bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombophilia is not associated with an increase in placental abnormalities in women with intra‐uterine fetal death
Authors: Morssink Leonard P. , Santema Job G. , Willemse Feike
Published: March 2004

Background.  The aim of this study was to investigate whether women with thrombophilia and intrauterine fetal death have a higher incidence of placental lesions as compared with those without thrombophilia.

Method.  In a case–control study comprising 50 women with an obstetrical history of intrauterine fetal death, placental histology comparison was made between those with thrombophilia and those without thrombophilia.

Results.  Of the women who had an intrauterine fetal death, eight (16%) had a thrombophilia factor. There were no differences in birth weight, gestational age and parity or in placental volume and weight between the eight women with and the 42 women without thrombophilia. There was no statistically significant difference between placentas of the women with and those without thrombophilia.

Conclusion.  In a group of women who had an obstetrical history of intrauterine fetal death, those with thrombophilia do not have a difference in placental histological lesions compared with the women without a thrombophilia factor. Future thrombophilia research should be focused on placental bed specimens.
Uterine contractility and directed sperm transport assessed by hysterosalpingoscintigraphy (HSSG) and intrauterine pressure (IUP) measurement
Authors: Kissler Stefan , Siebzehnruebl Ernst , Kohl Joachim , Mueller Anja , Hamscho Nadja , Gaetje Regine , Ahr Andre , Rody Achim , Kaufmann Manfred
Published: March 2004

Background.  Uterine peristalsis sustains sperm transport and can be detected by hysterosalpingoscintigraphy (HSSG). This study is the first to be designed to investigate utero‐tubal transport function by HSSG and uterine contractility by intrauterine pressure measurement (IUP) consecutively on the same day in the periovulatory phase.

Methods.  Twenty‐one female subjects (mean age 28.4 years) without a gynecologic history were examined sequentially by HSSG and IUP on the same day to evaluate uterine contractility in relation to the utero‐tubal transport function. In HSSG, intact transport function was visualized by the rapid uptake of 99m‐technetium‐marked albumin aggregates through the female genital tract. In IUP, the frequency of uterine contractions (UC/min), amplitude of uterine contractions and basal pressure tone were detected via a intrauterine catheter. HSSG and IUP were embedded in cycle monitoring with measurement of LH and estradiol.

Results.  In HSSG, a positive transport of inert particles was assessed in 20 of 21 subjects, in 76% to the side of the dominant follicle or on both sides of the oviduct, and in 19% a strict contralateral transport could be observed. In only one subject (5%), no transport was assessed. The mean value of uterine contractions was 3.4 UC/min (SD ± 0.7), the mean amplitude was 12.0 mmHg (SD ± 4.25 mmHg). Basal pressure tone was 70.7 mmHg. There was a statistically significant correlation with estradiol levels: none of the subjects with less than 3 UC/min showed an estradiol level higher than 100 pg/mL; nearly every patient (one exception) with more than 3 UC/min had an estradiol level higher than 100 pg/mL (p < 0.0001, Fisher's exact test).

Conclusions.  Intact periovulatory utero‐tubal transport function can be documented by HSSG and is caused by directed uterine contractility, measured consecutively by IUP. Uterine contractility is influenced by rising estradiol levels. Directed uterine contractility and intact utero‐tubal transport function are considered necessary for intact sperm transport, mainly to the side bearing the dominant follicle to maximize fertility.
Adiponectin is reduced in gestational diabetes mellitus in normal weight women
Authors: Ranheim Trine , Haugen Fred , Staff Anne Cathrine , Braekke Kristin , Harsem Nina K. , Drevon Christian A.
Published: March 2004

Background.  Adiponectin is an adipose tissue‐derived protein counteracting insulin resistance and inflammation. We have compared women with gestational diabetes mellitus (GDM; n = 22) and normal pregnancies (controls; n = 29) to evaluate whether adiponectin represents a link between endocrine function of adipose tissue and the development of diabetes during pregnancy.

Methods.  The participants were categorized according to their prepregnancy body mass index (BMI) into two classes: BMI < 25 and BMI = 25. Plasma concentrations of adiponectin, leptin and insulin were measured by radioimmunoassay (RIA). Total cholesterol, high density lipoprotein (HDL) cholesterol and triacylglycerol were determined by routine enzymatic methods. Expression of adiponectin/glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) was determined by real‐time reverse transcription polymerase chain reaction (RT‐PCR) in subcutaneous adipose tissues obtained by excision at cesarean delivery.

