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Electroacupuncture (EA) may reduce the severity of acute pancreatitis (AP) and provide additional pain relief in patients with chronic pancreatitis. However, the ability of EA to relieve pain in patients with AP has not been well documented.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ipm.2005.04.003 Byline: Sun Lee Bang (a), Jae Dong Yang (b), Hyung Jeong Yang (c) Keywords: Document categorization; Classification; Thesaurus; k-NN Abstract: In this paper, we propose a new algorithm, which incorporates the relationships of concept-based thesauri into the document categorization using the k-NN classifier (k-NN). k-NN is one of the most popular document categorization methods because it shows relatively good performance in spite of its simplicity. However, it significantly degrades precision when ambiguity arises, i.e., when there exist more than one candidate category to which a document can be assigned. To remedy the drawback, we employ concept-based thesauri in the categorization. Employing the thesaurus entails structuring categories into hierarchies, since their structure needs to be conformed to that of the thesaurus for capturing relationships between categories. By referencing various relationships in the thesaurus corresponding to the structured categories, k-NN can be prominently improved, removing the ambiguity. In this paper, we first perform the document categorization by using k-NN and then employ the relationships to reduce the ambiguity. Experimental results show that this method improves the precision of k-NN up to 13.86% without compromising its recall. Author Affiliation: (a) Department of Computer and Statistical Informatics, Chonbuk National University, Jeonju 561-756, South Korea (b) Division of Electronics and Information Engineering, Chonbuk National University, Jeonju 561-756, South Korea (c) Division of Electronics and Computer Engineering, Chonnam National University, Gwangju 500-757, South Korea Article History: Received 29 June 2004; Accepted 18 April 2005 Article Note: (footnote) [star] This is an extended version of the paper that appeared in Proceeding 11th International Conference of String Processing and Information Retrieval (SPIRE), Padova, Italy, 5-8 October 2004.

Following allogeneic transplantation, alloreactive T cells exhibit heightened metabolic requirements that represent a promising area for therapeutic intervention. We have shown previously that during acute graft-versus-host-disease (aGVHD), murine T cells upregulate activity of the cellular energy sensor AMP-activated protein kinase (AMPK). Importantly, transfer of allogeneic T cells deficient in AMPK (AMPK KO) increased recipient survival while still preserving leukemia clearance. In the current studies, we demonstrate a novel role for AMPK in regulating glycolysis, with significant therapeutic implications for the prevention and treatment of aGVHD.

The article discusses various aspects of China-Maldives cooperation, including China's involvement in infrastructure projects, transport, IT, and security. Topic include highlights China's strategic interests in the Maldives, such as the Ihavan Integrated Development project, transport acquisitions, IT infrastructure development, and defense cooperation, indicating potential shifts in the region's geopolitical dynamics.

