bluuebunny/crossref_metadata_2025 huggingface dataset:
Conversion of Micronodular Cirrhosis into Macronodular Cirrhosis
Authors: Fauerholdt Lis , Schlichting Poul , Christensen Erik , Poulsen Hemming , Tygstrup Niels , Juhl Erik
Published: July 2010

The conversion from micro- to macronodular cirrhosis is claimed to be a general phenomenon. In this study, the conversion was quantitated by means of liver needle follow-up biopsies and autopsy in 156 patients followed in a controlled clinical trial of prednisone treatment in cirrhosis.

In the initial biopsy, 75 patients were classified as micronodular cirrhosis, and of them, 68 had macronodular cirrhosis at autopsy indicating a conversion ratio of about 0.9 in 10 years. This may overestimate the true conversion ratio slightly since conversion in many cases only was demonstrated at autopsy where the diagnosis of macronodular cirrhosis is made with greater certainty than from a needle biopsy. The median time interval between the diagnosis of micro- and macronodular cirrhosis was 2.25 years which is a maximum estimate of the conversion time due to irregular spacing between biopsies (or biopsy and autopsy). No significant difference was found between the conversion time in females and males. The conversion was faster in patients not drinking alcohol compared to patients drinking alcohol, but the difference was not significant. Prednisone treatment tended to accelerate the conversion, but not significantly.
Chemoprotective Effects of Two Dithiolthiones and of Butylhydroxyanisole Against Carbon Tetrachloride and Acetaminophen Toxicity
Authors: Ansher Sherry S. , Dolan Patrick , Bueding Ernest
Published: July 2010

Administration of tert-butyl-4-hydroxyanisole or of two dithiolthiones to female CD-I mice protected against the acute toxic effects of two hepatotoxic agents, acetaminophen and carbon tetrachloride. Reduced mortality of mice was observed following pretreatment with tert-butyl-4-hydroxyanisole or dithiolthiones. Pretreatment reduced or prevented hepatic glutathione depletion produced by these two hepatotoxic agents. Liver damage, i.e., as determined by serum transaminase and sorbitol dehydrogenase activities, was less after pretreatment with tert-butyl-4-hydroxyani-sole or dithiolthiones. Administration of dithiolthiones resulted in increased (from four- to over six-fold) activities of liver glutathione-S-transferases.
Benefits and risks of combination therapy for hepatitis B #
Authors: Terrault Norah A.
Published: July 2010

In successful antiviral therapy of hepatitis B, drug combinations, particularly combinations without cross-resistance, can delay or prevent the emergence of drug-resistant mutants. Because drug-resistant mutants are archived and may limit future therapeutic options, prevention is important for long-term therapeutic efficacy. Additionally, combining drugs may achieve synergistic or additive antiviral effects compared with single drug therapy. Undesirable aspects of combination therapy include higher treatment costs and possibly lower adherence rates (due to pill number or complexity of regimen). Potentially harmful effects of combination therapy include higher rates of side effects, reduced efficacy due to drug competition, and the risk of multidrug-resistant hepatitis B virus (HBV) if combination therapy is insufficient to prevent resistance. Combination therapy has been shown to reduce the rate of drug resistance in chronic hepatitis B, but only when drugs with a low barrier to resistance are used (lamivudine, adefovir). Combination therapies may achieve greater degrees of HBV DNA suppression, but this has not been associated with higher rates of seroconversion (hepatitis B e antigen or hepatitis B surface antigen) compared to single drug therapy. The benefit of combination therapy has yet to be demonstrated with agents that are associated with a high barrier to resistance (tenofovir, entecavir). The use of combination therapy is recommended in specific patient groups: those with decompensated cirrhosis, those coinfected with human immunodeficiency virus and HBV who are on antiretroviral therapy, those who have undergone liver transplantation, and those with drug-resistant HBV infection. There is insufficient evidence to recommend combination therapy as first-line therapy for all patients with chronic hepatitis B. (Hepatology 2009;49:S122–S128.)
Benefits and risks of interferon therapy for hepatitis B #
Authors: Perrillo Robert
Published: July 2010

Alpha interferon is the only licensed drug for hepatitis B with immunomodulatory as well as viral inhibitory properties. Potential advantages of interferon compared to nucleoside analogs include a lack of drug resistance, a finite and defined treatment course, and a higher likelihood for hepatitis B surface antigen (HBsAg) clearance. Approximately 30% of hepatitis B e antigen (HBeAg)-positive and 40% of HBeAg-negative cases have a sustained virological response (when defined as HBeAg seroconversion and/or hepatitis B virus (HBV) DNA levels below 20,000 copies/mL, respectively) 6 months after completion of a 48-week course of peginterferon alfa-2a These responses remain durable in 80% and 50% of cases, respectively, when evaluated several years later. Recent studies have shown that changes in HBsAg and HBeAg concentration during treatment predict sustained virological response and serial monitoring of HBsAg is helpful in predicting HBsAg clearance. HBeAg-positive patients with genotype A have higher rates of HBeAg and HBsAg clearance, whereas HBeAg-negative patients with genotype D have the lowest rate of response to interferon therapy. Long-term follow-up of virological responders to either standard alpha interferon or peginterferon has demonstrated a progressive increase in the rate of HBsAg clearance, particularly in patients who were initially HBeAg-positive. Future studies need to address if specific virological benchmarks during therapy can be used to tailor treatment duration. Conclusion: Peginterferon alfa has a place as first-line therapy of hepatitis B in patients who are carefully selected on the basis of pretreatment serum HBV DNA and aminotransferase levels, safety considerations, and viral genotype. (Hepatology 2009;49:S103–S111.)
Human papillomavirus infection in a population‐based sample of women in Algiers, Algeria
Authors: Hammouda Doudja , Clifford Gary M. , Pallardy Sophie , Ayyach Ghassan , Chékiri Asma , Boudrich Arab , Snijders Peter J.F. , van Kemenade Folkert J. , Meijer Chris J.L.M. , Bouhadef Anissa , Zitouni Zahia , Habib Djamila , Ikezaren Nadia , Franceschi Silvia
Published: July 2010

