bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of X‐Irradiation on N‐Methyl‐N‐nitrosourea‐induced Multi‐organ Carcinogenesis in Rats
Authors: Morishita Vukio , Tanaka Takuji , Mori Hideki , Sasaki Shunsaku
Published: August 2005

The effects of X‐irradiation on N‐methyl‐N‐nitrosourea (MNU)‐induced multi‐organ carcinogenesis were examined in both sexes of ACI/N rats. At 6 weeks of age, rats in groups 1 (25 males, 25 females) and 3 (24 males, 23 females) received a single i.p. injection of MNU (25 mg/kg body weight), while those in groups 2 (25 males, 26 females) and 4 (25 males, 25 females) were administered the carcinogen at a dose of 50 mg/kg body weight. At 10 weeks of age, groups 3 and 4 were X‐irradiated at a dose of 3 Gy. Group 5 (24 males, 24 females) received X‐irradiation alone. Group 6 (21 males, 21 females) served as an untreated control. As a result, neoplasms developed mainly in the digestive tract, kidney, uterus, and hematopoietic organ in groups 1–5. The incidences of adenocarcinoma in small and large intestines of male rats of group 4 (50 mg/Ag MNU and X‐irradiation) (small intestine: 48%, large intestine: 32%) were significantly higher than those of group 2 (50 mg/kg MNU) (small intestine: 17%, P<0.05; large intestine: 8%, P<0.05), and also the frequency of adenocarcinoma in the large intestine of males of group 3 (25 mg/kg MNU and X‐irradiation) (22%) was significantly greater than that of group 1 (25 mg/kg MNU) (0%, P<0.O5). These results indicated that X‐irradiation enhanced the development of intestinal neoplasms induced by MNU in male ACI/N rats.
The Mechanism of the Difference in Cellular Uptake of Platinum Derivatives in Non‐small Cell Lung Cancer Cell Line (PC‐14) and Its Cisplatin‐resistant Subline (PC‐14/CDDP)
Authors: Ohmori Tohru , Morikage Toshihiko , Sugimoto Yoshikazu , Fujiwara Yasuhiro , Kasahara Kazuo , Nishio Kazuto , Ohta Sei , Sasaki Yasutsuna , Takahashi Terumi , Saijo Nagahiro
Published: August 2005

A cisplatin‐resistant non‐small cell lung cancer cell line, PC‐14/CDDP, was established from PC‐14 by stepwise escalation of CDDP concentrations in vitro. PC‐14/CDDP cells were 11.4‐fold more resistant to CDDP compared with PC‐14 cells. This resistant cell line was cross‐resistant to platinum analogues, such as carboplatin (CBDCA) (X 3.5), cis‐diammine(glycolate‐O, O′)platinum(II) (254‐S) (X 5.6) and cis‐dichloro(ethylenediammine)platinum(II) (cis‐DEP) (X 4.2). On the other hand, relative resistance value to ormaplatin was only 1.4‐fold. To elucidate the mechanism(s) of CDDP resistance and of its circumvention by ormaplatin, we investigated the characteristics of this cell line. Total sulfhydryl content was slightly elevated in PC‐14/CDDP cells compared with PC‐14 cells. There was no significant difference in the DNA repair ability between the two cell lines. Cellular accumulations of CDDP, CBDCA, 254‐S, and cis‐DEP in PC‐14/CDDP cells were markedly decreased to 23%, 27%, 29%, and 32% of those in PC‐14 cells, respectively. However, the accumulation of ormaplatin in PC‐14/CDDP was almost the same as that in PC‐14. To elucidate the mechanisms of uptake of these platinum analogs in the cells, we studied the effects of ouabain, an Na+, K+ ‐ATPase inhibitor, on cellular drug uptake in both cell lines. Preincubation with 300 nM ouabain for 1 h inhibited approximately 60% of CDDP accumulation in PC‐14. However ouabain preincubation at any concentration up to 300 nM did not affect CDDP accumulation in PC‐14/CDDP. The accumulation of ormaplatin was not inhibited by ouabain in either of the cell lines. These data suggest that the mechanism of the uptake of ormaplatin is different from that of CDDP, and that ormaplatin exerts a cytotoxic effect in CDDP‐resistant cells which have defective cisplatin accumulation.
Antitumor Activity of Oenothein B, a Unique Macrocyclic Ellagitannin
Authors: Miyamoto Ken‐ichi , Nomura Masaaki , Sasakura Mitsugu , Matsui Eiichi , Koshiura Ryozo , Murayama Tsugiya , Furukawa Toru , Hatano Tsutomu , Yoshida Takashi , Okuda Takuo
Published: August 2005

The antitumor effect of oenothein B, a macrocyclic ellagitannin from Oenothera erythrosepala Bordas, on rodent tumors was studied, Oenothein B exhibited a strong antitumor activity against MM2 ascites tumors upon intraperitoneal administration to the mice before or after the tumor inoculation. The tannin also inhibited the growth of Meth‐A solid type tumor in mice. This antitumor effect of the tannin could not be attributed to its direct cytotoxic action on tumor cells, because the cytotoxicity was very weak in the presence of serum protein. When oenothein B was injected into the peritoneal cavity of mice, peritoneal exudate cells, including cytostatic macrophages, were induced. Furthermore, in the in vitro treatment of macrophages from mice and humans, the tannin stimulated release of an interleukin 1 (IL‐1)‐like activity and IL‐1β from the cells. These results suggest that oenothein B exerts its antitumor effect through potentiation of the host‐immune defense via activation of macrophages.
Enhancing Effect of Cadmium on Rat Ventral Prostate Carcinogenesis Induced by 3,2′‐Dimethyl‐4‐aminobiphenyl
Authors: Shirai Tomoyuki , Iwasaki Shogo , Masui Tsuneo , Mori Toshio , Kato Toshio , Ito Nobuyuki
Published: August 2005

