bluuebunny/crossref_metadata_2025 huggingface dataset:
4E-BP functions as a metabolic brake used under stress conditions but not during normal growth
Authors: Teleman Aurelio A. , Chen Ya-Wen , Cohen Stephen M.
Published: August 2005

4E-BP is an important regulator of overall translation levels in cells. By binding eIF4E, 4E-BP impairs recruitment of the 40S ribosomal subunit to the cap structure present at the 5′-end of all eukaryotic cellular mRNAs. 4E-BP activity is controlled by TOR (Target of Rapamycin). 4E-BP has been studied extensively in cell culture; however, the biological role of 4E-BP in developing organisms is unclear to date. Since TOR has been shown to control tissue growth during animal development, 4E-BP has also been assumed to serve as a growth regulator. Here, we study the relevance of 4E-BP function for organismal development, and present evidence for an alternate view. We show that 4E-BP strongly affects fat metabolism in Drosophila. We suggest that 4E-BP works as a metabolic brake that is activated under conditions of environmental stress to control fat metabolism. 4E-BP mutants lack this regulation, reducing their ability to survive under unfavorable conditions.
Redescription of Mastacembelus liberiensis Boulenger, 1898 and description of a new West African spiny‐eel (Synbranchiformes: Mastacembelidae) from the Konkoure River basin, Guinea
Authors: Vreven E. J. , Teugels G. G.
Published: August 2005

Mastacembelus liberiensis
Boulenger, 1898 of West Africa is discussed with reference to its distribution within the Konkoure River basin (Guinea). The synonymies of M. reticulatusBoulenger, 1911 and M. laticaudaAhl, 1937 with M. liberiensis are both confirmed. Further, intraspecific meristic, morphometric and colour pattern variation within M. liberiensis is documented and discussed. Finally, a new species, M. kakrimensis sp. nov., endemic to the Konkoure River basin is identified and described.
Community structure of an assemblage of tidepool fishes on a tropical eastern Pacific rocky shore, Colombia
Authors: Castellanos‐Galindo G. A. , Giraldo A. , Rubio E. A.
Published: August 2005

The composition, abundance, species richness and diversity of a rocky intertidal fish assemblage in the central zone of the Pacific coast of Colombia were determined. From July to December 2002, 10 tidepools with volumes ranging from 0·087 to 1·350 m3 were surveyed. A total of 893 fishes belonging to 14 species and 12 families were found. The most abundant species were Bathygobius ramosus and Abudefduf concolor, representing 71% of all fishes collected. Bathy gobius ramosus, Malacoctenus zonifer and Gobiesox adustus were residents, Abudefduf concolor, Abudefduf troschelii, Microsphatodon bairdii, Chaenomugil proboscideus, Halichoeres aestuaricola and Echidna nocturna were transients, and Apogon dovii, Sargocentron suborbitalis, Cerdale sp, Rypticus nigripinnis and Ctenochaetus marginatus were considered as accidental visitors. The temporal and spatial variation of assemblage structure was tested. The fish assemblage structure did not differ between months and there was not a clear relationship between tidepool surface area and depth, and community variables. Diversity and species richness were negatively correlated with tidepool height. It is suggested that the tidepool assemblage was stable and resilient in time on short (annual) scales. The constancy in time and space could have been a consequence of eurytopic features of the organisms and the lack of drastic seasonal changes in the tropics.
Effect of LHRHa on the expression of stress‐related molecules in the ovary of wild caught Sphoeroides annulatus held in captivity
Authors: Barrón‐Vivanco B. , Duncan N. J. , García‐Aguilar N. , Gutiérrez J. , García‐Gasca A.
Published: August 2005

Two cDNA fragments corresponding to a heat shock protein and a cell death receptor were isolated from the ovary of the bullseye puffer Sphoeroides annulatus that were arrested in vitellogenesis or induced to ovulate with LHRHa. A reduced expression of both genes was observed following injections of LHRHa, suggesting these genes may participate in processes associated with the arrested ovarian development and preparation for atresia or ovulation.
Shrinkage correction and length conversion equations for Theragra chalcogramma, Mallotus villosus and Thaleichthys pacificus
Authors: Buchheister A. , Wilson M. T.
Published: August 2005

Preservation of walleye pollock Theragra chalcogramma, capelin Mallotus villosus and eulachon Thaleichthys pacificus by freezing decreased fork length (LF) up to 1·8, 5·6 and 2·7% and reduced mass by up to 8·4, 3·5 and 1·1%, respectively. Shrinkage of walleye pollock standard length (LS) was greater for fish in 95% ethanol v. 5% formalin and for fish in 10% formalin v. frozen. Equations describing the shrinkage and loss in mass for these species are presented as well as conversions between different length measurements (LS, LF and total length, LT) for fishes that were frozen.
What cephalopod remains from Xiphias gladius stomachs can imply about predator‐prey interactions in the Mediterranean Sea?
Authors: Peristeraki P. , Tserpes G. , Lefkaditou E.
Published: August 2005

Analysis of the cephalopod beaks found in the stomachs of 69 swordfish Xiphias gladius caught in the Aegean Sea resulted in the identification of nine cephalopod taxa. Cephalopod consumption was higher in summer and autumn, and larger swordfish were more likely to feed on cephalopods. Todarodes sagittatus was the most abundant species, a finding suggesting its abundance in the Mediterranean sea.
Rodlet cell distribution in the gall bladder epithelium of Fundulus heteroclitus
Authors: Kramer C. R. , Kramer A. J. , Konovalov A.
Published: August 2005

