bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Genes Associated with Dedifferentiation of Hepatocellular Carcinoma with Expression Profiling Analysis
Authors: Midorikawa Yutaka , Tsutsumi Shuichi , Taniguchi Hirokazu , Ishii Masami , Kobune Yuko , Kodama Tatsuhiko , Makuuchi Masatoshi , Aburatani Hiroyuki
Published: August 2005

To identify the genes associated with dedifferentiation of hepatocellular carcinoma (HCC), gene expression profiles of HCCs of well‐and moderately differentiated grades were compared by means of oligonucleotide arrays. One tumor showed a nodule‐in‐nodule appearance (NIN), which is occasionally observed in the course of progression of HCC from well to less differentiated grade, when an inner, moderately differentiated tumor (MD) develops sequentially from the outer, well‐differentiated tumor (WD). Seventy‐six genes were identified to be up‐regulated more than 3‐fold and 33 genes were down‐regulated in the inner nodule in NIN. By statistical analysis of the profiles from 10 individual additional liver tumors, 5 WDs and 5 MDs, we were able to identify 12 genes, LAMA3, PPIB, ADAR, PSMD4, NDUFS8, D9SVA, CCT3, GBAP, ARD1, RDBP, CSRP2, and TLE1, with significantly elevated expression, and 4 genes, CP, IL7R, CD48, and PLGL, with decreased expression in MD. These selected genes were further validated using another 12 tumors, 5 WDs and 7 MDs, with semi‐quantitative RT‐PCR. We also applied neighborhood analysis to list the genes with high predictability values as most closely correlated with WD‐MD distinction. Seven genes, ADAR, PSMD4, D9SVA, CCT3, GBAP, RDBP, and CSRP2, whose expression was elevated and one gene, IL7R, whose expression was decreased, were included among the top 50 predictor genes. These genes are likely to be associated with dedifferentiation of HCC and their identification may help to elucidate the mechanism of liver cancer progression.
Expression of Vascular Endothelial Growth Factor and E‐Cadherin in Human Ovarian Cancer: Association with Ascites Fluid Accumulation and Peritoneal Dissemination in Mouse Ascites Model
Authors: Akutagawa Noriyuki , Nishikawa Akira , Iwasaki Masahiro , Fujimoto Takashi , Teramoto Mizue , Kitajima Yoshimitsu , Endo Toshiaki , Shibuya Masabumi , Kudo Ryuichi
Published: August 2005

Ascites formation and peritoneal dissemination are critical problems in patients with advanced ovarian cancer. Vascular endothelial growth factor (VEGF), also known as angiogenic growth factor, is a potent mediator of peritoneal fluid accumulation and angiogenesis of tumors. E‐Cadherin is an adhesion molecule that is important for cell‐to‐cell interaction. To elucidate the molecular mechanism of ascites formation and peritoneal dissemination of ovarian cancer, we examined the expression of VEGF and E‐cadherin in different ovarian cancer cell lines and utilized nude mice to compare the biological characteristics of ovarian cancer cells. Three human ovarian cancer cell lines (AMOC‐2, HNOA and HTBOA) were used in this study. Expression of genes was analyzed by northern blotting and RT‐PCR methods. AMOC‐2 expressed E‐cadherin, but not VEGF. HNOA expressed VEGF without E‐cadherin expression. HTBOA expressed both VEGF and E‐cadherin. Each human ovarian cancer model revealed a specific feature. The AMOC‐2 mouse had a single large peritoneal tumor without ascites or remarkable peritoneal dissemination. HTBOA and HNOA mice had bloody ascites and marked peritoneal dissemination. Introduction of VEGF antisense into HTBOA cells could inhibit the ascites formation. It is suggested that VEGF is important for the ascites formation via the increased vascular permeability effect. The deregulation of E‐cadherin expression might be involved in the peritoneal dissemination. These molecules are important for the formation of specific features of advanced ovarian cancer. Ovarian cancer cell lines that had different gene expression patterns produced nude mouse human ovarian cancer models with different characteristics.
Clinicopathologic Comparison between the API2‐MALT1 Chimeric Transcript‐positive and ‐negative Gastric Low‐grade B‐Cell Lymphoma of Mucosa‐associated Lymphoid Tissue Type
Authors: Nakamura Tsuneya , Nakamura Shigeo , Yokoi Takio , Suzuki Hiroko , Ohashi Kazuhiko , Seto Masao
Published: August 2005

Little is known about the clinicopathological differences between API2‐MALT1 chimeric transcript‐positive and ‐negative gastric low‐grade B‐cell lymphomas of mucosa‐associated lymphoid tissue (MALT) type. The aim of this study was to clarify those differences in gastric MALT lymphoma. Twenty‐three patients with gastric MALT lymphoma were enrolled in a unicenter study. Helicobacter pylori (H. pylori) infection status and clinical stages were investigated. Antibacterial treatment was performed for every patient. Responsiveness of MALT lymphoma to this treatment was assessed by means of regular follow‐up endoscopy combined with biopsy. All cases were examined for API2‐MALT1 chimeric transcript by means of RT‐PCR and sequencing analyses. H. pylori infection status was assessed as positive in 20 patients and negative in three. With regard to responsiveness to antibacterial treatment, complete remission was observed in two patients, partial remission in 12 and no change in nine. API2‐MALT1 chimeric transcript was detected in seven patients, all of whom showed no change in response to antibacterial treatment. API2‐MALT1 positivity was found to be significantly correlated with responsiveness to antibacterial treatment (P=0.0001), absence of H. pylori infection (P=0.0198), and gross cobblestone mucosa observed endoscopically (P=0.0198). For the other factors (age, sex, dominant site of lesion, high‐grade component, infiltrated layer of gastric wall, nodal involvement or clinical stages), there were no differences between API2‐MALT1 chimeric transcript‐positive and ‐negative cases. Gastric API2‐MALT1 chimeric transcript‐positive MALT lymphoma generally features unresponsiveness to antibacterial treatment, and is thought to be unrelated to H. pylori infection in its pathogenesis. Our findings indicate the presence of different clinical subtypes in gastric MALT lymphomas.
MUM1/IRF4 Expression Is an Unfavorable Prognostic Factor in B‐Cell Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Authors: Ito Masato , Iida Shinsuke , Inagaki Hiroshi , Tsuboi Kazuya , Komatsu Hirokazu , Yamaguchi Motoko , Nakamura Naoya , Suzuki Ritsuro , Seto Masao , Nakamura Shigeo , Morishima Yasuo , Ueda Ryuzo
Published: August 2005