Abstract: This manuscript is a review of the preclinical and early clinical findings related to a unique fluorinated polyphosphazene nanolayer device surface modification. Polyzene-F (PzF) is a novel, high-molecular weight, highly pure polyphosphazene that was designed to enhance the biologic interface between a medical device surface and human tissue or blood. The polymer also has unique mechanical properties that for the first time allow implants to be paved with a coating that has a nanoscale thickness of < 50 nm. The coating has inherent thrombus resistant properties and takes on biomimetic properties soon after implant due to favorable protein adhesion. Over the last 1.5 decades, PzF has undergone extensive preclinical testing including benchtop endothelial cell migration and platelet adhesion studies followed by increasingly sophisticated evaluation in 16 different animal models. The coating consistently has shown reduced platelet adhesion, decreased clotting, reduced inflammation, and accelerated healing compared with different surfaces as well as uncoated controls. These preclinical findings have translated into early compelling clinical evidence that suggest enhanced healing and reduced thrombosis can be achieved with a PzF-coated implant. There are now two PzF nanocoated products approved by the US Food and Drug Association (FDA), embolic spheres, and a coronary stent. This is the first detailed overview of the history, preclinical findings, and current clinical results attributed to the PzF coating with emphasis on the coronary stent Cobra-PzF. Lay Summary: Over the last few decades, we have seen remarkable advances in medical technology including the development of less invasive surgical alternatives for the treatment of heart and vascular disease. One of the key advances in treating or preventing heart attack, stroke, and limb loss has been the development of stents. Stents are small, metallic, mesh-like devices that can be expanded within blocked vessels via small catheters placed through the groin or wrist. These stents provide structural support while the vessel heals. One of the challenges with stents and other permanent device implants is related to how our bodies react to foreign materials. One of the most feared complications of stents is clotting, which can result in abrupt closure of the treated artery. In the case of heart stents, abrupt closure can cause a heart attack or even sudden death whereas clotting within stents in the neck arteries (carotids) can cause stroke. Additional normal body defense mechanisms include complicated immune responses that trigger inflammation and can cause scarring resulting in early recurrence of the blockage or so-called “restenosis.” In an effort to eliminate restenosis, many stents are now coated with drugs that slow or prevent healing. The downside of this approach has been the need for long-term blood-thinning medications like Plavix and aspirin. In this article, we review the history and current clinical findings of a new way to potentially make medical implants invisible to the normal foreign body defense responses that cause subsequent complications. The innovation involves the development of a new compound called Polyzene-F (CeloNova BioSciences, San Antonio, TX) that can be placed on the surface of a device in a layer that is extremely thin. This new coating is so thin it cannot be seen with even the strongest available microscopes and falls into a new category of material science called nanotechnology. Nanotechnology involves materials that are measured on a molecular level rather than the traditional measurements used in the field of medical devices. We describe many experiments done on the benchtop alongside animal studies and early clinical results that support the hypothesis that an enhanced biologic response can be expected for implants coated with Polyzene-F. The initial types of heart disease patients being studied with this new coated stent (Cobra-PzF) are those at high risk for bleeding since we know these patients are less tolerant of blood-thinning medicine. This initial narrow focus was selected based on the experience from our team and others suggesting animal studies do not always predict how humans respond to new treatments coupled with the knowledge that drug-eluting stents are getting better each day. We do see signals in the completed Cobra-PzF clinical trials that clotting and recurrence (restenosis) are low, but these studies do not directly compare this device to alternative stents in a type of study we call a “randomized trial.” There is an ongoing large randomized trial comparing the Polyzene-F nanocoated stent (Cobra PzF) with contemporary drug-eluting stents in patients at high risk for bleeding, which should complete enrollment in 2019. At the same time, the US FDA-approved Polyzene-F-coated microbeads (Embozene, Boston Scientific, Marlborough, MA) are being studied for the treatment of tumors and cancer. If an enhanced biologic response is proven in the ongoing randomized trials being conducted on the currently approved Polyzene-F-coated devices, then this new surface enhancement may have broader application for a variety of medical device implants.

•AMPK plays a key role in driving both and oxidative and glycolytic metabolism in T cells during GVHD.•Absence of AMPK simultaneously impairs both glycolytic enzyme activity, most notably by aldolase, and interferon gamma production.

A study was conducted to develop a statistical test and assess the fit of parametric item response theory models through statistical comparison with nonparametric item characteristic curve (ICC) estimation. Findings indicate that three nonparametric procedures implemented produced ICCs that are similar to that of the 2PL for items simulated to fit the 2PL.

A study aims to understand the cultural relevance of adult attachment from a Korean sample using the Rasch modeling scale. Results reveal that most items measured either anxiety or avoidance and that scores on the ECRR-K are reasonable measures of attachment for Korean adults.

