program may be downloaded to be run locally on Linux computers.
Nasopharyngeal Cancer
Authors: Wee Joseph , Tan Eng Huat
Published: July 2006

Nasopharyngeal carcinoma (NPC) is unusual in several ways. Its epidemiology, associated with ethnicity, genetic predisposition, viral, and environmental dietary exposure, is unique in itself. In addition, the predilection for certain geographic areas, with relative sparing of adjacent regions is noteworthy. Unjustly perhaps, NPC poses a formidable public health hazard to countries that are relatively compromised in their ability to provide the technical diagnostic and therapeutic approaches considered to be necessary for optimal management today. However, what sets it apart from most diseases is the anatomic challenge it presents to the oncology team because of the proximity of the nasopharynx to critical anatomic structures and the high predilection for distant metastasis once the primary and regional lymph‐node areas are extensively involved, which is all too frequent.

In this chapter we discuss prognostic factors of importance in the management of NPC using the classification proposed earlier in this book. Factors will be considered by whether they relate to the
disease
itself, the patient (or
host
), or the
environment
which influences the opportunity for optimal treatment and diagnosis. The classification may not always apply since, in the case of NPC, there may be overlap among factors and arbitrary placement of factors may be necessary. We will also attempt to categorize the available evidence into factors which are essential to our ability to treat the disease (
essential
factors), those which add valuable information about the disease but do not affect treatment decisions (
additional
factors), and finally those that are being described and may provide important understanding of disease behavior and therapeutic approaches in future years. In the interest of relevance to the treatment of the disease, and for brevity, the discussion of the final group of factors (those termed
new and promising
), will be restricted to experience of patient outcome. Therefore, preclinical studies will not receive attention.

Special attention to the classification of stage of disease will be given. This is because for NPC anatomic features are so important that a relevant and reproducible system of classification merits attention above other prognostic factors. In fact, few diseases received the same level of attention in the preparation of the 5th edition (TNM) stage classification of the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC). A major revision of the NPC stage was accomplished by a substantial collaborative consultation among radiation oncologists in Southeast Asia, with support from diagnostic radiologists, pathologists, and surgeons there and elsewhere.
Thyroid Cancer
Authors: Brierley James D. , Asa Sylvia L.
Published: July 2006

The thyroid gland is composed of follicular cells, parafollicular cells, and connective tissue with occasional lymphocytes. Each of these cell types can give rise to histologically distinct tumors that differ significantly in behavior, prognosis, and response to treatment. The commonest tumors by far are those derived from follicular epithelial cells; these tumors are classified as differentiated (papillary and follicular), poorly differentiated (insular), and undifferentiated (anaplastic). Medullary thyroid cancers are derived from parafollicular cells. Tumors derived from lymphocytes and connective tissue cells are similar to such lesions elsewhere in the body, but a detailed discussion of those entities is beyond the scope of this chapter.

In one of the earliest studies on prognostic factors in thyroid cancer, the multivariate analysis of the European Organization for Research and Treatment of Cancer (EORTC) Thyroid Cancer Co‐operative Group, all histologies were combined. The 5‐year survival ranged from 80% in differentiated carcinoma (papillary and follicular), to 55% in medullary thyroid carcinoma (MTC), to 10% in anaplastic carcinoma. Most subsequent studies of prognostic factors in thyroid cancer were developed for individual histologic types [differentiated papillary–follicular, poorly differentiated (insular), medullary, and anaplastic thyroid carcinomas] and they will be considered separately in this review. Some studies combine papillary and follicular, while others do not. The focus of this chapter is a review of the tumor‐, host‐ and environment‐related prognostic factors in differentiated thyroid cancer, with an additional discussion of prognostic factors in other thyroid histologies.
Esophageal Cancer
Authors: Stein Hubert J. , von Rahden Burkhard H.
Published: July 2006

In contrast to other tumors of the gastrointestinal tract, independent prognostic factors have only recently been identified in patients with esophageal carcinoma. This is because most studies assessing the prognosis of patients with esophageal cancer were retrospective univariate analyses of small patient populations that were usually not treated according to standardized protocols. Due to interrelations between various patient‐ and tumor‐related factors and their alterations by therapeutic strategies, the independent prognostic effect of individual parameters cannot be deducted from these analyses. This can only be achieved by multiple stepwise regression analysis applied to a sufficiently large patient population that has undergone standardized treatment and has been followed for a sufficiently long period of time. Studies that meet these criteria have become available only during the past decade. The chapter critically reviews the currently available literature on prognostic factors in patients with esophageal cancer, which are classified into the three categories: (1) tumor‐ or disease‐related prognostic factors; (2) patient‐related factors; and (3) environment‐ or treatment‐related factors.
Lung Cancer
Authors: Brundage Michael D. , Mackillop William J.
Published: July 2006

Lung cancer is best conceptualized as a group of heterogeneous clinical entities with common molecular and cellular origins, but with different clinical behaviors, and hence, different prognoses. Lung cancer has a major impact on population health; taken together, lung cancers are the most common cause of cancer death in both males and females in North America. Overall, only 13% of patients survive more than 5 years after being diagnosed.

