bluuebunny/crossref_metadata_2025 huggingface dataset:
Multilayer Capsules with Cell‐like Topology: Fabrication and Spontaneous Loading of Various Substances in Aqueous and Ethanol Solutions
Authors: Tong Weijun , Dong Wenfei , Gao Changyou , Möhwald Helmuth
Published: August 2005

Summary: Multilayer microcapsules are fabricated by layer‐by‐layer assembly of sodium poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) on porous CaCO3 microparticles, followed by removal of the sacrificial template. Confocal microscopy (CLSM) reveals that the obtained capsules have polyelectrolyte complex cores, which connect with the shells through polyelectrolyte complex fibers (so called cell‐like topology). The complex is composed of PSS and PAH bound by electrostatic interaction during the assembly procedure, as evidenced by confocal Raman image. CLSM characterization demonstrates that positively charged rhodamine 6G, neutral Nile red and negatively charged 6‐carboxyfluorescein can all be spontaneously encapsulated either in aqueous or in ethanol solution.

CLSM images of the cell‐like microcapsule.

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CLSM images of the cell‐like microcapsule.
Anisotropic Dimensional Swelling of Membranes of Ultrafine Hydrogel Fibers
Authors: Jin Xing , Hsieh You‐Lo
Published: August 2005

Summary: Interconnecting fibrous membranes were generated by electrospinning an aqueous mixture of poly(acrylic acid) and poly(vinyl alcohol) at a 3.5 COOH/OH molar ratio. The membranes containing 200 to 500 nm diameter fibers were crosslinked by heat‐induced esterification and behaved like anionic hydrogels, i.e., they swelled significantly more at a pH above 4. The dimensional expansion of these fibrous membranes was far greater in their thickness than in their planar areas. The anisotropic dimensional expansion was associated with the spatial arrangement of fibers, i.e., much smaller inter‐fiber spaces along the thickness direction than in the planar directions. Crosslinking under constraint caused further fiber compaction in the thickness direction, leading to anisotropic and accordion‐like dimensional expansion upon swelling.

SEM image of the PAA/PVA membrane (C1) thermally crosslinked under high constraint.

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SEM image of the PAA/PVA membrane (C1) thermally crosslinked under high constraint.
Photodeformable Polymers: A New Kind of Promising Smart Material for Micro‐ and Nano‐Applications
Authors: Yu Yanlei , Ikeda Tomiki
Published: August 2005

Summary: Starting in the 1960s, several kinds of photodeformable polymers have been developed, such as monolayers, polymer gels, solid films and liquid‐crystalline elastomers with different photodeformation mechanisms. This field evolved slowly until recently when significant achievements have been made. Most recently, Lendlein and co‐workers have put forward another new concept – using photo‐crosslinking to prepare deformable polymers with various pre‐determined shapes (Nature 2005, 434, 879). This highlight gives a general introduction into photodeformable polymers and brings forth future challenges.

A polymer film doped with SCAA molecules where (a) is the permanent shape, (b) is the temporary shape and (c) is the recovered shape.

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A polymer film doped with SCAA molecules where (a) is the permanent shape, (b) is the temporary shape and (c) is the recovered shape.
Factors affecting the complexation of polyacrylic acid with uranyl ions in aqueous solutions: A luminescence study
Authors: Dubolazov Artem V. , Güven Olgun , Pekel Nursel , Mun Grigoriy A. , Nurkeeva Zauresh S.
Published: August 2005

A study was carried out in aqueous solutions using luminescence technique to investigate the effects of pH, salt concentration, and temperature on the polyacrylic acid/uranyl ion (PAA/UO) complex formation as well as competitive phenomena of enhancement and quenching effects on photoexcited state of uranyl ions. It was found that excess of H+ and OH− is not favorable for complexation between uranyl ions and polymer. Added nitrate salts of Na+ and K+ had significant enhancement effect on emission spectra of PAA/UO complex. These results indicated that the metal ion/polymer chain complex collapsed by addition of salts and then complex became more compact with consequent phase separation. No significant effect of temperature on the PAA/UO complex stability has been observed between 25–50 °C. The quenching rate constants obtained from Stern–Volmer plots were found to be in the order of kq(H+) >> kq(K+) > kq(Na+). © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 2737–2744, 2005
Retirement as a strategy for land transmission: a micro-study of pre-industrial rural Sweden
Authors: DRIBE MARTIN , LUNDH CHRISTER
Published: August 2005

In pre-industrial Sweden (and other parts of northwestern Europe) retirement arrangements were used by peasants to keep their property intact and to transfer it to one of the children while the other children were compensated with, for example, movable property or plots of land. In this article we study the frequency and form of this strategy in pre-industrial rural Sweden. While the literature on retirement arrangements mainly concentrates on the functionality of this system, the focus of this study is on what happened to the institution of peasant retirement in the nineteenth century when an active land market developed and the relative price of land rose. In this study, we use two different sources of land transmission: poll-tax registers, indicating the management of farms, and records of land certificates, showing changes in ownership. The results clearly show that peasant retirement remained an important strategy of intergenerational land transmission at least until the mid-nineteenth century, but the way it was carried out changed profoundly from being mainly an intra-family affair to being channelled through the market.
Chinese whispers and Welsh weddings
Authors: PROBERT REBECCA
Published: August 2005

It has been claimed that in the late eighteenth century sixty per cent of couples in the Welsh village of Llansantffraid Glyn Ceiriog married by jumping over a broomstick, and a number of commentators have inferred that informal marriage was widespread in this period. Yet an examination of the primary and secondary sources shows that both the initial claim and subsequent speculations are based on ‘Chinese whispers’ rather than evidence. This casts a new light on the way in which people reacted to the 1753 Marriage Act, and illustrates how myths may be created through uncritical reliance on secondary sources.
Altered expression of aquaporin 4 and H+/K+‐ATPase in the stomachs of peptide YY (PYY) transgenic mice
Authors: Carmosino M. , Mazzone A. , Laforenza U. , Gastaldi G. , Svelto M. , Valenti G.
Published: August 2005