Rodlet cells within the epithelial mucosa of the gall bladder of the estuarine killifish Fundulus heteroclitus (L.) obtained from a highly contaminated creek adjacent to a landfill, were arranged within the constraints of the epithelium. Furthermore, the rodlet cells established a close intimate association with electron dense epithelioid cells. A comparison with fish from a non impacted estuary revealed a significantly greater number of rodlet cells in the ‘contaminated’ group. The abundance of rodlet cells within the gall bladder of the fish exposed to contaminants further strengthens the hypothesis that these cells participate in the fish's immune system.
Recovery from handling stress in Gadus morhua
Authors: Artigas M. L. , Skjæraasen J. E. , Utne‐Palm A. C. , Nilsen T.
Published: August 2005

The time needed for juvenile cod Gadus morhua to recover from handling stress, and also whether observer presence or haemoglobin genotype influenced recovery time, were investigated. Time to recovery after handling was found to be 1·5 h based on opercular beat frequencies and behaviour. No effects of haemoglobin genotype or observer presence were found.
A comparison of prey capture kinematics in hatchery and wild Micropterus salmoides floridanus: effects of ontogeny and experience
Authors: Wintzer A. P. , Motta P. J.
Published: August 2005

Analysis of high‐speed videography demonstrated that juvenile wild Florida largemouth bass Micropterus salmoides floridanus captured live prey with very rapid movements and large excursions. Hatchery fish of the same age, raised on pelleted feed, however, used slower kinematics with smaller excursions, yielding strikes with a higher degree of ‘suction’. Capture events of hatchery Florida largemouth bass fed live prey for the first time were characterized by movements that had smaller excursion measurements than wild fish and resulted in a decreased level of capture success. After five exposures to elusive mosquitofish Gambusia holbrooki, hatchery Florida largemouth bass adapted their behaviour to capture prey at the kinematic level of wild fish.
Allometric growth and sperm competition in fishes
Authors: Stoltz J. A. , Neff B. D. , Olden J. D.
Published: August 2005

The allometric relationship between body mass and gonad mass in males of 23 fish species from 11 families was examined. There was no evidence of a single allometry for all fishes. A cross species analysis suggested a scaling coefficient of 1·04, which was significantly different from a previous study that reported a scaling coefficient of 0·904. A within species analysis generated scaling coefficients from 0·68 to 3·90. Furthermore, for those species characterized by alternative mating tactics, there was no correlation between the scaling coefficients of bourgeois‐type males and parasitic‐type males. These results are discussed in the context of the gonado‐somatic index and its use in testing sperm competition theory.
Impact implantation of a transmitter on Sarpa salpa behaviour: study with a computerized video tracking system
Authors: Jadot C. , Donnay A. , Ylieff M. , Poncin P.
Published: August 2005

Two transmitter masses (2 and 6% of the fish's mass) were selected to examine the interference of tags with the behaviour of Sarpa salpa using a computerized video tracking system based on digital imaging techniques. The study demonstrated that light transmitters had no effect on the behavioural variables studied, and a substantial bias in behaviour is introduced if heavier (6%) tags are used.
Pall eBDS: an enhanced bacterial detection system for screening platelet concentrates
Authors: McDonald C. P. , Pearce S. , Wilkins K. , Colvin J. , Robbins S. , Colley L. , Taylor J. , Barbara J. A. J.
Published: August 2005

summary.  Bacterial contamination of blood components remains a significant problem in transfusion medicine. The Pall enhanced bacterial detection system (Pall eBDS) detects the presence of bacteria in leucodepleted platelet concentrates by measuring the reduction of oxygen in the sample, due to aerobic bacterial growth. Pooled platelet concentrates were spiked at 10 cfu mL−1 with 10 organisms (one species per bag). Pall eBDS pouches were inoculated with the spiked platelet concentrates. After 24 and 30 h of incubation, the oxygen level was measured. A further set of pouches were taken from the inoculated platelet concentrates at 24 h. Incubation and reading intervals were as for the initial set of pouches. A sensitivity study was also performed comparing the Pall eBDS with the BacT/ALERT system. Spiking at 10 cfu mL−1 and immediately sampling into Pall eBDS pouches resulted in 97·6 and 100% detection after an incubation period of 24 and 30 h, respectively. After 24 h of incubation of the spiked platelet concentrates and then sampling into Pall eBDS pouches, 99·1% detection was obtained after incubation for both 24 and 30 h. The sensitivity of the Pall eBDS and BacT/ALERT is similar and in the order of 1 cfu mL−1. Implementation of either BacT/ALERT or Pall eBDS for routine screening of platelet concentrates has the potential to further increase the safety of the blood supply.
Knowledge, attitude and practice survey regarding blood donation in a Northwestern Chinese city
Authors: Zaller N. , Nelson K. E. , Ness P. , Wen G. , Bai X. , Shan H.
Published: August 2005

summary. Recruitment of low‐risk blood donors in developing countries is challenging. We studied the attitudes towards blood donation in several populations in a city in Western China. A survey of knowledge, attitude and practice was performed including 1280 individuals from eight distinct populations in Urumqi, Xinjiang Uyghur Autonomous Region, China. Included were Han Chinese and Uyghur populations of blood donors, non‐donors, injection drug users, students and factory workers. Knowledge about blood donation varied between the groups. Factors motivating blood donation included social pressure, desire to know screening results and altruism. Inhibiting factors included fear of contracting an infection and other adverse health effects, including loss of vitality. Misconceptions about the effects of blood donation are widespread, even among educated persons in Urumqi. Fear of acquiring a serious infection may have been increased by the reports of HIV acquisition during plasma donations in China.
A study of the prevalence of iron deficiency and its related factors in blood donors of Yazd, Iran, 2003
Authors: Javadzadeh Shahshahani H. , Attar M. , Taher Yavari M.
Published: August 2005