Results.  Among individuals with GDM and BMI < 25 kg/m2 (n = 8), plasma adiponectin concentration was lower than in the controls (n = 20), 8.1 ± 1.2 µg/mL vs. 12.2 ± 1.1 µg/mL; p = 0.04). The mean plasma leptin concentrations did not differ between the GDM and control groups. Plasma concentrations of insulin and C‐peptide were significantly higher among GDM than control individuals independent of BMI. For all the women included in the study, we found that plasma adiponectin only correlated negatively with prepregnancy and third‐trimester (sampling day) BMI (p = 0.03 vs. p = 0.01). In abdominal subcutaneous adipose tissue of pregnant women, adiponectin mRNA levels were lower in GDM than in control subjects (0.77 ± 0.18 vs. 1.39 ± 0.15; p = 0.05).

Conclusions.  These results indicate that low plasma adiponectin concentration is associated with GDM. In addition, we found that adiponectin mRNA levels in adipose tissue biopsies from GDM subjects were reduced.
Levonorgestrel‐releasing intrauterine system or hysterectomy in the treatment of essential menorrhagia: predictors of outcome
Authors: Hurskainen Ritva , Teperi Juha , Aalto Anna‐Mari , Grenman Seija , Kivelä Aarre , Kujansuu Erkki , Vuorma Sirkku , Yliskoski Merja , Rissanen Pekka , Paavonen Jorma
Published: March 2004

Levonorgestrel‐releasing intrauterine system (LNG‐IUS) has been advocated as an effective alternative to hysterectomy in the treatment of menorrhagia. The outcome predictors have been poorly known. In this study the amount of menstrual blood loss (MBL) turned out to be the single most important outcome predictor of these treatments. However, the treatment with LNG‐IUS seemed to be an appropriate alternative to hysterectomy for all women who perceived their MBL heavy.
Guillain–Barré syndrome in pregnancy
Authors: Chan Louis Yik‐Si , Tsui Michelle Hang‐Yuet , Leung Tse Ngong
Published: March 2004

Guillain–Barré syndrome (GBS) complicating pregnancy is a rare event. Reports before the mid‐1980s suggested that GBS in pregnancy carries a high maternal morbidity and mortality. However, it is uncertain whether availability of active treatment such as plasmapheresis and intravenous immunoglobulin together with advancement in intensive care has improved maternal outcome. This review examines the maternal and fetal outcomes of GBS complicating pregnancy reported in the recent English literature.
Stable haploid poplar callus lines from immature pollen culture
Authors: Deutsch Frank , Kumlehn Jochen , Ziegenhagen Birgit , Fladung Matthias
Published: March 2004

Embryogenesis and plant regeneration have been obtained from isolated immature pollen of two poplar hybrids (Populus nigra L. × hybrid ‘Aue1’ and ‘Aue2’). In total, 1487 calli or embryos, respectively, larger than 1 mm were generated in a 2‐year study. By using a cytokinin containing induction medium, on average 19 calli per responsive immature catkin were formed. Additional supplementation with auxin in 2002 increased the frequency to 72 calli per catkin. Microsatellite marker analyses confirmed haploid origin in most regenerants studied. So far six out of eight obtained regenerative callus lines have maintained their haploid level up to 24 months of development. A number of haploid and doubled haploid plants of different lines are available and have been transferred to soil.
Unguioblastoma and unguioblastic fibroma – an expanded spectrum of onychomatricoma
Authors: Ko Christine J. , Shi Linda , Barr Ronald J. , Mölne Lena , Ternesten‐Bratel Annika , Headington John T.
Published: March 2004