Background information. The hormone PYY (peptide YY), synthesized by endocrine cells in the pancreas, ileum, colon and stomach has widespread inhibitory effects on gastrointestinal and pancreatic fluid secretion. Transgenic mice expressing a viral oncoprotein under the control of the PYY gene 5′‐flanking region develop well‐differentiated colonic endocrine tumours producing mainly PYY and enteroglucagon. In the present study, we investigated the expression of AQP4 (aquaporin 4) water channel and H+/K+‐ATPase in stomachs from both control and transgenic mice.

Results. Semi‐quantitative RT (reverse transcriptase)–PCR showed an increase in the AQP4 transcript compared with control mice. Quantitative Western‐blot analysis of stomachs from control and transgenic mice confirmed a significant increase in the 30 kDa AQP4 protein in transgenic mice. In control mice, AQP4 is specifically expressed in the basolateral membrane of gastric parietal cells, located in the basal region of the fundic glands. This particular location suggests that parietal cells in the base region of gastric pits might have a major role in water transport when compared with the more superficial parietal cells. Interestingly, immunofluorescence studies on transgenic mice revealed that the quantitative increase of AQP4 expression was actually due to an increase in the number of AQP4‐expressing epithelial cells rather than to a higher expression of AQP4 in parietal cells. In fact, immunofluorescence experiments using the specific antibody raised against the AE2 isoform of Cl−/HCO3− exchanger specifically expressed in parietal cells confirmed that the number of parietal cells was comparable in both PYY and control stomachs. Moreover, in transgenic mice, a parallel significant decrease in the expression of H+/K+‐ATPase was observed, as revealed by RT—PCR, quantitative immunoblotting and immunofluorescence.

Conclusions. In the present study, we demonstrate that the sustained inhibition of gastric secretion due to tumours producing PYY/enteroglucagon in transgenic mice is associated with an increase in AQP4 expression and a down‐regulation of H+/K+‐ATPase in parietal cells that acquire the characteristics of basal parietal cells. The absence of H2 receptors‐mediated signalling due to the inhibition of histamine release from ECL (enterochromaffin‐like) cells by PYY may be in part responsible for the observed increase in the number of parietal cells expressing AQP4.
The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions
Authors: Takahashi Hiroyuki , Shibuya Masabumi
Published: August 2005

The VEGF (vascular endothelial growth factor) family and its receptors are essential regulators of angiogenesis and vascular permeability. Currently, the VEGF family consists of VEGF-A, PlGF (placenta growth factor), VEGF-B, VEGF-C, VEGF-D, VEGF-E and snake venom VEGF. VEGF-A has at least nine subtypes due to the alternative splicing of a single gene. Although the VEGF165 isoform plays a central role in vascular development, recent studies have demonstrated that each VEGF isoform plays distinct roles in vascular patterning and arterial development. VEGF-A binds to and activates two tyrosine kinase receptors, VEGFR (VEGF receptor)-1 and VEGFR-2. VEGFR-2 mediates most of the endothelial growth and survival signals, but VEGFR-1-mediated signalling plays important roles in pathological conditions such as cancer, ischaemia and inflammation. In solid tumours, VEGF-A and its receptor are involved in carcinogenesis, invasion and distant metastasis as well as tumour angiogenesis. VEGF-A also has a neuroprotective effect on hypoxic motor neurons, and is a modifier of ALS (amyotrophic lateral sclerosis). Recent progress in the molecular and biological understanding of the VEGF/VEGFR system provides us with novel and promising therapeutic strategies and target proteins for overcoming a variety of diseases.
Genetics of Paget's disease of bone
Authors: Daroszewska Anna , Ralston Stuart H.
Published: August 2005

PDB (Paget's disease of bone) is a common condition characterized by focal increases in bone turnover affecting one or more sites throughout the skeleton. Genetic factors are important in the pathogenesis of PDB and many families have been described where PDB is inherited in an autosomal-dominant fashion. Several candidate loci for susceptibility to PDB and related syndromes have been identified by genome-wide scans and recent evidence suggests that mutations in genes that encode components of the RANK [receptor activator of NF-κB (nuclear factor-κB)]/NF-κB signalling pathway play an important role in the pathogenesis of this group of diseases. Insertion mutations in the TNFRSF11A gene encoding RANK have been identified as the cause of familial expansile osteolysis, some cases of early onset PDB and expansile skeletal hyperphosphatasia. Inactivating mutations in the TNFRSF11B gene that encodes OPG (osteoprotegerin) have been found to cause the syndrome of juvenile PDB. Polymorphisms in OPG also appear to increase the risk of developing PDB. The most important causal gene for classical PDB is Sequestosome 1 (SQSTM1), which is a scaffold protein in the NF-κB signalling pathway, and mutations affecting the UBA (ubiquitin-associated) domain of this protein occur in between 20–50% of familial and 10–20% of sporadic PDB cases. The rare syndrome of IBMPFD (inclusion body myopathy, PDB and fronto-temporal dementia) is due to mutations in the VCP gene and these also cluster in the domain of VCP that interacts with ubiquitin, suggesting a common disease mechanism with SQSTM1-mediated PDB.
Piezo-induced sensitivity enhancements in electro-optic field sensors
Authors: Garzarella A. , Qadri S. B. , Wieting Terence J. , Wu Dong Ho
Published: August 2005