summary.  Iron deficiency anaemia is an important limiting factor for the number of donations in regular donors. Limited data is available on the iron status in Iranian donors. This study was conducted to evaluate the prevalence of iron deficiency and its related factors in blood donors at Yazd blood transfusion centre, Iran. In this descriptive study, 337 persons accepted for donation in 2003 were selected randomly. Haemoglobin, serum iron, total iron‐binding capacity and ferritin concentrations were measured. Results showed that the prevalence of reduction in iron stores increased with an increase in the number of donations (P = 0·0001), such that reduction in iron stores was seen in all regular female donors (100%) and 48% of regular male blood donors. The prevalence of iron deficiency in female and male regular donors was 78 and 28%, whereas 55·6 and 16% of these donors had iron deficiency anaemia. Just one blood donation resulted in a significant increase in the prevalence of iron deficiency in women (P < 0·05), but in men, a significant increase was seen only in regular donors (P < 0·05). It is therefore recommended that blood donors should be educated about iron deficiency, and research studies should be performed to determine the best method of iron supplementation with minimal complications for all regular blood donors and women of childbearing age on their first donation.
Costs associated with blood transfusions in Sweden – the societal cost of autologous, allogeneic and perioperative RBC transfusion
Authors: Glenngård A. H. , Persson U. , Söderman C.
Published: August 2005

summary.  Anaemia is characterised by an insufficient number of red blood cells (RBCs) and might occur for different reasons, e.g. surgical procedures are often with associated blood loss. Patients who suffer from anaemia have the option of treatment with blood transfusion or medical treatment. In this study, the societal cost, for the case of Sweden, of RBC transfusion using three different techniques, i.e. allogeneic, autologous and intraoperative transfusion, was estimated. The analysis was based on information from interviews with hospital staff at large Swedish hospitals and from published data. The average cost for a 2 units transfusion was found to be Swedish kronor (SEK) 6330 (€702) for filtered allogeneic RBCs and SEK5394 (€598) for autologous RBCs for surgery patients. Transfusion reactions accounted for almost 35 per cent of the costs of allogeneic RBC transfusions. The administration cost was found to be much higher for autologous transfusions compared with allogeneic transfusions. The cost of intraoperative erythrocyte salvage was calculated to be SEK2567 (€285) per transfusion (>4 units).
A retrospective study evaluating single‐unit red blood cell transfusions in reducing allogeneic blood exposure
Authors: Ma M. , Eckert K. , Ralley F. , Chin‐Yee I.
Published: August 2005

summary.  Although guidelines recommend the use of single‐unit red blood cell (RBC) transfusions to minimize allogeneic blood exposure, clinical practice remains dominated by two‐unit transfusions. This study assesses the potential impact of a single‐unit transfusion policy on reducing RBC utilization. We performed a retrospective analysis of adult patients admitted to a tertiary care hospital who received one or two RBC units. In subjects transfused two units, the effect of one unit was estimated by dividing the change in haemoglobin by 2. The proportion of patients reaching a haemoglobin threshold of 70, 75, 80, 85 and 90 g L−1 with a single RBC unit was estimated. Of 302 included patients, only 65 received a one‐unit transfusion. Based on thresholds of ≥90, ≥80 and ≥70 g L−1, a single‐unit transfusion would be sufficient in 42·0% (RRR = 0·54), 79·6% (RRR = 0·23) and 98·0% (RRR = 0·02) of cases, respectively. This corresponds to 0·21, 0·57 and 0·82 mean RBC units saved per patient. In the orthopaedic subpopulation, the mean RBC units saved are 0·53, 0·88 and 1·00 for the same haemoglobin targets. Adopting a policy of transfusing RBC in single‐unit aliquots could significantly improve RBC utilization and decrease patient exposure to allogeneic blood.
Harvesting peripheral blood progenitor cells from healthy donors with a short course of recombinant human granulocyte‐colony‐stimulating factor
Authors: Martino M. , Morabito F. , Callea I. , Pontari A. , Irrera G. , Pucci G. , Dattola A. , Messina G. , Console G. , Iacopino P.
Published: August 2005

summary.  A short‐course administration of non‐glycosylated granulocyte‐colony‐stimulating factor (G‐CSF) was investigated in 68 healthy donors (HDs) in order to collect ≥4 × 106 CD34+ cells per kilogram of recipient's body weight. G‐CSF was given at 10 µg/kg per day administered in two divided doses for 3 days. Leukapheresis was scheduled on day 4, 12 h after the last dose of G‐CSF. A median of 35·6 circulating CD34+ cells µL−1 (range, 3·1–185) was found on the day of leukapheresis. This allowed a median collection of CD34+ cells of 4·2 × 106 per kilogram of recipient's weight (range, 1·0–17·4). One single procedure was sufficient to reach the target level of CD34+ cells in 36 (53%) of 68 donors; significant correlations were found between the number of CD34+ cells collected on day 4 and the patient's sex, body‐weight and volume of blood processed. A retrospective analysis was made with a historical group of HDs collected on day 5. The day 5 schedule allowed a more consistent achievement of the target cell dose with one leukapheresis (P = 0·005) and resulted in the initial collection of a significantly larger number of CD34+ cells (P = 0·006).
Resilience in the Face of Potential Trauma
Authors: Bonanno George A.
Published: August 2005

Until recently, resilience among adults exposed to potentially traumatic events was thought to occur rarely and in either pathological or exceptionally healthy individuals. Recent research indicates, however, that the most common reaction among adults exposed to such events is a relatively stable pattern of healthy functioning coupled with the enduring capacity for positive emotion and generative experiences. A surprising finding is that there is no single resilient type. Rather, there appear to be multiple and sometimes unexpected ways to be resilient, and sometimes resilience is achieved by means that are not fully adaptive under normal circumstances. For example, people who characteristically use self-enhancing biases often incur social liabilities but show resilient outcomes when confronted with extreme adversity. Directions for further research are considered.
A PACT Against Conflict Escalation in Negotiation and Dispute Resolution
Authors: De Dreu Carsten K.W.
Published: August 2005