The present study was aimed to investigate the effects of 3D8 scFv-secreting Probiotic Lactobacillus reuteri(L. reuteri) on growth performance, inflammatory responses, and intestinal microbial flora in chickens. To this end, a total of 14 healthy wild-type chickens were divided into two experimental groups. Each group was orally administrated with a daily dose of 109colony-forming units (CFU) of 3D8 scFv-producing L. reuterior wild-type (WT) for 35 days. Administration of L. reuteri/3D8 scFv significantly improved the body weight of chickens when compared to L. reuteri/WT group. The bacterial taxonomic composition of the fecal microbiota was determined by pyrosequencing of 16S rRNA gene amplicons. Firmicutes, Actinobacteria, and Proteobacteriawere dominant phyla in two experimental groups. However, in 3D8 L. reuteritreatment groups at genus level, the Lactobacilluswas highly abundant, being represented by 18.12%. In addition, serum levels of primary cytokines such as IL-6, IL-8, TNF-α, IFN-γ, IL-4, and IGF1 were markedly reduced in the probiotic L. reuteri3D8 group. In summary, our results indicate that the administration of L. reuteriexpressing 3D8 scFv has a modulatory effect on inflammatory responses, improves weight gain while not affecting the common microbial composition of the chicken intestine.

Background:

Standard and Poor's raised Korea's sovereign credit rating, which is measured by the country's intention and ability to pay back foreign debts, to BBB+ in late 2001, up from lower ratings caused by the foreign debt crisis of 1997. Korean GDP, at US$9,697 per capita, is higher than the average GDP for the BBB+ group. Although the rating has improved, Standard and Poor's has identified structural issues that limit chances for a full recovery.

Seldom in medicinal chemistry does one ligand present the ability to study two separate phenomena in a pharmacological process. The discovery of biphalin with other homodimeric ligands has given scientists a tool that not only explores how to increase the efficacy of the ligand, but also explore the possible interactions of hetero and homo dimerization of the receptors themselves. As a straight ligand, biphalin has allowed scientists to increase efficacy by direct modification of the residues to affect the message-address interactions with receptors. This led to the exploration of ligand linkers to increase efficacy and it was this modification of the linkers led to discoveries that suggested dimerization of receptor system occurs as a secondary modulation of signal transduction. Even more recently, exploration of the advances in linkers through the discovery of bitopicity seems to modulate the actual receptors to increase the binding and signal transdcution of the ligand. This is accomplished by possible slight conformational changes in the receptors before binding of the ligand located at the end of the linker. These advances were made by the work of the late Prof. Andrzej W. Lipkowski. This review gives the foundation of biphalin and in turn celebrates the contributions of Prof. Lipkowski made in this area.

For decades the opioid receptors have been an attractive therapeutic target for the treatment of pain. Since the first discovery of enkephalin, approximately a dozen endogenous opioid peptides have been known to produce opioid activity and analgesia, but their therapeutics have been limited mainly due to low blood brain barrier penetration and poor resistance to proteolytic degradation. One versatile approach to overcome these drawbacks is the cyclization of linear peptides to cyclic peptides with constrained topographical structure. Compared to their linear parents, cyclic analogs exhibit better metabolic stability, lower offtarget toxicity, and improved bioavailability. Extensive structure-activity relationship studies have uncovered promising compounds for the treatment of pain as well as further elucidate structural elements required for selective opioid receptor activity. The benefits that come with employing cyclization can be further enhanced through the generation of polycyclic derivatives. Opioid ligands generally have a short peptide chain and thus the realm of polycyclic peptides has yet to be explored. In this review, a brief history of designing ligands for the opioid receptors, including classic linear and cyclic ligands, is discussed along with recent approaches and successes of cyclic peptide ligands for the receptors. Various scaffolds and approaches to improve bioavailability are elaborated and concluded with a discourse towards polycyclic peptides.