The effects of cadmium given at different stages during 3,2′‐dimethyl‐4‐aminobiphenyl (DMAB)‐induced rat prostate carcinogenesis were investigated using male F344 rats. Animals were given 10 subcutaneous injections of 50 mg/kg body weight of DMAB or the corn oil vehicle at two‐week intervals. In addition, cadmium was administered at doses of 0, 10, or 30 /μmol/kg body weight as single intramuscular injection on the 1st day of the experiment or one day after the last injection of DMAB at week 20. Two further groups were subjected to administration of cadmium at 10 μmol/kg at week 20 and then 5 μmol/kg at week 40, or 10 μmol/kg at week 20 and then 5 μmol/kg at weeks 30, 40 and 50. At the termination, 60 weeks after the beginning of the experiment, the incidences and multiplicity of ventral prostate carcinomas in the groups given cadmium plus DMAB demonstrated a consistent tendency for increase over control values (groups receiving DMAB or cadmium alone). The numbers of carcinomas per rat and per unit area of prostate section were significantly elevated in the two groups given low doses of cadmium after cessation of DMAB administration. Cadmium alone also induced a few prostate carcinomas. The influence on development of prostate tumors did not appear to be a result of the induced severe testicular atrophy because serum testosterone levels were not affected. The results indicate that cadmium and DMAB can act synergistically to cause rat prostate carcinogenesis.
K‐ras Gene Mutation in Early Ductal Lesions Induced in a Rapid Production Model for Pancreatic Carcinomas in Syrian Hamsters
Authors: Tsutsumi Masahiro , Kondoh Satoshi , Noguchi Osamu , Horiguchi Kohsuke , Kobayashi Eisaku , Okita Shunji , Ohashi Kazuo , Honoki Kanya , Tsujiuchi Toshifumi , Konishi Yoichi
Published: August 2005

The presence of K‐ras gene mutation was examined in experimentally induced preneoplastic pancreatic ductal lesions. Syrian hamsters received 70 mg/kg of N‐nitrosobis(2‐oxopropyl)amine (BOP) followed by repeated exposure to an augmentation pressure regimen consisting of choline‐deficient diet combined with dl‐ethionine and l‐methionine and administration of 20 mg/kg BOP. After two augmentation pressure cycles, pancreatic ductal cell hyperplasias appeared and after three cycles, atypical hyperplasias of pancreatic ductal cells and intraductal carcinomas developed. K‐ras mutations were detected by single‐strand conformation polymorphism analysis of polymerase chain reaction products and nucleotide sequencing. The results showed that K‐ras mutation had occurred in one of 9 simple hyperplasias of pancreatic ductal epithelium, in 5 of 9 atypical hyperplasias, and in 4 of 8 intraductal carcinomas. The findings thus suggested that K‐ras is activated in association with very early stage malignant transformation of pancreatic ductal cells in hamsters.
Immunohistochemical Detection of Hepatocyte Growth Factor/Scatter Factor in Human Cancerous and Inflammatory Lesions of Various Organs
Authors: Yoshinaga Yasuteru , Matsuno Yoshihiro , Fujita Shin , Nakamura Toshikazu , Kikuchi Masahiro , Shimosato Yukio , Hirohashi Setsuo
Published: August 2005

Hepatocyte growth factor (HGF)/scatter factor (SF) is a multifunctional factor considered to be potentially involved in tissue regeneration, wound healing, embryogenesis, angiogenesis and cancer invasion. Here we examined immunohistochemically the distribution of HGF/SF in human tissues, including cancerous and inflammatory tissues, using anti‐HGF antibody. HGF/SF accumulation was clearly detected in the extracellular matrix, particularly along the basement membrane, in cancerous and inflammatory tissues, but only a little was detected in normal tissues. HGF/SF is well known to have a strong affinity for heparin in vitro, and from the results of our immunohistochemical assay, we considered that HGF/SF was bound to heparin or heparan sulfate of the extracellular matrix and basement membrane. HGF/SF was well localized in cancerous and inflammatory lesions of human lung, liver and pancreas, and in apparently normal tissues of kidney, adrenal gland and pancreas obtained at autopsy. In lung, HGF/SF was localized along the basement membranes of cancer cell nests, in the extracellular matrix of the cancer cell surface, cancer stroma and tissues invaded by cancer, and the basement membranes of bronchial epithelium and capillary vessels in inflammatory stroma. Since HGF/SF makes some cancer cells more invasive in vitro, the accumulation of HGF/SF in cancerous tissue suggests that the invasiveness of some cancer cells may be increased by HGF/SF in vivo.
Induction of Glandular Stomach Cancers in C3H Mice Treated with N‐Methyl‐N‐nitrosourea in the Drinking Water
Authors: Tatematsu Masae , Yamamoto Masami , Iwata Hitoshi , Fukami Hiroko , Yuasa Hirofumi , Tezuka Noriaki , Masui Tsuneo , Nakanishi Hayao
Published: August 2005