Responsivity measurements are reported for LiNbO3 electro-optic field sensors operated under applied electric fields at ac frequencies in the vicinity of the acoustic resonance values of the crystals. At these frequencies, piezoelectric effects dominate the sensor output. These resonance effects are well known and commonly considered parasitic. However, we propose their use as a sensitivity-enhancing mechanism for electric-field detection. We have found that our field sensors operated within these resonances responded linearly with the applied field strength and exhibited increases in their intrinsic sensitivities as high as 350 times larger than their normal, electro-optic values. Our modeling of the data suggests that the sensitivity enhancements are produced by the interplay between photoelastic shifts in the refractive indices and the physical vibration modes of the crystals. Aside from narrowband applications, these resonant enhancements can be exploited with fields at frequencies well beyond the narrow bandwidth of the acoustic resonance, if the fields are properly modulated.
Improving organic light-emitting devices by modifying indium tin oxide anode with an ultrathin tetrahedral amorphous carbon film
Authors: Chen B. J. , Sun X. W. , Divayana Y. , Tay B. K.
Published: August 2005

The characteristics of organic light-emitting devices based on tris-(8-hydroxyqunoline) aluminum with an ultrathin tetrahedral amorphous carbon (ta-C) film on indium tin oxide have been investigated. The device with a 1.0-nm ta-C layer has the highest current and power efficiency. The current efficiency of a device with a ta-C layer thickness of 1.0nm is 3.7cd∕A at 20mA∕cm2, however, the current efficiency of a standard device without a ta-C layer is 2.56cd∕A at the same current density. The current efficiency is improved by 46% compared to the standard device. Although there is a 1.2-V increase in driving voltage for 100-cd∕m2 luminance, the power efficiency is still improved by 22% compared to that of the standard device. The improvement of the efficiency is due to smoothing indium tin oxide surface, blocking hole injection from anode and balancing hole and electron currents. The optimal thickness of ta-C layer for hole injection mechanics can be understood by tunneling.
The New Imperialism? On Continuity and Change in US Foreign Policy
Authors: Glassman Jim
Published: August 2005

The unilateral militarism of the George W Bush administration has rekindled interest in imperialism within geography and elsewhere in the social sciences, leading some authors to refer to a new imperialism, or neo-imperialism. This paper critically interrogates the notion that the foreign policy of this administration represents a significant break from past US practices, with the use of concepts from Gramsci and Poulantzas to analyze the class and class-fractional bases of US foreign policy both during and after the Cold War. It is argued that there are certain important continuities in contemporary US imperialism and that there are also differences that owe to the present, post-Cold-War context. It is suggested that if this analysis of continuities is correct then the problems and dangers posed by the “new imperialism” may not be as readily resolvable within a capitalist framework as is suggested by various contemporary commentators.
Why Community? Reading Difference and Singularity with Community
Authors: Panelli Ruth , Welch Richard
Published: August 2005

Geographers have increasingly recognised that communities are not homogeneous social formations but contain great diversity and are meaningful in a variety of material, relational and political ways. This has resulted in the apparently contradictory notion of “community with difference”; that community may be performed even while heterogeneity and disagreement are present. But geographers have yet to address satisfactorily the question of why communities continue to be the subject of fascination and study when attempts at definition have proved so problematic. Following on from Young's critique of community, this paper first engages the work of Nancy and Secomb to consider Nancy's conceptualisation of ‘singularity’ as a way to explain the human construction of—and possible need for—notions of community. In short we address the why community? question. Using a rural Australian case study, we demonstrate that meanings of community reflect many differences. This case also illustrates the role of human singularity in the negotiation of these differences, defining the manner in which individual perspectives of community are articulated as well as underpinning people's responses and struggles when ideas of community are challenged.
Flower choice copying in bumblebees
Authors: Worden Bradley D , Papaj Daniel R
Published: August 2005

We tested a hypothesis originating with Darwin that bees outside the nest exhibit social learning in flower choices. Naive bumblebees,
Bombus impatiens
, were allowed to observe trained bees or artificial bees forage from orange or green flowers. Subsequently, observers of bees on green flowers landed more often on green flowers than non-observing controls or observers of models on orange flowers. These results demonstrate that bumblebees can change flower choice by observations of non-nest mates, a novel form of social learning in insects that could provide unique benefits to the colony.
EFFECTS OF ADMINISTRATION OF ORAL MAGNESIUM ON PLASMA GLUCOSE AND PATHOLOGICAL CHANGES IN THE AORTA AND PANCREAS OF DIABETIC RATS
Authors: Soltani Nepton , Keshavarz Mansoor , Minaii Bagher , Mirershadi Fatemeh , Asl Saleh Zahedi , Dehpour Ahmad Reza
Published: August 2005

1. Magnesium deficiency has recently been proposed as a novel factor implicated in the pathogenesis of the complications of diabetes. The purpose of the present study was to determine the relationship between oral Mg supplementation and changes in plasma glucose, calcium, haemogolobin, Ca/Mg ratio, blood pressure and the histology of the pancreas and vascular system in streptozotocin‐induced diabetic rats.

2. Ten days after the induction of diabetes in male Wistar rats, half the diabetic animals were divided into six groups, receiving 0, 1, 3, 10, 30 or 50 g/L MgSO4 added into the drinking water for 8 weeks. Plasma glucose and Mg were measured at days 1, 2, 3, 5, 7, 14 and 21 to find the optimum dose of Mg and the time‐course of its effect. In addition, histological observations were undertaken. Eight weeks later, all animals were decapitated, the pancreas and thoracic aorta were removed carefully and immersed immediately in 10% formaldehyde for histological study.