ABSTRACTThis study explored relationships of food insecurity with cognitive restraint, uncontrolled eating, and emotional eating behaviors among congregate meal participants in northeast Georgia [n = 118 years, age 60 years and older, mean (SD) age = 75 (8) years, 75% female, 43% Black, 53% obese (Body Mass Index ≥ 30)]. Food insecurity was assessed with a 6-item questionnaire. Scores ranged from 0 to 6 and were defined as high or marginal food security, FS, 0–1 (70%); low food security, LFS, 2–4 (20%); very low food security, VLFS, 5–6 (10%); and low and very low food security, LVLFS, 2–6 (30%). Eating behavior was assessed with an 18-item Three-Factor Eating Questionnaire R-18. In bivariate analyses food insecurity was consistently associated with cognitive restraint scores above the median split and to a lesser extent with uncontrolled eating scores (p ≤ 0.05). No association was found between emotional eating and food insecurity. In multivariate linear and logistic regression analyses, food insecurity was consistently associated with cognitive restraint (p ≤ 0.05) even when controlled for potential confounders (demographics, Body Mass Index, and chronic diseases). Food insecurity was also associated with uncontrolled eating (p ≤ 0.05), but the relationship was attenuated when controlled for potential confounding variables. Although cognitive restraint is defined as the conscious restriction of food intake to control body weight or promote weight loss, these findings suggest there may be other dimensions of cognitive restraint to consider in nutritional assessment and interventions among food-insecure older adults.

Six known triterpenoid compounds, 3-oxoolean-12-en-27-oic acid (1), gypsogenic acid (2), 3α-hydroxyolean-12-en-27-oic acid (3), 3β-hydroxyolean- 12-en-27-oic acid (4), aceriphyllic acid A (5), and oleanolic acid (6), were isolated from the roots of Aceriphyllum rossii. Their chemical structures were determined by comparison with available ¹H-NMR and 13C-NMR data on known compounds. All the isolated compounds were evaluated for inhibitory activity against human diacylglycerol acyltransferases 1 and 2. Most of the isolates exhibited a better inhibitory activity against diacylglycerol acyltransferase 2 (IC50: 11.6-44.2 μM) than against diacylglycerol acyltransferase 1 (IC50: 22.7-119.5 μM). In particular, compounds 1 and 5 showed strong inhibition efficacy towards diacylglycerol acyltransferases 1 and 2, and appeared to act competitively against oleoyl-CoA in vitro. The results also indicated that both compounds reduced newly synthesized triacylglycerol in HuTu80 and HepG2 cells. Oral administration of compound 1 significantly reduced postprandial triacylglycerol in mice following an oral lipid challenge. In conclusion, the current study indicates that compound 1 suppresses both de novo triacylglycerol biosynthesis and resynthesis through the inhibition of diacylglycerol acyltransferase activity, and therefore may be a useful agent for treating diseases associated with a high triacylglycerol level. [ABSTRACT FROM AUTHOR]

AbstractThis is a preliminary analysis of the Ewha Global Empowerment Program (EGEP), a unique educational program for women activists from Asia and Africa offered by Ewha Womans University. Many feminist scholars teaching women's studies or feminist courses at universities and in adult education programs remark on the many changes feminism has produced in terms of awareness regarding gender discrimination, the numerous social advances for empowering women individually and socially and contributing to the creation of real life changes. The capacity of women's studies to bring about individual and social change is not only because of feminist ideology, but also due to the praxis of feminist pedagogy. Accordingly, research and analysis on feminist pedagogy should reveal the praxis and impact of feminisms, and are very important for the expansion of women's studies and feminist education. In this context, the present study, based on the case of EGEP as a field of ‘Asian Feminist Pedagogy,’ will look at the concrete makeup of the program and analyze the effects of its praxis on its Asian women activist participants. This study has three parts. The first will briefly review the concept and theory of ‘Asian feminisms,’ which comprise the epistemological backdrop and theoretical framework of EGEP. The second part explains how the concept of Asian Feminisms is being implemented and practiced as feminist pedagogy. The third part analyzes the experience of the Asian women activists who participated in EGEP to show how it empowers women and produces ‘Asian women subjects.’

