bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of treatment response in chronic posttraumatic stress disorder: An application of latent growth mixture modeling
Authors: Elliott Peter , Biddle Dirk , Hawthorne Graeme , Forbes David , Creamer Mark
Published: August 2005

This study attempts to differentiate groups of individuals who exhibit different patterns of recovery following treatment for chronic posttraumatic stress disorder (PTSD) and describes these groups in terms of relevant characteristics at program intake. A sample of 2,219 Vietnam veterans who had completed a 12‐week treatment program was followed up at 6, 12, and 24 months post admission using self‐report measures. With change in PTSD symptoms over time as the focus, latent growth mixture modeling was used to assign individual veterans to subgroups. A three‐group solution provided the best account of the data. Two groups showed moderate and consistent improvement over time although the larger group (n = 1,380) began treatment with more PTSD symptoms and improved more quickly over time. The smallest group (n = 87) showed a substantially different trajectory, with almost no net change in symptom levels over the 24‐month period. The groups also varied significantly in terms of their characteristics, with symptom severity and improvements over time reflecting greater comorbidity and younger age. The results have both research and clinical implications.
Preparation and Properties of Cholesteric Network Polymers Based on Liquid Crystalline Epoxides
Authors: Hartwig Andreas , Mahato Tapan Kumar , Kaese Torsten , Wöhrle Dieter
Published: August 2005

Summary: Polyether network polymers with cholesteric superstructure are formed by the photochemically induced cationic copolymerisation of a nematic diepoxide with chiral epoxides. If a cholesteric superstructure is formed or not, depends on the temperature at which the photopolymerisation is carried out. The storage modulus is higher above TG in samples with cholesteric superstructure. Optical rotations and vibrational circular dichroism spectra (VCD) depend strongly on the surface state of the substrates. From the VCD spectra it is concluded that the copolymerisation leads to different superstructures depending on the rub directions of the substrates.

IR absorption spectrum and VCD spectrum of the cholesterol derivative 4.

magnified image

IR absorption spectrum and VCD spectrum of the cholesterol derivative 4.
Dietary iron deficiency induces ventricular dilation, mitochondrial ultrastructural aberrations and cytochrome c release: involvement of nitric oxide synthase and protein tyrosine nitration
Authors: Dong Feng , Zhang Xiaochun , Culver Bruce , Chew Herbert G. , Kelley Robert O. , Ren Jun
Published: August 2005

Iron deficiency is associated with multiple health problems, including the cardiovascular system. However, the mechanism of action of iron-deficiency-induced cardiovascular damage is unclear. The aim of the present study was to examine the effect of dietary iron deficiency on cardiac ultrastructure, mitochondrial cytochrome c release, NOS (nitric oxide synthase) and several stress-related protein molecules, including protein nitrotyrosine, the p47phox subunit of NADPH oxidase, caveolin-1 and RhoA. Male weanling rats were fed with either control or iron-deficient diets for 12 weeks. Cardiac ultrastructure was examined by transmission electron microscopy. Western blot analysis was used to evaluate cytochrome c, endothelial and inducible NOS, NADPH oxidase, caveolin-1 and RhoA. Protein nitrotyrosine formation was measured by ELISA. Rats fed an iron-deficient diet exhibited increased heart weight and size compared with the control group. Heart width, length and ventricular free wall thickness were similar between the two groups. However, the left ventricular dimension and chamber volume were significantly enhanced in the iron-deficient group compared with controls. Ultrastructural examination revealed mitochondrial swelling and abnormal sarcomere structure in iron-deficient ventricular tissues. Cytochrome c release was significantly enhanced in iron-deficient rats. Protein expression of eNOS (endothelial NOS) and iNOS (inducible NOS), and protein nitrotyrosine formation were significantly elevated in cardiac tissue or mitochondrial extraction from the iron-deficient group. Significantly up-regulated NADPH oxidase, caveolin-1 and RhoA expression were also detected in ventricular tissue of the iron-deficient group. Taken together, these results suggest that dietary iron deficiency may have induced cardiac hypertrophy characterized by aberrant mitochondrial and irregular sarcomere organization, which was accompanied by increased reactive nitrogen species and RhoA expression.
Circumvention of Atypical Multidrug Resistance with Tumor Necrosis Factor
Authors: Cimoli Guido , Valenti Monica , Parodi Silvio , De Sessa Fabio , Russo Patrizia
Published: August 2005

Some “multidrug‐resistant” (MDR) cell lines are not associated with a defect in drug accumulation or with the overexpression of P‐glycoprotein. These cell lines are defined as “atypical MDR” (at‐MDR) and they often express altered or mutated topoisomerase II. We investigated the ability of tumor necrosis factor to reverse at‐MDR (in the human ovarian cancer cell line A2780 DX3) on the basis of its efficacy in potentiating in vitro topoisomerase II‐targeted drugs, and because there is convincing evidence that the synergy is due to an increased number of topoisomerase‐associated strand‐breaks as well as to an increased level of extractable topoisomerase
Different Clinicopathologic Findings in Two Histologic Types of Carcinoma of Papilla of Vater
Authors: Kimura Wataru , Futakawa Noriaki , Yamagata Seiichi , Wada Yoshiyuki , Kuroda Akira , Muto Tetsuichiro , Esaki Yoshiyuki
Published: August 2005