Determining the prognosis for an individual patient with lung cancer is difficult, in part, because the clinical course of the disease in the individual case can evolve along a seemingly infinite combination of branching pathways. Over 90% of lung cancer patients present with signs or symptoms of disease, and since no symptoms or signs are pathognomonic for lung cancer, the disease has a capacity clinically to mimic other cancers and other nonmalignant diseases with a constellation of possible presenting symptoms. These varying presentations, and potential clinical evolutions, are in turn due to the multiple potential manifestations of the primary tumor, metastatic sites of involvement, and paraneoplastic syndromes.

Despite the heterogeneity of the clinical manifestations of lung cancer, the prognosis for a population of patients with lung cancer is remarkably predictable. The overall mortality rates for lung cancer in North America over the last 15 years have remained unchanged. A population‐based study of over 12,000 patients with unresected non‐small‐cell lung cancer registered in seven Ontario Regional Cancer Centers (1982–1991) demonstrated no significant differences in patient survival either between Centers or over time. The predictability of population survival outcomes is of limited usefulness, however, due to the marked heterogeneity of patients making up the overall population. Prognostic factors are thus used to divide the overall population of lung cancer patients into subgroups in order to realize the benefits of prognostic stratification. A number of studies have addressed the identification and application of such factors.
Malignant Thymoma
Authors: Bezjak Andrea , Payne David G.
Published: July 2006

The thymus gland, located in the anterior mediastinum, plays a crucial role in the development of immunological competence during fetal development and infancy. It is composed of both thymic epithelial cells and lymphoid cells, many originating in the bone marrow. During the development period, the complex system of T lymphocytes evolves, underpinning functions of foreign antigen processing and self‐recognition of the organism's histocompatibility complex. The gland undergoes significant involution in childhood, resulting in a twin‐lobed organ composed of fibrous, lymphatic, and epithelial elements. Its function in the adult is unknown; however, evidence for its immunologic role is seen in the involution associated with various disorders, including autoimmune diseases and AIDS, and conversely in the immunodeficiency associated with primary thymic aplasia. Tumors of the thymus are unusual, but account for about 15% of mediastinal tumors (or over 50% of masses in the anterior mediastinum). These neoplasms contain varying proportions of lymphocytes and of thymic epithelial cells, with a generally benign appearance. However, all thymomas are considered to be malignant tumors possessing differing degrees of aggressivity, or invasiveness. When frank cytologic features of malignancy are seen in epithelial cells, the tumor is regarded as a thymic carcinoma.

Clinical features typically relate to the size of the mass and proximity to other organs. The introduction of the Masaoka classification, based on the extent of local invasion by malignant cells, was an important advance in the addressing the need for comparative studies. However, the association of thymoma with various autoimmune disorders is distinctive and possibly prognostic. These conditions include myasthenia gravis, hypogammaglobulinemia, and red‐cell aplasia. Interestingly these syndromes are not associated with thymectomy in another context. A variety of other paraneoplastic syndromes are seen; about 40% of thymoma patients have one, and many suffer from multiple such disorders. For the purpose of this discussion these will be considered to be tumor‐related factors. Note that in accordance with the guidelines for this text, only factors that are required for clinical decision making are considered “essential.”
Cutaneous Malignant Melanoma
Authors: Beer Trevor W. , Heenan Peter J.
Published: July 2006

The most important prognostic factor in patients with cutaneous malignant melanoma (CMM) is the anatomic extent of disease and, specifically, presence of metastasis. In those patients without clinical metastasis at the time of diagnosis, direct measurement of tumor thickness by the method of Breslow remains the most accurate single prognostic factor. The improvement in survival rates recorded over time has been associated with a decrease in tumor thickness, and geographical differences in prognosis have been related to differences in tumor thickness. Furthermore, the prognostic effects of such features as the histologic type and level of invasion are overridden by the effect of tumor thickness. The measurement of tumor thickness by means of an ocular micrometer is also more reproducible among pathologists than the recognition of histologic subtypes and the assessment of level of invasion according to anatomical landmarks, both of which are more prone to subjective interpretation and interobserver variation.

It is also apparent, however, that although tumor thickness remains the best available single prognostic index, it provides only a rough guide to the outcome for an individual patient. Increasing efforts have been made, therefore, to discover more accurate means of assessing the risk of metastasis in patients with melanoma by using multifactorial prognostic models and by searching for molecular markers of metastatic potential. Prognostic models, however, although yielding impressive results in some studies, may not always be accurate in their application to individual patients, and the search for molecular markers of metastatic potential, although providing initially promising results, has as yet failed to identify prognostic factors that are as accurate or as practically applicable as the measurement of tumor thickness.
Uterine Cervix Cancer
Authors: Hauspy Jan , Harley Ian , Fyles Anthony W.
Published: July 2006