The effects of gas velocity (0.094−0.189 m/s), gas temperature (60−120 °C), cooling water flow rate (4.8 × 10-3−9.0 × 10-3kg/s), and the cooling method (direct or indirect) on the drying characteristics (drying rate and specific energy consumption) of cotton lint in a 0.15-m-inner diameter (ID) × 0.9-m-high recirculating fixed-bed dryer have been determined. The drying rate increases, but the amount of specific energy consumption decreases, as the air temperature increases. With the direct cooling method, the drying rate increases as the cooling water flow rate increases. Further research is required to investigate the drying rate and the specific energy consumption as a function of the direct and indirect cooling methods.

Cholecystokinin (CCK) has been identified as a pronociceptive endogenous peptide which also possesses antiopioid actions. CCK may be upregulated in conditions of chronic pain or during sustained morphine administration resulting in attenuation of opioid-mediated pain relief. These complex interactions between opioids and endogenous CCK receptor systems have suggested the need for a new paradigm in drug design for some states of chronic pain. In these circumstances the rational design of potential drugs for the treatment of these conditions must be based on one ligand for multiple targets. We have designed a single peptide which can interact with δ and μ opioid receptors as agonists and with CCK receptors as antagonists. The ligands were designed based on a model of overlapping pharmacophores of opioid and CCK peptide ligands, which incorporates opioid pharmacophores at the N-terminal and CCK tetrapeptide pharmacophores at the C-terminal of the designed ligands. We measured binding and activities of our bifunctional peptides at opioid and CCK receptors. Compound 11 (Tyr-d-Ala-Gly-d-Trp-NMeNle-Asp-Phe-NH2) demonstrated opioid agonist properties at δ and μ receptors (IC50 = 63 ± 27 nM and 150 ± 65 nM, respectively in MVD and GPI tissue assays) and high binding affinity at CCK-1 and CCK-2 receptors (Ki = 320 and 1.5 nM, respectively). Compound 9 (Tyr-d-Nle-Gly-Trp-Nle-Asp-Phe-NH2) displayed potent agonist activity at δ and μ receptors (IC50 = 23 ±10 nM and 210 ± 52 nM, respectively in MVD and GPI tissue assays), with a balanced binding affinity for CCK-1 and CCK-2 receptors (Ki = 9.6 and 15 nM, respectively). These results provide evidence supporting the concept that opioid and CCK receptors have overlapping pharmacophores required for binding affinity and biological activity and that designing overlapping pharmacophores of two peptides into a single peptide is a valid drug design approach.

A series of hydrazide-linked bifunctional peptides designed to act as agonists for δ/μ opioid receptors and antagonists for CCK-1/CCK-2 receptors was prepared and tested for binding to both opioid and CCK receptors and in functional assays. SAR studies in the CCK region examined the structural requirements for the side chain groups at positions 1‘, 2‘, and 4‘ and for the N-terminal protecting group, which are related to interactions not only with CCK, but also with opioid receptors. Most peptide ligands that showed high binding affinities (0.1−10 nM) for both δ and μ opioid receptors generally showed lower binding affinities (micromolar range) at CCK-1 and CCK-2 receptors, but were potent CCK receptor antagonists in the GPI/LMMP assay (up to Ke = 6.5 nM). The results indicate that it is reasonable to design chimeric bifunctional peptide ligands for different G-protein coupled receptors in a single molecule.