No data exist on the population prevalence of, nor risk factors for, human papillomavirus (HPV) infection in the predominantly Muslim countries of Northern Africa. Cervical specimens were obtained from 759 married women aged 15–65 years from the general population of Algiers, Algeria. Liquid‐based cytology and HPV DNA detection, using a GP5+/6+‐based polymerase chain reaction assay that detects 44 HPV types, were performed according to the standardized protocol of the International Agency for Research on Cancer HPV Prevalence Surveys. HPV prevalence in the general population was 6.3% (4.0% of high‐risk types), with no significant variation by age. The prevalence of cervical abnormalities was 3.6%. HPV positivity was significantly higher among divorced women, women in polygamous marriages and those reporting husband's extramarital sexual relationships. HPV16/18 accounted for only 15% of HPV‐positive women in the general population, compared with 77% of invasive cervical cancer diagnosed in the same city. In conclusion, we report that HPV infection among married women in Algeria is much lower than in sub‐Saharan Africa and also lower than in the majority of high‐resource countries.
Thioredoxin reductase activity at the surface of human primary cutaneous melanomas and their surrounding skin
Authors: Schallreuter Karin U. , Jänner Michael , Mensing Hartwig , Breitbart Eckard W. , Berger Jürgen , Wood John M.
Published: July 2010

Plasma membrane‐associated thioredoxin reductase activities have been determined on primary melanoma tissues and their surrounding skin in 29 patients. Compared to patient's normal skin, enzyme activities in melanoma were higher in some patients (n = 24) and lower in others (n = 5). Those melanomas with high TR activities yielded low activities in the adjacent epidermis, reaching normal activity 3 to 5 cm away from each primary site (n = 4). Tumors with low activities showed higher than normal activities on the immediate surrounding skin (i.e., I cm away from the tumor) compared to the normal skin (n = 3). Earlier it was shown that in both keratinocytes and melanoma cells, calcium regulates thioredoxin reductase activity by an allosteric mechanism. The differences in TR activities within the high and low groups may be caused by a calcium flux between the primary tumor and the surrounding epidermis, and Wee versa. A comparison of TR activities to tumor invasiveness (Breslow level) in 28 primary melanomas showed a significant correlation using regression analysis (p = 0.031). A 4‐fold difference in TR activity corresponds to a one‐unit change in Breslow determination. These preliminary results suggest that TR activity may be another useful and sensitive assay for melanoma spread.
Case‐control study of risk factors for cervical neoplasia in Denmark. I: Role of the “male factor” in women with one lifetime sexual partner
Authors: Kjaer Susanne K. , de Villiers Ethel‐Michele , Dahl Claus , Engholm Gerda , Bock Johannes E. , Vestergaard Bent F. , Lynge Elsebeth , Jensen Ole M.
Published: July 2010

Possible risk factors for cervical cancer were investigated in 645 women, 20–49 years of age from Copenhagen, with histologically confirmed cervical cancer or carcinoma in situ and in 614 controls drawn at random from the female population of the same area. To study the role of the “male factor”, monogamous cases and controls together with their husbands were invited for further examination. This included a personal interview, a blood sample for analysis of herpes simplex virus antibodies, and a penile swab for papillomavirus analysis. In total, 41 case couples and 90 control couples were enrolled (89% and 92% of eligibles, respectively). The most significant risk determinants were a history of genital warts in the male (RR = 17.9 for ever vs. never) and ever having used condoms (RR = 0.2). Other potentially important factors, although not statistically significant, were ever having visited prostitutes (RR = 2.6, p = 0.14), circumcision (RR = 0.3, p=0.18), and a history of genital warts in the female (RR = 4.6, p= 0.09). Having a husband with a history of multiple sexual partners was also associated with an increased crude risk, but when adjustment was made for husband ever having had genital warts, use of condom, and age, no significant excess risk was observed. Human papillomavirus DNA, which was tested for with ViraPap and ViraType, was detected in one of the controls, and in only 2 case husbands. This study points to the importance of “high‐risk males” for the development of cervical cancer in their sexual partner; the results support the infectious nature of the disease.
Selective homing of phenotypically lytic cells within nasopharyngeal carcinoma biopsies: Numerous CD8‐ and CD16‐positive cells in the tumor
Authors: Lakhdar M. , Aribia M. H. Ben , Maalej M. , Ladgham A.
Published: July 2010

We present a comparative analysis of cell‐mediated immunity between circulating lymphocytes and tumor‐infiltrating lymphocytes (TIL) from patients with nasopharyngeal carcinoma (NPC). Phenotypic analysis using a panel of monoclonal antibodies (MAbs) to define lymphocytic subsets has revealed a selective homing of phenotypically lytic cells such as CD8‐and CD 16‐positive cells, but a low percentage of macrophages when compared to PBL of NPC patients. Also, PBL and TIL contain an equivalent percentage of activated T‐lymphocytes expressing HLA‐DR molecules and IL‐2 receptors. Functionally, TIL exhibit an abolished NK‐cell activity and concomitant decrease of proliferative response to phytohemaglutinin (PHA) and concanavalin A (ConA) stimulation when compared with PBL.
Effects of interferon‐gamma and its interaction with retinoic acid on human neuroblastoma differentiation
Authors: Wuarin L. , Verity M. A. , Sidell N.
Published: July 2010