Establishment of an animal model of stomach carcinogenesis in mice was attempted using N‐methyl‐N‐nitrosourea (MNU) in the drinking water. One hundred and forty‐eight male 6‐week‐old C3H mice were given MNU in their drinking water at a concentration of 120 ppm (group 1), 60 ppm (group 2), 30 ppm (group 3) or 0 ppm (group 4) for 30 weeks. At the end of this time, dose‐related induction of adenomatous hyperplasias was found. From weeks 31 to 54 adenocarcinomas developed in a dose‐dependent manner in groups 1, 2 and 3. In total, 6 well differentiated and 5 poorly differentiated adenocarcinomas as well as 6 signet ring cell carcinomas arose in 15 stomach cancer‐bearing animals in group 1, 4 well differentiated and 2 poorly differentiated adenocarcinomas with one signet ring cell carcinoma in 5 mice of group 2 and one well differentiated adenocarcinoma in group 3. In the forestomach, only one squamous cell carcinoma was found at week 54 in group 1 along with a single well differentiated adenocarcinoma in the duodenum. Thus, MNU in the drinking water selectively induced neoplastic lesions in the glandular stomach epithelium of mice.
Transmission Routes of HTLV‐I: An Analysis of 66 Families
Authors: Take Hiromichi , Umemoto Masakazu , Kusuhara Kouichi , Kuraya Kazue
Published: August 2005

HTLV‐I transmission routes were found for 66 carrier pregnant women by studying sera, from the carrier pregnant women, their mothers, and their husbands, and by obtaining detailed family histories at interview. Forty‐one cases (62.1%) were considered to be instances of vertical transmission, 15 (22.8%) of sexual transmission, 6 (9.1%) of blood transfusion, and 4 (6.1%) undecided. To date, most cases of adult T‐cell leukemia (ATL) have been considered to result from vertical transmission. Our results therefore imply that about 30% (22.8%+ 9.1%) of the carrier pregnant women are at minimal risk of ATL. Moreover, in case of presumed husband‐to‐wife transmission, more than half (6/11) were infected between one year and four years after marriage.
Presence of a Regulatory Element within the First Intron of the Human Platelet‐derived Growth Factor‐A Chain Gene
Authors: Takimoto Yasuo , Kuramoto Atsushi
Published: August 2005

We detected a suppressive element in the first intron of the human platelet‐derived growth factor A chain (PDGF‐A) gene. Two or more proteins, at least 110‐kd and 90‐kd proteins, were bound over a wide region of this fragment, and the fragment suppressed the expression of the FDGF‐A chain via these proteins in vivo. Since the fragment also had suppressor activity on the promoter of the PDGF‐B chain, it may be involved in a suppressive mechanism of gene expression common to PDGF‐A and ‐B chains. Four tandem repeats of CCCCAT(CCCC) and three direct repeats of GGGGAG were observed in this region. The expression of the PDGF‐A chain is considered to be regulated by a mechanism involving not only the 5’upstream region but also introns.
Progression of Androgen‐sensitive Mouse Tumor (Shionogi Carcinoma 115) to Androgen‐insensitive Tumor after Long‐term Removal of Testosterone
Authors: Sato Naohide , Watabe Yoshio , Suzuki Hiroyoshi , Shimazaki Jun
Published: August 2005

Shionogi Carcinoma 115 (SC115) is an androgen‐sensitive transplantable mouse tumor. To study the mode of progression from androgen‐sensitive to ‐insensitive tumor, cloned SC115 cells were serially cultured without androgen. Shortly after withdrawal of androgen, SC115 cells showed markedly decreased growth, but growth resumed gradually with loss of response to androgen and the cells 60 weeks after androgen removal [A(—)60 cells] grew faster than SC115 cells cultured in the presence of androgen. A(—)60 cells showed malignant phenotype with morphological changes and tumorigenicity in male and female mice. Although mRNA and binding capacity of androgen receptor were maintained, the cells after removal of androgen rapidly lost expression of mouse mammary tumor virus‐related gene and the loss was irreversible in A(—)60 cells. The stimulating effect of basic flbroblast growth factor (bFGF) temporarily decreased, then recovered to the initial level after long‐term androgen removal. This fluctuation of response to bFGF was accompanied with changes in the number of bFGF receptors and amount of bFGF‐like substance(s) secreted. The substance(s) seemed to be an FGF‐like growth factor different from known factors. It was concluded that progression of SC115 cells to androgen‐insensitive ones under an androgen‐deprived condition proceeded with adaptation by means of increases in production of an FGF‐like growth factor and in binding capacity to this factor.
Helicobacter pylori May Be Transmitted through Gastrofiberscope Even after Manual Hyamine Washing
Authors: Katoh Masaru , Saito Daizo , Noda Takeshi , Yoshida Shigeaki , Oguro Yanao , Yazaki Yoshio , Sugimura Takashi , Terada Masaaki
Published: August 2005

Endoscopy is an effective diagnostic technique for gastric cancer, which is believed to be associated with Helicobacter pylori. Manual Hyamine washing is a widely used fiberscope cleaning method. Urease B gene of Helicobacter pylori was detected in 50% of the wash‐out samples from the biopsy‐suction channel of a fiberscope after manual Hyamine washing by nested polymerase chain reaction, and bacterial culture revealed viable Helicobacter pylori in 19%. However, Helicobacter pylori was not detected by either of the above methods in the biopsy‐suction channel of the fiberscope after mechanical washing. These findings indicate that manual Hyamine washing of fiberscopes is insufficient to prevent iatrogenic Helicobacter pylori transmission, and that mechanical washing after manual Hyamine washing is essential.
Time‐dependent Modulation of Liver Lesion Development in Opisthorchis‐infected Syrian Hamster by an Antihelminthic Drug, Praziquantel
Authors: Thamavit Witaya , Moore Malcolm A. , Sirisinha Stitaya , Shirai Tomoyuki , Ito Nobuyuki
Published: August 2005