Support Vector Machines (SVMs) have been very successful in text classification. However, the intrinsic geometric structure of text data has been ignored by standard kernels commonly used in SVMs. It is natural to assume that the documents are on the multinomial manifold, which is the simplex of multinomial models furnished with the Riemannian structure induced by the Fisher information metric. We prove that the Negative Geodesic Distance (NGD) on the multinomial manifold is conditionally positive definite (cpd), thus can be used as a kernel in SVMs. Experiments show the NGD kernel on the multinomial manifold to be effective for text classification, significantly outperforming standard kernels on the ambient Euclidean space. [ABSTRACT FROM AUTHOR]

Migration experiments with polystyrene were performed in two-sided contact with n-heptane and distilled water as the food simulants at temperatures of 10, 24 and 40, and 40, 60 and 90°C, respectively. The surface/volume ratios in the migration cell were set at 8.04 and 10.05 dm2 l−1for n-heptane and distilled water, respectively. Styrene monomer, styrene dimers and styrene trimers migrating to the food simulants were determined by GC-FID analysis. Heptane fully extracted the styrene monomer and the oligomers from the polystyrene sheet, whereas in the distilled water only the migrated styrene trimers could be detected. To determine the apparent diffusion coefficient, the migration process was analysed based on Fick's law. The higher the molecular weight of the oligomers, the more significant the reduction in the diffusion coefficient. Higher molecular weight oligomers also had lower activation energy of diffusion when the temperature dependence of diffusivity was analysed by the Arrhenius equation. The diffusion coefficient of the trimers was much higher for heptane contact than for water. The activation energy of the diffusion of trimers for water contact was higher than that for heptane.

We address the problem of integrating objects from a source taxonomy into a master taxonomy. This problem is not only currently pervasive on the web, but also important to the emerging semantic web. A straightforward approach to automating this process would be to learn a classifier that can classify objects from the source taxonomy into categories of the master taxonomy. The key insight is that the availability of the source taxonomy data could be helpful to build better classifiers for the master taxonomy if their categorizations have some semantic overlap. In this paper, we propose a new approach, co- bootstrapping, to enhance the classification by exploiting such implicit knowledge. Our experiments with real-world web data show substantial improvements in the performance of taxonomy integration. [ABSTRACT FROM AUTHOR]

The pharmacokinetic characteristics of a mouse/human chimeric monoclonal antibody (C-17-1A) were determined in 10 patients with metastatic adenocarcinoma following the administration of either 10-mg or 40-mg infusions as a single or multiple dose. The administration of single 10-mg (n = 5) and 40-mg (n = 5) doses infused over 1 hr resulted in mean apparent steady-state distribution volumes of 4.13 ± 0.97 and 5.16 ± 1.92 liters, respectively, indicating that C-17-1A appears to distribute throughout the vascular compartment and into limited extracellular fluid volume. The disposition of C-17-1A was adequately characterized using a two-compartment open model with mean distribution half-lives of 15.8 and 18.5 hr and mean elimination half-lives of 90.0 and 97.6 hr for the 10- and 40-mg groups, respectively. A linear relationship was observed between AUC and dose (µLg/kg). The clearance of C-17-1A was correlated linearly with total Ig, IgG, and tumor size. Multiple administration of either 10-mg (n = 3) or 40-mg (n = 3) doses of C-17-1A infused over 1 hr every 14 days for a total of three doses resulted in superimposable mean serum concentration versus time data and consistent mean pharmacokinetic characteristics. These data indicate that C-17-1A exhibits linear, nonsaturable distribution and elimination characteristics in man over the dose range studied (i.e., 130 to 880 µg/kg). The multiple-dose pharmacokinetics of C-17-1A were predictable, indicating a lack of an antibody response to C-17-1A over a period of 42 days. The clearance of C-17-1A exhibited large interindividual variability with significant correlations to circulating IgG levels and tumor size.

Human hybridoma cell lines secreting IgG specific for the major allergen in the pollen of short ragweed, Amb a I, were established from patients who had been receiving antigen injections for immunotherapy. Recombinant Ig genes were then constructed by cloning the heavy and light chain variable region genes of the human hybridoma cell line and joining them to the human α or κ constant region genes in mammalian expression vectors. Amb a I-specific IgA was expressed in two mouse myeloma cell lines, NSO and Sp2/0. In both systems, transfected α and κ chains were assembled into IgA monomers or into dimers covalently linked by the endogenous murine J chains. We propose that recombinant IgA monoclonal antibodies specific for airborne allergens may be applied to the mucosal surface of the nasal linings or of the lower airway of sensitized individuals to inhibit the entry of allergenic molecules across the mucosal epithelium and, therefore, to prevent the development of allergic responses.