The aim of this study was to investigate the differences between the clinicopathological findings in two histologic types of carcinoma of the papilla of Vater. We histologically classified carcinoma of the papilla into two types: 1) an intestinal type that resembles tubular adenocarcinoma of the stomach or colon, and 2) a pancreaticobiliary type that is characterized by papillary projections with scant fibrous cores. We examined 53 cases of resected carcinoma of the papilla. The intestinal‐type carcinomas were similar to the intestinal mucosa in that they had lysozyme‐containing, Paneth or argyrophil cells, as demonstrated by the immunohistochemically positive stainings for the anti‐lysozyme antibody. Although both the sizes of the two types of carcinomas and the age distributions of cases with the two types of carcinoma were almost the same, the prognosis of the cases with the intestinal type was much better than that of the cases with the pancreaticobiliary type. Histological lymph node metastasis was found significantly more often in the pancreaticobiliary type. This result was supported by the fact that small carcinomas of the intestinal type showed little or no invasion into the surrounding interstitium, as opposed to the pancreaticobiliary type, which had a strong infiltrative tendency. The pathogenesis of carcinoma of the papilla of Vater should be further evaluated, taking into consideration the existence of these two histologic types.
Salty Food Intake and Risk of Helicobacter pylori Infection
Authors: Tsugane Shoichiro , Tei Yuko , Takahashi Tosei , Watanabe Shaw , Sugano Kokichi
Published: August 2005

To clarify the risk factors for Helicobacter pylori infection, which is considered to play an etiologic role in atrophic gastritis, duodenal ulcer and gastric cancer, various parameters including diet and socioeconomic characteristics were compared between H. pylori‐infected and non‐infected men. In a cross‐sectional study of 634 men aged 40 to 49 years selected randomly from five areas with different rates of gastric cancer mortality, 474 of 628 men evaluated were positive for IgG antibody against H. pylori. After logistic regression analysis adjusted for area, the results showed a significant association between frequent intake of pickled vegetables and prevalence of H. pylori antibody (odds ratios against men who consume < 1 day/week were 1.19 for 1–2 days/week, 1.92 for 3–4 days/week, 1.90 for 5–7 days/week; P for trend = 0.02). Daily consumption of miso soup was also associated with an increased risk (odds ratio against non‐daily consumer = 1.60, 95% confidence interval = 1.03–2.49). Occupation, number of siblings, education, smoking and alcohol drinking, and other dietary habits were not significantly associated with the prevalence of infection in this population. Although there are limitations in a cross‐sectional study such as this, consumption of salty foods appears to increase the risk of H. pylori infection, which could be a marker of salty food intake or an intermediate risk factor in the etiologic sequence between salty food intake and gastric cancer.
Light and Electron Microscopic Analysis of Liver Sinusoids during Hepatocarcinogenesis with 2‐Acetylaminofluorene in Rats
Authors: Shoji Yutaka , Kaneda Kenji , Wake Kenjiro , Mishima Yoshio
Published: August 2005

To clarify the sequential changes and morphological differences of the sinusoidal structures between hepatocellular carcinoma (HCC) and hepatocellular adenoma (HA), we examined morphological changes of sinusoidal cells and related structures such as basement membrane during hepatocarcinogenesis in the rat. During continuous feeding of carcinogenic diets containing 2‐acetylaminofluorene to rats, HA appeared at the 8th week in the periportal area and then extended toward the centrolobular area. The appearance of HCC was recognized at the 27th week. In the HA lesion, the morphology of sinusoidal cells and related structures was basically the same as that of normal liver except for a slight thickening of the basement membrane and a decreased amount of vitamin A‐lipid droplets of stellate cells. In HCC, the fenestrations of endothelial cells disappeared and the basement membrane became continuous, thick and often multilayered. Stellate cells contained almost no vitamin A‐lipid droplets and were associated with abundant collagen fibers. Kupffer cells and pit cells were not seen inside the sinusoid. All these features of the sinusoids in HCC resembled the morphological characteristics of the capillary. The present study has revealed that HCC possesses sinusoid structures distinct from those of HA. This suggests that HCC may not derive directly from HA but may develop newly within the HA.
An in vivo Study of Hepatic and Splenic Interleukin‐lβ mRNA Expression Following Oral PSK or LEM Administration
Authors: Morinaga Hideo , Tazawa Kenji , Tagoh Hiromi , Muraguchi Atsushi , Fujimaki Masao
Published: August 2005

The effects of orally administered biological response modifiers (BRMs) in preventing postoperative micro liver metastasis of primary colorectal cancer were examined in experimental animals. The twoBRMs tested were Krestin (PSK) and Lentinus edodes mycelia (LEM). In previous experiments, we found that oral administration of PSK or LEM suppressed liver metastasis and prolonged the survival period. We also found that these agents elevated the liver natural killer (NK) and liver macrophage activities. In the present study in vivo, using reverse transcriptase‐polymerase chain reaction (RT‐PCR), we examined whether or not the liver and spleen have cytokines which would induce NK cells and macrophages, and whether or not the liver and spleen have cytokines induced by NK cells or macrophages. We placed emphasis on the examination of interleukin (IL)‐1β expression in the liver and spleen in vivo. Two to six hours after oral administration of PSK or LEM (1 g/kg) to mice, IL‐β levels in the liver and spleen rose, and they returned to their baseline levels 24 h later. These findings suggest two possibilities: (1) hepatic IL‐1β is potentiated by these agents soon after administration, resulting in activation of liver NK cells or macrophages, or (2) these agents stimulate IL‐β production by liver macrophages, and the produced IL‐lβ activates liver NK cells or liver macrophages (Kupffer cells). The results of this in vivo study suggest that the potentiation of hepatic and splenic IL‐β by PSK and LEM is involved in the early phases of suppression of micro liver metastases of colorectal cancer.
Enzyme‐linked Immunosorbent Assay of Pro‐gastrin‐releasing Peptide for Small Cell Lung Cancer Patients in Comparison with Neuron‐specific Enolase Measurement
Authors: Yamaguchi Ken , Aoyagi Katsumi , Urakami Ken‐ichi , Fukutani Toyoharu , Maki Noboru , Yamamoto Shigehiro , Otsubo Kotomi , Miyake Yoshio , Kodama Tetsuro
Published: August 2005