Carcinoma of the cervix accounts for approximately 20% of all gynecologic cancers and 2% of all malignancies in women. Numerous prognostic factors have been studied in patients with cervical carcinoma, using both univariate and multivariate analysis. Differences in endpoints of analysis, whether survival (disease‐free or overall), relapse‐free rate, or local control rate, make comparison of such studies difficult. The failure to perform a multivariate analysis, or the use of different covariates in multivariate analyses, can further complicate comparisons between studies. Not all factors are relevant to all patients; for example, depth of tumor invasion and presence of vascular‐space invasion can only be reliably determined in patients treated with surgery, whereas hemoglobin level is important in patients treated with radiation. This review concentrates largely on those factors identified using multivariate techniques, such as log rank or Cox regression analysis, in order to account for interactions between various factors. Where available, estimates such as hazard ratios will be included in order to indicate the strengths of the individual variables.
Endometrial Cancer
Authors: Herrera Fernanda G. , Milosevic Michael F.
Published: July 2006

In many industrialized countries, endometrial cancer has surpassed cervical cancer as the most common form of malignancy affecting the female genital tract. This has occurred due to the effectiveness of screening programs in reducing both the incidence and mortality rates for cervical cancer. Improvement in life expectancy for many women also has led to an increased number of patients being diagnosed with endometrial cancer, which is predominantly a disease of postmenopausal women.

Endometrial cancer most often presents with the symptom of postmenopausal bleeding. Because this manifestation is often found early in the course of the disease and is significantly alarming, women generally present themselves promptly to their physicians for investigation. The majority of endometrial cancers are thus diagnosed as stage I lesions. In certain situations, however, this condition has the potential to behave in an aggressive fashion, resulting in recurrence and ultimately death. The identification of those factors that place patients at high risk for recurrence has been the primary focus of much of the research on this condition in the past 20 years.

Although endometrial cancer is predominantly a disease of postmenopausal women, approximately 20–25% of cases will occur before menopause and a further 5% occur before age 40. Obesity, particularly upper body obesity, nulliparity, and late menopause have all been associated with an increase in risk for endometrial cancer. Use of exogenous unopposed estrogen and tamoxifen have also been associated with an increased risk for the development of endometrial cancer. Use of oral contraceptive tablets and smoking, however, have been associated with a decrease in the risk for endometrial cancer and women who develop endometrial cancer while on exogenous estrogen appear to have favorable prognosis.
Gestational Trophoblastic Disease
Authors: Ngan Hextan Y. S. , Chan Karen K. L. , Tam Kevin Fai
Published: July 2006

Gestational trophoblastic disease (GTD) is a disease of the proliferative trophoblastic allografts and includes partial mole (PM), complete hydatidiform mole (CM), invasive mole, metastatic mole, choriocarcinoma (CC), and placental site trophoblastic tumor (PSTT). While CC and PSTT are definitely neoplastic, the various types of molar pregnancies are basically benign, but with a potential to behave like a malignant disease that requires chemotherapy. This potential malignant behavior is identified by the failure of regression of the human chorionic gonadotrophin (hCG) in the absence of a normal pregnancy and is termed gestational trophoblastic tumor (GTT) or gestational persistent trophoblastic disease (GPTD). The criteria for the diagnosis of postmolar GTT varies among different centers in the world. Basically, if the hCG level fails to fall satisfactory over 3–4 weeks, or when there is a rise in the hCG level over 2–3 weeks, GTT is diagnosed and further investigations should be done to assess the extent of the disease. The risk or predictive factors of PTD following mole will be discussed in the first major section below.

In GTT, unlike other solid malignancies, metastasis does not always mean poor prognosis. If the metastatic lesion is a mole rather than CC, the prognosis is much better. However, histological confirmation is uncommon because most cases of GTT are treated with chemotherapy. Thus, other prognostic factors in addition to metastasis have to be taken into consideration in assessing the prognosis of a GTT. The prognostic factors of GTT are be discussed in the second major section below. PSTT arises from the intermediate trophoblasts and behaves quite differently from that of GTT and will be discussed separately in the final major section below.
Gliomas
Authors: Minniti Guiseppe , Brada Michael , Kleihues Paul , Ohgaki Hiroko
Published: July 2006

Tumors of the nervous system amount to less than 2% of the total human cancer burden, the overall incidence being in the range of 7–9 new cases a year per 100,000 population. They affect all age groups and their etiology is largely unknown. More than 40 clinicopathological disease entities have been classified by the World Health Organization (WHO) and this makes the identification of factors with unequivocal prognostic value difficult. Large, randomized therapy studies with long‐term follow‐up of a significant number of patients have concentrated on malignant gliomas of astrocytic and oligodendroglial origin.

During the past decade, numerous studies have been published that, in addition to conventional clinical and histopathological parameters, suggested certain genetic alterations as potential prognostic factors, but for tumors of the nervous system, few of these have been confirmed in subsequent reports. The establishment of reliable prognostic factors requires the critical, unbiased evaluation of large databases and often remains an elusive goal.
Pediatric Cancers
Authors: Bouffet Eric , Hodgson David C. , Koh Eng‐Siew
Published: July 2006

Pediatric cancers include a broad spectrum of diseases. Cancer is diagnosed in only 8400 children in the United States less than 15 years of age annually, although death from cancer is the second major cause of mortality in developed countries. Childhood cancers differ from adult cancers in their origins and histologic subtypes, their etiologies, their response to treatment, and the outcomes. In the adult population, epithelial cancers are most common and many are related to environmental carcinogens. In contrast, pediatric malignancies more commonly arise in hematopoietic tissue or in the central nervous system (CNS).