B‐Cell chronic lymphocytic leukemia (B‐CLL)/small lymphocytic lymphoma (SLL) consists of heterogeneous diseases that are distinguished by morphological, immunophenotypic and molecular features. MUM1 (multiple myeloma oncogene 1) is a protooncogene that is deregulated as a result of (6;14)(p25;q32) chromosomal translocation in multiple myeloma, and is also expressed in a variety of malignant lymphoma entities. We examined the expression of MUM1 in B‐CLL/SLL, and found that 2 of 4 B‐CLL‐derived cell lines and 14 of 29 patients' specimens expressed MUM1 by immunohistochemical analysis. MUM1 expression was not associated with CD38 expression, somatic hypermutation of immunoglobulin heavy chain gene variable region (IgVH), or any other clinical characteristics of the patients. Interestingly, the patients who were positive for MUM1 showed shorter overall survival tunes than those who were negative for MUM1 (50% survival: 22 months vs. 82 months) (P=0.0008, log‐rank test). Multivariate analysis by Cox's proportional‐hazards regression model showed that MUM1 expression and unmutated IgVH status were independent unfavorable prognostic factors in patients with B‐CLL/SLL. These findings suggest that MUM1 expression is a useful prognostic factor in B‐CLL/SLL. The biological role and mechanism of action of MUM1 in B‐CLL/SLL need to be clarified for the development of therapies for patients with the poor prognostic subtype.
Dose of Adenoviral Vectors Expressing Interleukin‐2 Plays an Important Role in Combined Gene Therapy with Cytosine Deaminase/5–Fluorocytosine: Preclinical Consideration
Authors: Nakamori Mikihito , Iwahashi Makoto , Ueda Kentaro , Tsunoda Takuya , Terasawa Hiroshi , Hamada Hirofumi , Yamaue Hiroki
Published: August 2005

Using a syngeneic murine model, we investigated the therapeutic efficacy of combined gene therapy using adenoviral vectors expressing murine interleukin‐2 (AdmIL‐2) and Escherichia coli cytosine deaminase (AdCD). In a subcutaneous tumor model, tumor‐bearing mice were treated with an intratumoral injection of adenoviral vectors and received an intraperitoneal administration of 5–fluorocytosine (5–FC). Only the mice treated with AdCD (2×108 pfu) and an intermediate dose of AdmIL‐2 (1×106 pfu) survived significantly longer than mice treated with AdCD alone (P<0.01). Moreover, 40% of these treated mice obtained complete remission from tumor‐bearing status. The cytotoxicity of splenocytes obtained from the treated mice was related to the survival period. Tumor‐specific cytotoxic T lymphocyte assay showed that the cell‐mediated cytotoxic response was specific for parental tumor cells. In a hepatic metastasis model, mice treated with an intravenous administration of both AdCD (2×l08 pfu) and an intermediate dose of AdmIL‐2 (1×106 pfu) demonstrated the most significant reduction of metastatic foci and the longest survival following a 5–FC administration. These results suggest that gene therapy combined with AdmIL‐2 and AdCD may be a promising strategy for clinical application and, in addition, that translation of combined gene therapy from murine models into the clinical setting will require careful attention to the variables of cytokine expression levels in the design of clinical trials and in the evaluation of treatment efficacy.
Hammerhead Ribozyme against γ‐Glutamylcysteine Synthetase Attenuates Resistance to Ionizing Radiation and Cisplatin in Human T98G Glioblastoma Cells
Authors: Tani Masaharu , Goto Shinji , Kamada Kensaku , Mori Katsuharu , Urata Yoshishige , Ihara Yoshito , Kijima Hiroshi , Ueyama Yoshito , Shibata Shobu , Kondo Takahito
Published: August 2005

Glioblastoma cells are highly malignant and show resistance to ionizing radiation, as well as anti‐cancer drugs. This resistance to cancer therapy is often associated with a high concentration of glutathione (GSH). In this study, the effect of continuous down‐regulation of γ‐glutamylcysteine synthetase (γ‐GCS) expression, a rate‐limiting enzyme for GSH synthesis, on resistance to ionizing radiation and cisplatin (CDDP) was studied in T98G human glioblastoma cells. We constructed a hammerhead ribozyme against a γ‐GCS heavy subunit (γ‐GCSh) mRNA and transfected it into T98G cells. (1) The transfection of the ribozyme decreased the concentration of GSH and resulted in G1 cell cycle arrest of T98G cells. (2) The transfection of the ribozyme increased the cytotoxicity of ionizing radiation and CDDP in T98G cells. Thus, hammerhead ribozyme against γ‐GCS is suggested to have potential as a cancer gene therapy to reduce the resistance of malignant cells to ionizing radiation and anti‐cancer drugs.
Sensitivity to Anticancer Agents and Resistance Mechanisms in Clear Cell Carcinoma of the Ovary
Authors: Itamochi Hiroaki , Kigawa Junzo , Sultana Habiba , Iba Takahiro , Akeshima Ryoji , Kamazawa Shunji , Kanamori Yasunobu , Terakawa Naoki
Published: August 2005