Our previous study demonstrated that pro‐gastrin‐releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme‐linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non‐SCLC patients and patients with non‐tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron‐specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.
The Relation of Smoking, Alcohol Use and Obesity to Risk of Sigmoid Colon and Rectal Adenomas
Authors: Honjo Satoshi , Kono Suminori , Shinchi Koichi , Wakabayashi Kazuo , Todoroki Isao , Sakurai Yutaka , Imanishi Koji , Nishikawa Hiroshi , Ogawa Shinsaku , Katsurada Mitsuhiko
Published: August 2005

We conducted a case‐control study, using 429 cases with histologically confirmed sigmoid adenoma, 75 cases with rectal adenoma, and 3101 controls showing normal colonoscopy at least up to 60 cm from the anus. The subjects were male Self‐Defense Forces personnel aged 48–56 who received a retirement health examination including a routine sigmoid‐ or colonoscopy. Lifestyle characteristics were ascertained by a self‐administered questionnaire. Smoking in the recent past (ġ 10 years preceding the colonoscopy) and smoking in the remote past (>10 years before the colonoscopy) were both significantly associated with risk of sigmoid adenoma but not with rectal adenoma as a whole. After reciprocal adjustment for smoking in the two periods, only smoking in the recent past was associated with both sigmoid colon and rectal adenomas. Odds ratios (OR) of sigmoid adenoma (and 95% confidence interval) for the categories of 0, 1‐150, 151‐250 and ġ251 cigarette‐years were 1.0 (reference), 1.9 (1.3‐2,8), 2.1 (1.4‐3.0) and 3.0 (1.9‐4.7), respectively (P for trend < 0.01), and those for rectal adenoma were 1.0 (reference), 1.2 (0.4‐3.2), 3.5 (1.4‐8.5) and 2.0 (0.6‐6.7), respectively (P for trend = 0.03). Alcohol use was significantly positively associated with sigmoid adenoma, and insignificantly associated with rectal adenoma. Body mass index was significantly positively associated with sigmoid adenoma, especially large ones. No such association was found for rectal adenoma. These findings suggest that smoking, especially in the recent past, and alcohol use are common risk factors for sigmoid colon and rectal adenomas while obesity may be exclusively related to the growth of sigmoid adenoma.
Absence of ras Mutations and Low Incidence of p53 Mutations in Renal Cell Carcinomas Induced by Ferric Nitrilotriacetate
Authors: Akiyama Takashi , Hamazaki Shuji , Okada Shigeru
Published: August 2005

Renal cell carcinomas induced in male Wistar rats by iron chelate of nitrilotriacetate (Fe‐NTA) were examined for mutations in ras oncogenes and p53 tumor suppressor gene. Fourteen primary tumors and two metastatic tumors from 11 animals were evaluated. Exons 1 and 2 of the H‐, K‐, and N‐ras genes were amplified by polymerase chain reaction (PCR), and the presence of mutations was examined by direct sequencing. Exon 5 through exon 7 of p53 gene, including the 3’half of the conserved region II and the entire conserved region III through V, were surveyed for point mutations by PCR‐single stranded conformation polymorphism (SSCP) analysis. Direct sequencing of the ras genes showed no mutations in codon 12, 13, or 61 among the tumors evaluated. SSCP analysis of p53 gene exon 6 indicated conformational changes in two primary tumors. One tumor had a CCG‐to‐CTG transition at codon 199, and the other had an ATC‐to‐ATT transition at codon 229 and two nonsense C‐to‐T transitions. These results suggest that neither ras genes nor p53 gene play a major role in the development of renal cell carcinomas induced by Fe‐NTA.
Low Incidence of Point Mutations in H‐, K‐ and N‐ras Oncogenes and p53 Tumor Suppressor Gene in Renal Cell Carcinoma and Peritoneal Mesothelioma of Wistar Rats Induced by Ferric Nitrilotriacetate
Authors: Nishiyama Yasuyuki , Suwa Hirofumi , Okamoto Keisei , Fukumoto Manabu , Hiai Hiroshi , Toyokuni Shinya
Published: August 2005