The most common pediatric malignancies are acute leukemia, non‐Hodgkin's lymphoma, Hodgkin's disease, and primary CNS tumors. Neuroblastoma, Wilms' tumor, rhabdomyosarcoma, and retinoblastomas are the most common solid tumors occurring in children. The etiology of most childhood malignancies is unknown, although some solid tumors do occur in association with recognized genetic defects. Bilateral retinoblastoma, for instance, occurs in children with mutations in the retinoblastoma tumor suppressor gene
RB1
. Wilms' tumor occurs in association with mutations in the
WT1
gene in the Denys‐Drash Syndrome. Rhabdomyosarcomas are seen in children with the LiFraumeni syndrome with
p53
gene mutations.

Major advances in cancer genetics and the molecular biology of cancer have been gained through research in pediatric malignancies. Despite its rarity in comparison to adult malignancies, many of the most important discoveries about cancer biology and cancer genetics have come from research in pediatric cancers. In addition, the role of prognostic factors in determining treatment for an individual patient is best exemplified by neuroblastoma which is discussed in this chapter. At the present time, only a limited number of cancers in children have prognostic factors that have been prospectively evaluated and confirmed. In this chapter, we review those pediatric cancers that have clearly defined prognostic factors. The understanding of cancer genetics gained from the study of pediatric cancers, the identification of prognostic factors, their confirmation in clinical trials, and their widespread acceptance can be viewed as a paradigm for prognostic factors in cancer patient management.
Prognostic Factors in Population‐Based Cancer Control
Authors: Groome Patti A.
Published: July 2006

How prognosis facilitates cancer control in unbiased (entire) cancer populations is the subject of this chapter. Prognosis applies to the period posttreatment and relates to the entire period postdiagnosis. Changes in population‐level cancer incidence are therefore used to measure the impact of prevention strategies. As implied in the definition, “those who develop cancer” are the group to whom improvements in the probability of cure, survival, and quality of life are targeted. These outcomes are the key ones in this study of the determination and impact of prognostic factors. Prevention through screening (early detection) and effective treatment are key interventions. The concept of prevention is best defined in the context of levels, traditionally called primary, secondary, and tertiary prevention. In the cancer setting, it is more aptly defined thus: secondary prevention as early detection and treatment, and tertiary prevention as targeting prolonged survival and increased quality of life. Secondary and tertiary prevention are aimed at cancer patient populations. Cancer registries and tumor banks are increasingly aware of their role in understanding cancer control factors that describe the care received and access to care in a population and these can be more relevant. Prevention spans the disease trajectory and linking cancer control to prevention reminds us that cancer control is a public health activity.
Prognostic Factors in Terminal Cancer
Authors: Glare Paul
Published: July 2006

Predicting life expectancy in terminally ill cancer patients is very important for patients, their families, clinicians, researchers, and policy makers. Accurate prognosis is a key skill the physician can bring to the management of patients with terminal cancer. Life expectancy is the usual outcome under consideration in patients with terminal cancer and the main focus of this chapter. Some of the trends to over‐aggressively treat patients with advanced cancer being seen in recent years might be avoided if physicians were better prognosticators. Prognostication in terminal cancer is
subjective
judgment, where the physician consciously combines and processes the data to render a judgment about the prognosis. This may also be called “clinical acumen”. Patient‐related factors that might affect prognosis include demographics, comorbidities, performance status, symptoms, psychological status, quality of life, and laboratory parameters. The role of psychological factors in cancer survival remains controversial and confusing. The physician's clinical prediction of survival (CPS) is best used in conjunction with other parameters and could be integrated into prognostic models and scores. Proinflammatory cytokines, such as IL‐6, may prove to be useful prognostic markers. Subjective judgment will remain important and it is apparent that the CPS contains some useful prognostic information. Objective prognostic factors, such as performance status, symptoms of the cancer cachexia syndrome, breathlessness, cognitive impairment, and simple blood test results can be used to inform clinical acumen. Accurate prognostication is a clinical skill that needs to be resurrected, as it is crucial to good end‐of‐life care in terminal cancer. It should be included in cancer medicine curricula.
Simultaneous determination of degradation products related to chemical warfare agents by high‐performance liquid chromatography/mass spectrometry
Authors: Wada Takeharu , Nagasawa Eiko , Hanaoka Shigeyuki
Published: July 2006