3. To evaluate the effects of Mg on plasma glucose, calcium, haemoglobin, Mg and blood pressure, another group of animals was divided into four experimental groups, as follows: (i) non‐diabetic controls received tap water for 8 weeks; (ii) acute diabetics received tap water for 10 days; (iii) chronic diabetic controls received tap water for 8 weeks; and (iv) Mg‐treated chronic diabetic rats received 10 g/L MgSO4 added into the drinking water 10 days after the induction of diabetes for 8 weeks.

4. Magnesium dose dependently affects plasma glucose levels. The peak effect was reached during the first 24 h following oral administration. Administration of 10 g/L MgSO4 results in the return of normal structure in the diabetic pancreas and aorta. Moreover, this concentration of MgSO4 causes glucose, haemoglobin, calcium, the Ca/Mg ratio and blood pressure to reach normal levels. Although the Mg level increases slightly following the administration of 10 g/L MgSO4 to diabetic rats, it never reaches control levels.

5. On the basis of the results of the present study, it may be concluded that chronic Mg administration may have beneficial effects on diabetes.
Ornamental plumage coloration and condition are dependent on age in eastern bluebirds Sialia sialis
Authors: Siefferman Lynn , Hill Geoffrey E. , Dobson F. Stephen
Published: August 2005

Male eastern bluebirds Sialia sialis have striking ultraviolet (UV)‐blue coloration on their heads, backs, rumps, wings, and tails and bold chestnut coloration on their breasts. These colored areas are ornaments that correlate with pairing date and reproductive effort, and thus probably influence the choice of mates by females. Such ornaments are expected to increase in color with age and body condition. We investigated the effects of age on body condition and the UV‐blue and chestnut coloration of males over four years using both cross‐sectional (comparing age classes) and longitudinal analyses (following individuals as they age). We found that both the body condition index and brightness of UV‐blue rump coloration increased with age, while UV‐blue tail plumage coloration increased between yearling and older males, and the chestnut breast coloration decreased in the oldest age class. The proximate mechanisms whereby individuals reliably signal age via rump brightness and tail coloration are probably different. Contour feathers, including rump feathers, are molted at approximately the same time in all age classes and are likely subject to the same production costs in all age classes. In contrast, the molt schedule of the tail and wing feathers differs between individuals of yearling and older age classes, with yearlings retaining wing and tail feathers for several months longer than adults. The relationship between tail color and age was probably, in part, a consequence of yearlings expressing tails that have increased feather wear and accumulation of dirt. In general, UV‐blue coloration increased with age while chestnut plumage decreased with age, indicating that older individuals may tradeoff investing energy in structural and melanin ornaments. By assessing overall plumage coloration, female eastern bluebirds could estimate age class when choosing mates.
Climatic effects on timing of spring migration and breeding in a long‐distance migrant, the pied flycatcher Ficedula hypoleuca
Authors: Both Christiaan , G. Bijlsma Rob , E. Visser Marcel
Published: August 2005

Climate change has advanced the breeding dates of many bird species, but for few species we know whether this advancement is sufficient to track the advancement of the underlying levels of the food chain. For the long‐distance migratory pied flycatcher Ficedula hypoleuca the advancement in breeding time has been insufficient to maintain the synchrony with their main food sources. The timing of arrival in the breeding areas from their African wintering grounds is likely to constrain the advancement of breeding date. We hypothesise that this is because in Africa they cannot predict the advancement of spring in their breeding habitat. However, long‐distance migrants may advance their arrival time by migrating faster when circumstances en route are favourable. In this study we show that both arrival and breeding date depend on temperatures at their main North African staging grounds, as well as on temperature at the breeding grounds. Male arrival and average laying date were not correlated, but the positive effect of temperature in North Africa on breeding dates suggests that breeding date is indeed constrained by arrival of females. Long‐distance migrants thus are able to adjust arrival and hence breeding by faster spring migration, but the degree of adjustment is probably limited as timing schedules in spring are tight. Furthermore, as climate change is affecting temperatures differently along the migratory flyway and the breeding areas, it is unlikely that arrival dates are advanced at the same rate as the timing of breeding should advance, given the advancement of the underlying levels of the food chain.
Repeatability of chick growth and food provisioning in Manx shearwaters Puffinus puffinus
Authors: Gray Catherine M. , Brooke M. de L. , Hamer Keith C.
Published: August 2005

In animals that produce few offspring during their lifetime, the ability to raise high‐quality offspring through the provision of parental care is particularly important for individual fitness. In this paper, we use repeatability analysis of data from two separate time‐periods, in the 1970s and the 1990s, to examine parental and environmental effects on chick growth and food provisioning in a long‐lived seabird, the Manx shearwater Puffinus puffinus. We test the hypothesis that asymptotic body masses of chicks are most strongly influenced by an individual's genotype, with growth rates intermediate and food provisioning rates most strongly affected by environmental conditions during growth. Peak body masses of chicks raised by the same parents showed significant repeatability in both samples, whereas mass growth rates up to the attainment of peak mass showed significant repeatability only in the 1970s. Several different measures of food provisioning by parents showed no individual consistency in either time‐period, in keeping with our predictions. Food provisioning rate was a major determinant of annual variation in chick growth, and so it may seem surprising that Manx shearwaters showed repeatable patterns of chick growth but not of food provisioning, and several possible explanations for this pattern are discussed.
Enhanced Vascular Permeability in Solid Tumor Is Mediated by Nitric Oxide and Inhibited by Both New Nitric Oxide Scavenger and Nitric Oxide Synthase Inhibitor
Authors: Maeda Hiroshi , Noguchi Youichiro , Sato Keizo , Akaike Takaaki
Published: August 2005