An iron chelate, ferric nitrilotriacetate (Fe‐NTA), induces renal proximal tubular damage, a consequence of iron‐catalyzed free radical reactions, that finally leads to a high incidence of renal cell carcinoma (RCC) in rodents. Previous studies have identified, within 24 h after administration of Fe‐NTA, lipid peroxidation products, aldehyde‐modified proteins and a variety of modified DNA bases such as 8‐hydroxyguanine that may be mutagenic in vivo. In the present study, pathological features of the RCCs were studied, and, in an effort to correlate them with carcinogen‐specific molecular events in Fe‐NTA‐induced carcinogenesis, the H‐, K‐ and N‐ras oncogenes and the p53 tumor suppressor gene were investigated for the presence of mutations. Fe‐NTA‐induced RCCs showed similarity to human RCCs in that they are often invasive, metastatic and fatal. None (0 of 12) of the tumors had mutation in codons 12, 13 and 61 of the H‐, K‐ and N‐ras genes by direct sequencing. Only one (1 of 12) tumor with high grade histology revealed a CGC‐to‐CTC (Arg to Leu) transversion in codon 246 of the p53 gene by the use of single strand conformation polymorphism (SSCP) analysis and direct sequencing. High expression of mutant p53 protein was confirmed by Western blotting and immunohistochemistry. Study of three peritoneal mesotheliomas induced by Fe‐NTA revealed no mutation in ras and p53 genes. These results suggest that the ras and p53 genes are not the major targets of mutation in Fe‐NTA‐induced carcinogenesis of kidney and mesothelium. Instead, p53 mutation may work for potentiation of malignant character in Fe‐NTA‐induced renal carcinogenesis.
Comparison of in vivo Efficacy of Hypoxic Cytotoxin Tirapazamine and Hypoxic Cell Radiosensitizer KU‐2285 in Combination with Single and Fractionated Irradiation
Authors: Shibata Toru , Shibamoto Yuta , Sasai Keisuke , Oya Natsuo , Murata Rumi , Takagi Takehisa , Hiraoka Masahiro , Abe Mitsuyuki
Published: August 2005

Development of strategies to eradicate radioresistant hypoxic cells would be of great benefit for clinical radiotherapy. In the present study, the in vivo effects of a promising hypoxic cytotoxin, tirapazamine (3‐amino‐1,2,4‐benzotriazine 1,4‐di‐N‐oxide), were examined in comparison with those of KU‐2285, one of the best hypoxic cell radiosensitizers, in combination with both single and fractionated irradiation. The tumor response was assessed by the standard in vivo‐in vitro clonogenic assay using SCCVII tumors in C3H mice and EMT‐6/KU tumors in Balb/c mice with different characteristics of tumor hypoxia. With single‐dose irradiation (18 Gy), both tirapazamine and KU‐2285 showed significant enhancement of cell killing in a dose‐dependent manner, but tirapazamine was more effective for SCCVII tumors with acutely hypoxic cells, while KU‐2285 was more effective for EMT‐6/KU tumors predominantly with chronically hypoxic cells. In fractionated irradiation regimens (4 fractions of 5 Gy at 12 h intervals), tirapazamine showed more marked combined effects at 10 and 20 mg/kg than KU2285 at 100–200 mg/kg in both SCCVII and EMT‐6/KU tumors. We concluded that the effectiveness of KU‐2285 and tirapazamine was correlated with the nature of tumor hypoxia with single‐dose irradiation, whereas tirapazamine appeared more potent than KU‐2285 with fractionated irradiation. These findings suggest the potential usefulness of tirapazamine in clinical fractionated radiotherapy.
Serial Transplantation of Adult T Cell Leukemia Cells into Severe Combined Immunodeficient Mice
Authors: Imada Kazunori , Takaori‐Kondo Akifumi , Sawada Hitoshi , Imura Akihiro , Kawamata Shin , Okuma Minoru , Uchiyama Takashi
Published: August 2005

The precise mechanism of the neoplastic cell growth of adult T cell leukemia (ATL) still remains unclear. In the present study, we have succeeded in serial transplantation of ATL cells from a patient into severe combined immunodeficient (SCID) mice. In this model, we found that only a leukemic cell clone from an ATL patient could be successively transplanted into SCID mice, although it was difficult to maintain leukemic cell clones in vitro, suggesting that the microenvironment provided by SCID mice is suitable for leukemic cell growth. We could not detect human T cell leukemia virus type I (HTLV‐I) mRNA or interleukin 2 (IL‐2) mRNA in either the tumor cells growing in mice or the original leukemic cells. Thus, it appears that neither HTLV‐I viral expression nor the IL‐2 autocrine mechanism is directly involved in the neoplastic cell growth of fresh ATL cells as well as HTLV‐I‐infected cell lines, at least in SCID mice. In addition, we could passage frozen cells and obtain a large number of expanded leukemic cells in this model. Such a serial transplantation model, which can avoid the changes in the nature of leukemic cells that are frequently observed in in vitro culture, and which can propagate leukemic cell clones, would be very suitable not only to study the mechanism of neoplastic cell growth, but also to test potential therapeutic agents for ATL.
Isolation of STLV–I from Orangutan, a Great Ape Species in Southeast Asia, and Its Relation to Other HTLV–Is/STLV–Is
Authors: Ibuki Kentaro , Ido Eiji , Setiyaningsih Surachmi , Yamashita Masahiro , Agus Lelana R. P. , Takehisa Jun , Miura Tomoyuki , Dondin Sajuthi , Hayami Masanori
Published: August 2005

To study the evolutionary origin of human T–lymphotropic virus type I/simian T–lymphotropic virus type I (HTLV–I/STLV–I), we isolated and characterized STLV–I from orangutans (Pongo pygmaeus). Plasma samples from 3 out of 41 animals examined were reactive by particle agglutination and immunofluorescence, and one of these three was confirmed to be anti–HTLV–I antibody–positive by western blotting (WB). Cultured peripheral blood mononuclear cells from the WB–positive orangutan were reactive to anti–STLV–I–positive rhesus monkey plasma. The proviral long terminal repeat region was amplified by polymerase chain reaction and sequenced. A phylogenetic analysis indicated that orangutan STLV–I is related to the Melanesian group of HTLV–Is and other Asian STLV–Is, but the degree of divergence is considerable.
Contiguous Four‐guanosine Sequence in c‐myc Antisense Phosphorothioate Oligonucleotides Inhibits Cell Growth on Human Lung Cancer Cells: Possible Involvement of Cell Adhesion Inhibition
Authors: Saijo Yasuo , Uchiyama Bine , Abe Tatsuya , Satoh Ken , Nukiwa Toshihiro
Published: August 2005