Onychomatricoma is a rare tumor that appears to originate from cells of the nail matrix. Three cases of onychomatricoma that met Perrin et al.'s1 histologic criteria of onychomatricoma are described. However, using a single term to classify all three tumors ignores the apparent microscopic differences that exist among them. To demonstrate better the spectrum of so‐called onychomatricoma and properly acknowledge the noticeable disparity among our cases, a series of terms is proposed. This terminology is based on the histologic spectrum of epithelial–stromal ratio of stromal cellularity and of extent nuclear pleomorphism. Use of such criteria has a precedent in the classification of follicular and odontogenic fibroepithelial neoplasms. This new nomenclature includes ‘unguioblastoma’ for tumors with a predominant epithelial component and ‘unguioblastic fibroma’ for tumors where a cellular stroma is more prominent and characteristic. The term ‘atypical unguioblastic fibroma’ is used to describe a third rare neoplasm, in which the cellular stroma shows nuclear pleomorphism and atypia with an increase of mitotic activity.
Atypical lymphocytic lobular panniculitis
Authors: Magro Cynthia M. , Neil Crowson A. , Byrd John C. , David Soleymani A. , Shendrik Igor
Published: March 2004

Background:  Although subcutaneous T‐cell lymphoma (SCTCL) is considered an aggressive form of lymphoma, some patients manifest a long waxing and waning phase unaccompanied by constitutional symptoms.

Methods:  Twelve patients were prospectively encountered, presenting with a lymphocytic panniculitis accompanied by lymphoid atypia, although not fulfilling criteria for SCTCL. Clinical, histologic, phenotypic, and genotypic analyses were conducted.

Results:  There were five men, one boy, and six women; none had symptoms compatible with lupus erythematosus or aggressive SCTCL. All but two had a waxing and waning course of years. Four patients had periodic cytopenias accompanied by fevers. While responding somewhat to prednisone, the lesions relapsed. In one patient, treatment with alemtuzumab (CAMPATH‐1) led to complete lesional resolution with no recurrence. Light microscopy showed expansion of the interstices of the fat lobule by mildly atypical lymphocytes of the CD4 subset in 10 biopsies from eight patients; in the other four patients, there was an increase in CD8 lymphocytes. There was diminished expression of CD5 and/or CD7 in the majority of biopsies. Ten of 13 biopsies showed clonal T‐cell receptor‐γ rearrangements.

Conclusions:  We apply the term atypical lymphocytic lobular panniculitis to this distinctive form of lymphocytic panniculitis manifesting this light microscopic, phenotypic, and genotypic profile.
Congenital pauci‐melanotic cellular blue nevus
Authors: Busam Klaus J. , Lohmann Christina M.
Published: March 2004

Abstract:  Unusual or atypical melanocytic nevi can be confused with malignant melanoma. Two patients are presented here with a rare variant of melanocytic nevus. Both were men. One was 39 years old and sought medical attention after trauma of a ‘congenital mole’. The other was 24 years old and presented with a history of a slowly growing lesion, which had been known since childhood. In both patients, the lesion occurred on the buttock. They were dermal and superficial subcutaneous nodules measuring 1.5 and 2.3 cm in greatest dimension, respectively. The tumors were composed of densely cellular fascicles of melanocytes arranged in a lobulated growth pattern. Rare nests of small epithelioid melanocytes were also seen. No melanin pigment was seen on hematoxylin and eosin‐stained sections. Focal minimal pigment was noted by Fontana–Masson stain in one case. Involvement of numerous peripheral nerve trunks by fusiform melanocytes was a prominent feature. Rare mitotic figures were seen in melanocytes [1–2 mitoses per 50 high‐power fields (HPF)]. The MIB‐1 labeling index was low (less than 5% of the lesional cell population was immunopositive). Both tumors were excised with negative surgical margins. One patient underwent sentinel lymph node biopsy because there was controversy regarding the biologic potential of the lesion. No melanocytic tumor deposits were found in the lymph nodes. On clinical follow up of 11 years and 18 months after complete excision, both patients are alive and well with no evidence of recurrence. We regard these lesions as congenital monophasic and pauci‐melanotic variants of cellular blue nevus. The nevi are presented here to enhance our knowledge of the morphologic spectrum of melanocytic tumors and to help avoid confusion with malignant melanoma.
Pilomatrix carcinoma with lymph node metastases
Authors: Bassarova Assia , Nesland Jahn M. , Sedloev Theophil , Danielsen Håvard , Christova Svetlana
Published: March 2004