We conducted the present study to determine the chemoresistance mechanisms in clear cell carcinoma of the ovary (CCC). Five human CCC cell lines (HAC‐2, RMG‐I, RMG‐II, KK, and KOC‐7c) were used in this study. The sensitivity of the cells to the anticancer agents was determined by 3–(4,5–dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and we assessed drug sensitivity by calculating assay area under the curve (AUC) for each agent. The expression of multi‐drug resistance genes (MDR‐1, MRP‐1, MRP‐2) was detected by reverse transcription‐polymerase chain reaction (RT‐PCR). Glutathione (GSH) concentration was measured by an enzymatic assay. Topoisomerase (topo) I activity was assayed in terms of relaxation of supercoiled plasmid substrate DNA. The IC50 to anticancer agents ranged widely. The assay AUC indicated that 3 of 5 cell lines (RMG‐I, RMG‐II, and KK) were sensitive to paclitaxel (PTX), 3 (HAC‐2, RMG‐I, and RMG‐II) were sensitive to 7–ethyl‐10‐hydroxycamptothecin (SN‐38), which is an active metabolite of camptothecin (CPT‐11), and only one (HAC‐2) was sensitive to cisplatin (CDDP). All cell lines were resistant to mitomycin‐C (MMC) and etoposide (VP‐16). The MRP‐1 gene was detected in all cell lines. Only one cell line showed both MRP‐2 and MDR‐1 gene expression. Except for HAC‐2 cells, expression of MRP genes was related to CDDP resistance, and MDR‐1 gene expression was associated with PTX resistance. GSH concentrations increased after exposure to CDDP or MMC in all cell lines. There was a significant correlation between topo‐I enzymatic activity and the response to SN‐38. The present study revealed several resistance mechanisms in CCC and the results suggested that PTX and CPT‐11 might be effective agents to treat CCC.
Ratio of Expression of p16INK4a to p14ARF Correlates with the Progression of Non‐small Cell Lung Cancer
Authors: Moriyama Satoru , Nakashima Yoshiaki , Yano Motoki , Kaji Masahiro , Yamakawa Yosuke , Toyama Tatsuya , Yamashita Hiroko , Iwase Hirotaka , Sasaki Hidefumi , Saito Yushi , Kiriyama Masanobu , Kato Jyoji , Fujii Yoshitaka
Published: August 2005

The CDKN2 gene is located on the short arm of chromosome 9p and encodes two unrelated proteins, p16INK4a and p14ARF, through the use of independent first exons and shared exons 2 and 3. p16INK4a is a cyclin‐dependent kinase inhibitor, whereas p14ARF regulates the cell cycle through a p53 and MDM2–dependent pathway. We have examined the expression of p16INK4a and p14ARF using competitive RT‐PCR in 60 non‐small cell lung cancers (NSCLCs) and matching normal lung tissues. The intensities of bands for p16INK4a and p14ARF were nearly equal or the intensity of the p16INK4a band slightly exceeded that of p14ARF in the normal lung tissues (n=60). In 38 tumors the intensity of the p16INK4a band was similar to or slightly weaker than that of p14ARF. In 6 tumors the intensity of the p16INK4a band was weaker than that of p14ARF. In 15 tumors the intensity of the p14ARF band was very strong and the p16INK4a band was barely visible. In only one tumor was the intensity of the p16INK4a band very strong, while the band of p14ARF was barely visible. The ratio of the intensity of p16INK4a to p14ARF had an interesting correlation with the tumor's clinicopathological characteristics. The p stage II‐IV tumors had significantly lower p16INK4a to p14ARF ratios than the p stage I tumors (P=0.036). The T2–4 tumors had significantly lower p16INK4a to p14ARF ratios than the T1 tumors (P=0.005). The N1–3 tumors had significantly lower p16INK4a to p14ARF ratios than the NO tumors (P=0.014). Our results suggest that the ratio of expression of p16INK4a to p14ARFtends to decrease during the progression of NSCLC.
Differential Expression of Progesterone Receptor Isoforms A and B in the Normal Ovary, and in Benign, Borderline, and Malignant Ovarian Tumors
Authors: Akahira Jun‐ichi , Suzuki Takashi , Ito Kiyoshi , Kaneko Chika , Darnel Andrew D. , Moriya Takuya , Okamura Kunihiro , Yaegashi Nobuo , Sasano Hironobu
Published: August 2005

Human epithelial ovarian neoplasm is well‐known to be sex steroid‐related, but the possible biological significance of progesterone actions in these tumors remains controversial. In this study, we examined the differential expression patterns of the two progesterone receptor (PR) isoforms, PRA and PRB, using immunohistochemistry and real‐tune quantitative RT‐PCR in normal and neoplastic ovarian tissues, and in cell lines derived from a normal ovarian surface epithelium and an ovarian epithelial carcinoma in order to further elucidate the possible involvement of progesterone in the development of ovarian neoplasms. The median H scores for PR isoforms in normal (n=8), benign (n=10), borderline (n=8) and malignant (n=24) ovarian tissues were as follows; PRA: 194.0, 171.0, 49.5, 0 (P<0.05), and PRB: 175.0, 180.5, 251.5, 168.5, respectively. In ovarian cancer cell lines (OVCAR–3 and Caov–3), the PRB/PRAB mRNA ratio was increased by 17β‐estradiol, both tune‐and dose‐dependently. However, this ratio was unaltered following the addition of 17β‐estradiol in a normal ovarian epithelial cell line (NOV–31). Immunoblotting analysis demonstrated that PRB protein expression was markedly up‐regulated in OVCAR–3, whereas the PRA and PRB isoforms both appeared to be increased in NOV–31. These results suggest that down‐regulation of PRA is associated with the development of ovarian epithelial carcinoma.
An Anti‐GD2 Monoclonal Antibody Enhances Apoptotic Effects of Anti‐cancer Drugs against Small Cell Lung Cancer Cells via JNK (c‐Jun Terminal Kinase) Activation
Authors: Yoshida Shoko , Kawaguchi Haruhiko , Sato Shigeki , Ueda Ryuzo , Furukawa Koichi
Published: August 2005