For social and economic relations to develop and prosper people need to negotiate and resolve disputes. Whereas past work has focused on psychological barriers to negotiation and dispute resolution, recent research shifts focus towards motivated information processing. This new work identifies when and why individuals fail or succeed in constructive negotiation and solving their disputes. I discuss four key variables—power balance, accountability to process, cooperative motivation, and time, grouped under the acronym PACT—that may reduce or reverse the psychological tendencies towards conflict escalation by turning disputants from “selfish misers,” who have difficulty negotiating constructively, into “pro-social thinkers” who solve their disputes to mutual benefit.
Self-Esteem Development Across the Lifespan
Authors: Robins Richard W. , Trzesniewski Kali H.
Published: August 2005

After decades of debate, a consensus is emerging about the way self-esteem develops across the lifespan. On average, self-esteem is relatively high in childhood, drops during adolescence (particularly for girls), rises gradually throughout adulthood, and then declines sharply in old age. Despite these general age differences, individuals tend to maintain their ordering relative to one another: Individuals who have relatively high self-esteem at one point in time tend to have relatively high self-esteem years later. This type of stability (i.e., rank-order stability) is somewhat lower during childhood and old age than during adulthood, but the overall level of stability is comparable to that found for other personality characteristics. Directions for further research include (a) replication of the basic trajectory using more sophisticated longitudinal designs, (b) identification of the mediating mechanisms underlying self-esteem change, (c) the development of an integrative theoretical model of the life-course trajectory of self-esteem.
Mood and Emotion in Major Depression
Authors: Rottenberg Jonathan
Published: August 2005

Nothing is more familiar to people than their moods and emotions. Oddly, however, it is not clear how these two kinds of affective processes are related. Intuitively, it makes sense that emotional reactions are stronger when they are congruent with a preexisting mood, an idea reinforced by contemporary emotion theory. Yet empirically, it is uncertain whether moods actually facilitate emotional reactivity to mood-congruent stimuli. One approach to the question of how moods affect emotions is to study mood-disturbed individuals. This review describes recent experimental studies of emotional reactivity conducted with individuals suffering from major depression. Counter to intuitions, major depression is associated with reduced emotional reactivity to sad contexts. A novel account of emotions in depression is advanced to assimilate these findings. Implications for the study of depression and normal mood variation are considered.
Affective Forecasting
Authors: Wilson Timothy D. , Gilbert Daniel T.
Published: August 2005

People base many decisions on affective forecasts, predictions about their emotional reactions to future events. They often display an impact bias, overestimating the intensity and duration of their emotional reactions to such events. One cause of the impact bias is focalism, the tendency to underestimate the extent to which other events will influence our thoughts and feelings. Another is people's failure to anticipate how quickly they will make sense of things that happen to them in a way that speeds emotional recovery. This is especially true when predicting reactions to negative events: People fail to anticipate how quickly they will cope psychologically with such events in ways that speed their recovery from them. Several implications are discussed, such as the tendency for people to attribute their unexpected resilience to external agents.
Hearing Loss in Older Adulthood
Authors: Wingfield Arthur , Tun Patricia A. , McCoy Sandra L.
Published: August 2005

Adult aging is accompanied by declines in many areas of cognitive functioning, including reduced memory for new information. Potential sources of these declines are well established and include slowed processing, diminished working-memory capacity, and a reduced ability to inhibit interference. In addition, older adults often experience sensory decline, including decreased hearing acuity for high-frequency sounds and deficits in frequency and temporal resolution. These changes add to the challenge faced by older adults in comprehension and memory for everyday rapid speech. Use of contextual information and added perceptual and cognitive effort can partially offset the deleterious effects of these sensory declines. This may, however, come at a cost to resources that might otherwise be available for “downstream” operations such as encoding the speech content in memory. We argue that future research should focus not only on sensory and cognitive functioning as separate domains but also on the dynamics of their interaction.
Lower Incidence of K‐ras Codon 12 Mutation in Flat Colorectal Adenomas than in Polypoid Adenomas
Authors: Yamagata Seiichi , Muto Tetsuichiro , Uchida Yoshihiro , Masaki Tadahiko , Sawada Toshio , Tsuno Nelson , Hirooka Takashi
Published: August 2005

In order to clarify genetic changes in flat adenomas, K‐ras codon 12 point mutations were examined in 56 flat adenomas, 81 polypoid adenomas and 42 cancers of colon and rectum. The mutation frequency in flat adenomas was 23% (13/56), significantly lower than that in polypoid adenomas (67%: 54/81) and cancers (76%: 32/42). Even mildly dysplastic adenomas or small (less than 5 mm) adenomas showed higher mutation incidence in polypoid type (62%, 57%) than in flat type (23%, 19%). Among flat adenomas, flat elevated lesions exhibited relatively higher mutation frequency than completely flat or depressed ones. As for cancers, 14 tumors (33%) contained mutations only in a minor tumor cell population, indicating that these mutations occur at a late stage of tumorigenesis. These results suggest that the adenoma‐carcinoma sequence through flat adenomas may he different from that through polypoid adenomas, and genetic changes may be heterogeneous in colorectal carcinogenesis.
Regulation of Gelatinase Production in Metastatic Renal Cell Carcinoma by Organ‐specific Fibroblasts
Authors: Gohji Kazuo , Nakajima Motowo , Fabra Angels , Bucana Corazon D. , von Eschenbach Andrew C. , Tsuruo Takashi , Fidler Isaiah J.
Published: August 2005