Summary A chimeric antibody was constructed in which the murine H- and L-chain variable regions of mAb 17-1A, raised against human colorectal cancer cells, were joined with the human constant µ and ? regions. Transfection of these constructs into the murine myeloma Sp2/0 resulted in the expression and secretion of a pentameric Ig, designated chimeric 17-1A IgM. The chimeric 17-1A IgM was subsequently compared to a previously described chimeric 17-1A IgG1 for biological activities. Both chimeric mAbs were equally effective (weight basis) in competing against the binding of murine125I-17-1A to cultures of HT-29 colon carcinoma cells. The calculated association constants for the chimeric 17-1A IgM and IgG1 were 1.63 × 108 1/mol and 3.41 × 107 1/mol, respectively. Unlike chimeric 17-1A IgG1, the chimeric 17-1A IgM was able to render colon carcinoma target cells susceptible to lysis by both xenogeneic (rabbit) and human complement. The extent of complement-mediated lysis dependent upon chimeric 17-1A IgM was correlated to 17-1A antigen expression on target cells. HT-29 colon carcinoma cells treated with chimeric 17-1A IgM did not directly result in antibody-dependent cellular cytotoxicity by human peripheral blood monocytes. However, chimeric 17-1A IgM greatly enhanced the deposition of C3 on complementtreated HT-29 cells, and concomitant incubation with monocytes resulted in heightened lysis of the tumor cells. The feasibility of enhancing host defense against gastrointestinal malignancies by the administration of this chimeric 17-1A IgM may have certain clinical advantages.

Murine monoclonal antibody (MAb) G3-519 has been shown to recognize a conserved neutralizing epitope in the fourth constant (C4) region of the external glycoprotein gp120 of HIV-1. Inasmuch as this antibody effectively neutralized the infectivity of diverse HIV-1 isolates, it has been selected to be developed for passive immunization against HIV-1 infection in humans. In order to minimize the problem of immunogenicity of murine antibodies and to confer additional accessory immune functions, we have constructed mouse/human chimeric and humanized forms of the antibody. The chimeric antibody was constructed by cloning the murine variable regions and replacing the mouse constant regions with those from human Igγ1,κ. The humanized antibody was constructed using the human KAS variable region framework sequences as template. Engineering was guided by a three dimensional model of the murine variable region. The murine, chimeric and humanized forms of the antibody exhibited similar reactivity with the peptidic antigen in ELISA, and comparably neutralized the infectivity of HIV-1 in vitro. Taken together, our results show that the chimeric and humanized forms of G3-519 essentially retain the binding activity of the mouse parental antibody. Clinical development is planned to assess the prophylactic and therapeutic usefulness of these reshaped antibodies in humans.

Summary Rabbit antibodies to cytoplasmic estrogen receptors (ER) of human breast carcinoma were utilized for investigating steroid-triggered in-vitro translocation of cytoplasmic ER to the nuclear compartment of the estrogen target cells. The immunofluorescent method (IF) previously described (S Raam et al., Eur J Cancer Clin Oncol 18: 1–12, 1982) was employed for immunohistochemical localization of ER. Four cases of normal endometrium, two cancers of the endometrium, and MCF-7 human breast cancer cells were maintained in a steroid free medium and exposed at 37°C for two hours to growth medium alone (control) or to 2.5, 25 or 250 nanomoles of estradiol (E2), diethylstilbestrol (DES), or monohydroxytamoxifen (OH-TX). At the end of the incubation period the cells were processed for intracellular localization of ER.