Small cell lung cancer (SCLC) cell lines specifically express ganglioside GD2, and anti‐GD2 monoclonal antibodies (mAbs) caused suppression of cell growth and induced apoptosis of SCLC cells with single use. Here, enhancement of the cytotoxic effects of various anti‐cancer drugs with an anti‐GD2 mAb was demonstrated. The cytotoxicity of all six drugs examined was markedly enhanced, i.e. 2.4–7.8–fold increase of cell sensitivity in terms of IC50. In particular, the combination of cisplatin (CDDP) with an anti‐GD2 mAb resulted in prominent enhancement of cytotoxicity even in low‐moderate GD2–expressing lines. The anti‐GD2 mAb induced weak activation of c‐Jun terminal kinase (JNK) in SCLC cells, and all anti‐cancer drugs also induced its activation to various degrees. When CDDP and an anti‐GD2 mAb were used together, significantly stronger JNK activation was observed corresponding to the cytotoxic effects, suggesting that synergistic phosphorylation of JNK with two reagents induced prominent apoptosis. The essential role of JNK in the induction of SCLC apoptosis with CDDP and anti‐GD2 mAb was confirmed by experiments with a JNK inhibitor, curcumin. These results suggest that anti‐GD2 mAbs would be very efficient in combination with anti‐cancer drugs, both to achieve SCLC‐specific cytotoxicity and to enhance its magnitude.
Sensitivity of Human Cancer Cells to the New Anticancer Ribo‐nucleoside TAS–106 Is Correlated with Expression of Uridine‐cytidine Kinase 2
Authors: Shimamoto Yuji , Koizumi Katsuhisa , Okabe Hiroyuki , Kazuno Hiromi , Murakami Yuko , Nakagawa Fumio , Matsuda Akira , Sasaki Takuma , Fukushima Masakazu
Published: August 2005

TAS–106 [l–(3–C‐ethynyl‐β‐d‐ribo‐pentofuranosyl)cytosine] is a new anticancer ribo‐nucleoside with promising antitumor activity. We have previously presented evidence suggesting that the TAS–106 sensitivity of cells is correlated with intracellular accumulation of the triphosphate of TAS–106, which may be affected both by cellular membrane transport mechanisms and uridine‐cytidine kinase (UCK) activity. Since the presence of a UCK family consisting of two members, UCK1 and UCK2, has recently been reported in human cells, we investigated the relation between expression of UCK1 and UCK2 at both the mRNA and protein levels and UCK activity (TAS–106 phosphorylation activity) in a panel of 10 human cancer cell lines. Measurement of UCK activity in these cell lines revealed that it was well correlated with the cells' sensitivity to TAS–106. In addition, the mRNA or protein expression level of UCK2 was closely correlated with UCK activity in these cell lines, but neither the level of expression of UCK1 mRNA nor that of protein was correlated with enzyme activity. We therefore compared the protein expression level of UCK2 in several human tumor tissues and the corresponding normal tissues. Expression of UCK2 protein was barely detectable in 4 of the 5 human tumor tissues, but tended to be high in the pancreatic tumor tissue. It could not be detected at all in any of the normal tissues. Thus, expression of UCK2 appeared to be correlated with cellular sensitivity to TAS–106, and it may contribute to the tumor‐selective cytotoxicity of TAS–106.
Association between Helicobacter bilis in Bile and Biliary Tract Malignancies: H. bilis in Bile from Japanese and Thai Patients with Benign and Malignant Diseases in the Biliary Tract
Authors: Matsukura Norio , Yokomuro Shigeki , Yamada Sirikan , Tajiri Takashi , Sundo Trichak , Hadama Tohru , Kamiya Shigeru , Naito Zenya , Fox James G.
Published: August 2005

Japan and Thailand have high incidences of bile duct carcinoma and gallstones. The presence of Helicobacter bilis (H. bilis) detected by polymerase chain reaction (PCR) and 16S rRNA analysis in bile samples from Chileans with chronic cholecystitis was reported. The association between H. bilis in bile and biliary tract malignancies has not been investigated, and therefore the aim of this study is to determine whether malignant diseases of the biliary tract are associated with the presence of H. bilis in bile samples obtained from two high‐risk populations. Bile samples from 45 Japanese and 40 Thai patients were subjected to PCR analysis using H. bilis‐specific primers, and six of the H. bilis amplicons were sequenced. Thirteen out of 15 (87%) Japanese and 11 out of 14 (79%) Thai patients with bile duct or gallbladder cancer tested positive for the presence of H. bilis in their bile. Eight out of 16 (50%) Japanese and 10 out of 26 (38%) Thai patients with gallstone and/or cholecystitis tested positive for H. bilis. Only 4 out of 14 (29%) subjects without biliary disease tested positive for H. bilis among the Japanese. Bile duct and gallbladder cancer showed significantly higher positive rates for H. bilis than did the non‐biliary diseases among the Japanese (P<0.01) and the odds ratios for bile duct or gallbladder cancer with H. bilis in comparison with gallstone and/or cholecystitis were 6.50 (95%CI 1.09–38.63) in the Japanese and 5.86 (1.31–26.33) in the Thai patients. In conclusion, H. bilis infection in bile was associated with biliary tract and gallbladder cancers in two high risk populations, Japanese and Thai.
The Sprouty‐related protein, Spred‐1, localizes in a lipid raft/caveola and inhibits ERK activation in collaboration with caveolin‐1
Authors: Nonami Atsushi , Taketomi Takaharu , Kimura Akiko , Saeki Kazuko , Takaki Hiromi , Sanada Takahito , Taniguchi Koji , Harada Mine , Kato Reiko , Yoshimura Akihiko
Published: August 2005