We have recently established a human renal cell carcinoma KG‐2 line that is tumorigenic in the subcutis (ectopic) and kidney (orthotopic) of nude mice but spontaneously metastasizes to the lung only after orthotopic implantation. KG‐2 cells growing in the kidney (orthotopic) and lung metastases secreted higher levels of gelatinase than did cells growing in the subcutis (ectopic). We examined whether organ‐specific fibroblasts play a role in the regulation of gelatinase production and invasion by renal carcinoma cells. The gelatinase level in the culture supernatants of KG‐2 cells was increased by their cultivation with mouse kidney or lung fibroblasts. In contrast, cocultivation of KG‐2 cells with mouse skin fibroblasts resulted in a significant reduction of gelatinase activity. Similar results were obtained by culturing KG‐2 cells in the media conditioned by the different mouse fibroblasts. We, therefore, investigated effects on KG‐2 cells of cytokines and growth factors known to be produced by fibroblasts of various origins. Of ten cytokines and growth factors tested, basic fibroblast growth factor, hepatocyte growth factor, and transforming growth factor‐β1 (TGF‐β1) stimulated gelatinase expression by the cultured KG‐2 cells. Parallel immunohistochemical analyses revealed that mouse kidney and lung fibroblasts produced higher levels of TGF‐β1 than did skin fibroblasts. These results indicate that gelatinase production by KG‐2 renal cell carcinoma cells is influenced by the organ microenvironment. Specifically, organ‐specific fibroblasts regulate the production of degradative enzymes by KG‐2 cells and, hence, profoundly influence their invasive and metastatic capacity.
Cyclosporin A Enhances Susceptibility of Multi‐drug Resistant Human Cancer Cells to Anti‐P‐glycoprotein Antibody‐dependent Cytotoxicity of Monocytes, but Not of Lymphocytes
Authors: Yano Seiji , Sone Saburo , Nishioka Yasuhiko , Naito Mikihiko , Tsuruo Takashi , Ogura Takeshi
Published: August 2005

Cyclosporin A (CsA) was previously found to bind to P‐glycoprotein expressed on multidrug‐resistant (MDR) cancer cells. In the present study, the effect of CsA on anti‐P‐glycoprotein monoclonal antibody (mAb)‐dependent cell‐mediated cytotoxicity (ADCC) against human MDR cells was examined. The ADCC reaction was assessed by 4‐h 51Cr‐release assay. Highly purified lymphocytes (> 99%) and monocytes (>99%) obtained from blood mononuclear cells (MNC) of healthy donors were used as effector cells. CsA decreased the cytotoxic activity of MNC against MDR cells, but enhanced their ADCC activity in the presence of anti‐P‐glycoprotein mAb MRK16. Lymphocyte‐mediated ADCC and natural killer activity against MDR cells were also suppressed by addition of CsA. CsA induced a significant dose‐dependent increase in monocyte‐mediated ADCC activity. Interestingly, pretreatment of MDR cancer cells, but not of monocytes, with CsA significantly enhanced ADCC activity mediated by monocytes, but not by lymphocytes. A CsA analog (PSC833) and FK‐506, but not verapamil also increased the sensitivity of MDR cells to ADCC by monocytes. CsA did not affect the binding of monocytes to MDR cells in the presence of MRK16 mAb. These results indicate that CsA may directly enhance the susceptibility of MDR cancer cells to the monocyte‐mediated ADCC reaction.
Analysis of T Cell Receptor Variability in Fresh Tumor‐infiltrating Lymphocytes from Human Head and Neck Cancer
Authors: Chikamatsu Kazuaki , Eura Masao , Nakano Koji , Kanzaki Yuichi , Matsuoka Hiroaki , Masuyama Keisuke , Ishikawa Takeru
Published: August 2005

In this study, we analyzed T cell receptor (TCR) gene rearrangements in tumor‐infiltrating lymphocytes (TIL) freshly obtained from 15 patients with head and neck cancer using the reversely transcribed polymerase chain reaction (RT‐PCR) method. These TILs showed preferential expression of Vα10, Vα8 and Vα1, detected in 13 (87%), 11 (73%), and 9 cases (60%), respectively. The TCRVβ gene revealed diversity without preferential usage. The head and neck region is exposed to bacteria and viruses, so it is possible that the tumor site can become infected and accumulate T cells involved in infection and inflammation. Therefore, we also investigated TCR gene usage in T cells infiltrating in chronic sinusitis mucosa to address the question of whether the Vα1, Vα8, and Vα10 subfamilies are characteristic in TIL from squamous cell carcinoma of head and neck. TCR Vα10 gene usage was also the most common in Vα segment in T cells infiltrating the sinus mucosa, but Vα and Vα8 were not detected in the T cells in sinusitis. These results indicate that the Vα10 subfamily, the preferred T cell population in both TIL and T cells in inflammatory disease, might he involved mainly in inflammation or infection. On the other hand, Vα1 and Vα8 appear to be relatively specific populations for antitumor immunity in head and neck cancer.
K‐ras and p53 Alterations in Genomic DNA and Transcripts of Human Pancreatic Adenocarcinoma Cell Lines
Authors: Suwa Hirofumi , Yoshimura Tsunehiro , Yamaguchi Nozomi , Kanehira Kazunori , Manabe Tadao , Imamura Masayuki , Hiai Hiroshi , Fukumoto Manabu
Published: August 2005