Differentiation‐promoting effects of interferon‐gamma (IFN‐γ), both alone and in combination with retinoic acid RA), were studied on the human neuroblastoma cell line, LA‐N‐5. The results show that IFN‐γ inhibited the growth and induced morphological differentiation in a dose‐ and time‐dependent manner with measurable effects appearing at 20–40 IU/ml after 3 to 4 days of treatment in vitro. Acetylcholinesterase activity, used as a biochemical index of neuroblastoma differentiation, increased up to 2.5‐fold in the presence of IFN‐γ with a half maximal concentration of approximately 100 IU/ml. Concomitantly, modest IFN‐induced increases (≤2‐fold) in choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) activities were seen. Combination treatment of cells with IFN‐γ and RA resulted in synergistic effects on morphological differentiation, growth inhibition and induction of ChAT. Reversal of IFN‐γ's ability to influence neuroblastoma cell growth as well as potentiate the anti‐tumor effects of RA was obtained in the presence of an antibody against the IFN‐γ receptor, implying receptor‐mediated physiological events. Taken together, these data confirm the differentiating effects of IFN‐γ on human neuroblastoma cells and suggest that combination therapy with RA may be beneficial in the treatment of this disease.
Epstein‐barr virus and gastric cancer: Data and unanswered questions
Authors: Leoncini Lorenzo , Vindigni Carla , Megha Tiziana , Funtò Ilaria , Pacenti Lorenzo , Musarò Mariantonietta , Tosi Piero , Renieri Alessandra , Seri Marco , Anagnostopoulos Joannes
Published: July 2010

Sixty‐five unselected cases of gastric cancer have been analysed for EBV DNA by polymerase chain reaction,in situhybridization and immunohistochemistry for CD21 antigen expression. Four cases were found EBV‐positive by PCR, while ISH yielded positive results in 3 of these cases, demonstrating EBV in the nuclei of cancerous cells. CD21 antigen was expressed in cancerous cells in all 3 ISH‐positive cases. All the EBV‐positive cancers of the present series were poorly to moderately differentiated adenocarcinomas with prominent lymphoid infiltration. These results are discussed also on the basis of the literature.
Corn and wheat‐flour consumption and mortality from esophageal cancer in shanxi, China
Authors: Chen Fan , Cole Philip , Mi Zhibao , Xing Li‐Ying
Published: July 2010

In order to identify factors that may explain the great variation in mortality from esophageal cancer in Shanxi Province, China, an ecological study was carried out in 21 communes in that province. Mortality data were obtained from the registration records of the population of 148,928 during 1983 to 1988, which provided 744,640 person‐years of observation. The data regarding average consumption of each kind of grain, potatoes and sweet potatoes were from food allocation records. The data regarding consumption of meat, eggs, fruit, vegetables and the data regarding alcohol drinking were from interviews. The concentrations of nitrite and of nitrate in pickled vegetables and in drinking water were measured. A significant positive relation was found between mortality rate and the consumption of dietary corn and wheat flour. Also, a significant inverse relation was found between the mortality rate and the dietary sorghum and millet level. The age‐ and sex‐adjusted mortality‐rate ratio of esophageal cancer for residents in the third and highest quartiles of corn‐ and wheat‐flour consumption are 1.4 (95% CI: I.I ‐2.0) and 3.2 (2.5‐4.2), respectively, compared with those in the lowest quartile. Other factors studied did not contribute to the great variation in esophageal cancer mortality in the areas studied.
Detection of human papillomaviruses from histologically normal lymph nodes of Japanese cervical cancer patients by nested polymerase chain‐reaction assay
Authors: Nawa Akihiro , Kikkawa Fumitaka , Kawai Michiyasu , Mano Hisao , Goto Setsuko , Suganuma Nobuhiko , Tomoda Yutaka , Nishiyama Yukihiro , Nakashima Nobuo
Published: July 2010

To determine the prognostic significance of human papilloma virus (HPV) DNA in histologically normal lymph nodes, we developed a nested polymerase chain‐reaction (PCR) method on HPV16, 18 and 33 DNAs for formalin‐fixed, paraffin‐embedded tissues. We investigated 370 histologically normal lymph nodes from 15 patients treated for stage‐IB/IIB (FIGO) invasive cervical cancer. HPV16 DNA was detected in 7 (47%) and HPV18 DNA in 3 (20%) of the cervical cancers. Examination of histologically normal lymph nodes from these 10 patients by nested PCR revealed HPV DNA in 5 (50%) of them; in all cases HPV type in lymph nodes and tumor was the same. Two of these 5 patients had a recurrence (pelvic cavity or lung) and died of cancer, although all 5 had had pelvic radiotherapy after radical hysterectomy and lymphadenectomy. These findings indicate that nested PCR is useful for evaluating early lymph‐node involvement retrospectively in HPV‐positive cases.
Thrombin stimulates melanoma tumor‐cell binding to endothelial cells and subendothelial matrix
Authors: Klepfish A. , Greco M. A. , Karpatkin S.
Published: July 2010