Caveolin‐1 (Cav‐1) has been suggested to function as a negative regulator of mitogen‐stimulated proliferation and the Ras‐p42/44 ERK (MAP kinase) pathway in a variety of cell types. However, the molecular basis of this suppression has not been clarified. Spred/Sprouty family proteins are also negative regulators of the ERK pathway by interacting with Raf‐1. The Spred/Sprouty family proteins contain a cysteine‐rich (CR) domain at the C‐terminus, which is thought to be palmitoylated like Cav‐1 and necessary for membrane anchoring. In this study, we demonstrated that Spred‐1 localized in cholesterol‐rich membrane raft/caveola fractions and interacted with Cav‐1. To clarify the biological effect of Cav‐1/Spred‐1 interaction, we used hematopoietic cells that lacked expression of caveolins but expressed Spred‐1. Forced expression of Cav‐1 suppressed SCF‐ and IL‐3‐induced proliferation and ERK activation. Furthermore, forced expression of exogenous Spred‐1 in Cav‐1‐expressing cells further suppressed proliferation and ERK activation. These data suggest that Spred‐1 inhibits ERK activation in collaboration with Cav‐1.
Smicl is a novel Smad interacting protein and cleavage and polyadenylation specificity factor associated protein
Authors: Collart Clara , Remacle Jacques E. , Barabino Silvia , A. van Grunsven Leo , Nelles Luc , Schellens Ann , Van de Putte Tom , Pype Stefan , Huylebroeck Danny , Verschueren Kristin
Published: August 2005

Ligand‐bound receptors of the Transforming Growth Factor‐β (TGF‐β) family promote the formation of complexes between Smad proteins that subsequently accumulate in the nucleus and interact there with other transcriptional regulators, leading to modulation of target gene expression. We identified a novel nuclear protein, Smicl, which binds to Smad proteins. Smicl and Smads cooperate and enhance TGF‐β mediated activation of a Smad‐responsive reporter gene. A domain with five CCCH‐type zinc fingers in Smicl is structurally and functionally, at least in vitro, similar to a domain in CPSF‐30, the 30 kDa subunit of Cleavage and Polyadenylation Specificity Factor (CPSF). Like CPSF‐30, Smicl can associate with some other CPSF subunits characterized previously. Its effect on the induction of a reporter gene for TGF‐β requires the cleavage/polyadenylation signal downstream of the coding sequence of that gene. Thus, Smicl is a novel protein that displays CPSF‐30‐like activities, interacts in the nucleus with activated Smads, and potentiates in TGF‐β stimulated cells Smad‐dependent transcriptional responses, possibly in conjunction with the activity of CPSF complexes.
Analysis of combinatorial effects of Wnts and Frizzleds on β‐catenin/armadillo stabilization and Dishevelled phosphorylation
Authors: Takada Ritsuko , Hijikata Hiroko , Kondoh Hisato , Takada Shinji
Published: August 2005

Both Wnt ligands and Frizzled (Fz) receptors each constitute a large family in vertebrates, but the receptor specificity of each Wnt has remained largely unknown. Here, we examined the receptor specificity of two typical Wnts, Wnt‐3a and Wnt‐5a, in signal transmission. To investigate systematically the combinatorial effects of these Wnts, various Fzs on canonical Wnt/β‐catenin signaling, we analyzed the ability of these Wnt proteins to increase stability of armadillo/β‐catenin proteins in Drosophila S2 cells expressing vertebrate Fzs. Wnt‐3a increases the amount of armadillo proteins in cells expressing Fzs 4, 5 and 8, but not Fzs 3 and 6; whereas Wnt‐5a does not increase it in any cell line. In contrast, both Wnt‐3a and Wnt‐5a increase the phosphorylation of Dsh in combination with most of the Fzs. This Dsh phosphorylation is abrogated by decreasing the levels of casein kinase I α by double‐stranded RNA‐mediated translational interference. These observations indicate that both Wnt proteins can interact with the majority of Fz receptors and elicit signaling reactions exemplified by Dsh phosphorylation but that the stabilization of β‐catenin/armadillo proteins in the Wnt/β‐catenin signaling occurs only when specific combinations of Wnt and Fz meet.
Nomogram for estimating an individual's risk of having a fetus with open spina bifida
Authors: WALD NICHOLAS J. , CUCKLE HOWARD S.
Published: August 2005

Summary. A nomogram indicating the risk of having a fetus with open spina bifida in relation to a particular maternal serum and amniotic fluid α‐fetoprotein (AFP) level is described. The nomogram is designed for counselling patients with borderline amniotic fluid AFP results, who on average are only marginally at risk of having a fetus with open spina bifida. The use of the nomogram will refine the estimate of risk for a particular woman by combining the estimate derived from the amniotic fluid AFP level with that derived from the maternal serum AFP level. Details are also given for further refining the estimate of risk by using information from an amniotic fluid gel acetylcholinesterase determination.
Obstetric implications of burns in pregnancy
Authors: MATTHEWS R. N.
Published: August 2005

Summary. Analysis of 50 patients with burns in pregnancy has allowed the objective consideration of obstetric implications. Patients in the second and third trimester of pregnancy with burns of 50% should be delivered immediately as maternal death is otherwise certain and fetal survival rate is not improved by waiting. Vaginal delivery has always proved possible, even in the presence of perineal burns but caesarean section should be considered and may be preferred. Patients in the first trimester may survive with more extensive burns and possible reasons for this are discussed. Pregnancy testing on admission should be mandatory in burns of women of reproductive age. In patients with burns of >40% in the second and third trimesters, spasmolytics should be used to suppress spontaneous labour and to cover operations. Greater fetal maturity without worsening maternal prognosis can thus be achieved. Insufficient data exist to recommend this for burns of between 40 and 50%.
Old burns and pregnancy
Authors: MATTHEWS R. N.
Published: August 2005