We analyzed 15 human pancreatic adenocarcinoma cell lines for alterations of the K‐ras and the p53 genes and their transcripts. In 11 cell lines (73.3%), point mutations of the K‐ras gene were found at codon 12 in exon 1. In 9 cell lines one allele was mutated and the other was wild type, and both the alleles were expressed into mRNA. In one cell line both alleles of codon 12 were mutated to TGT and GTT, respectively, hut only TGT was transcribed into mRNA. Alterations in mRNA of the p53 gene were detected in 10 cell lines (66.7%). Analysis of the genomlc sequence of the p53 gene revealed that the alterations consisted of 6 cases of base pair substitutions and 1 case of 1‐bp deletion in evolutionarily conserved exons 5 to 8, 2 cases of splicing mutations in exon 4, and 1 case of novel deletion from exons 2 to 9. In 14 cell lines (93.3%), alterations were identified in the K‐ras or p53 gene. Of these, 4 cell lines harbored K‐ras mutations without p53 alteration, whereas 3 cell lines exhibited p53 alterations without K‐ras mutation. Thus, it is suggested that activation of the K‐ras gene and inactivation of the p53 gene are strongly and cooperatively associated with pancreatic carcinogenesis.
Difference in Allelic Expression of Genes Probably Associated with Tumor Progression in Murine Fibrosarcomas and Cell Lines
Authors: Ohtsuka Hiroshi , Mafune Yoshiro , Tsunashima Katsumasa , Takahashi Hideaki , Kominami Ryo
Published: August 2005

Allelic expression was examined by single‐strand conformation polymorphism analysis in murinc fibrosarcomas from inter‐subspecific F1 mice between C57BL/6 and MSM. Ten genes encoding p53, mdni2, E‐cadherin, 72 kD metalloproteinase and its inhibitor (Timp2), thymidine kinasc and four glucose transporters (Gluts) were examined. These genes were chosen because of their probable association with tumor development and progression. In some of the tumors and cell lines, p53, E‐cadherin and Glut3 genes showed remarkable differences in allelic expression, one allele being poorly expressed. The allele‐specificity persisted in nine cell lines obtained by repeated transplantations from one tumor. These results suggest that expression of some genes is allele‐specific in tumor cells and the pattern of specificity is stable. Such a decrease or a loss of expression in one of the alleles may be functionally equivalent to the loss of heterozygosity of the gene, and therefore this may confer malignant properties on tumor cells. It is also suggested that differential expression of two alleles is a common event in tumor cells.
Enhancement of T Cell Receptor Signaling of Tumor‐infiltrating Lymphocytes by Retrovirally Mediated fyn Gene Transduction
Authors: Fujita Kazuyuki , Ikarashi Hirokazu , Takakuwa Koichi , Kodama Shoji , Akagi Tsuyoshi , Yamamoto Tadashi , Tanaka Kenichi
Published: August 2005

We conducted retrovirally mediated transduction of fyn gene into tumor‐infiltrating lymphocytes (TILs) in an attempt to augment T cell receptor‐CD3 complex signal transduction, using TILs obtained from six patients with epithelial ovarian cancer. The expression of the transduced gene was more than five times that of endogenous fyn gene. In all preparations, the cytolytic activity of the TILs against autologous tumor cells, but not allogeneic tumor cells, was significantly enhanced (P 0.01) by transduction of fyn gene. In addition, when TILs were treated with anti‐CD3 antibody to stimulate T cell receptor‐CD3 complex, fyn‐gene‐transduced TILs showed about two times higher proliferation (P<0.05) and secreted 2.2 to 11.7 times more tumor necrosis factor‐β (P<0.05) than nontransduced TILs. These results could have important implications for TILs‐mediated gene therapy for cancer.
High Frequency of p53 Abnormality in Laryngeal Cancers of Heavy Smokers and Its Relation to Human Papillomavirus infection
Authors: Suzuki Takeshi , Shidara Kouichi , Kara Futoshi , Nakajima Takashi
Published: August 2005

A series of 41 laryngeal squamous cell carcinomas was examined for p53 abnormalities and human papillomavirus (HPV) infection by an immunohistochemical and/or molecular approach. Immuno‐histochemically, p53 over‐expression was observed in about 60% of the cancers, of which 12 were revealed to contain point mutations of p53 by a combination of the single‐strand conformatioiial polymorphism technique and direct sequencing. The p53 point mutations ranged from codons 157 to 278 and most of these mutations lay in two “hot spots” (codon 157 in four cancers and codon 248 in three cancers). The majority of p53 mutations, both transversions (seven cancers) and transitions (five cancers), occurred at the G nucleotide of the codons. An analysis of the clinical information indicated that p53 point mutation was frequently observed in heavy smokers with an average Brinkman index score of more than 1000. On the other hand, HPV DNA, type 16 or 18, was detected in a quarter of the laryngeal cancers. Of eleven HPV‐positive cases, nine were immunohistochemically positive for p53, of which four contained a p53 point mutation. These results suggested no inverse relation between p53 mutation and HPV infection in laryngeal cancers. Our study indicates that p53 abnormalities are related to smoking history and the correlation might be better for smoking and chemical mutagenesis than for HPV.
Potentiation of cis‐Diammine(1, 1‐cyclobutanedicarboxylato)platinum(II) by Amphotericin B in BALB/c Nude Mice Bearing Human Ovarian Carcinoma Cells
Authors: Kojima Masayoshi , Kikkawa Fumitaka , Oguchi Hidenori , Tamakoshi Koji , Maeda Osamu , Suganuma Nobuhiko , Tomoda Yutaka
Published: August 2005