Chemical munitions that include organoarsenic chemical agent were manufactured by Japanese imperial forces and abandoned in various locations of Japan and China at the end of World War II. These organoarsenic compounds and various decomposition products have caused environmental contamination and damage to health. For the analysis of chemical warfare agents (CWA) and related compounds in environmental samples, determination was carried out using high‐performance liquid chromatography/tandem mass spectrometry of nine CWA‐related compounds: 2‐chlorovinylarsonic acid (CVAOA), phenylarsonic acid (PAA), thiodigricol (TDG), phenylmethlarsinic acid (PMAA), 2‐chlorovinylarsine oxide (CVAO), phenylarsine oxide (PAO), diphenylarsenic acid (DPAA), bis(2‐chlorovinyl)arsinous acid (BCVAA) and bis(diphenylarsine)oxide (BDPAO). TDG and eight arsine compounds could be simultaneously measured by LC/MS/MS equipped with a reversed‐phase column (C8). The limits of detection of CVAOA, PAA, PMAA, DPAA and other compounds were 0.5, 0.05, 0.001, 0.0001 and 0.01 µg/ml, respectively. Copyright © 2006 John Wiley & Sons, Ltd.
Association between the interleukin‐1 family gene cluster and psoriatic arthritis
Authors: Rahman Proton , Sun Shuying , Peddle Lynette , Snelgrove Tara , Melay William , Greenwood Celia , Gladman Dafna
Published: July 2006

Objective

The interleukin‐1 (IL‐1) cytokine elicits a wide variety of biologic activities that initiate and promote an inflammatory response. The loci in the IL1 gene cluster have recently been associated with ankylosing spondylitis (AS). Since there is clinical and immunologic overlap between psoriatic arthritis (PsA) and AS, we wanted to examine the association between a panel of single‐nucleotide polymorphisms (SNPs) in the IL1 gene family cluster and chromosome 2q12–13 in a PsA cohort.

Methods

Two hundred twelve PsA patients and 150 ethnically matched controls were genotyped with 11 SNPs in IL1A, 9 SNPs in IL1B, and 9 SNPs in IL1F5–10. Univariate analyses of the 29 single markers and short intragenic haplotypes identified several associated regions. Seventeen markers of interest were noted and further investigated to determine which markers or short haplotypes independently predict case–control status, using a stepwise logistic model.

Results

Two regions contributing independently to risk of disease in PsA were noted: a region spanned by markers rs3783547, rs3783543, and rs17561 in IL1A, and a region near the end of IL1B, through IL1F7, IL1F8, and into IL1F10. The best model contained markers rs3811047, rs1562304, and rs3811058, and 1 haplotype constructed from the 3 markers in region 1, with a likelihood ratio of 25.34 (4 degrees of freedom).

Conclusion

The IL1 locus appears to be a high‐priority susceptibility locus in PsA, with at least 2 independent regions that confer increased risk.
An extended performance reporting framework for social and environmental accounting
Authors: Yongvanich Kittiya , Guthrie James
Published: July 2006

Internationally, there is growing awareness of the environmental and social impacts of the business activities of organizations. This awareness was heightened by the 1987 report Our Common Future by the World Commission on Environment and Development (WCED, 1987). In order to address the concerns raised, companies have increasingly reported the social and environmental impacts of their business activities to secure their right to operate from society. This paper argues for the importance of an integrated reporting framework that provides information on economic performance via intellectual capital (IC) information and non‐economic performance, including that used in the management of performance across social and environmental impacts. This paper briefly reviews three extended reporting approaches, namely IC, balanced scorecard (BSC) and social and environmental reporting. The paper demonstrates that the emphases of these reporting approaches, while diverse, could be complementary to one another and be integrated into an extended performance reporting framework (EPRF), which would provide a more complete account of the management and performance of an organization. The EPRF could empower stakeholders and facilitate change in the way organizations conduct their activities. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
CCL17 transgenic mice show an enhanced Th2‐type response to both allergic and non‐allergic stimuli
Authors: Tsunemi Yuichiro , Saeki Hidehisa , Nakamura Koichiro , Nagakubo Daisuke , Nakayama Takashi , Yoshie Osamu , Kagami Shinji , Shimazu Kiyo , Kadono Takafumi , Sugaya Makoto , Komine Mayumi , Matsushima Koji , Tamaki Kunihiko
Published: July 2006

CC chemokine ligand (CCL)17 is implicated in the pathogenesis of atopic dermatitis (AD). To study the effect of CCL17 produced by keratinocytes (KC) during inflammation, we created transgenic (Tg) mice in which CCL17 is overexpressed in KC. Th2‐type contact hypersensitivity (CHS) was enhanced and Th1‐type CHS was suppressed in these mice. Increased numbers of CC chemokine receptor (CCR)4+ cells and mast cells infiltrated in Tg mice. Levels of IL‐4 mRNA were higher and those of IFN‐γ mRNA were lower in both acute and chronic CHS. Higher levels of serum IgE were observed after CHS. Numbers of CCR4+ cells among PBMC were increased in Tg mice challenged acutely on the trunk. Chronic irritation with croton oil induced dermatitis and an elevation of serum IgE levels. Tg mice showed enhanced ear swelling after tape stripping. CCL17 was thought to modify the inflammation caused by sensitizing reagents as well as irritant reagents by attracting CCR4+ cells into the lesional skin and creating a Th2‐dominant condition. AD‐like conditions such as increased number of mast cells and elevated levels of serum IgE were observed. Thus, CCL17 may participate in the pathogenesis of skin diseases such as AD by regulating both allergic and irritant inflammation.
Correlation between physicochemical analysis and radical‐scavenging activity of vegetable oil blends as affected by frying of French fries
Authors: Ramadan Mohamed Fawzy , Amer Mohamed Mostafa Afify , Sulieman Abd El‐Rahman Mohamed
Published: July 2006