Summary. Burns rarely cause problems in subsequently occurring pregnancies. Occasionally abdominal wall scarring is so dense and extensive that consequent maternal pain in the second half of pregnancy demands surgical decompression. This does not usually precipitate labour and the resultant raw areas should be covered with split skin autografts. It is exceptional for burns to destroy the entire breast disc; residual breast mound development occurs during puberty, and hypertrophy and engorgement during and after pregnancy. Although absence of the nipple‐areola complex precludes breast feeding, distortion of it does not prevent feeding in all cases. Split skin autografting with customized pressure therapy is the best remedy for correction of contracture deformity.
Inhibition of prostaglandin synthase by maternal plasma factor(s) in early human pregnancy
Authors: BRENNECKE S. P. , LENTON E. A. , TURNBULL A. C. , MITCHELL M. D.
Published: August 2005

Summary. Using an enzyme incubation‐radioimmunoassay technique, we have tested the hypothesis that an increase in a maternal plasma factor(s) that inhibits prostaglandin synthase (EC 1.14.99.1) is responsible for the suppression of decidual prostaglandin production that occurs in early human pregnancy. Measurements made on serial maternal samples failed to reveal any significant increase in plasma inhibitory activity at this time, and it was concluded that the conceptus achieves the reduction in prostaglandin synthesis by a mechanism other than a systemically mediated direct inhibition of decidual prostaglandin synthase.
Production of active and inactive renin by cultured explants from the human female genital tract
Authors: WARREN A. Y. , CRAVEN D. J. , SYMONDS E. M.
Published: August 2005

Summary. Myometrium, decidua, chorio‐decidua and amnion were collected from women undergoing caesarean section and from pregnant women at hysterectomy and hysterotomy for comparison with myometrium, cervix and endometrium taken from non‐pregnant women at hysterectomy. Homogenates of chorio‐decidua and amnion contained the largest concentrations of active and inactive renin. Cultured explants of all tissues except amnion were found to produce both types of renin. The percentage of active renin produced before 20 days of culture was significantly greater in cultures of chorio‐decidua than in those of myometrium (P < 0,0005) or decidua Vera (P< 0.029, which suggests that renin synthesis in vivo is probably confined to the chorio‐decidua.
Acute effect of an antihypertensive drug, labetalol, on uteroplacental blood flow
Authors: LUNELL N. O. , NYLUND L. , LEWANDER R. , SARBY B.
Published: August 2005

Summary. The effect of a new antihypertensive drug, labetalol, on uteroplacental blood flow was determined in eight pre‐eclamptic women. After injection of 0.5 mCi of 113mIn the radioactivity in the placenta was recorded by a gamma camera linked to a computer and the placental blood‐flow index was calculated from the ratio between the maximum radioactivity of the isotope‐accumulation curve and the rise time of the curve. Labetalol, a combined α‐ and β‐adrenoceptor antagonist was given intravenously and after 30 min a second uteroplacental blood‐flow index was calculated. There was a significant mean decrease of blood pressure from 147/98 to 128/83 mmHg, but no change in uteroplacental blood‐flow index, so that uteroplacental vascular resistance tended to decrease.
Ovarian transplantation by selective microvascular anastomoses in the rabbit
Authors: DENJEAN R. , BOECKX W. , GORDTS S. , BROSENS I.
Published: August 2005

Summary. Autotransplantation of the ovary by microvascular anastomoses was performed in 42 rabbits by three different procedures: orthotopic replantation with selective end‐to‐end anastomoses of the ovarian vessels; heterotopic transplantation in the groin area, with anastomosis of the ovarian vessels on the inferior epigastric vessels; heterotopic transplantation in the groin with the ovary included in a peritoneal sac to prevent adhesions. Three weeks later, at day 3 of a pseudo‐pregnancy, the grafts were examined and morphology, presence of adhesions and ovulation were compared with those of a control group. The long‐term vascular patency rate was 78%. The ovulation rate was 71.5% in the orthotopic group, 50% in the heterotopic group and 83.5% in the heterotopic group with the ovary in a peritoneal sac. Subcutaneous transplantation of the ovary within a peritoneal sac provides a new and useful experimental model for the study of tubo‐ovarian function and for recovery of postovulatory oocytes.
Effects of the climacteric and sequential mestranol and norethisterone on the cervix and genital tract
Authors: PATERSON M. E. L. , ALLEN J. , JORDAN J. A.
Published: August 2005

Summary. The effects of the climacteric and sequential mestranol and norethisterone on the epithelium of the cervix and genital tract were determined in 12 postmenopausal women. Before treatment the squamocolumnar junction was visible in only six of the 12 women, but after treatment with sequential mestranol and norethisterone the squamocolumnar junction became visible due to a minor degree of eversion. Mucus, which was always absent before therapy, was always seen afterwards and any atrophic effects were reversed by therapy within 3 months. The effects of oestrogen and progestogen deficiency were more easily seen by scanning electron microscopy (SEM) than with conventional histology. Before treatment six of the nine women studied by SEM had a cervix covered by mature squamous epithelium, but after therapy all the women had mature squamous epithelium. The pretreatment lateral vaginal wall and urinary sediment smears showed mainly immature squamous cells; this correlated poorly with the histology and SEM of the cervix. There was a good correlation between urinary sediment and lateral vaginal wall smears both before and after treatment.
Management of severe fetal bradycardia with ritodrine
Authors: HUTCHON D. J. R.
Published: August 2005