A newly discovered nitric oxide radical scavenger, an imidazolineoxyl N‐oxide derivative, was used to investigate the role of nitric oxide radical (*NO) in the vascular permeability enhancement of solid tumor. Sarcoma‐180 solid tumor in ddY mice was used for this experiment. Electron spin resonance spectroscopy was used to quantitate the reacted and unreacted scavenger. The results showed that extensive extravasation, assessed by intravenous injection of Evans blue, could be greatly suppressed by both *NO scavenger administered orally and *NO synthase inhibitor administrated intraperitoneally. This indicates that *NO is responsible for the vascular permeability in solid tumors.
Proto‐oncogene Expression in a Human Chondrosarcoma Cell Line: HCS‐2/8
Authors: Zhu Jing‐de , Pan Hai‐Ou , Suzuki Fujio , Takigawa Masaharu
Published: August 2005

HCS‐2/8 is a stable human chondrosarcoma cell line with many chondrocytic characteristics and has the capacity to form chondrosarcomas in nude mice. The cells display both biochemically and morphologically definable changes in sparse, subcontinent, confluent and over‐confluent phases of in vitro culture. Such features of HCS‐2/8 cells may reflect the processes of both proliferation and differentiation of chondrocytes in vivo. We examined the correlations of these changes of HCS‐2/8 cells with their transcript levels of 21 proto‐oncogenes by Northern analysis. We found no detectable transcripts of 9 proto‐oncogenes (c‐sis, c‐met, c‐src, c‐lyn, c‐fgr, c‐ros, c‐pim, Blym and N‐myc), but detected transcripts of 12 other proto‐oncogenes (int‐2, erbB, c‐abl, c‐raf‐1, c‐fyn, K‐ras, H‐ras, c‐mos, c‐myc, c‐myb, c‐fos, and c‐jun). In the over‐confluent phase, the levels of c‐fos and c‐raf‐1 were increased several dozen times and about 5 times, respectively, while the level of c‐abl was about 1/5th of that in the sparse, subconfluent and confluent phases of culture. The level of int‐2 increased about 10‐fold in the confluent and overconfluent phases of in vitro culture. The transcript levels of c‐mos and K‐ras were high in the sparse phase, low in the subconfluent and confluent phases and high in the over‐confluent phase. The levels of the other 6 proto‐oncogenes in HCS‐2/8 cells were constant in all phases of in vitro culture.
Improvement of Therapeutic Effect by Using Fab' Fragment in the Treatment of Carcinoembryonic Antigen‐positive Human Solid Tumors with Adriamycinentrapped Immunoliposomes
Authors: Uyama Ichiro , Kumai Koichiro , Yasuda Tatsuji , Tagawa Toshiaki , Ishibiki Kyuya , Kitajima Masaki , Tadakuma Takushi
Published: August 2005

To improve the therapeutic efficiency adriamycin entrapped in antibody‐conjugated liposomes, Fab' fragment was used instead of the whole antibody molecule. The murine monoclonal antibody, 21B2, against human carcinoembryonic antigen (CEA) was digested with pepsin, and the thiol residue of intra‐heavy chain produced by reduction of F(ab')2 with dithiothreitol was conjugated to liposomes containing adriamycin. The tissue distribution of adriamycin delivered with these liposomes was studied in BALB/c nu/nu female mice bearing CEA‐positive human gastric cancer strain MKN‐45. An increase in delivery of adriamycin to the tumor was observed in the mice given liposomes with Fab' fragment as compared to those given liposomes with whole antibody. However, the preferential distribution of adriamycin in liposomes to the reticuloendothelial cells remained the same regardless of the use of Fab' fragment. For investigation of in vivo therapeutic effect, three i.v. injections of free adriamycin or adriamycin in liposomes equivalent to 5 mg/kg were given, and adriamycin in Fab' fragment‐conjugated liposomes was found most effective in the inhibition of tumor growth. This was confirmed in terms of actual tumor weights excised and CEA concentration in the blood, as well as by pathological observations. The advantages of using Fab' fragment instead of whole antibody are discussed.
Biphasic Modifying Effect of Indole‐3‐carbinol on Diethylnitrosamine‐induced Preneoplastic Glutathione S‐Transferase Placental Form‐positive Liver Cell Foci in Sprague‐Dawley Rats
Authors: Kim Dae Joong , Lee Kook Kyung , Han Beom Seok , Ahn Byeongwoo , Bae Jong Hee , Jang Ja June
Published: August 2005

The biphasic modifying effects of indole‐3‐carbinol (I3C), a naturally occurring constituent of edible cruciferous vegetables, on the development of glutathione S‐transferase placental form (GST‐P)‐positive liver cell foci were investigated by using a medium‐term liver bioassay system and a newborn rat hepatocarcinogenesis system. In Experiment 1, a total of 65 male Sprague‐Dawley (SD) rats were divided into 5 groups. Animals were given a single intraperitoneal (i.p.) injection of 200 mg/kg diethylnitrosamine (DEN) dissolved in saline for groups 1, 2, and 3 or a single i.p. injection of saline for groups 4 and 5. Group 1 was given the diet containing 0.25% I3C for 2 weeks prior to DEN initiation and then basal diet for 8 weeks. Group 2 was given basal diet for 4 weeks prior to and after DEN initiation and then the diet containing 0.25% I3C for 6 weeks. The rats of group 3 were placed on basal diet during the experiment. Animals of groups 4 and 5 were treated in the same manner as those of groups 1 and 2 except for injection with saline instead of DEN solution. All rats were subjected to two‐thirds partial hepatectomy at week 3 and were killed at week 8 after DEN or saline injection. In Experiment 2, a total of 45 female SD rats were dosed with DEN (100 mg/kg, i.p.) or saline at 24 h after birth. After weaning at week 3, the rats were fed diet containing 0.25% I3C for 9 weeks and then were killed at week 12. In Experiment 1, preinitiation exposure to 0.25% I3C caused a significant decrease in numbers of GST‐P‐positive liver cell foci (P<0.05), while postinitiation exposure to 0.25% I3C caused significant increases in both number (No./cm2) and area (mm2/cm2) of GST‐P‐positive liver cell foci (P<0.05 or 0.01). In Experiment 2, the relative liver weight in the DEN + I3C group was significantly increased (P<0.001). The numbers and areas of GST‐P‐positive liver cell foci in the DEN + I3C group were significantly increased as compared to the values of the DEN‐alone group (P<0.001). These results clearly demonstrated that I3C exerts a promoting effect on the postinitiation stage as well as an inhibitory effect on the preinitiation stage in the medium‐term liver bioassay.
Interrelationship between Estradiol and Tamoxifen Responses for Clinical Breast Carcinoma Cells Cultured on Contact‐sensitive Plates
Authors: Matsuoka Hideo , Nakamura Yasuya , Ueo Hiroaki , Sugimachi Keizo , Tomoda Hirotsugu , Saito Takao , Seo Yousuke
Published: August 2005