Human ovarian carcinoma cells (HRA) were sensitized to cis‐diammine(l, l‐cyclobutanedicarboxylato)platinum(II) (CBDCA) 1.2‐, 2.1‐ and 3.4‐fold by treatment with amphotericin B (AMB) at concentrations of 2.1, 5.4, and 10.8 μM, respectively. Moreover, the intracellular accumulation of platinum after 2‐h exposure to CBDCA was increased significantly by AMB treatment. For estimating the enhancing effect of AMB on CBDCA cytotoxicity in vivo, we prepared HRA cell‐inoculated nude mice. Ascites was evident 7 to 9 days after intraperitoneal (i.p.) inoculation of HRA cells, and the mice died of intraabdominal carcinomatosis 11 to 14 days (mean survival time (MST): 12.0±1.0 days) after inoculation. Treatment with AMB (2.0 mg/kg) alone increased the MST by only 1.2 days. Simultaneous treatment with CBDCA (12 or 15 mg/kg) and AMB (0.5 to 2.0 mg/kg) produced a significant increase in MST compared to treatment with CBDCA alone. Maximal MST (38.5 days) was obtained by treatment with 15 mgAg CBDCA plus 2.0 mg/kg AMB, whereas the MST with 15 mg/kg CBDCA alone was 15.8 days. A drug accumulation study demonstrated that platinum accumulation in tumor tissues after i.p. treatment with CBDCA and AMB in tumor‐bearing nude mice was increased significantly compared to treatment with CBDCA alone. These findings indicate that intraperitoneal combination chemotherapy with CBDCA and AMB is useful in nude mice with advanced ovarian carcinoma.
High‐yield Induction of Uterine Endometrial Adenocarcinomas in Donryu Rats by a Single Intra‐uterine Administration of N‐Ethyl‐N‐nitro‐N‐nitrosoguanidine via the Vagina
Authors: Ando‐Lu Jin , Takahashi Masakazu , Imai Shigeru , Ishihara Roza , Kitamura Tsuyoshi , Iijima Tetsuo , Takano Satoshi , Nishiyama Kan , Suzuki Kenji , Maekawa Akihiko
Published: August 2005

A total of 130 female Donryu rats (10‐week‐old) were divided into two groups; 80 animals in the experimental group were given a single intra‐uterine administration of 20 mg/kg N‐ethyl‐N‐nitro‐N‐nitrosoguanidine (ENNG) dissolved in polyethylene glycol (PEG) via the vagina without laparotomy, and 50 animals in the control group received PEG alone in the same manner. Small numbers of animals in both groups were killed at 3, 6, 9 and 12 months after ENNG treatment for sequential histological and endocrinological examination, and at 12.5 experimental months (15 months of age) all survivors were killed. At the termination, endometrial adenocarcinomas were present in 49% of the experimental group, compared to 0% in the control group. Severe endometrial hyperplasias were also found only in the experimental group and sequential histological examination showed first appearance of hyperplasia at 6 months and adenocarcinoma at 9 months. No tumors other than uterine carcinomas were induced by ENNG and the carcinogen treatment did not affect the endocrine environment of rats, persistent estrus appearing at 6 months after the start and increasing with age in both groups. The estradio‐17β:progesterone (E:P) ratio was also increased after 6 months, with further elevation at 12 months to about 8 times higher than the level at 6 months. These results indicate that an increased E:P ratio might act as a promoter of development of endometrial proliferative lesions initiated by ENNG in this rat strain. The study indicates that the present simple method using Donryu rats provides a good animal model for endometrial adenocarcinoma development in women.
Semi‐quantitative Analysis of DNA Topoisomerase‐I mRNA Level Using Reverse Transcription‐Polymerase Chain Reaction in Cancer Cell Lines: Its Relation to Cytotoxicity against Camptothecin Derivative
Authors: Niwa Kenji , Misao Ryou , Hanabayashi Takabiro , Morishita Shigeo , Murase Toshiko , Itoh Miho , Itoh Naoki , Mori Hidehiro , Tamaya Teruhiko
Published: August 2005

Expression of DNA topoisomerase (Topo)‐I mRNA in various cancer cell lines was detected using the reverse transcription‐polymerase chain reaction (RT‐PCR) method. The cytoplasmic polyadenylated RNA isolated from cancer cell lines was reverse‐transcribed and the complementary DNA was amplified by PCR primed with Topo‐I specific primers. Fidelity of the amplified sequence was confirmed by restriction endonuclease digestion and Southern blot hybridization. The level of Topo‐I mRNA was correlated positively with the cytotoxicity of a Topo‐I inhibitor, a camptothecin derivative. This RT‐PCR method may be applicable to the assessment of sensitivity of cells to Topo‐I targeted drugs, especially when only small quantities of cell samples are available.
p53 Gene Mutations in Human Prostate Cancers in Japan: Different Mutation Spectra between Japan and Western Countries
Authors: Watanabe Masatoshi , Ushijima Toshikazu , Kakiuchi Hideki , Shiraishi Taizo , Yatani Ryuichi , Shimazaki Jun , Kotake Toshihiko , Sugimura Takashi , Nagao Minako
Published: August 2005

The involvement of p53 mutations in prostate cancers in Japan was investigated. To evaluate any possible clinicopathological significance, p53 mutations in 40 samples from 36 Japanese prostate cancers of different stages (five cases of latent tumors, three of stage A cancers, 10 of stage B, five of stage C and 13 of stage D), including four lymph node metastases of stage D cases, were examined by polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) analysis and sequencing. Mutations were detected in five of 40 samples (12.5%); four were in primary cancers and the other in a lymph node metastasis from one of them. All mutation‐positive cases were in stage D, and the mutation frequency in stage D cases was 31%. This result indicates that p53 mutations may play a role in the progression of a subgroup of prostate cancers in Japanese, as observed for Americans and Europeans. However, a difference was noted between Japanese and Americans in the p53 mutational spectrum (at CpG site), presumably arising from variation in the underlying etiotogic factors.
Effects of Apple Pectin on Fecal Bacterial Enzymes in Azoxymethane‐induced Rat Colon Carcinogenesis
Authors: Ohkami Hideo , Tazawa Kenji , Yamashita Iwao , Shimizu Tetsuro , Murai Kenji , Kobashi Kyoichi , Fujimaki Masao
Published: August 2005