Summary. Four patients with severe fetal bradycardia in labour were treated with ritodrine; recovery of the fetal heart rate occurred immediately. The infants were delivered in satisfactory condition and paediatric follow‐up has not shown any neurological abnormality.
Outcome of third trimester pregnancies after cryotherapy of the uterine cervix
Authors: HEMMINGSSON ERIK
Published: August 2005

Summary. A retrospective study was undertaken to assess the effect of cryotherapy of the uterine cervix on the outcome of third trimester pregnancies. It was concluded that cryosurgery of the cervix hadno effect on the onset or progress of labour, or on the infant, an important advantage compared with cold‐knife conization as a therapy for young women with cervical intraepithelial neoplasia.
IUCD liability
Authors: ELSTEIN MAX
Published: August 2005

Summary. In the UK the marketing and quality control of all intrauterine devices (IUCDs) is controlled by the Medicines Act (1968). Training is supervised by the Joint Committee of Contraception (JCC), and Trainers have to ensure that the trainee has acquired safe standards before the JCC certificate is granted. Patients must be adequately counselled and consent obtained. There is no unequivocal evidence of its mode of action in humans, which might limit its acceptability to certain individuals. There are a number of problem areas. How long should a copper‐containing IUCD be retained when there is clinical evidence of continued effectiveness for more than the statutory 2 years? Perforation of the uterus and the resulting abnormal situation of an IUCD can be potentially dangerous. Sound technique minimizes its occurrence but if perforation occurs there must be defined and documented action. Because the IUCDs’ primary intrauterine action is to prevent implantation, should pregnancy occur, there is an increased likelihood of ectopic gestation. Awareness of this, and appropriate early action, should prevent a disastrous outcome. There is clear evidence that ascent of organisms relates to the cervical thread. Perhaps tailless devices should be made available for women who are at risk of developing pelvic inflammatory disease? Other potential problem areas, where there might be legal liability involving practitioners, include the management of abnormal bleeding and difficult removals.
Early postpartum insertion of the Multiload Cu250 intrauterine device
Authors: EMENS J. M. , SHAH S. R.
Published: August 2005

Summary. The Multiload Cu250 intrauterine device was inserted in the early postpartum period, most often between day 2 and 5. In 74% of 86 patients the device was found correctly placed at postnatal examination at 6 weeks. The 26% expulsion rate was unacceptably high and it is concluded that no intrauterine device, including the Multiload, should be fitted in postpartum women, less than 1 week after delivery.
Post‐termination contraception: use of the Multiload Cu250
Authors: LOUDON J. D. O. , SCOTT RHODA , HUTCHON D. J. R.
Published: August 2005

Summary. During a period of 27 months Multiload intrauterine devices were inserted immediately after suction evacuation of the uterus into 125 patients in two hospitals. Sixty‐one patients were lost to follow‐up despite careful explanation of the need to attend. The remaining 64 patients provided a total of 630 women months for analysis. Eleven patients requested removal of the Multiloads for various personal reasons. Four devices were spontaneously expelled, three in the first 2 months. Eight devices were removed on account of pain or bleeding and one because of infection. Five other patients were considered to have less severe uterine infection not requiring removal of the devices. These complications have to be viewed against those inherent in the procedure of termination: 4·4% pain or bleeding 3·6% uterine infection. Forty women are known to be continuing to wear the devices. They show no differences in terms of parity, gestation at the time of termination or degree of dilatation of the cervix at the time of termination from the other groups. One pregnancy occurred after 10 months of use. While acknowledging the deficiency of the study due to the high defaulter rate the immediate insertion of a Multiload at the time of termination of pregnancy can be considered as an acceptable method of contraception.
General assessment of the Multiload Cu250 intrauterine device UK network of IUCD Research Clinics*
Authors: SNOWDEN R.
Published: August 2005

Summary. A total of 803 fittings of the Multiload Cu250 were undertaken between May and December 1979 in the UK IUCD network co‐ordinated by the Institute of Population Studies, University of Exeter. Each woman fitted with the device was followed in a prospective study until a pregnancy, expulsion or removal occurred or the woman was released from follow‐up after 2 years of continuous use. Because of the large number of fittings undertaken it is possible to compare the experience of groups of women determined by a number of criteria. The most useful distinction was between those of differing parity. Comparisons have been made between nulliparous women, women of low parity (1 or 2) and those of high parity (≥3). By concentrating on the characteristics of the woman receiving the IUCD it is possible to provide those responsible for fitting IUCDs with information that will have predictive value in relation to specific categories of women. The results of the study show that, despite some variation between women of different parity, the Multiload Cu250 is comparable with other IUCDs currently available in the UK in terms of the relative risks of pregnancy and removal of the device after a complaint of bleeding or pain. The removal rate is biased towards complaints of pain among nulliparous women which is also reported to be present at the times of IUCD fitting and removal. As expected with a device of this configuration, the expulsion rate is low when compared with other devices. Once into the uterus this device appears to be an effective contraceptive but fittings in nulliparous women more frequently necessitate dilatation of the cervix and this is associated with more frequent reports of difficulty at fitting and complaints of pain.
3. Antenatal care, formal education and child‐bearing
Authors: ROSSITER C. E. , CHONG H. , LISTER U. G. , BANO Q. , BRIGGS N. D. , EKWEMPU C. C. , MEMBERR M. T.
Published: August 2005