In the North‐east of Thailand, repeated antihelminthic therapy has been introduced for control of the opisthorchiasis known to be a major risk factor for cholangiocellular carcinomas. What influence this may have on tumorigenesis, however, remains unclear. The effects of administration of praziquantel, an antihelminthic drug, at different time points subsequent to infection with Opisthorchis viverrini (OV) on 2,2′‐dihydroxy‐di‐n‐propylnitrosamine (DHPN)‐initiated lesion development in the liver of female Syrian hamsters were therefore investigated. Praziquantel (250 mg/kg body weight, i.p.) was given 4, 12 or 20 weeks after infection of DHPN‐treated animals (two 1000 mg/kg i.p. injections at weeks 0 and 2) with 60 OV metacercariae (at week 4). Survivors at week 38 were killed and examined. It was found that whereas praziquantel administration at the earlier two time points was effective at reducing hepatocellular nodule development, the results for cholangiocellular lesions were less pronounced, significant reduction only being evident in hamsters treated 4 weeks after parasite infestation. The findings thus indicate that enhancement of DHPN‐initiated bile duct carcinogenesis by opisthorchiasis is both rapid and to a large degree irreversible. Hepatocellular lesion development in this model, on the other hand, appears to correlate more closely with the duration of parasite‐associated proliferative stimulus.
Construction of Immunoradiometric Assay for Circulating c‐erbB‐2 Protooncogene Product in Advanced Breast Cancer Patients
Authors: Hosono Makoto , Saga Tsuneo , Sakahara Harumi , Kobayashi Hisataka , Shirato Makoto , Endo Keigo , Yamamoto Tadashi , Akiyama Tetsu , Toyoshima Kumao , Konishi Junji
Published: August 2005

The human c‐erbB‐2 protooncogene product (erbB‐2 protein) is a 185 kilodalton glycoprotein closely related to epidermal growth factor receptor protein. In this study, we measured the concentration of circulating erbB‐2 protein in cancer patients by means of a new immunoradiometric assay (IRMA). Two monoclonal antibodies (MoAbs), SV2‐61γ and 6G10, recognize erbB‐2 protein but bind to separate epitopes. SV2‐61γ was used as an immunoadsorbent and 6G10 as an 125I‐labeled probe. A serum was considered positive for erbB‐2 protein if the percent binding exceeded the mean of the normal group by more than 3 standard deviations. Eleven of 21 patients with advanced breast cancer and 1 of 15 with advanced gastric cancer were positive. Serum erbB‐2 protein levels correlated well with the therapy and the status of the patients with breast cancer. On the contrary, all patients with advanced colon, ovarian, or pancreatic cancers, showed levels below the cut‐off value. These results suggest that circulating erbB‐2 protein can be measured using the newly constructed IRMA. Since c‐erbB‐2 protooncogene amplification and overexpression are accepted as a good marker of aggressiveness, relapsing potency, and poor prognosis, this IRMA should be a promising tool with which to help manage breast cancer patients.
Infrequent ras Mutation in Human Stomach Cancers
Authors: Koshiba Masahiro , Ogawa Osamu , Habuchi Tomonori , Hamazaki Shuji , Shimada Toshihide , Takahashi Rei , Sugiyama Taketoshi
Published: August 2005

Mutations of ras oncogenes in 37 human stomach cancers and 13 adenomas were investigated with regard to the histological phenotypes using polymerase chain reaction (PCR), allele‐specific oligonucleotide hybridization and/or direct sequencing of the PCR products. The ras mutation was found only in one case (2.7%), the histology of which was poorly differentiated adenocarcinoma. We found no mutation in stomach adenomas. The mutation consisted of a guanine‐to‐adenine transition in the first base of codon 13 of c‐Ki‐ras which replaced wild‐type glycine with serine, indicating that a putative glycine‐to‐aspartic acid change is not necessarily the critical event for c‐Ki‐ras gene activation in codon 13. These results further confirm the infrequency of ras mutation in stomach tumors and also suggest that ras mutations are not specific to the differentiated type of stomach cancer.
Reduced Expression of nm23 Is Associated with Metastasis of Human Gastric Carcinomas
Authors: Nakayama Hirofumi , Yasui Wataru , Yokozaki Hiroshi , Tahara Eiichi
Published: August 2005

Reduced expression of nm23 gene is implicated in high metastatic potential In a variety of malignancies. To elucidate the role of nm23 in human gastric carcinomas, we examined loss of heterozygosity (LOH) of nm23 gene by Southern blotting, nm23 mRNA expression by Northern blotting and nm23 protein expression by Western blotting as well as immunohistochemistry in both primary and metastatic tumors. LOH of nm23 gene was found in 2 (8%) out of the 23 informative gastric carcinomas. Twenty‐two (84%) out of the 26 cases expressed nm23 mRNA at higher levels in primary tumor tissue than in corresponding non‐neoplastic mucosa. No obvious correlation was observed between clinico‐pathological features and LOH of nm23 gene or nm23 mRNA expression. On the other hand, 52% of the gastric carcinomas showed reduction of nm23 immunoreactivity in the metastatic tumor of regional lymph nodes, as compared to the primary tumor. Interestingly, 71% of the gastric carcinomas showed weaker nm23 immunoreactivity in the liver metastasis than in the primary tumor. These results suggest that nm23 overexpression is linked with development of gastric carcinomas and the decrease in expression of nm23 participates in metastasis.
Abnormal Hepatic Iron Accumulation in LEC Rats
Authors: Kato Junji , Kohgo Yutaka , Sugawara Naoki , Katsuki Shinichi , Shintani Naoaki , Fujikawa Kohshi , Miyazaki Etsu , Kobune Masayoshi , Takeichi Noritoshi , Niitsu Yoshiro
Published: August 2005