The main goal of the present work was to compare and correlate the results of physicochemical parameters and antiradical performance of some oil blends during deep‐frying, which will be an initial indicator for applying antiradical tests for monitoring deep‐frying oils. Two oil blends were prepared. The first blend was a mixture (1 : 1, wt/wt) of sunflower seed oil and palm olein (SO/PO) and the second was a mixture (1 : 1, wt/wt) of cottonseed oil and palm olein (CO/PO). The oil blends were evaluated during intermittent frying of French fries on two consecutive days for 16 h, with oil replenishing after 8 h. Changes in the fatty acid profile and some physicochemical parameters (peroxide value, color index, viscosity, total polar compounds and UV absorbance at 232 and 270 nm) were used to evaluate the alterations during frying. A quick spectrophotometric method was developed to assess deep‐frying oil quality. With the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) method, the neutralization of the stable radical DPPH by antioxidants present in the oil during frying was measured. Radical‐scavenging activity (RSA) of both oil blends was recorded during frying, wherein the results showed that the SO/PO blend had the highest RSA. It was evident from the results that a proportional correlation and positive relationship existed between the levels of fatty acids and the physicochemical characteristics of the vegetable oil blends and their RSA. The initial results obtained allow us to suggest that antiradical measurements could be used to quantify the oxidative and hydrolytic deterioration of vegetable oils upon frying.
Identification of novel Runx1 (AML1) translocation partner genes SH3D19, YTHDf2, and ZNF687 in acute myeloid leukemia
Authors: Nguyen TuDung T. , Ma Lisa N. , Slovak Marilyn L. , Bangs Charles D. , Cherry Athena M. , Arber Daniel A.
Published: July 2006

Three patients diagnosed with acute myeloid leukemia (AML) with reciprocal 21q22/RUNX1(AML1) translocations involving chromosomes 1 and 4 were studied. Three novel RUNX1 translocation partner genes on 1q21.2 (ZNF687), 1p35 (YTHDF2), and 4q31.3 (SH3D19) were identified using a panhandle polymerase chain reaction and the 3′ rapid amplification of cDNA ends method. The translocation events occurred between exons 3 and 7 of the RUNX1 gene. The partner gene breakpoints localized to the region in the partner gene with the highest Alu density, suggesting that Alus may contribute to the recombination events. Two out of three of the cases retained RUNX1's entire RUNT domain in the translocation, and RUNX1 mutations were absent in the fusion transcripts, confirmed by reverse transcription‐polymerase chain reaction and sequencing analysis. SH3D19 encodes a cytoplasmic protein EBP known to suppress RAS‐induced cellular transformation, which can be inhibited by nuclear recruitment. The t(4;21) created a hybrid RUNX1‐EBP protein retaining RUNX1's DNA binding domain, which may result in nuclear localization of the chimeric protein and inhibition of EBP's RAS‐suppressive functions. Future studies would be useful to further characterize these novel fusion protein products. © 2006 Wiley‐Liss, Inc.
A scan statistic for identifying chromosomal patterns of SNP association
Authors: Sun Yan V. , Levin Albert M. , Boerwinkle Eric , Robertson Henry , Kardia Sharon L.R.
Published: July 2006

We have developed a single nucleotide polymorphism (SNP) association scan statistic that takes into account the complex distribution of the human genome variation in the identification of chromosomal regions with significant SNP associations. This scan statistic has wide applicability for genetic analysis, whether to identify important chromosomal regions associated with common diseases based on whole‐genome SNP association studies or to identify disease susceptibility genes based on dense SNP positional candidate studies. To illustrate this method, we analyzed patterns of SNP associations on chromosome 19 in a large cohort study. Among 2,944 SNPs, we found seven regions that contained clusters of significantly associated SNPs. The average width of these regions was 35 kb with a range of 10–72 kb. We compared the scan statistic results to Fisher's product method using a sliding window approach, and detected 22 regions with significant clusters of SNP associations. The average width of these regions was 131 kb with a range of 10.1–615 kb. Given that the distances between SNPs are not taken into consideration in the sliding window approach, it is likely that a large fraction of these regions represents false positives. However, all seven regions detected by the scan statistic were also detected by the sliding window approach. The linkage disequilibrium (LD) patterns within the seven regions were highly variable indicating that the clusters of SNP associations were not due to LD alone. The scan statistic developed here can be used to make gene‐based or region‐based SNP inferences about disease association. Genet. Epidemiol. 2006. © 2006 Wiley‐Liss, Inc.
Identification of HLA class I dependent immunogenic peptides from clonotypic TCRβ expressed in cutaneous T‐cell lymphoma
Authors: Zeng Jinyang , Müller‐Berghaus Jan , Nguyen Xuan Duc , Klüter Harald , Schönhaber Hiltrud , Song Mingxia , Schwinn Nicole , Schadendorf Dirk , Goerdt Sergij , Eichmüller Stefan , Dippel Edgar
Published: July 2006