Summary. Both formal education and antenatal care had tremendous impact on the results of childbearing. In women who had never had any formal education nor received antenatal care, that is 33% of the survey population, maternal mortality was 29 per 1000 deliveries, perinatal mortality was 258 per 1000 total births and 26% of the babies weighed ≤2.50 kg. With education and antenatal care combined, as was the case in 10% of the survey population, the maternal death rate was 2.5 per 1000 deliveries, perinatal mortality rate was 30 per 1000 total births, and only 8% of the babies were of low birthweight. Among women in their thirties and beyond, the average number of previous births per woman in the illiterate group (5.4) was double that in those who had received post‐secondary education and child mortality rate at 25% was three times as high. Formal education, by changing social attitudes, holds the key to improvements in maternal and perinatal health.
4. The influence of maternal age and parity on child‐bearing with special reference to primigravidae aged 15 years and under
Authors: ROSSITER C. E. , CHONG H. , LISTER U. G. , BANO Q. , BRIGGS N. D. , EKWEMPU C. C. , MEMBERR M. T.
Published: August 2005

Summary. In singleton births, maternal and fetal survival were poorest among primigravidae aged ≤15 years and also in the highly parous women aged ≥30 years. The young teenage girls constituted 6% of the survey population and 30% of the 174 maternal deaths, while the highly parous older women made up 10% of the survey population and 20% of the maternal deaths. The perinatal death rates per 1000 singleton deliveries were 180 for the young teenage girls, 150 for the highly parous groups had under 100 for the others. The major obstetric problems were dystocia due chiefly to contracted pelvis, anaemia, eclampsia, haemorrhage and infections. Emphasis is laid on the fact that the problems of these high‐risk groups have their roots in the prevailing social attitudes which universal formal education stands the best chance of changing.
10. Easily identifiable congenital malformations
Authors: EKANEM A. D. , CHONG H.
Published: August 2005

Summary. At birth, the prevalence of easily identifiable congenital malformations was 14 per 1000 babies. Polydactyly was very common and cleft lip/cleft palate very rare as they are in other black populations. The prevalence of neural‐tube defects was only 1.6 per 1000 babies and there was little to indicate that the socially disadvantaged were any more vulnerable than those with better living standards. As a group, congenital malformations contribute very little towards the poor maternal and fetal outcomes in Zaria.
11. Perinatal mortality
Authors: LISTER U. G. , ROSSITER C. E. , CHONG H.
Published: August 2005

Summary. The perinatal mortality rate in all singleton births was 103 per 1000; 67% of all perinatal deaths were stillbirths and in 77% of stillbirths, intrauterine death had already occurred before admission to hospital. Nine per cent of live births but 40% of stillbirths and 50% of neonatal deaths were of low birthweight (≤2.5 kg). The principal obstetric causes of perinatal deaths were obstructed labour and its consequences, anaemia, antepartum haemorrhage, eclampsia and low fetal birthweight. Nearly half of all perinatal deaths were associated with complicated deliveries of which vaginal breech delivery was by far the most hazardous. Both the proportion of babies with low birthweight and the perinatal mortality rates rose dramatically and progressively with haematocrit <0.30. A raised perinatal mortality rate was also associated with raised haematocrit >0.40. Of the biosocial factors influencing perinatal health, lack of antenatal care, residence outside Zaria, early teenage pregnancy and high parity exerted the most deleterious effect and literacy and antenatal care the most favourable effect on pregnancy outcome.
Inadequate maternal vascular response to placentation in pregnancies complicated by pre‐eclampsia and by small‐for‐gestational age infants
Authors: KHONG T. Y. , DE WOLF F. , ROBERTSON W. B. , BROSENS I.
Published: August 2005

Summary. An examination of the maternal vascular response to placentation shows that physiological changes in the placental bed normally extend from the decidua into the inner myometrium. In pre‐eclampsia and in a proportion of pregnancies with small‐for‐gestational age infants (SGA) the physiological changes are restricted to the decidual segments alone. In addition, complete absence of physiological changes throughout the entire length of some spiral arteries is seen in pre‐eclampsia and SGA. This new observation is confirmed in a study of basal plates of placentas from abnormal pregnancies. Intraluminal endovascular trophoblast may be seen in the placental bed spiral arteries in the third trimester in pre‐eclampsia and SGA, a feature not seen beyond the second trimester in normal pregnancy. These findings point to a defect in the normal interaction between migratory trophoblast and maternal uterine tissues in pre‐eclampsia and in SGA.
The relation between the need for intubation at birth, abnormal cardiotocograms in labour and cord artery blood gas and pH values
Authors: LISSAUER T. J. , STEER P. J.
Published: August 2005

Summary. A consecutive series of 56 infants of 32 weeks gestation or more who were resuscitated at birth by endotracheal intubation was studied to determine the occurrence of abnormal cardiotocograph traces and acidosis as determined by cord artery blood measurements. Thirty‐two infants (57%) had neither cardiotocographic abnormalities nor acidosis; in this group the factors associated with the need for intubation were meconium stained amniotic fluid, operative delivery, anaesthetic agents given to the mother, a tight nuchal cord, and traumatic vaginal delivery. The need for intubation at birth should not automatically be regarded as evidence of intrapartum hypoxia or disturbed acid‐base balance.
Fetal distress during labour in diabetic pregnancy
Authors: OLOFSSON PER , INGEMARSSON INGEMAR , SOLUM THORE
Published: August 2005

Summary. The frequency of fetal distress in labour was studied in 46 diabetic women and in 46 non‐diabetic matched controls. Fetal distress was assessed by electronic fetal heart rate (FHR) monitoring and fetal scalp blood pH determinations in late first stage of labour. Ominous FHR and/or low pH (<7·26) was more common in the diabetic group than in the control group (17·4% and 10·9%, respectively) but the difference was not statistically significant. The frequency of caesarean section and low Apgar score at 1 min was significantly higher in the diabetic group (P<0·05). There was no correlation between maternal blood glucose regulation and the occurrence of fetal distress in the diabetic group. The results suggest that fetal distress may be slightly more common in labour in diabetic women compared with controls managed in a similar way. Careful FHR monitoring and liberal use of fetal scalp blood pH determinations is recommended.