The LEC (Long‐Evans cinnamon) rat is a mutant strain displaying hereditary hepatitis and spontaneous hepatocellular carcinoma, and shows abnormal hepatic copper accumulation similar to that occurring in Wilson's disease. We evaluated the iron metabolism of LEC rats compared to LEA (Long‐Evans agouti) rats. Hepatic iron and ferritin concentrations were remarkably increased depending on age in LEC rats but not in LEA rats. Increased hepatic iron is normally associated with decreased serum transferrin and total iron binding capacity in hepatic iron overload. In LEC rats, however, both serum transferrin and total iron binding capacity increased with increasing hepatic iron. This increase of serum transferrin and hepatic iron may be an additional important factor contributing to liver injury in LEC rats.
Demonstration of Initiation Potential of Carcinogens by Induction of Preneoplastic Glutathione S‐Transferase P‐Form‐positive Liver Cell Foci: Possible in vivo Assay System for Environmental Carcinogens
Authors: Tsuda Hiroyuki , Matsumoto Kazuyuki , Ogino Hiroshi , Ito Mitsuya , Hirono Iwao , Nagao Minako , Sato Kiyomi , Cabral Ricardo , Bartsch Helmut
Published: August 2005

In a development trial for an initiation bioassay system, 7 known carcinogens and 1 suspected carcinogen were examined. In experiment 1, group 1 animals were initially subjected to partial hepatectomy (PH) 12 h before administration of diethylnitrosamine, 2‐amino‐3‐methylimidazo[4,5‐F]‐quinoline (IQ), captafol, α‐hexachlorocyclohexane or diethylstilbestrol (DES), then 2 weeks later underwent a promotion procedure comprising administration of phenobarbital (0.05% in diet) for 8 weeks and D‐galactosamine (300 mg/kg, i.g.) at week 3. Group 2 received the promotion protocol alone as in group 1. Initiating potential was assayed on the basis of significant increase in values of preneoplastic placental form glutathione S‐transferase‐positive (GST‐P+) foci of more than 3 cells in cross section at week 10. Numbers and areas of GST‐P+ foci in group 1 given IQ, captafol and DES were significantly increased as compared to group 2, confirming the validity of the protocol as an initiation assay. In Experiment 2, group 1 rats were subjected to PH and 12 h later received a suspected carcinogenic mixture of opium pyrolysate (OP) or carcinogenic pesticide p, p′‐dichlorodiphenyltrichloroethane or hexachlorobenzene. Application of a modified promotion procedure comprising cholic acid (0.15%) and carbon tetrachloride (1 ml/kg, i.g.) revealed significant initiation potential for OP. Overall the results indicate that the current protocols may be useful for detection of the initiation potential of carcinogens irrespective of their mutagenicity.
Correlation between Medium‐term Multi‐organ Carcinogenesis Bioassay Data and Long‐term Observation Results in Rats
Authors: Hagiwara Akihiro , Tanaka Hikaru , Imaida Katsumi , Tamano Seiko , Fukushima Shoji , Ito Nobuyuki
Published: August 2005

The effects of four test chemicals [2‐acetylaminofluorene (2‐AAF), D, L‐ethionine (ethionine), butylated hydroxyanisole (BHA), and catechol] were compared in medium‐ and long‐term in vivo systems. In the medium‐term assay, animals were sequentially treated with N‐diethylnitrosamine (100 mg/kg body weight, i.p., single injection), N‐methylnitrosourea (20 mg/kg body weight, i.p., 4 times during weeks 1 and 2), N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine (0.05% in the drinking water during weeks 1 and 2), 1,2‐dimethylhydrazine (40 mg/kg body weight, s.c., 4 times during weeks 3 and 4) and dihydroxy‐di‐N‐propylnitrosamine (0.1% in the drinking water during weeks 3 and 4) for multi‐organ initiation, and then treated with one of the four test chemicals for 24 weeks, and killed at week 28 (group 1). In the long‐term assay, animals were treated in the same manner and then given hasal diet and tap water (group 3) or test chemical continuously (group 4) for the remainder of the lifespan. Animals receiving multi‐organ initiation and then maintained on hasal diet for 24 weeks (group 2) or their lifespan (group 5) served as controls. Detailed histopathological examinations were performed on all rats. Hepatocellular carcinoma incidences in the long‐term assay were found to reflect closely the respective medium‐term results. Induction of proliferative forestomach or glandular stomach lesions by BHA and/or catechol, and bladder lesions by 2‐AAF and BHA in the mediumterm assay also correlated with tumor development in the long‐term. Furthermore, inhibition of thyroid proliferative lesions by all test chemicals corresponded with low thyroid tumor incidences in the long‐term assay. The observed strong correlation between medium‐ and long‐term results confirms the applicability of our medium‐term multi‐organ carcinogenesis bioassay system for detection of modifying effects of test chemicals in different organs.
Genotypic Analysis of Epstein‐Barr Virus Associated with Nasopharyngeal Carcinoma of Japanese Patients
Authors: Tamura Shinji , Kunimoto Masaru , Tabata Toshihide , Yoshie Osamu
Published: August 2005

Types and certain genetic markers were studied for Epstein‐Barr virus present in 10 specimens of nasopharyngeal carcinoma (NPC) from Japanese patients. The type 1 virus was predominant in our NPC specimens, as in the general Japanese population, and the type 2 virus was found only in one NPC specimen. The type C variant, which lacks the BamHI site between the BamHI‐W1* and ‐I1* regions, appeared to be common among Japanese strains as in those in Southern China. The type f variant which has an extra BamHI site in the BamHI‐F region and has been shown to be strongly associated with NPC in Southern China was found in only one NPC specimen. This virus strain was also the only type 2 virus among our specimens. The present study, therefore, does not show any specific association of the type f variant with NPC in Japan.
Structure of 85 kDa Subunit of Human Phosphatidylinositol 3‐Kinase Analyzed by Using Monoclonal Antibodies
Authors: Tanaka Shinya , Matsuda Michiyuki , Nagata Satoshi , Kurata Takeshi , Nagashima Kazuo , Shizawa Yasuhiko , Fukui Yasuhisa
Published: August 2005