Thrombin has been shown to activate tumor‐cell adhesion to platelets, fibronectin and von Willebrand factor 2‐ to 3‐fold in vitro, and enhance metastasis 10‐ to 156‐fold in vivo. We therefore elected to determine whether thrombin binds to tumor cells and whether thrombin‐treated tumor cells enhance their adhesion to endothelial cells, the first barrier to tumor invasion and metastasis. Thrombin‐treated human and hamster melanoma cells (SK‐Mel‐28 and HM‐29) enhanced their adhesion to bovine aortic endothelial cells 2.1‐ to 2.3‐fold, respectively. Similar results were obtained with bovine capillary endothelial cells. Thrombin activation of tumor cells was rapid, reaching its peak 15 min after thrombin activation; and transient, declining to baseline levels by 60 min. 125I‐thrombin bound to both SK‐Mel‐28 and HM‐29 cells in a saturation‐dependent manner, was inhibitable by unlabelled thrombin, and could be 90% washed away with buffer following 30 min of incubation. Electron microscopy of tumor cells bound to fibronectin‐coated millipore filters revealed adhesion of naive as well as thrombin‐treated tumor cells to endothelial cells and subendothelial matrix between endothelial cells. Neither mode of adhesion was preferentially enhanced by thrombin‐treated tumor cells. Both naive and thrombin‐treated SK‐Mel‐28 cells had the adhesive ligand integrin receptors: α3β1 (fibronectin, laminin, collagen); α5β1 (fibronectin); α,βx (vitronectin). Receptors for the β2 integrin family (LFA‐1 and Mac‐1) were not found, nor were receptors of the β3 integrin family, GPIIIa. The receptor ligands fibronectin and vitronectin were present. None of the above receptors or ligands increased their density or appeared de novo after thrombin stimulation. Thus, 2 melanoma cell lines have thrombin receptors which, when occupied, lead to enhanced adhesion of tumor cells to endothelium and subendothelial matrix.
Relevance of DT‐diaphorase activity to mitomycin C (MMC) efficacy on human cancer cells: Differences in in vitro and in vivo systems
Authors: Nishiyama Masahiko , Saeki Shuji , Aogi Kenjiro , Hirabayashi Naoki , Toge Tetsuya
Published: July 2010

Using 4 human cancer cell lines, 4 tumors xenografted into nude mice, and 11 fresh tumor specimens removed at surgery, we investigated the relevance of NAD(P)H:quinone oxidoreductase (DT‐diaphorase, DTD) activity (nmoles/min/mg protein) to mitomycin C (MMC)‐induced cytotoxicity. In culture cell lines, KB cells had significantly higher levels of DTD activity (8260) than PH101 (1934), SH101 (1805) or K562 (1796), and the highest sensitivity to MMC. In contrast, the higher the DTD activity of xenografts, the greater their resistance to MMC, while the inhibition rate of relative tumor growth for MMC, as evaluated by the NCI protocol, was highest in SH‐6, high in CH‐5, lower in CH‐4 and lowest in EH‐6. The investigation using 11 fresh tumor specimens also showed an inverse relationship between IC50 values after a 30‐min MMC treatment, as evaluated by ATP assay and DTD activities. Moreover, a non‐toxic DTD inhibitor, dicoumarol (DIC), or flavin adenine dinucleotide (FAD), suppressed the efficacy of MMC in culture cells, but enhanced it in xenografts. Thus, we suggest that DTD may play an important role in MMC‐induced cytotoxicity but MMC metabolism by DTD in solid tumors may differ from that in culture cells.
Altered dexamethasone responsiveness and loss of growth control in tumorigenic mouse lung cell lines
Authors: Droms Kurt A. , Hanson Laurie A. , Beer David G. , Malkinson Alvin M.
Published: July 2010

Glucocorticoid hormones induce differentiation, inhibit proliferation, and, in mice, reduce carcinogen‐induced tumorigenesis of lung epithelial cells. Therefore we examined dexamethasone effects on tumorigenic and non‐tumorigenic mouse lung epithelial‐derived cell lines. Non‐tumorigenic cells were growth inhibited and exhibited CAT activity in pMMTV‐CAT transfectants in response to dexamethasone. Tumorigenic cell lines exhibited a range of responses to dexamethasone. While one tumorigenic line was growth‐inhibited and responsive in CAT assays, 2 other tumorigenic cell lines were unresponsive both in CAT and in growth assays. A fourth tumorigenic cell line exhibited intermediate sensitivity in CAT assays and was actually growth‐enhanced by dexamethasone. Although no difference between cell lines was observed in the abundance of glucocorticoid receptor protein on Western blots, the least dexamethasone‐responsive tumorigenic lines exhibited very little binding of 3H‐dexamethasone. Clones of turnorigenic lines stably transfected with the rat glucocorticoid receptor gene were more dexarnethasone‐sensitive in CAT assays and were growthinhibited by dexamethasone. These data suggest that the neoplastic progression of cell lines derived from mouse lung frequently involves the acquisition of diminished glucocorticoid responsiveness.
Conditional expression and oncogenicity of c‐myc linked to a CD2 gene dominant control region
Authors: Stewart M. , McFarlane R. , Cameron E. , Lang K. , Campbell M. , Toth S. , Onions D. , Neil J. C.
Published: July 2010

Over‐expression of the c‐myc gene is widely implicated in the genesis of lymphoid neoplasia, including tumours of the T‐cell lineage. To study the effects of deregulated c‐myc expression on T‐cell development and oncogenesis, we sought to generate a transgenic mouse model in which c‐myc expression was targeted specifically to the T‐cell lineage. A plasmid construct containing a dominant control region (DCR) from the human CD2 locus linked 5′ to the human c‐myc gene was used to generate 2 lines of transgenic mice. Both strains developed thymic lymphoma at low frequency, but thymic development and peripheral T‐cell numbers were otherwise apparently normal. Low tumour penetrance was consistent with the observed lack of stable CD2‐myc transgene mRNA in tissues of healthy transgenic mice. In contrast, transgene RNA was detected in all malignant tumours as well as in early lymphomatous lesions. RNase protection analyses confirmed these findings and showed that the PI human c‐myc promoter was active in all neoplastic tissues but not in the thymus or other tissues of healthy transgenic mice. Despite the low spontaneous tumour incidence, the presence of the transgene markedly and uniformly accelerated the onset of tumours after neonatal infection with Moloney murine leukaemia virus. All tumours were rearranged for T‐cell receptor f3‐chain genes and were of T‐cell origin from their surface phenotype (Thy‐I +. CD3+, CD4+/‐, CDB+, slg‐). Virus‐accelerated tumours contained clonal integrations of Moloney murine leukaemia virus, suggesting that proviral insertional mutagenesis may have played a role in tumour development. Analysis of several candidate myccooperating genes failed to reveal any rearrangements apart from a low frequency involving proviral insertion at the pim‐I locus. The CD2‐myc mouse should therefore be a valuable system in screening for novel myc‐collaborating genes involved in T‐cell lymphoma.
Flow cytometric DNA ploidy defines patients with poor prognosis in node‐negative breast cancer
Authors: Balslev Ingegerd , Christensen Ib J. , Rasmussen Birgitte Bruun , Larsen Jørgen K. , Lykkesfeldt Anne E. , Thorpe Susan M. , Rose Carsten , Briand Per , Mouridsen Henning T.
Published: July 2010