A contiguous four‐guanosine (4G) sequence in c‐myc antisense phosphorothioate oligonucleotides caused an antiproliferative effect in smooth muscle cells. To investigate the antiproliferative effect of c‐myc antisense oligonucleotides on human lung cancer cell lines, we synthesized oligonucleotides of various lengths and sequences, focusing on the contiguous four‐guanosine (4G) sequence. While a c‐myc antisense oligonucleotide (20AS1 (4G)) targeted to the translation initiation codon of c‐myc mRNA inhibited cell growth of A549 cells by 69% at 10 μM, a scrambled oligonucleotide (20SCR1 (4G)) containing the contiguous four‐guanosine (4G) sequence also inhibited cell growth by 72% at the same dose. Although treatment with either 20AS1 (4G) or 20SCR1 (4G) inhibited cell adhesion by 70% at 10 μM, expression of c‐myc protein was significantly suppressed only by 20AS1 (4G) (62%), and was only weakly inhibited by 20SCR1 (4G) (32%). Furthermore, a small cell lung carcinoma cell line, Lu65, which can grow in suspension form, was highly resistant to 20AS1 (4G) treatment (IC50>20 μM). These results suggest that the cell growth inhibition by C‐myc antisense oligonucleotides containing the contiguous four‐guanosine (4G) sequence was possibly correlated with inhibition of cell adhesion, but not with inhibition of c‐myc protein expression, via a sequence‐specific non‐antisense mechanism.
Regression of Metastatic Liver Tumors in Rats Treated with Angiogenesis Inhibitor TNP‐470: Occurrence of Apoptosis and Necrosis
Authors: Ahmed Motahar H. , Aral Tomio , Konno Hiroyuki , Nahar Lutfun , Tanaka Tatsuro , Izumiyama Naotaka , Takubo Kaiyo , Nakamura Satoshi , Baba Shozo
Published: August 2005

To clarify the mechanism of the reduction of metastatic liver tumors in rats treated with angiogenesis inhibitor TNP‐470, the death of tumor cells was examined pathologically and ultrastructurally. Liver metastases were developed by intravenous injection of AH‐130 cells. TNP‐470 was given subcutaneously after tumor cell injection. Alterations in the size and number of metastatic tumors were examined at various time points, in association with the analysis of cell death pattern. The metastatic nodules were divided into 4 groups according to the morphological patterns of cell death; no cell death, scattered apoptosis, central necrosis, and diffuse necrosis. The number and size of the metastatic tumors at 2 weeks in untreated rats were larger than those in treated rats. The number of tumors in untreated rats decreased, but the tumor size increased. All rats treated with TNP‐470 were alive and free from tumors after 4 weeks, whereas all the untreated rats died of liver metastases. The percentages of the tumors with necrosis in untreated rats (61.2% at 2 weeks and 100% at 4 weeks) were significantly higher than that (31.8% at 2 weeks) in treated rats (P< 0.01). The percentage of the tumors containing apoptotic cells in treated rats was significantly higher than that in untreated rats (54.5% vs. 30.6%; P< 0.05). The growth of metastatic tumors without treatment might be faster than the growth of vessels in untreated tumors, resulting in central necrosis due to ischemia. On the other hand, the reduction of metastatic liver tumors treated with TNP‐470 might be caused by inhibition of angiogenesis, providing a weak ischemic stimulus which triggers apoptosis, rather than by a direct cytotoxic effect on tumor cells, because previous in vivo experiments demonstrated that TNP‐470 affected endothelial cells but not tumor cells.
Comparison of DNA Copy Numbers in Original Oral Squamous Cell Carcinomas and Corresponding Cell Lines by Comparative Genomic Hybridization
Authors: Komiyama Takayuki , Matsumura Kouji , Tsuchida Nobuo
Published: August 2005

We analyzed regional DNA copy numbers in 4 oral squamous cell carcinomas (SCCs) by using comparative genomic hybridization, and compared them with those in cell lines derived from the SCCs. In the original tumors, DNA copy number increases were observed on chromosomes 5p (4/4 cases), 8q (4/4), 20p (3/4), 3q (2/4), 5q (2/4), 7p (2/4), 7q (2/4), 1ip (2/4), 11q (2/4) and 13q (2/ 4). Although most of these changes have been described previously for SCC tumors in the head and neck, the incidence of increases in 8q and 20p was much higher in the present study; this may be important in relation to cell line establishment, since 8q contains c‐myc, which is involved in immortalization. No common chromosomal region with DNA copy number decreases was observed, except for 18q (2/4). When the original tumors and the cell lines were compared, their profiles were essentially similar with one exception. Further, there was no region that commonly changed in the cell lines, but not in the original tumors, suggesting that the DNA copy number changes observed in the cell lines mostly represent those of the original tumors.
Effect of CPT‐11 on Lipid Peroxide Level in Mouse Tissues
Authors: Sadzuka Yasuyuki , Hirota Sadao
Published: August 2005