An 85 kDa subunit (p85α) of phosphatidylinositol 3‐kinase (PI‐3K) has one SH3 and two SH2 regions [SH2(N) and SH2(C)], which direct protein‐protein interaction. We have established eighteen hybridomas producing monoclonal antibodies against p85α to study the structure‐function relationship of this protein. Epitope mapping using a series of deletion mutants expressed in E. coli showed that the monoclonal antibodies bound to at least 5 distinct epitope regions, which were well dispersed on p85α except for its carboxyl‐terminus. Monoclonal antibodies against ammo‐terminal regions and polyclonal antibodies against carboxyl‐terminal regions immunoprecipitated p85α expressed in human cells and in E. coli. On the other hand, monoclonal antibodies against the central part of p85α failed to immunoprecipitate p85α efficiently; however, they could immunoprecipitate p85α mutants with deletion of either the amino‐ or the carboxyl‐terminal region. Similar results were obtained by immunocytochemistry using confocal microscopy. These results suggested that steric hindrance prevents binding of monoclonal antibodies to the central part of p85α where SH2(N) is located. The SH2(N) may have a distinct function from SH2(C), which is located at the carboxyl‐terminal region and has been shown to mediate the binding of PI‐3K to activated growth factor receptors.
Use of Serum Gamma‐enolase and Aldolase A in Combination as Markers for Renal Cell Carcinoma
Authors: Takashi Munehisa , Sakata Takao , Kato Kanefusa
Published: August 2005

To clarify whether measurement of serum γ‐enolase and aldolase A in combination is useful for diagnosis and prediction of prognosis in cases of renal cell carcinoma (RCC), levels of both markers were evaluated by enzyme immunoassay in 132 patients with RCC. Serum γ‐enolase was elevated in 53 of the cases (40%) whereas serum aldolase A was elevated in 45 (34%). At least one of the two markers was elevated in 54% of the patients (71/132), this value being significantly higher than the positive rates for either γ‐enolase (40%) or aldolase A (34%) evaluated singly. Expression of the two markers assessed in combination became more positive with stage progression, values being 37% in stage I, 59% in stage II, 72% in stage III, and 74% in stage IV. In contrast, patients with benign urological diseases demonstrated positive rates for γ‐enolase and aldolase A as low as 3% and 6%, respectively. Increase in serum γ‐enolase was correlated with stage, tumor size, and histological grade, whereas elevated levels of serum aldolase A were associated only with advancing stage. In 15 patients with recurrent diseases, 11 (73%) had elevated levels of γ‐enolase and 5 (33%) had elevated levels of aldolase A, indicating that γ‐enolase is the more sensitive of the two for detection of recurrence. Patients with elevated levels of both γ‐enolase and aldolase A had less favorable survival than those expressing no or only one of the markers, indicating that simultaneous measurement of the two markers provides information directly relevant to prognosis in cases of RCC.
Mental disorders in current and former heavy ecstasy (MDMA) users
Authors: Thomasius R. , Petersen K. U. , Zapletalova P. , Wartberg L. , Zeichner D. , Schmoldt A.
Published: August 2005

Background  Ecstasy use has often been found to be associated with psychopathology, yet this research has so far been based largely on subjective symptom ratings.

Aims  To investigate whether ecstasy users suffered from long‐term psychopathological consequences.

Measurements  We compared the prevalence of Diagnostic and Statistical Manual version IV (DSM‐IV) mental disorders in 30 current and 29 former ecstasy users, 29 polydrug and 30 drug‐naive controls. Groups were approximately matched by age, gender and level of education. The current ecstasy users reported a life‐time dose of an average of 821 and the former ecstasy users of 768 ecstasy tablets.

Findings  Ecstasy users did not significantly differ from controls in the prevalence of mental disorders, except those related to substance use. Substance‐induced affective, anxiety and cognitive disorders occurred more frequently among ecstasy users than polydrug controls. The life‐time prevalence of ecstasy dependence amounted to 73% in the ecstasy user groups. More than half of the former ecstasy users and nearly half of the current ecstasy users met the criteria of substance‐induced cognitive disorders at the time of testing. Logistic regression analyses showed the estimated life‐time doses of ecstasy to be predictive of cognitive disorders, both current and life‐time.

Conclusions  The motivation for ecstasy use is not likely to be self‐medication of pre‐existing depressive or anxiety disorders as these did not occur more frequently in the ecstasy users than in control groups or in the general population. Cognitive disorders still present after over 5 months of ecstasy abstinence may well be functional consequences of serotonergic neurotoxicity of 3,4‐methylenedioxymethamphetamine (MDMA).
Changes in the prevalence of alcohol use in rap song lyrics, 1979–97
Authors: Herd Denise
Published: August 2005

Aims  This paper explores the role of changing images of drinking and alcoholic beverage use in rap music from its beginnings in the United States in the late 1970s to the late 1990s.

Design  A sample of 341 rap music song lyrics released from 1979 to 1997 were selected using Billboard and Gavin rating charts. Song lyrics were coded for music genres, alcohol beverage types and brand names, drinking behaviors, drinking contexts, intoxication, attitudes towards alcohol and consequences of drinking.

Findings  From 1979 to 1997, songs with references to alcohol increased fivefold (from 8 to 44%); those exhibiting positive attitudes rose from 43% to 73%; and brand name mentions increased from 46% to 71%. There were also significant increases in songs mentioning champagne and liquor (mainly expensive brand names) when comparing songs released after 1994 with those from previous years. In addition, there were significant increases in references to alcohol to signify glamour and wealth, and using alcohol with drugs and for recreational purposes. The findings also showed that alcohol use in rap music was much more likely to result in positive than negative consequences.