p53 mutations are known to occur frequently in human cancers, including gastric carcinomas. Previous studies of its incidence in gastric carcinomas had shown a varying incidence ranging from a low of 4% to as high as 57%. In this study, 42 cases of gastric carcinomas were analyzed for p53 using a commercially available mouse monoclonal antibody in routinely formalin-fixed paraffin-embedded tissue sections. These included 22 intestinal-type (7 well/moderately differentiated and 15 poorly differentiated), 16 diffuse-type and 4 mixed. Altogether, 60% of our cases stained positively for p53. Overall, well/moderatety differentiated intestinal-type carcinomas stained more frequently for p53 than poorly differentiated intestinal-type carcinomas (p<0.075). A comparison between the incidence in diffuse-type (69%) and intestinal type (55%) was unremarkable, p53 staining was also present in 3 of the 4 early cases studied. The results suggest that p53 mutations play an important role in carcinogenesis in gastric carcinoma and further implies that p53 mutation may be an early occurrence during tumor transformation.

p53 gene mutations are among the most common genetic lesions in human cancers. While previous studies have established the presence of p53 protein in ovarian carcinomas some have not shown the alteration of the p53 gene to be a feature in benign or borderline ovarian epithelial neoplasms. In this study we examined both benign and borderline malignant/malignant mucinous neoplasms for p53 protein accumulation by the means of an anti-human p53 protein monoclonal antibody on paraffin sections. Our results show that p53 protein accumulation is associated to a similar degree with both malignant mucinous cystadenocarcinomas and mucinous cystademonas of borderline malignancy. This suggests that p53 mutations may play an important and early role in the malignant transformations of one-third or more of mucinous ovarian neoplasms. Furthermore, among the mucinous cystadenomas of borderline malignancy where p53 staining was present, staining could be found in the morphologically benign areas thus indicating that, despite their innocuous appearance, such epithelial cells might have already taken a very important step in their evolution to frank malignancy.

We have cloned and sequenced a rearranged Vλ gene from a Burkitt's lymphoma cell line PA682(PB). This cell line has two rearranged K loci and has been shown to be expressing K light chains (1). This Vλ gene has been identified as a member of the Vλ subgroup III gene family based on the homology of the predicted amino acid sequence of PAVλ with the reported sequences of the Vλ protein DEL of subgroup III. Nine cross-hybridizing bands have been detected on Southern blots and the chromosomal orientation of the Vλ subgroup III gene family has been determined in relation to the Vλ subgroup I gene family. Although the PAVλ rearrangement has occurred via a legitimate V-J joining and a normal size transcript is detected on Northern blots, the nucleotide sequence reveals a high level of mutations resulting in multiple termination signals within the V gene coding sequence and only a truncated Vλ protein can be translated. This confirms previous observations that although multiple light chain genes may be transcribed, only one functional light chain protein can be synthesized.

We have cloned and mapped the sequences extending 38 kb 3' of the c-myc gene. This region is found to be highly repetitive in nature and hybridizes extensively with a BLUR 8 Alu probe. Unique sequence probes derived from this region were used to map the chromosomal breakpoints of a number of lymphoma cell lines with t(2;8) or t(8;22) translocations. In five of the cell lines (PA682, LY67, LY47, LY66 and LY91), the immunoglobulin light chain locus translocates into a region which is greater than 47 kb downstream of c-myc. For one of the cell lines, JI, the location of the breakpoint on the 8q+ chromosome was found to be 25–32 kb 3' of c-myc. The breakpoint for the BL2 cell line had been previously mapped at 10 kb 3' of the c-myc oncogene. Analyses of steady-state levels of c-myc mRNA in cell lines with chromosomal break points ranging from 10 kb to greater than 47 kb 3' of c-myc range from 0.5 to 10X the levels in lymphoblast controls. The different levels of c-myc transcripts is not a direct function of the distance between the c-myc gene and the translocated immunoglobulin light chain locus.