An in vitro assay system for predicting the estradiol (E2) sensitivity of clinical cancer cells was applied to 54 patients with breast carcinoma to compare the responses to E2 and tamoxifen (TAM) with the estrogen receptor (ER) status. We found that 18 of the 35 cases in the ER‐positive group and 6 of the 19 cases in the ER‐negative group were stimulated by E2. It is suggested that ER status alone can not predict the response of cultured cells to E2 in clinical breast cancer. Cell growth of 11/35 (31%) of the ER‐positive cases and that of 8/19 (42%) of the ER‐negative cases was inhibited by E2. Since the cases inhibited by E2 could not be distinguished by ER status alone, an assay system based on a quantitative proliferative response was considered necessary. There were 20 (83%) cases of inhibition by TAM among the 24 stimulated by E2. Only 18/35 (51%) of the ER‐positive group exhibited growth inhibition by TAM. In our (CSP) assay, 20 (83%) of the 24 cases stimulated by E2 were inhibited by TAM, 10 (91%) of the 11 E2‐insensitive cases were insensitive to TAM and 13 (68%) of the 19 cases inhibited by E2 were stimulated by TAM. In short, TAM response and E2 response tended to be inversely related (43/54=80%,P<0.01). Furthermore, the E2‐response rate showed a good correlation with the TAM‐response rate (R2= 0.825). These results indicate the feasibility of predicting individual tumor responses to either E2 or TAM by using CSPs.
Rapid Polymerase Chain Reaction Assay to Detect Variation in the Extent of Gene‐specific Damage between Cisplatin‐ or VP‐16‐resistant and Sensitive Lung Cancer Cell Lines
Authors: Oshita Fumihiro , Saijo Nagahiro
Published: August 2005

We previously established a rapid and facile polymerase chain reaction (PCR)‐stop assay for quantitation of specific gene damage in very small numbers of cells. The present study investigated whether the PCR‐stop assay was able to detect variation in the extent of DNA damage in transcribed active genes between cisplatin‐ or VP‐16‐resistant and sensitive cells. The assay demonstrated that about twice as much genetic damage occurs in PC‐9 cells than in cisplatin‐resistant PC‐9/CDDP cells following cisplatin exposure and about 4.6 times more damage occurs in H69 than in VP‐16‐resistant H69/VP cells following VP‐16 exposure. These results show that DNA damage, as detected by PCR‐stop assay, correlates with cytotoxicity. In conclusion, the PCR‐stop assay could be useful in detecting variation in DNA damage in specific genes.
Aberrant CYP1A1 Induction: Discrepancy of CYP1A1 mRNA and Aryl Hydrocarbon Hydroxylase Activity in Mutant Cells of Mouse Hepatoma Line, Hepa‐1
Authors: Kikuchi Hideaki , Usuda Masahiro , Sagami Ikuko , Ikawa Shuntaro , Watanabe Minro
Published: August 2005

We have isolated new benzo[α]pyrene‐resistant clones, cl‐21 and cl‐32, of the mouse hepatoma line, Hepa‐1. CYP1A1‐dependent aryl hydrocarbon hydroxylase activity is not inducible by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin or 3‐methylcholanthrene in these two cell lines. However, mRNA of CYP1A1 is inducible in cl‐21 and cl‐32 cells, as in the wild‐type cells, in spite of an undetectable level of cytosolic Ah receptor. The cl‐21 cDNA of Cypla‐1 was found to have a single mutation leading to an amino acid substitution from Leu (118) to Arg (118). However, the CYP1A1 protein band was not detected on Western immunoblots. The cDNA of cl‐32 was found to have a single mutation leading to an amino acid change from Arg (359) to Trp (359). The presence of the mature protein in cl‐32 was confirmed by Western blot analysis. Somatic cell hybridization experiments demonstrated that the phenotype of cl‐21 and cl‐32 is recessive and that these clones belong to the same complementation group. These data suggest that there may be a non‐Ah receptor‐mediated mechanism of CYP1A1 induction.
A Glycoprotein Secreted by Lung Cancer Cells Is Present in Human Serum as an Immunoglobulin‐binding Protein
Authors: Nonaka Noritaka , Kobayashi Kunihiko , Hirai (deceased) Hidematsu
Published: August 2005