We examined the effects of CPT‐11 on lipid peroxide level and glutathione peroxidase (GSHpx) activity as indices of the toxicity of this antitumor agent in mouse and rat tissues. After CPT‐11 (100 mg/kg, i.p.) administration, the lipid peroxide level in the heart increased 1.5 fold (mice) and 1.3 fold (rats) over the control levels. GSHpx activity decreased to 64% of the control. In the lung, the lipid peroxide level and GSHpx activity increased 2.5 fold and decreased to 74% after CPT‐11 administration, respectively, compared with the control values. These results suggested that CPT‐11 may cause cardiotoxicity and pulmotoxicity. In rat hone marrow, the lipid peroxide level increased on the 2nd day after CPT‐11 injection. We suggest that in both single and combination treatment with CPT‐11, the possibility of side effects should be taken into consideration.
Inhibitory Activity of Green and Black Tea in a Free Radical‐generating System Using 2‐Amino‐3‐methylimidazo[4,5‐f]quinoline as Substrate
Authors: Hasaniya Nahidh , Youn Kristi , Xu Meirong , Hernaez Judith , Dashwood Roderick
Published: August 2005

Green tea and black tea inhibit colon carcinogenesis in rats exposed to the cooked meat mutagen 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ). In the present investigation, green tea, black tea and (‐)‐epigallocatechin gallate (EGCG) were shown to block the production of oxygen free radicals derived from IQ in the presence of NADPH‐cytochrome P450 reductase. In kinetic studies using IQ as tbe substrate and DMPO as a free radical spin trap, EGCG increased the Km of the reaction without altering Vmax, suggesting competitive enzyme inhibition (Ki=9.% mUM). This was confirmed in spectrophotometric studies using cytochrome c as the substrate, in which EGCG acted as a competitive inhibitor of NADPH‐cytochrome P450 reductase (Ki=9.7 μM). These results suggest that the inhibitory activities of green tea and black tea in electron spin resonance assays using IQ as the substrate for the rednctase are related to an indirect effect on the enzyme rather than via direct scavenging of the free radicals. The possible implications of these findings are discussed in the context of pathways involved in the activation and detoxification of IQ in the colon.
Breastfeeding, soluble CD14 concentration in breast milk and risk of atopic dermatitis and asthma in early childhood: birth cohort study
Authors: Rothenbacher D. , Weyermann M. , Beermann C. , Brenner H.
Published: August 2005

Background
Breast milk contains a variety of bioactive substances, among them, soluble CD14 (sCD14), which plays an important role in innate immunity.

Objective
We analysed data of a large prospective birth cohort study to examine the determinants of sCD14 in breast milk, and investigated whether breastfeeding practice and sCD14 concentrations in breast milk are determinants of the risk of atopic dermatitis (AD) and asthma in children.

Methods
Eight hundred and three mothers and their newborns were included in this analysis. We measured sCD14 concentrations in breast milk samples collected 6 weeks post‐partum. During a 2‐year follow‐up the cumulative incidences of AD and asthma were recorded.

Results
Overall, AD was reported for 20.6% of the 2‐year‐olds and asthma was reported for 19.6%. We found the lowest incidence of physician‐reported AD in children of mothers without a history of atopic diseases if breastfed for 6 to less than 9 months. Furthermore, we found an inverse association between duration of breastfeeding and risk of asthma, which was especially evident in children with mothers without a history of atopic disease (P=0.01). These patterns persisted after control for other factors by multivariate analysis methods. The protective effect of breastfeeding seemed to be synergistic with sCD14 concentrations in breast milk (P for trend 0.0005).

Conclusions
The results of this prospective birth cohort study suggest that a longer duration of breastfeeding does decrease the risk for asthma in early childhood, especially in children of mothers without a history of atopic disease. The beneficial effects of breastfeeding might be further supported by high levels of sCD14 in breast milk.
The rhizosphere as a reservoir for opportunistic human pathogenic bacteria
Authors: Berg Gabriele , Eberl Leo , Hartmann Anton
Published: August 2005

During the last years, the number of human infections caused by opportunistic pathogens has increased dramatically. One natural reservoir of opportunistic pathogens is the rhizosphere, the zone around roots that is influenced by the plant. Due to a high content of nutrients, this habitat is a ‘microbial hot‐spot’, where bacterial abundances including those with strong antagonistic traits are enhanced. Various bacterial genera, including Burkholderia, Enterobacter, Herbaspirillum, Ochrobactrum, Pseudomonas, Ralstonia, Staphylococcus and Stenotrophomonas, contain root‐associated strains that can encounter bivalent interactions with both plant and human hosts. Mechanisms responsible for colonization of the rhizosphere and antagonistic activity against plant pathogens are similar to those responsible for colonization of human organs and tissues, and pathogenicity. Multiple resistances against antibiotics are not only found with clinical strains but also with strains isolated from the rhizosphere. High competition, the occurrence of diverse antibiotics in the rhizosphere, and enhanced horizontal gene transfer rates in this microenvironment appear to contribute to the high levels of natural resistances. While opportunistic bacteria from the rhizosphere have some properties in common, each of these emerging pathogens has its own features, which are discussed in detail for Burkholderia, Ochrobactrum and Stenotrophomonas.
Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH‐based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5‐nations trial
Authors: Hoogma R. P. L. M. , Hammond P. J. , Gomis R. , Kerr D. , Bruttomesso D. , Bouter K. P. , Wiefels K. J. , De La Calle H. , Schweitzer D. H. , Pfohl M. , Torlone E. , Krinelke L. G. , Bolli G. B. ,   on behalf of the 5‐Nations Study Group
Published: August 2005

Aims  The goal of the study was to determine whether continuous subcutaneous insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen based on neutral protamine hagedorn (NPH) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes.