Flow cytometric DNA analysis was performed on fine‐needle aspirates from frozen tumour biopsies from 421 node‐negative, non‐adjuvantly‐treated breast‐cancer patients with a median observation time of 6.75 years. Among premenopausal patients (n = 175), those having at least one DNA “hypoploid” sub‐population defined as DNA index (DI) <0.96 or 1.44 ≤ Dl < 1.92 (n = 81) were characterized by early recurrences (log‐rank p = 0.05, Wilcoxon p = 0.007), poor overall survival (OS) (p < 0.001) and poor survival after recurrence (p < 0.001). In the postmenopausal group (n = 246), there were no significant differences among 7 different Dl classes regarding either recurrence‐free survival (RFS) or OS. S‐phase fraction (SPF), divided into quartiles, predicted OS in premenopausal patients only (p = 0.02). Conventional multivariate Cox analysis of OS in the premenopausal group revealed hypoploidy to be the only independent prognostic factor involving a relative risk (RR) of 22.8. Age ≤ 40 years was of marginal significance, whereas SPF, histological grade (WHO), oestrogen and progesterone receptor (PgR) content, tumour size and number of lymph nodes removed were excluded from the model. Application of the conventional Cox model to the premenopausal group regarding RFS was found inappropriate due to lack of proportionality of the hazards of hypoploidy, SPF and histological grade. However, introduction of time‐dependent co‐variates using 2 years as cut‐off level showed hypoploidy with a RR of 3.52 and age ≤ 40 years with a RR of 3.28 to be independent prognostic factors. In the postmenopausal group, the conventional Cox model identified the number of lymph nodes removed to be the only independent prognostic factor regarding RFS as well as OS, whereas SPF < 9% (lowest quartile) was of marginal significance in RFS analysis. Hypoploidy was correlated to high SPF, low PgR content and low differentiation, indicating that hypoploid tumours proliferate rapidly and hormone‐independently. These patients may therefore benefit from adjuvant chemotherapy administered while tumour burden and risk of drug resistance are still low. © 1994 Wiley‐Liss, Inc.
Expression of type‐IV collagenases in human tumor cell lines that can form liver colonies in chick embryos
Authors: Tsuchiya Yuri , Endo Yoshio , Sato Hiroshi , Okada Yasunori , Mai Masayoshi , Sasaki Takuma , Seiki Motoharu
Published: July 2010

Chick embryo has been used as a model system for evaluating the metastatic potential of tumor cells. We have previously demonstrated that expression of the tissue inhibitor of matrix metalloproteinase‐1 (TIMP‐I) gene can suppress liver colonization of tumor cells in chick embryo, probably by inhibiting the activity of matrix metalloproteinases (MMP) produced by tumor cells. In an attempt to identify MMP associated with liver colonization, we examined 24 human tumor cell lines for their potential to form metastatic colonies in chick‐embryo liver after the cells had been inoculated into the chorioallantoic membrane (CAM) vein. We compared the results with the mRNA expression of MMP (MMP‐1, MMP‐2, MMP‐3, MMP‐9) studied previously. Three of 8 cell lines from mesenchymal tumors (fibrosarcoma HT1080, osteosarcomas SK‐ES and MNNG/ HOS) and 2 of 16 cell lines from epithelial tumors (gastric carcinoma KKLS and bladder carcinoma T24) proliferated in the livers. MMP‐2 and MMP‐9 were the enzymes whose transcripts were more frequently expressed in these 5 metastatic cell lines (MMP‐1; 2/5, MMP‐2; 4/5, MMP‐3; 0/5, MMP‐9; 3/5), but other cell lines that did not form liver colonies expressed the transcripts at lower frequency (MMP‐2; 7/19, MMP‐9; 3/19). Although either or both MMP‐2 and MMP‐9 transcripts were expressed in 4 of the 5 metastatic cell lines, they were undetectable in T24 cells. However, induced expression of both enzymes was detected by immunostaining in the T24 cells colonized in the liver. Thus, type‐IV collagenases expressed by tumor cells may play a role in facilitating colonization in chick embryos. © 1994 Wiley‐Liss, Inc.
Expression pattern of breast‐cancer‐associated protein pS2/BCEI in colorectal tumors
Authors: Welter C. , Theisinger B. , Rio M.‐C. , Seitz G. , Schüder G. , Blin N.
Published: July 2010

Recently, several carcinomas of the gastrointestinal tract were tested for pS2/BCEI activity, a gene isolated from breast‐cancer cells and coding for a small secreted peptide. In the latter tumors, its activity is under estrogen control; surprisingly, it was also found expressed in carcinomas of the stomach, biliary tract and pancreas. We have now investigated the expression of this gene in 64 colorectal carcinomas, 31 adenomas and 13 polyps in comparison with their matrix tissues by applying molecular (RNA analysis) and immunohistochemical (pS2 antibody) techniques. Positive pS2 immunostaining (ranging from focal to strong immunoreaction) was noted in 89% of human colon cancers, while 11% remained negative. Furthermore, all 40 transitional mucosae were strongly positive, whereas normal mucosa was negative. Of hyperplastic polyps, 68.2% displayed a significant immunoreaction, and 80.6% of adenomas were focally positive. Finally, 6 out of 16 cases showed significant pS2 transcription in Northern blot analysis. These data clearly indicate that the breast‐cancer‐associated pS2 protein also plays an as yet undetermined role in the tumorigenesis of human colorectal carcinomas. © 1994 Wiley‐Liss, Inc.
The relative prognostic significance of total cathepsin D and HER‐2/neu oncogene amplification in breast cancer
Authors: Seshadri Ram , Horsfall David J. , Firgaira Frank , McCaul Kieran , Setlur Vittal , Chalmers Anthony H. , Yeo Robyn , Ingram D. , Dawkins Hugh , Hahnel Roland , South Australian Breast Cancer Study Group
Published: July 2010