The 6B3‐Ag recognized by a monoclonal antibody 6B3 to human large cell lung carcinoma cell line (HLC‐2) is a high‐molecular‐weight glycoprotein of 1,000,000. Its serum level is increased in various adenocarcinoma patients. When a patient's serum with a high concentration of 6B3′Ag (54μg/ml) or concentrated 6B3‐Ag from normal human serum was analyzed by immunoelectrophoresis, 6B3‐Ag showed a long bimodal precipitin line extending from the per‐β to β globulin region. However, the precipitin line of 6B3‐Ag in the HLC‐2 culture medium was formed only in the pre‐β globulin region. The 6B3‐Ag was purified from pooled patients serum by salting out, precipitation by acidification at pH 4.5 and Sepharose 4B and immunoaffinity chromatographies. Western blotting indicated that the 6B3‐Ag from human serum contained IgG and/or IgM. The 6B3‐Ag from human serum showed a dose‐dependent reaction in a sandwich enzyme‐linked immunosorbent assay with anti‐6B3‐Ag antibody as a solid‐phase antibody and anti‐human IgG or anti‐human IgM antibody labeled with alkaline phosphatase. The 6B3‐Ag was concluded to be partly present as a complex with IgG and/or IgM in humanβ serum, and this complex showed a precipitin line in the /3 globulin region on immunoelectrophoresis.
Paradoxical Enhancement of Tumor Growth in Mice with Severe Combined Immunodeficiency which Produce a Human Immunoglobulin G Reactive against Tumor Cells
Authors: Furukawa Toshiharu , Watanabe Masahiko , Kubota Tetsuro , Kitajima Masaki
Published: August 2005

Mice with severe combined immunodeficiency reconstituted with human splenic tissue (SCID‐sp) taken from 22 patients with advanced gastric cancer and 8 with idiopathic thrombocytopenic purpura (ITP) received subsequent implants of COLO 205 human colon cancer cells. A human immunoglobulin G (IgG) reactive against COLO 205 cells (COLO 205‐reactive human IgG) was produced by SCID‐sp mice reconstituted with splenic tissue from 8 of the 22 gastric cancer patients, but from none of the ITP patients. Tumor growth in SCID‐sp mice which produced the COLO 205‐reactive human IgG was greater (tumor weight range, 106–143%) than that in the control SCID mice, while that in SCID‐sp mice reconstituted with splenic tissue from 8 ITP patients and that in SCID‐sp mice reconstituted with splenic tissue from the other 14 gastric cancer patients which did not produce the COLO 205‐reactive IgG were considerably lower and slightly lower, respectively, than those in the control SCID mice (tumor weight range, 56.7–108% and 79.4–119%, respectively). When the COLO 205‐reactive human IgG liters in the sera of the SCID‐sp mice, expressed as a ratio of the titers in the corresponding patient's serum, were plotted against the tumor weight in each SCID‐sp mouse, significant correlations were observed in those that received splenic tissues from 6 of the 8 patients in which the COLO 205‐reactive human IgG was produced. Furthermore, the tumor growth rates increased in proportion to the increased COLO 205‐reactive human IgG titers in SCID‐sp mice. Therefore, the SCID‐sp model should be useful to study the paradoxical tumor growth possibly due to impaired immune reaction in patients with advanced gastric cancer.
Facilitation of Autonomous Phenotype Acquisition in Androgen‐dependent Shionogi Carcinoma 115 Cells by Transfection of Androgen‐induced Growth Factor Expression Vector
Authors: Miyashita Yoshihiro , Koga Masafumi , Kouhara Haruhiko , Tanaka Akira , Kishimoto Tadamitsu , Sato Bunzo
Published: August 2005

Androgen‐induced growth factor (AIGF) is an autocrine growth factor for androgen‐dependent SC‐3 cells, which is induced by androgen stimuli. To elucidate the mechanism of the progression from hormone‐dependent to ‐independent tumor, we transfected an expression vector of cDNA encoding AIGF into SC‐3 cells and established a stable transfectant (Al) expressing AIGF. Al cells showed enhanced DNA synthesis. This enhanced DNA synthesis was blocked by exposing the cells to AIGF autisense oligonucleotides, heparin, or suramin, indicating that enforced AIGF expression is responsible for the increase in DNA synthesis. However, Al cells did not grow in serum‐free medium unless stimulated with androgen. Recloning from Al cells in semi‐solid agar supplemented with fetal calf serum but without androgen quickly generated an autonomous subline that was able to grow rapidly in the serum‐free medium irrespective of androgen stimulus. Mock‐transfected SC‐3 cells failed to form any colony under identical conditions. These results suggest that stable expression of AIGF alone is not sufficient for, but facilitates the conversion of SC‐3 cells from androgen‐dependent to ‐independent phenotype.
Inhibitory Effect of Oversulfated Fucoidan on Invasion through Reconstituted Basement Membrane by Murine Lewis Lung Carcinoma
Authors: Soeda Shinji , Ishida Satoshi , Shimeno Hiroshi , Nagamatsu Atsuo
Published: August 2005