Because of the potential significance of colonic bacteria in colon carcinogenesis, we investigated the effect of pectin of different types on fecal bacterial enzymes (β‐glucuronidase, β‐glucosidase and tryptophanase) at various periods of time after feeding rats with pectin‐containing diets during azoxymethane‐induced colon carcinogenesis. The diet supplemented with 20% apple pectin or 20% citrus pectin decreased the multiplicity of colon tumors, and the number of tumors was significantly decreased in the group fed apple pectin. The incidence of colon tumors in the apple pectin group was lower than that in the control group. The mean tumor size was similar among the three groups. Apple pectin feeding decreased fecal β‐glucosidase and tryptophanase levels. Furthermore, a significant decrease in the activity of β‐glucuronidase was observed in the apple pectin group during the initiation phase. These findings suggest that the protective effect of pectin on colon carcinogenesis may be dependent on the type of pectin and be related to the decrease of β‐glucuronidase activity in the initiation stage of carcinogenesis.
A Specific Chromosome Change and Distinctive Transforming Genes Are Necessary for Malignant Progression of Spontaneous Transformation in Cultured Chinese Hamster Embryo Cells
Authors: Shimizu Takahisa , Kato Mituo V. , Nikaido Osamu , Suzuki Fumio
Published: August 2005

Chinese hamster embryo (CHE) cell strains, each initiated from a separate cell stock obtained from different mothers, were transferred successively at intervals of 3 days and the changes in growth properties and karyotypes at various passages were examined. All nine cell strains proliferated at varying growth rates for 60 passages but only 2 (designated CHE A1 and CHE A2) of them expressed malignant phenotypes. The acquisition of tumorigenicity in nude mice was observed in CHE A1 and CHE A2 cells at passages 40 and 10, respectively. After 5 passages, 8 of 9 cell strains contained one or two common additional chromosomes, chromosome 3q and/or chromosome 5, although one cell strain (designated CHE A3) maintained a normal diploid karyotype for 60 passages. Trisomy of chromosome 3q was observed in all tumorigenic CHE A1 and A2 cells. One or two 3q chromosomes were detected in all tumor‐derived cell lines established from tumors produced by these tumorigenic cells. DNA from tumorigenic cells and tumor‐derived cell lines exhibited a high ability to transform mouse NIH3T3 cells, but we could not detect any activation of Ha‐ras, Ki‐ras, hst, erbB‐2, mos, met or raf in any of the transformed NIH3T3 cells. These results suggest that even though cultured CHE cells can transform spontaneously, without any specific chromosome change, to immortal cells, activation of unknown oncogene(s) in addition to a specific chromosome change may be required for their malignant progression. Our results suggest that trisomy of chromosome 3q is this specific chromosome change.
Intracranial Germ Cell Tumors: Detection of p53 Gene Mutations by Single‐strand Conformation Polymorphism Analysis
Authors: Feng Xuelian , Zhang Shujing , Ichikawa Tomio , Koga Hisashi , Washiyama Kazuo , Motoyama Teiichi , Kumanishi Toshiro
Published: August 2005

Using polymerase chain reaction‐single‐strand conformation polymorphism (PCR‐SSCP) analysis, p53 gene mutation was examined in 12 intracranial germ cell tumors (5 yolk sac carcinomas and 7 germinomas), many of which were derived from young patients in the first to the second decade. A total of 10 mutations were detected in 4 of the 12 cases and, in 3 of them, the mutations were multiple or tandem. Among the 10 mutations, 7 were missense, 1 was splicing and 2 were silent. The 7 missense mutations were located at previously proposed hot spot codons or in their vicinity or, when outside the hot spots, at a codon encoding an amino acid conserved in most vertebrates. These findings suggested that all 7 missense mutations may actually give rise to functional alteration of the p53 protein. The splicing mutation was considered to be a germ‐line mutation, though its biological effect was equivocal, since the neoplastic tissue contained an additional mutation. The pattern of the mutations was predominancy of G:C‐A:T transition with frequent involvement of the CpG site. These mutations were more frequently detected in yolk sac carcinomas (60%; 3/5 cases) than in germinomas (14%; 1/7 cases), suggesting that the contribution of the p53 mutation to carcinogenesis differed with the histological type of the intracranial germ cell tumor.
Effects of Methylxanthine Derivatives on Adriamycin Concentration and Antitumor Activity
Authors: Sadzuka Yasuyuki , Iwazaki Ayano , Miyagishima Atsuo , Nozawa Yasuo , Hirota Sadao
Published: August 2005

We studied the mechanism whereby caffeine acts as a biochemical modulator of adriamycin, and examined various methylxanthine derivatives to determine whether they would be of value as biochemical modulators. In an in vitro study of adriamycin efflux in Ehrlich ascites carcinoma cells, theophylline, pentoxifylline, and theobromine inhibited this efflux, while caffeine metabolites did not. The effects of several methylxanthine derivatives on the antitumor activity of adriamycin and on adriamycin concentration in tissue were also examined in CDF1 tumor‐bearing mice. Theobromine, which inhibited adriamycin efflux in vitro, increased the antitumor activity of adriamycin and the concentration of adriamycin in tumors. The caffeine metabolites, which had no effect on the adriamycin efflux, did not increase antitumor activity. These results suggest that the metabolism of caffeine may weaken its effect as a biochemical modulator, and that pentoxifylline and theobromine would be of value as biochemical modulators of adriamycin.