Total tumor cathepsin D (TCD) levels were determined prospectively by a radioimmunometric assay in tumor cytosol of 858 primary breast cancer patients diagnosed between 1989–1991. In 581 of these patients, tumor HER‐2/neu oncogene amplification was simultaneously determined. In a “training‐set” of 313 patients, “high” TCD was associated with significantly shorter disease‐free survival (DFS). For the whole group, there was no correlation between TCD and pathologic stage, number of axillary nodes with tumor deposits, tumor size, histologic type and grade, or hormone receptor levels. In the node‐positive group, high TCD level was associated with HER‐2/ neu amplification. After a median follow‐up duration of 31 months, univariate analysis indicated that high TCD level was significantly associated with shorter DFS only in node‐positive patients. The shorter DFS in association with high TCD levels was observed in both estrogen‐receptor‐positive and ‐negative patients. Cox multivariate analysis of DFS confirmed that high TCD level was predictive of shorter DFS in node‐positive patients only. Because of the short duration of follow‐up, the significance of TCD in overall survival was not determined. We conclude that high tumor TCD in node‐positive patients is predictive of shorter DFS, and is often associated with HER‐2/ neu amplification. The possibility exists that high tumor TCD may act in combination with HER‐2/neu amplification to promote dissemination of metastases. © 1994 Wiley‐Liss, Inc.
Amplification of the epidermal‐growth‐factor‐receptor gene correlates with different growth behaviour in human glioblastoma
Authors: Schlegel Jurgen , Merdes Annette , Stumm Gabi , Albert Fritz K. , Forsting Michael , Hynes Nancy , Kiessling Marika
Published: July 2010

The objective of our study was to determine the frequency of EGF‐receptor‐gene rearrangement in relation to tumour‐growth behaviour in an unselected group of glioma patients. We investigated 73 glial tumours with different grades of malignancy (17 low‐grade gliomas, 14 anaplastic variants, and 42 GBM) by Southern analysis, reverse transcriptase PCR (RT‐PCR) amplification of mRNA, and Western analysis. An amplification of the EGF‐receptor gene was present in 19/42 GBM but in only I anaplastic astrocytoma. By RT‐PCR, 4/19 GBM with gene amplification showed a specific amino‐terminal aberrant splice mutation of 801 bp in addition to undeleted mRNA. By Western analysis, 27/42 GBM showed expression of the EGF‐receptor protein. Protein levels, however, varied among individual tumours. Four GBM containing an aberrant splice mutation exhibited an immunoreactive protein of 130 kDa MW in addition to the normal EGF‐receptor protein p170. All GBM patients underwent surgery followed by a standard course of radiotherapy. Neuroradiological follow‐up in 31/42 GBM patients consisted of bimonthly MRJ examinations. There was a statistically significant difference in the mean latency period until tumour regrowth of patients suffering from GBM with and without EGF‐receptor‐gene amplification (9 weeks vs. 32 weeks). Our data indicate more rapid tumour regrowth kinetics of GBM with amplified EGF receptor genes in vivo. © 1994 Wiley‐Liss, Inc.
P‐glycoprotein epitope mapping. I. Identification of a linear human‐specific epitope in the fourth loop of the P‐glycoprotein extracellular domain by MM4.17 murine monoclonal antibody to human multi‐drug‐resistant cells
Authors: Cianfriglia Maurizio , Willingham Mark C. , Tombesi Marina , Scagliotti Giorgio V. , Frasca Giuliana , Chersi Alberto
Published: July 2010

A new murine monoclonal antibody (MAb), MM4.17, to human multi‐drug‐resistant (MDR) cells was found to be reactive in an ELISA with a synthetic 16‐amino acid peptide selected from the fourth loop of the P‐glycoprotein extracellular domain. Immunohistochemistry indicated that this MAb reacted in human tissues in the same pattern as that previously found with other human‐specific MAbs to P‐glycoprotein. For a precise definition of the MM4.17 epitope, a peptide library consisting of overlapping 4‐ to 10‐mer residues covering the entire P‐glycoprotein‐fragment was synthesized on polyethylene pins and tested for MAb binding. The results of this ELISA demonstrated that the MM4.17 epitope is constituted by the continuous‐linear TRIDDPET amino‐acid sequence (residues 750–757 of the human MDR I‐P‐glycoprotein). The MAb MM4.17 recognizes only the human MDRI ‐P‐glycoprotein isoform, and excess TRIDDPET peptide blocks the binding of the MAb to MDR variants of CEM cells. These results demonstrate that the amino‐acid sequence TRIDDPET from the human MDRI gene represents the first continuous‐linear epitope identified in the P‐glycoprotein extracellular domain.
Transcriptional regulatory networks associated with self‐renewal and differentiation of neural stem cells
Authors: Yun So Jeong , Byun Kyunghee , Bhin Jinhyuk , Oh Jee‐Hyun , Nhung Le Thi Hong , Hwang Daehee , Lee Bonghee
Published: July 2010