Conclusions  Many of these findings are consistent with the idea that rap music has been profoundly affected by commercial forces and the marketing of alcoholic beverages. In addition, it is possible that the increase in references to alcoholic beverages in rap music, particularly spirits, is a reflection of a broader advertising culture which increasingly associates African Americans with alcohol use.
Reducing adverse events in blood transfusion
Authors: Stainsby Dorothy , Russell Joan , Cohen Hannah , Lilleyman John
Published: August 2005

Against a background of ever increasing expenditure on blood safety, less attention has been paid to improving the safety of the transfusion chain within hospitals. Based on reports to the Serious Hazards of Transfusion (SHOT scheme) between 1996 and 2003, the risk of an error occurring during transfusion of a blood component is estimated at 1:16 500, an ABO incompatible transfusion at 1:100 000 and the risk of death as a result of an ‘incorrect blood component transfused’ (IBCT) is around 1:1 500 000. There are opportunities for error at a number of critical points in the transfusion chain, starting with the decision to transfuse, prescription and request, patient sampling, pretransfusion testing and finally the collection of the component from the blood refrigerator and administration to the patient, consistently the commonest error in successive SHOT reports. Successive ‘Better Blood Transfusion’ initiatives and the 2003 Annual Report of the Chief Medical Officer for England have drawn welcome attention to the importance of safe and appropriate transfusion and the National Patient Safety Agency has now set a target of reducing the number of ABO incompatible transfusions by 50% over 3–5 years.
The frequency of the sickle allele in Jamaica has not declined over the last 22 years
Authors: Hanchard N. A. , Hambleton I. , Harding R. M. , McKenzie C. A.
Published: August 2005

The ‘malaria hypothesis’ predicts that the frequency of the sickle allele, which is high in malaria‐endemic African populations, should decline with each generation in populations of African descent living in areas where malaria is no longer endemic. In order to determine whether this has been the case in Jamaica, we compared haemoglobin electrophoresis results from two hospital‐based screening programmes separated by more than 20 years (i.e. approximately one generation). The first comprised 100 000 neonates screened between 1973 and 1981, the second, 104 183 neonates screened between 1995 and 2003. The difference in frequency of the sickle allele was small (5·47% in the first cohort and 5·38% in the second screening cohort) and not significant (Z = 1·23, P = 0·22). The same was true of the sickle trait frequency (10·05% in the first cohort and 9·85% in the second, Z = 1·45, P = 0·15). These differences were smaller than predicted under simple deterministic models based on the malaria hypothesis, and suggest that these models may not capture important determinants of allele and trait frequency decline (or persistence) in contemporary populations. Refining the expectations for allele and trait frequency change for Jamaica and other similar populations is an area for future study.
Histopathology, cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma (MCL): a clinicopathological study from the European MCL Network
Authors: Tiemann Markus , Schrader Carsten , Klapper Wolfram , Dreyling Martin H. , Campo Elias , Norton Andrew , Berger Francoise , Kluin Philip , Ott German , Pileri Stephano , Pedrinis Ennio , Feller Alfred C. , Merz Hartmut , Janssen Dirk , Hansmann Martin L. , van Krieken Han , Möller Peter , Stein Harald , Unterhalt Michael , Hiddemann Wolfgang , Parwaresch Reza
Published: August 2005

Mantle cell lymphoma (MCL) is a distinct lymphoma subtype with a particularly poor clinical outcome. The clinical relevance of the morphological characteristics of these tumours remains uncertain. The European MCL Network reviewed 304 cases of MCL to determine the prognostic significance of histopathological characteristics. Cytomorphological subtypes, growth pattern and markers of proliferation (mitotic and Ki‐67 indices) were analysed. In addition to the known cytological subtypes, classical (87·5%), small cell (3·6%), pleomorphic (5·9%) and blastic (2·6%), we identified new pleomorphic subgroups with mixtures of cells (classical + pleomorphic type; 1·6%) or transitions (classical/pleomorphic type; 1·6%), which, however, did not differ significantly in overall survival time. Exactly 80·5% of cases displayed a diffuse growth pattern, whereas 19·5% of cases had a nodular growth pattern, which was associated with a slightly more favourable prognosis. A high proliferation rate (mitotic or Ki‐67 indices) was associated with shorter overall survival. Cut‐off levels were defined that allowed three subgroups with different proliferation rates to be discriminated, which showed significantly different clinical outcomes (P < 0·0001). Based on this large clinicopathological study of prospective clinical trials, multivariate analysis confirmed the central prognostic role of cell proliferation and its superiority to all other histomorphological and clinical criteria.
How the spiritual dimension is addressed in psychiatric patient–nurse relationships
Authors: Koslander Tiburtius , Arvidsson Barbro
Published: August 2005

Aim.  This paper reports a study describing nurses’ conceptions of how the spiritual dimension is addressed in psychiatric patient–nurse relationships.

Background.  In psychiatric care, it is essential that patient–nurse relationships be built on a holistic view. In this context, nursing research shows that there is a lack of integration of the spiritual dimension.

Method.  Twelve strategically selected psychiatric nurses were interviewed and analysed using a phenomenographic approach. The data were collected in 2003.

Findings.  The main findings were three descriptive categories: being a good carer, recognizing the spiritual dimension, and regarding the spiritual dimension as difficult to capture in patient–nurse relationships. The first descriptive category shows that nurses deal with spirituality by behaving as good carers. Those included in the second descriptive category reveal nurses who are aware of patients’ spiritual needs and who deal with these needs in different ways. The third descriptive category consists of conceptions revealing lack of knowledge of patients’ spiritual needs, both in abstract and real terms.