The clonotypic T‐cell receptor (TCR) is a potential target antigen for specific immunotherapy of cutaneous T‐cell lymphoma (CTCL). We identified T‐cell epitopes from the rearranged TCR β chain of the malignant T‐cell population by the “reverse immunology” approach. Peptide‐specific T‐cell lines were generated against predicted epitopes and tested for the recognition of tumor cells and cells transfected with the full‐length DNA coding for TCRV β chain. Two peptides derived from the clonotypic TCRVβ of a HLA‐A2 positive patient could induce peptide‐specific T cells from peripheral blood mononuclear cells of healthy donors and the patient as assessed by IFN‐γ ELISpot assay. Furthermore, the reactive CTLs efficiently recognized autologous Sézary tumor cells, as well as HLA‐A2 positive 293 cells transfected with recombinant plasmid expressing the corresponding TCRVβ29 protein. Similar results were obtained in a HLA‐A3+ patient for TCRVβ7‐Jβ2.7. In conclusion, our experiments show that the TCR β chain harbors epitopes suitable as targets for specific vaccination which might be a promising approach for the specific immunotherapy of cutaneous T‐cell lymphoma patients. © 2006 Wiley‐Liss, Inc.
Intestinal‐specific PPARγ deficiency enhances tumorigenesis in ApcMin/+ mice
Authors: McAlpine Christen A. , Barak Yaacov , Matise Ilze , Cormier Robert T.
Published: July 2006

Multiple investigations of the effects of peroxisome proliferator‐activated receptor γ (PPARγ) ligands on colon cancer have produced contradictory results. While some studies demonstrated increased numbers of colonic polyps in ApcMin/+ mice treated with various thiazolidinedione (TZD) PPARγ ligands, others reported amelioration of tumor multiplicity and progression in both ApcMin/+ mice and in mice with chemically‐induced colon cancer. Here, we addressed the role of PPARγ in murine intestinal tumorigenesis using gene knockout methodology. We found that either heterozygous or homozygous intestinal‐specific PPARγ deficiency enhanced the number of ApcMin/+ tumors in both the small intestine and colon, especially in the colon, where PPARγ deficiency also modulated tumor incidence. Gender significantly affected tumor multiplicity independent of PPARγ genotype. Female ApcMin/+ mice developed more tumors in the small intestine and more tumors overall, whereas male ApcMin/+ mice developed more tumors in the colon. Nevertheless, intestinal PPARγ deficiency enhanced tumorigenesis irrespective of gender. Our results suggest that PPARγ functions as a tumor resistance factor in the mouse intestine and warrant further investigation of the PPARγ‐dependent and independent actions of TZDs in cancer. © 2006 Wiley‐Liss, Inc.
Chromatographic analysis of penicillins in pharmaceutical formulations and biological fluids
Authors: Samanidou Victoria F. , Evaggelopoulou Evaggelia N. , Papadoyannis Ioannis N.
Published: July 2006

Natural penicillin (benzylpenicillin) is the oldest antibiotic observed by Alexander Fleming in 1928. To broaden its spectrum of activity, natural penicillin was modified, giving rise to a group of antibiotics under the name ‘penicillins’. Although an increasing number of bacteria appear to be resistant to them, penicillins are used to treat a variety of bacterial infections including Gram‐positive, Gram‐negative aerobic and anaerobic bacteria. Consequently, they are widely used in human and veterinary medicine to prevent and treat diseases. This review covers the analytical methodologies, mainly chromatographic, employed to the penicillins determination in pharmaceutical formulations, biological fluids and in production‐scale fermentations reported in the literature. Results of published assays are comparatively presented focusing on sample preparation regarding isolation and purification, chromatographic conditions and method validation. Information on chemical structure, spectrum of activity and action mechanism of common penicillins has also been given.
Motorenöle auf der Basis von Pflanzenölen – ein neuer Ansatz
Authors: Luther Rolf
Published: July 2006