Neural stem cells (NSCs) are self‐renewing, multipotent cells that can generate neurons, astrocytes, and oligodendrocytes of the nervous system. NSCs have been extensively studied because they can be used to treat impaired cells and tissues or improve regenerative power of degenrating cells in neurodegenerative diseases or spinal cord injuries. For successful clinical applications of NSCs, it is essential to understand the mechanisms underlying self‐renewal and differentiation of NSCs, which involve complex interplays among key factors including transcription factors, epigenetic control, microRNAs, and signaling pathways. Despite numerous studies on such factors, a holistic view of their interplays during neural development still remains elusive. In this review, we present recently identified potential regulatory factors and their targets by genomics and proteomics technologies and then integrate them into regulatory networks that describe their complex interplays to achieve self‐renewal and differentiation of NSCs. J. Cell. Physiol. 225: 337–347, 2010. © 2010 Wiley‐Liss, Inc.
TNFAIP8: A new effector for Galpha(i) coupling to reduce cell death and induce cell transformation
Authors: Laliberté Benoit , Wilson Ariel M. , Nafisi Houman , Mao Helen , Zhou Yi Yuen , Daigle Mireille , Albert Paul R.
Published: July 2010

Galpha(i)‐coupled receptors comprise a diverse family of receptors that induce transformation by largely unknown mechanisms. We previously found that the Galpha(i)‐coupled dopamine‐D2short (D2S) receptor transforms Balb‐D2S cells via Gαi3. To identify new Gαi effectors, a yeast two‐hybrid screen was done using constitutively active Gαi3‐Q204L as bait, and tumor necrosis factor‐alpha (TNFα)‐induced protein 8 (TNFAIP8, SCC‐S2/NDED/GG2‐1) was identified. In contrast, TNFAIP8‐related TIPE1 and TIPE2 showed a very weak interaction with Gαi3. In yeast mating, in vitro pull‐down, co‐immunoprecipitation and bioluminescence resonance energy transfer (BRET) assays, TNFAIP8 preferentially interacted with activated Gαi proteins, consistent with direct Gαi‐TNFAIP8 coupling. Over‐expression or depletion of TNFAIP8 using antisense constructs in Balb‐D2S cells did not affect D2S‐induced signaling to Gαi‐dependent inhibition of cAMP. In contrast, antisense depletion of TNFAIP8 completely inhibited spontaneous and D2S‐induced foci formation, consistent with a role for TNFAIP8 in Gαi‐dependent transformation. To address possible mechanisms, the effect of D2S signaling via TNFAIP8 on TNFα action was examined. D2S receptor activation inhibited TNFα‐induced cell death in Balb‐D2S cells, but not in cells depleted of TNFAIP8. However, depletion of TNFAIP8 did not prevent D2S‐induced inhibition of TNFα‐mediated caspase activation, suggesting that D2S/TNFAIP8‐induced protection from TNFα‐induced cell death is caspase‐independent. The data suggest that Gαi‐TNFAIP8‐mediated rescue of pre‐oncogenic cells enhances progression to oncogenic transformation, providing a selective target to inhibit cellular transformation. J. Cell. Physiol. 225: 865–874, 2010. © 2010 Wiley‐Liss, Inc.
The zeta potential of aluminium hydroxide in relation to water treatment coagulation
Authors: Hall E. S.
Published: July 2010

The zeta potentials of kaolinite particles in the presence of aluminium sulphate, aluminium nitrate and aged partly neutralised nitrate have been measured for various pH values. They are dependent on the concentration of a polynuclear ion. The results are compared with previous flocculation experiments, and support the view that in the presence of Al3+ ions, surfaces of kaolinite are coated with aluminium hydroxide having stability ranging from that of the amorphous form to almost that of the crystalline species. Optimum flocculation requires that the coating should be of the amorphous hydroxide, formed when the highest possible value of the solubility product [Al3+] [OH−]3 is attained.
The mechanical properties of films. I. Evaluation of the mechanical properties of some surface coating polymers by the Williams, Landel and Ferry method
Authors: Simpson W. , Bridge L. , Holt T.
Published: July 2010

This series of papers is concerned with an evaluation of the dynamic elastic properties of typical insulating varnish and enamel films and the observation of transition temperatures in these materials.

Dynamic elastic properties have been investigated in the temperature range, room temperature to 180°, and in the frequency range 40 to 2000 c/s. The results have been interpreted by the method of reduced variables. The Williams, Landel, Ferry (WLF) equation was found to be applicable to many of the materials including polyesters, silicones and epoxides; the product of the WLF parameters (C1°C2°) varied from 350 to 1300. The use of the Tg form of the WLF equation is deprecated, insofar as the relationship between Ts (the parameter in the WLF ‘universal’ equation) and Tg is demonstrably not constant.

Polyurethane varnishes showed large deviations from the WLF equation and this is almost certainly connected with the existence of more than one large transition in these materials. Multiple transitions may however be detected in materials conforming to the WLF equation and it does not seem possible to decide whether or not transitions established dilatometrically will influence the less sensitive dynamic properties in such a way as to produce clear deviations from WLF behaviour.
Kinetics of growth on aqueous — oil and aqueous — solid dispersed systems
Authors: Humphrey Arthur E. , Erickson Larry E.
Published: July 2010

Dispersed phase continuous culture systems are very complicated. Indeed, they can differ considerably in their behaviour from the usual homogeneous continuous culture systems. Experimental studies on cell adsorption—desorption rates under various conditions of surfactant concentrations and droplet coalescence and break‐up is needed in order to understand fully the mechanism of substrate utilisation in these continuous systems.
E.M.F. response of the iodide crystal membrane electrode in iodide solutions concentrated with NaCIO4, NaNO3, NaBr and NaSCN
Authors: Moorhead E. D. , The Paul W.
Published: July 2010