Methods  The 5‐Nations trial was a randomized, controlled, crossover trial conducted in 11 European centres. Two hundred and seventy‐two patients were treated with CSII or MDI during a 2‐month run‐in period followed by a 6‐month treatment period, respectively. The quality of glycaemic control was assessed by HbA1c, blood glucose values, and the frequency of hypoglycaemic events. For the evaluation of the quality of life, three different self‐report questionnaires have been assessed.

Results  CSII treatment resulted in lower HbA1c (7.45 vs. 7.67%, P < 0.001), mean blood glucose level (8.6 vs. 9.4 mmol/l, P < 0.001) and less fluctuation in blood glucose levels than MDI (± 3.9 vs. ± 4.3 mmol/l, P < 0.001). There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI, with an incidence ratio of 1.12 [95% confidence interval (CI): 1.08–1.17] and 2.61 (95% CI: 1.59–4.29) for mild and severe hypoglycaemia, respectively. The overall score of the diabetes quality of life questionnaire was higher for CSII (P < 0.001), and an improvement in pump users’ perception of mental health was detected when using the SF‐12 questionnaire (P < 0.05).

Conclusion  CSII usage offers significant benefits over NPH‐based MDI for individuals with Type 1 diabetes, with improvement in all significant metabolic parameters as well as in patients’ quality of life. Additional studies are needed to compare CSII with glargine‐ and detemir‐based MDI.
The metabolic syndrome and changing relationship between blood pressure and insulin with age, as observed in Aboriginal and Torres Strait Islander peoples
Authors: Schutte A. E. , Shemesh T. , Rowley K. , Best J. D. , McDermott R. , O'Dea K.
Published: August 2005

Aims  To determine the prevalence of the metabolic syndrome (MS) among Aboriginal and Torres Strait Islander peoples. A further objective was to investigate the relationships between fasting insulin and blood pressure (BP) within these groups with increasing age.

Methods  A cross‐sectional population‐based study included 369 Torres Strait Islanders (residing in Torres Strait and Far North Queensland), and 675 Aborigines from central Australia. Data necessary for classification of MS was collected, including fasting and 2‐h glucose and insulin, urinary albumin and creatinine, anthropometric measurements, BP, serum lipids.

Results  The ATPIII criteria classified 43% of Torres Strait Islanders and 44% of Aborigines with MS, whereas 32 and 28%, respectively, had the MS according to WHO criteria. Agreement between the two criteria was only modest (kappa coefficient from 0.28 to 0.57). Factor analyses indicated no cluster including both insulin and BP in either population. Significant correlations (P < 0.05) [adjusted for gender, body mass index (BMI) and waist circumference] were observed between BP and fasting insulin: a positive correlation for Torres Strait Islanders aged 15–29 years, and an inverse correlation for Aborigines aged 40 years and older.

Conclusion  Torres Strait Islanders and Aborigines had very high prevalences of the MS. Specific population characteristics (high prevalences of central obesity, dyslipidaemia, renal disease) may make the WHO definition preferable to the ATPIII definition in these population groups. The poor agreement between criteria suggests a more precise definition of the metabolic syndrome that is applicable across populations is required. This study showed an inverse relationship with age for the correlation of BP and fasting insulin.
Generic Strategy and Performance: an Empirical Test of the Miles and Snow Typology
Authors: Parnell John A. , Wright Peter
Published: August 2005

Previous research has considered the strategy‐performance relationship in industries of relatively low degrees of dynamism and volatility. This study empirically tests the Miles and Snow typology with a dynamic, growing and volatile service industry. Results support earlier research and suggest that, considering catalogue and mail‐order houses (SIC‐5961), reactors did not perform as well as businesses adopting other generic strategies. However, prospectors experienced significantly higher levels of revenue growth than other businesses. Further, analysers were significantly more profitable than businesses adopting other strategies. These results suggest that combination strategies are a viable means for sustaining competitive advantage.
Cognitive Function is not Impaired in People with a Long History of Migraine: A Blinded Study
Authors: Pearson AJ , Chronicle EP , Maylor EA , Bruce LAM
Published: August 2005

Little is known about the long-term consequences of migraine for cognitive functioning. This study compared older migraine patients with matched controls on four measures of cognitive ability, in a blinded design. Migraine patients and case-matched controls were recruited from the database records of a pre-existing study of ageing. Data were available from four tests of cognitive ability: verbal/arithmetic problem solving, spatial problem solving, processing speed, and vocabulary. There were no significant differences between the mean scores of migraine and control groups on any of the four cognitive tests. In addition, there were no significant differences between migraine and control groups in the effect of age on any of the four tests. A long history of migraine does not compromise scores on the four cognitive tests used in this study. These tests are predictive of memory and executive functioning in cognitive ageing, but it remains possible that lower-level cognitive processes, particularly as assessed by visual tasks, may be vulnerable to migraine.
Clinical-Biochemical Correlates of Migraine Attacks in Rizatriptan Responders and Non-Responders
Authors: Sarchielli P , Pini LA , Zanchin G , Alberti A , Maggioni F , Rossi C , Floridi A , Calabresi P
Published: August 2005