We investigated the effects of native, Oversulfated, and desulfated fucoidans and heparin on the invasion of 3LL cells through Matrigel. Of the four polysaccharides tested, Oversulfated fucoidan was the most potent inhibitor of tumor cell invasion and inhibited most potently and specifically the tumor cell adhesion to laminin. Sodium dodecyl sulfate‐polyacrylamide gel electrophoretic analysis of the binding of elastase‐cleaved laminin to fucoidan‐ and heparin‐Sepharoses showed that both polysaccharides bound to the 62 and 56 kDa fragments. Pretreatment of 3LL cells with native or Oversulfated fucoidan reduced their adhesive potency to laminin. The two fucoidans inhibited further the laminin binding of 3 LL cells which had been pretreated with a laminin‐based pentapeptide, YIGSR. These results suggest that fucoidan specifically binds to not only the heparin binding domain(s) of laminin but also site(s) other than the cell surface laminin receptor. 3 LL cells secreted a 50 kDa form of urokinase‐type plasminogen activator (u‐PA). The extracellular level of u‐PA activity was increased 1.7 times by addition of laminin but not type IV collagen. Oversulfated fucoidan most potently reduced the increased u‐PA levels. Therefore, the reduction in in vitro invasiveness of 3 LL cells in response to either fucoidan or its Oversulfated derivative may result from an inhibition of physical interaction between the tumor cells and the Matrigel (laminin), followed by a suppression of the laminin‐induced increase in extracellular u‐PA.
Photodynamic Therapy Using a Diode Laser with Mono‐l‐aspartyl Chlorin e6 for Implanted Fibrosarcoma in Mice
Authors: Katsumi Toichiro , Aizawa Katsuo , Okunaka Tetsuya , Kuroiwa Yukari , Ii Yoshiteru , Saito Kouichi , Konaka Chimori , Kato Harubumi
Published: August 2005

We have developed a new high‐power red (664 nm) laser diode system for photodynamic therapy (PDT) with mono‐L‐aspartyl chlorin e6 (NPe6). Meth‐A fibrosarcoma cells (1X106) were implanted subcutaneously in the right hind leg of 4‐week‐old BALB/c female mice. One week later, diode laser irradiation was applied 5 h after the intravenous administration of NPe6 to each tumor‐bearing mouse. In the first study, the time course of intratumor temperature increase during PDT was measured by using a 23‐guage thermocouple hypodermic needle at a depth of 2 mm from the tumor surface. In the second study, 6 groups of 10 to 17 tumor‐bearing mice were treated with the diode laser 5 h after intravenous administration of NPe6 at the dose of 1.25, 2.5, 5.0 or 7.5 mg/kg i.v. per mouse. Total photoirradiation ranged from 0 to 150 J/cm2 and the dose rate was adjusted to 100 mW/cm2. Percentages of cures were determined from numbers of mice apparently disease‐free 50 days after treatment. The results showed that this diode laser is effective in PDT of implanted fibrosarcoma after NPe6 administration. It also confirmed that the therapeutic effects of PDT were not due to hyperthermia. Moreover, the diode laser beam was demonstrated by CCD technology to be uniform in intensity throughout the photoirradiated field.
Non‐Hodgkin's Lymphomas in Turkey: Eighteen Years’Experience at the Hacettepe University
Authors: Barista Ibrahim , Tekuzman Gülten , Firat Dinçer , Baltali Esmen , Kansu Emin , Kars Ayse , Özisik Yavuz , Ruacan Sevket , Uzunalimoglu Bedri , Karaagaoglu Ergun
Published: August 2005

In this retrospective study, 470 patients with non‐Hodgkin's lymphoma (NHL) who had been followed in the Hacettepe University Medical Oncology Department between 1973 and 1990, were evaluated to establish their epidemiologic, clinical and therapeutic characteristics. Out of 470 patients, 302 (62.2%) were male and 168 (37.8%) were female. The ages ranged from 16 to 85, with a median of 44 years. Constitutional symptoms were present in 46.4% of the patients. According to the Working Formulation, low, intermediate, and high‐grade lymphomas comprised 33.4%, 54.9%, and 12.7%, respectively. The most common extranodal presentation was gastrointestinal. The chemotherapy regimens most commonly used were CVP (cyclophosphamide, vincristine, prednisone), BCNOP (bleomycin, cyclophosphamide, mitoxantrone, vincristine, prednisone), CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) and CHOP‐Bleo (cyclophosphamide, doxorubicin, vincristine, prednisone, bleomycin). The response rates and the survival figures attained with these regimens were not statistically significantly different (P > 0.05). In the Cox multivariate model, pathologic grade, leukopenia, responsiveness to chemotherapy, bone marrow involvement and age were the important factors influencing the disease‐free survival, while responsiveness to chemotherapy, age, presence of constitutional symptoms, pathologic grade, extranodal presentation and stage were the important factors influencing the overall survival. The distribution of NHL according to grade and stage was similar to that in western societies, while constitutional symptoms and lymphomas of the small intestine including immunoproliferative small intestinal disease were more common in Turkey.
Cell Adhesion Molecule Expression by Vascular Endothelial Cells as an Immune/Inflammatory Reaction in Human Colon Carcinoma
Authors: Suzuki Yukimasa , Ohtani Haruo , Mizoi Takayuki , Takeha Satoshi , Shiiba Ken'ichi , Matsuno Seiki , Nagura Hiroshi
Published: August 2005

The cell adhesion of inflammatory cells to vascular endothelial cells is an important process in the recruitment of inflammatory cells to the site. In cancer tissue, infiltration of inflammatory cells has been suggested to be a mechanism of host resistance. To clarify this infiltration mechanism, we investigated cell adhesion molecule expression (E‐selectin, P‐selectin, and ICAM‐1) in vascular endothelial cells by immunohistochemistry in colon carcinoma. Venules distributed along the invasive margin expressed E‐ and P‐selectins and ICAM‐1. These phenotypical features are identical to those of endothelial cells observed in active inflammatory lesions, and the vessels can, therefore, be designated as immunologically activated vessels. Nevertheless, the majority of blood vessels within the tumor lacked immunoreactivity for all these adhesion molecules and, therefore, could be designated as immunologically inactive vessels. Granulocytes, lymphocytes and macrophages, bearing the counter‐receptors of these adhesion molecules, were more densely distributed along the invasive margin. In contrast, few inflammatory cells were present within the tumor. In conclusion, the present study has demonstrated the phenotypical heterogeneity of tumor vessels; those for inflammatory cell infiltration to the tumor and those for the nutrient supply to the tumor.