In Motorenschmierstoffen werden heute vorwiegend Grundöle aus der Petrochemie verwendet. In einem Forschungsvorhaben wurden Möglichkeiten zum Einsatz von Pflanzenölen und deren Derivaten (Esteröle) in Motorenölen für die Umlaufschmierung (Viertaktmotoren) untersucht. In einer Variante wurde ein umweltverträgliches Hochleistungsmotorenöl auf Basis gesättigter Ester in Verbindung mit einer zink‐ und polymerfreien Additivierung entwickelt und mit Erfolg getestet. In einer zweiten Zielrichtung ist ein neuartiges Motorenschmierungskonzept realisiert worden, das erstmals den Einsatz von unverändertem Raps‐ oder Sonnenblumenöl in Motorenölen erlaubt. Bei dem hier vorgestellten Verfahren wird die prinzipiell geringe Alterungsbeständigkeit von Pflanzenölen durch ständiges Auffrischen ausgeglichen; das anfallende Gebrauchtöl wird dem Treibstoff zugemischt und mitverbrannt, ohne daß dabei die Verbrennungsabgase nachteilig beeinflußt werden. Die Additivierung der Pflanzenöle wurde aschearm und zinkfrei ausgelegt. Mit dieser Kombination von speziellem Öl und Verfahren konnten erste gute Einsatzerfahrungen an mehreren Dieselmotoren gesammelt werden. Im Bereich von Stationärmotoren ist der Aspekt des kontinuierlichen Ölwechsels mit einem besonders umweltverträglichen Motorenschmierstoff ein vielversprechender Ansatz.
Electromagnetic Activation of Shape Memory Polymer Networks Containing Magnetic Nanoparticles
Authors: Schmidt Annette M.
Published: July 2006

Summary: By incorporation of surface‐modified superparamagnetic nanoparticles into shape memory polymer matrices, remote actuation of complex shape transitions by electromagnetic fields is possible. The composite thermosets of oligo(ε‐caprolactone)dimethacrylate/butyl acrylate contain between 2 and 12 wt.‐% magnetite nanoparticles serving as nanoantennas for magnetic heating. It is shown that the particles are dispersed homogenously within the matrix and that the basic thermal and mechanical properties of the polymer matrix are maintained. The specific loss power of the particles is determined to be 30 W · g−1 at 300 kHz and 5.0 W. During the shape transition at 43 °C, no further temperature increase is observed.

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Self‐Assembling Synthetic Oligopeptide‐Based Gelators
Authors: Das Apurba K. , Banerjee Arindam
Published: July 2006

Synthetic self‐assembling oligopeptide gelators are an important class of compounds which form thermoreversible gels in various organic solvents as well as in aqueous medium. These gels are soft, viscoelastic materials which are envisaged for useful applications in biological and material sciences. The terminally protected self‐assembling synthetic tripeptide Boc‐Ala‐Aib‐β‐Ala‐OMe 1 (Aib: α‐aminoisobutyric acid i.e. dimethyl glycine and β‐Ala: β‐Alanine) forms gels in various organic solvents, whereas its structural analog i.e. the peptide Boc‐Ala‐Gly‐β‐Ala‐OMe 2 (another self‐assembling synthetic tripeptide) fails to form gels under similar conditions and this issue has been addressed. The terminally protected tripeptide Boc‐Ala‐Val‐Ala‐OMe 3 has been found to form gels in different aromatic organic solvents. Several structural analogs of peptide 3 [using small structural changes either in protecting groups (at the N or C‐terminal position) or in amino acid side chains] have been synthesized, characterized and studied for gelation to address the question how structural changes can regulate the gelation property. Results of the gelation studies indicate that some structural changes are useful to make new peptide gelators with some variations in gelation property and efficiency, while a few structural changes in the protecting groups are really detrimental, leading to abolition the gelation property. These gels are studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier‐Transform Infrared (FT‐IR) spectroscopy and 1H NMR studies.
Microfibrillar Networks: Polymer Thermoreversible Gels vs Organogels
Authors: Guenet Jean‐Michel
Published: July 2006

This paper is intended to review some aspects of fibrillar networks by comparing polymer thermoreversible gels and organogels, the latter being obtained through the self‐assembling of small organic molecules. The morphology, the rheological properties and the gelation mechanisms are particularly examined. The possibility of preparing hybrid materials is discussed.
Supramolecular Chemistry of Bile Acid Derivatives: Formation of Gels
Authors: Babu Ponnusamy , Sangeetha Neralagatta M. , Maitra Uday
Published: July 2006

This article describes some of the exciting results obtained during the study of the gelation behavior of bile acid derivatives in the authors laboratory. The serendipitous discovery of charge‐transfer interaction promoted gelation of organic solvents by (steroid)pyrene derivatives/TNF is presented. In this class of molecules, the effect of the location of the chiral center in chiral gelators on the overall chirality of the aggregates in the gel was studied. Also described are the aggregation behavior of bile acid based aqueous gelators which led us to postulate design principals to obtain bile acid based aqueous/organogelators.
Room‐Temperature Ionic Liquids: For a Difference in the Supramolecular Synthesis
Authors: Pedireddi V. R. , Shimpi Manishkumar R. , Yakhmi J. V.
Published: July 2006

Cu(I) and Ni(II) coordination polymers with 4,4′‐bipyridine and 2,2′‐bipyridine, respectively, that have been synthesized from an ionic liquid (1‐ethyl‐3‐methylimidazolium tetrafluoroborate) gave different coordination environment and supramolecular networks than the corresponding synthesis from the other solvents. The resultant complexes were characterized by single crystal x‐ray diffraction methods.