The present study was aimed at verifying the clinical characteristics of a typical attack in 20 migraine patients, 10 responders and 10 non-responders to rizatriptan, and at investigating any differences in the levels of neuropeptides of the trigeminovascular or parasympathetic systems [calcitonin gene-related peptide (CGRP), neurokinin A (NKA) and vasoactive intestinal peptide (VIP) measured by radio-immunoassay methods in external jugular blood] between responders and nonresponders. In all responders to rizatriptan, pain was unilateral, severe, and pulsating, and in five of them at least one sign suggestive of parasympathetic system activation was recorded. Five patients who were non-responders to rizatriptan referred bilateral and non-pulsating pain, even though severe in most of them. CGRP and NKA levels measured before rizatriptan administration were significantly higher in responders than in non-responders ( P < 0.0001 and P < 0.002, respectively). In the five patients with autonomic signs among rizatriptan responders, detectable VIP levels were found at baseline. One hour after rizatriptan administration, a decrease in CGRP and NKA levels was evident in the external jugular venous blood of rizatriptan responders, and this corresponded to a significant pain relief and alleviation of accompanying symptoms. VIP levels were also significantly reduced at the same time in the five patients with autonomic signs. After rizatriptan administration, CGRP and NKA levels in non-responder patients showed less significant variations at all time points after rizatriptan administration compared with rizatriptan responders. The present study, although carried out on a limited number of patients, supports recent clinical evidence of increased trigeminal activation associated with a better triptan response in migraine patients accompanied by parasympathetic activation in a subgroup of patients with autonomic signs. In contrast, the poor response seems to be correlated with a lesser degree of trigeminal activation, lower variations of trigeminal neuropeptides after triptan administration, and no evidence of parasympathetic activation at baseline.
Are Water Tables a Subdued Replica of the Topography?
Authors: Haitjema Henk M. , Mitchell‐Bruker Sherry
Published: August 2005

The water table in unconfined aquifers is often believed to be a subdued replica of the topography or land surface. However, this assumption has not been widely tested and in some cases has been found to be in error. An analysis of ground water rise in regional unconfined aquifers, using both a two‐dimensional boundary element model and a one‐dimensional Dupuit‐Forchheimer model, reveals the conditions under which the water table does or does not closely follow the topography. A simple decision criterion is presented to estimate in advance under which conditions the water table is expected to be largely unrelated to the topography and under which conditions the topography controls the position of the water table.
Optimization of bulked AFLP analysis and its application for exploring diversity of natural and cultivated populations of red clover
Authors: Herrmann D , Boller B , Widmer F , Kölliker R
Published: August 2005

Landraces and wild populations of red clover (Trifolium pratense L.) may represent a significant yet poorly characterized genetic resource of temperate grasslands. A bulking strategy with amplified fragment length polymorphism (AFLP) markers was optimized to characterize 120 red clover populations in 6 different groups: Swiss wild clover populations, Mattenklee landraces, Mattenklee cultivars, field clover cultivars, Dutch wild clover populations, and Dutch landraces. Analysis of 2 bulked samples/population consisting of 20 plants each with12 AFLP primer combinations was found optimal for determining genetic diversity and relationships within and among red clover populations and groups. Swiss wild clover populations were clearly separated from all other red clover groups and variability within and among populations was shown to be particularly high in wild clover populations and Mattenklee landraces, emphasising their value as genetic resources for improvement of red clover cultivars, as well as for conservation and restoration of biodiversity. This study shows that the ancestry of red clover landraces is primarily found in introduced cultivars rather than in natural wild clover populations. In addition, the methodological considerations presented here may help improve diversity analyses using bulked samples.Key words: AFLP, bulked samples, Trifolium pratense L., cultivars, landraces, wild populations.
DI-BOSON PHYSICS AT THE TEVATRON
Authors:   for the CDF and DØ Collaborations., Maravin Yurii Y.
Published: August 2005

Using almost twice the luminosity of Run I, we present preliminary results on di-boson final states production at the Tevatron. These results include cross section measurements of most di-boson final states including the first measurement of WW cross section.
A Search for Doubly Charged Higgs Boson Pair Production in the Muon Channel at DØ
Authors:   for the DØ Collaboration., TELFORD PAUL
Published: August 2005

Several theories predict the existence of light doubly charged Higgs bosons (H±±). A search for the pair production of H±± using the DØ detector is described, assuming a 100% branching ratio to muons. In the absence of signal, limits at 95% confidence level, of 118.4 GeV and 98.2 GeV are set for left-handed and right-handed doubly charged Higgs bosons respectively.
E865 RESULT: AN IMPROVED UPPER LIMIT ON THE DECAY K+ → π+μ+e-
Authors:   for E865 collaboration., SHER ALEKSEY
Published: August 2005

Based on results of a search for the lepton-family-number-violating decay K+ → π+μ+e- with data collected by experiment E865 in 1998 at the Alternating Gradient Synchrotron of Brookhaven National Laboratory we report an upper limit on the branching ratio at 2.2 × 10-11 (90% C.L.). In combination with results based on the data collected in 1995, 1996, and a previous experiment, E777, an upper limit on the branching ratio of 1.2 × 10-11 (90% C.L.) is obtained.
PHYSICS REACH OF THE ATLAS EXPERIMENT DURING THE FIRST LHC RUN
Authors:   on behalf of the ATLAS Collaboration., GROSSE-KNETTER JÖRN
Published: August 2005

We discuss the ATLAS physics programme for the first year of LHC operation. The layout of the initial (staged) detector will be described, as well as the impact of staging on the physics reach. The main data samples and strategies which will be used to calibrate, align and understand the detector response will be presented. Finally, the physics channels which will be addressed in the first months of operation will be discussed. These include a low-mass Higgs boson, for which a striking signal might be observed after only a few months of data taking. The impact of a realistic non-optimal detector performance, as expected at the beginning, will be illustrated in some cases.