An experimental study has been made of the e.m.f. response of the Orion iodide‐selective electrode in iodide solutions to ascertain the effect of a broad range of accompanying NaClO4 (0.0625 to 5.0 mol/kg), and for comparison, NaNO3, NaBr and NaSCN. For each salt the three‐parameter empirical equation of Stoughton et al. for calculation of the mean molal activity coefficient was combined with the Nicolsky equation to obtain estimates of an electrode selectivity ratio, K. Consideration of some of these results suggests the possibility of a slight NaClO4, NaNO3 interaction beyond the anticipated salt‐induced alteration in the activity of solution iodide.
Kinetics of dimerisation of gaseous keten
Authors: Blake P. G. , Davies H. H.
Published: July 2010

The dimerisation of gaseous keten in the temperature and pressure ranges 225 to 323 °C and 6 to 155 mmHg, respectively, is essentially homogeneous and of the second order in carbon‐coated reactors, k = 105.25 exp(−74 000/RT) l mol−1 s−1. The entropy of activation, at – 166.4 J K−1 mol−1, agrees closely with values obtained in solution for the dimerisation or cycloaddition reactions of other ketens.
Studies on the synthesis and chromatographic behaviour of the esters of gallic acid and galloylglycollic acid
Authors: Wijesekera R. O. B. , Ratnayake V. U.
Published: July 2010

Several esters of gallic acid, and galloylglycollic acid have been synthesised, the latter for the first time. Their behaviour on thin‐layer chromatograms have been examined and five suitable solvent systems are described, which enable their convenient separation and identification on the basis of Rf values.
Synthesis of isohydrazones by the reaction of chlorine and ammonia in the presence of a ketone (the basis of a new hydrazine process). I
Authors: Jermyn T. J. , Jeffreys G. V.
Published: July 2010

The chemical reaction between chlorine and ammonia in the presence of a ketone has been studied in the gas phase and in the gas and liquid phases in order to assess the suitability of this reaction process for the production of hydrazine. High yields of chloramine have been obtained with dilute chlorine—nitrogen gases and this has been explained in terms of the rate processes occurring in the bubbles in the gas—liquid reaction system.
The thermal decomposition of ferrous sulphate heptahydrate. II. Decomposition to ferric oxide
Authors: Kamel A. H. , Abdallah A. M.
Published: July 2010

The final stage of decomposition of ferrous sulphate heptahydrate to Fe2O3 and SO3, in a current of air, has been investigated. It was found that SO3 undergoes partial instantaneous dissociation to SO2 and O2, and that the degree of dissociation is dependent on the ignition temperature and the SO3: air ratio.

Data for the degree and rate of salt decomposition at temperatures from 500 to 1000 °C, are given.
Thermal reactions between MII sulphates and acid orthophosphates in the solid state
Authors: Berry E. E.
Published: July 2010

Two general types of high temperature reactions between MII sulphates and acid orthophosphates have been found and a survey of some representative examples has been made. The reactions are typified by two examples using Ca2+ salts:

and

.

Similar reactions have been found for other alkaline earth sulphates and phosphates and for corresponding mixed alkaline earth systems. The products have been found to be largely determined by the phase relationships in the respective MIIO–P2O5 systems.
Gypsum plasters. I. Preparation of β‐hemihydrates
Authors: Khalil A. A. , Gad G. M.
Published: July 2010

β‐Hemihydrate plasters were prepared in one way by continuous heating of gypsum at 90 °C. In addition to this, a new attempt has been made to prepare this material by making use of the phenomenon of rehydration of γ‐anhydrite. The hemihydrate formation, in both methods, was followed through periodical differential thermal analysis studies. Results showed that 4 days heating at 90 °C, as well as the rehydration of γ‐anhydrite at room conditions for 30 days, result in the formation of pure hemihydrate. The prepared plasters were found to be free from gypsum.
Gypsum plasters II. Constitution and properties of the prepared β‐hemihydrates
Authors: Khalil A. A.
Published: July 2010

The constitution of the two types of plasters, previously prepared, was followed using thin‐section microscopy and X‐ray diffractometry. Moreover, their hydraulic properties were determined to assess their suitability for use in various applications. Results showed that the plasters consist mainly of the β‐hemihydrate phase. The X‐rays and thin section microscopy in addition to the differential thermal analysis have omitted the presence of gypsum in the investigated plasters. The plaster prepared by rehydration of γ‐anhydrite shows better crystallinity than that prepared by direct calcination of gypsum at 90 °C. Both types require small amounts of water giving higher ultimate strength. The rehydrated γ‐anhydrite shows normal setting in accordance with the international specifications requirements. The other type exhibits a quick setting property which was related to the presence of minute amounts of gypsum, in the plaster, below the limits of identification of both the X‐rays and differential thermal analysis. The prepared plasters could be used for various purposes needing higher strength, lower normal consistency and quick or moderate setting properties.
Radiometric studies of mercury loss from fungicidal paints III. Loss from three paints with various mercury contents
Authors: Taylor C. G. , Hunter G. H.
Published: July 2010

Losses of mercury have been measured over a period of 220 days from paint films prepared from polyvinyl acetate emulsion (PVA), styrene/acrylic emulsion or alkyd gloss paints containing concentrations of mercury as phenyl mercuric acetate (PMA) from 0.005 to 0.16%. At all concentrations, simple PVA films lose mercury at lower rates than do comparable films prepared from PVA containing coalescing agent, or from styrene/acrylic emulsion.

Mercury losses from alkyd gloss films are lower than those from other films at the lower mercury concentrations studied, but percentage loss rates for alkyd films increase somewhat with increasing mercury concentration. A simple explanation for this difference is offered in terms of physical structures of the paint films.
The pyrolysis of chlorocarbons
Authors: Grant David
Published: July 2010

The formation of C6Cl6(bz), CCl4 and C2Cl6 by the sealed‐tube pyrolysis of chlorocarbons, has been confirmed. The chlorinolysis of C6Cl6(bz), C4Cl6 (1,3 diene) and C2Cl4 yields CCl4.