Conclusions.  Further research is needed to explore how patients describe their own spiritual needs, and how nursing staff can learn to be aware of and understand their own spirituality, thus enabling them to detect, discuss, clarify and deal with the concept of spirituality in patient–nurse relationships.
‘I'm just going to wash you down’: sanitizing the vaginal examination
Authors: Stewart Mary
Published: August 2005

Aim.  This paper reports findings from an ongoing study exploring the qualitative experiences of midwives and women in relation to vaginal examination in labour, focusing on how vaginal examination is discussed and on the wash‐down procedure used by some midwives.

Background.  The body is a source of considerable ambivalence in sociological terms. Women's bodies, in particular, have been viewed as problematic and as a potential source of dirt and pollution. It has been suggested that vaginal examinations during labour are used, at least in part, as a ritual procedure by which healthcare professionals demonstrate that they are in control of both the labouring woman and the process of labour itself.

Methods.  In‐depth interviews were undertaken during 2003 with six childbearing women and 10 midwives who had been involved in these women's care. Non‐participant observation was also carried out of each woman's labour and birth.

Findings.  During interviews, when discussing vaginal examination, midwives persistently used abbreviations or euphemisms as a means of distancing themselves from the realities of the procedure. Some midwives were observed washing women's genitals in a highly ritualized manner prior to vaginal examination, apparently as a strategy for establishing power differentials.

Conclusion.  Midwives commonly state that they are advocates for woman‐centred care but their behaviour in relation to vaginal examination belies this and suggests that they regard women's bodies as contaminated and polluting. Healthcare students need to be taught specific communication skills to enable them to discuss vaginal examination more fully with women so that they feel less need to resort to euphemisms and abbreviations when discussing the procedure. It is also important to carry out vaginal examination in a way that is not demeaning and does not reinforce notions that women's bodies are dirty.
Re‐engineering cardiac rehabilitation programmes: considering the patient's point of view
Authors: Pâquet Mariane , Bolduc Nicole , Xhignesse Marianne , Vanasse Alain
Published: August 2005

Aims.  The aim of this paper is to report a study to describe how cardiac patients experience the first 3 months following a cardiac event requiring hospitalization, identify differences between the needs expressed by patients and the support they received during their recuperation and produce a preliminary model for the development of cardiac rehabilitation programmes, taking into account the patient perspective.

Background.  Although cardiac rehabilitation should be standard care for patients with cardiovascular disease, less than 20% begin and maintain a rehabilitation programme. Cited barriers include inadequate rehabilitation services, sub‐optimal referral, low participation rates of women and older adults and travel considerations. The literature suggests that programmes better adjusted to patient needs could increase attendance, but little research has considered this perspective.

Methods.  Focus groups were conducted with a purposefully selected sample of 20 men and women who had been hospitalized for myocardial infarction, angina or percutaneous angioplasty. Data were analysed using qualitative content analysis.

Findings.  A gap exists between what traditional rehabilitation programmes offer and patients’ expressed needs during the recuperating process after hospitalization for a cardiac event. In our study, participants focused on stress management rather than on modifying health habits. Support groups were viewed as beneficial and, according to patients, accepting their condition, knowing their limits and better continuity of care would also help reduce stress. Based on the findings, we devised a model as the basis for developing cardiac rehabilitation programmes.

Conclusion.  Cardiac rehabilitation programmes need to shift their focus of attention from promoting healthier behaviours to responding to participants’ perceived needs, alongside risk factor reduction.
Levels of homocysteine are inversely associated with cardiovascular fitness in women, but not in men: data from the National Health and Nutrition Examination Survey 1999–2002
Authors: KUO H.‐K. , YEN C.‐J. , Bean J. F.
Published: August 2005

Objectives.  Cardiovascular fitness represents the ability of active skeletal muscle to utilize oxygen during aerobic exercise. Elevated homocysteine, causing tissue injury by such mechanisms as oxidative stress, endothelial damage, and protein homocysteinylation, is associated with increased risk of cardiovascular disease, dementia and osteoporotic fracture. However, the association between elevated homocysteine and cardiovascular fitness has not been reported.

Design.  Population‐based cross‐sectional study.

Setting.  National Health and Nutrition Examination Survey from 1999 to 2002 in the USA.

Subjects.  A total of 1444 noninstitutionalized adults aged 20–49 years with reliable measures of cardiovascular fitness and nonmissing values in homocysteine.

Main outcome measures.  Cardiovascular fitness, estimated maximal oxygen uptake or VO2max (mL kg−1 min−1), was obtained by a submaximal exercise test. Levels of homocysteine were measured by the Abbott homocysteine assay, a fully automated fluorescence polarization immunoassay method and were natural‐log‐transformed due to right skewness.

Results.  After adjustment for age, race and body mass index, there was a 0.70 mL kg−1 min−1 decrease (P = 0.033) in the estimated VO2max for each standard deviation (SD) increase in the natural‐log‐transformed homocysteine level for women. Additional adjustment of hypertension, diabetes, smoking status, alcohol intake, use of lipid‐lowering agents, physical activity, self‐report health condition, as well as levels of folate, vitamin B12, creatinine, C‐reactive protein, total cholesterol and haemoglobin seemed to influence the association. In the fully adjusted model, we observed a 1.18 mL kg−1 min−1 decrease (P = 0.003) in the estimated VO2max for each SD increase in the natural‐log‐transformed homocysteine level in women. There was no association between cardiovascular fitness and homocysteine levels in men.

Conclusion.  High homocysteine levels were inversely associated with cardiovascular fitness in women, but not in men. The results suggest that homocysteine levels are important indicators of exercise tolerance amongst women and may be useful in targeting female individuals requiring endurance intervention to prevent loss of cardiovascular fitness and function.