Pilomatrix carcinoma is a rare skin tumor with an origin from hair matrix cells. The tumor is locally aggressive with a great tendency for recurrence, but the metastatic potential is limited. A pilomatrix carcinoma in 76‐year‐old female with lymph node metastases is presented. In addition to classical histopathological criteria and DNA ploidy analysis, a broad panel of antibodies was used for evaluation of the metastatic potential. Both primary tumor and lymph node metastasis revealed extremely high proliferation and apoptotic rates. High constant expressions of CD44v6 and P‐cadherin were also observed. In the metastasis, significant reduction of E‐cadherin and β‐catenin was detected. The best approach for assessment of metastatic potential of pilomatrix carcinoma seems to be the complex evaluation of routine histological criteria like vessel invasion, mitotic index, apoptotic count, and new molecular markers of cell death and adhesion.
Milium‐like syringoma: a case study on histogenesis
Authors: Wang Kuo‐Hsien , Chu Jan‐Show , Lin Yun‐Ho , Hu Chung‐Hong , Lee Woan‐Ruoh
Published: March 2004

Background:  Milium‐like syringoma is a variant of syringoma first described in 1987. Only few cases have been reported in the literature. It may be misleading clinically, and its histogenesis has not been clarified.

Case report:  We present a case of periorbital milium‐like syringoma, with studies on the histopathologic, histochemical, and immunohistochemical features.

Results:  Histology showed a large keratin‐filled cyst in the upper portion of the lesion approximating the epidermis. Serial sections revealed that the cyst connected with the underlying syringomatous epithelial strands. Melanin was absent in the wall of the cyst, as demonstrated by Fontana–Masson stain. Cytokeratin 7 was expressed neither in the milia nor in the solid epithelial parts. Carcinoembryonic antigen (CEA) reactivity was seen in the luminal cells of the keratinous cysts. However, in the largest keratin‐filled cyst clinically suggesting a milium, only the lower half of the cyst was positive for CEA. These results proved that the milia were part of syringoma with eccrine duct differentiation. Fusion of the upper half of the largest cyst with the epidermis may explain the absence of CEA positivity in this part, analogous with eccrine duct milia. Review of the literature indicated that this variant of syringoma occurs more often in Asians.

Conclusion:  We present evidence, and propose the histogenesis of milium‐like syringoma, that it is a variant of syringoma with a prominent cystic component showing features of eccrine duct milia. Recognition of its nature is of therapeutic significance. Further studies are required to verify its clinical characteristics as compared with ordinary syringomas.
Paget's disease of the glans penis secondary to transitional cell carcinoma of the bladder: a report of two cases and review of the literature
Authors: Salamanca J. , Benito A. , García‐Peñalver C. , Azorín D. , Ballestín C. , Rodríguez‐Peralto J. L.
Published: March 2004

Background:  Extramammary Paget's disease of the glans penis secondary to transitional cell carcinoma (TCC) of the bladder is rare, with only a few cases reported in the literature. We report two new cases, one detected before diagnosing bladder TCC.

Methods:  We describe the clinicopathologic features of two patients with intraepithelial spread of glans TCC and the histochemical and immunohistochemical features of the neoplasm.

Results:  Light microscopy detected intraepithelial proliferation of neoplastic, large, pale cells located predominantly in the basal and parabasal layers of the epithelium. The pagetoid cells showed positive cytoplasmic staining for mucosubstances and immunoreactivity for CK20. The previously reported cases are reviewed and the differential diagnosis is discussed.

Conclusions:  As many benign and malignant glans lesions may be clinically similar, histologic study is necessary to correctly diagnose primary lesions and promptly detect underlying asymptomatic visceral malignancies initially presenting as Paget's disease.
Loss of heterozygosity on chromosome 4q32–35 in sporadic basal cell carcinomas: evidence for the involvement of p33ING2/ING1L and SAP30 genes
Authors: Sironi Elena , Cerri Amilcare , Tomasini Dario , Sirchia Silvia Maria , Porta Giovanni , Rossella Franca , Grati Francesca Romana , Simoni Giuseppe
Published: March 2004

Background:  Studies on basal cell carcinoma (BCC) have demonstrated that patched gene and p53 gene located at 9q22.3 and 17p13 are the main genes responsible for the onset of this tumor. In order to identify a possible involvement of other tumor suppressor genes, we screened 19 cases of BCCs for loss of heterozygosity (LOH).

Methods:  The analysis was performed on tumoral tissue and on corresponding normal tissue by using a panel of 37 polymorphic markers spanning 26 chromosomal regions.

Results:  We observed that only four chromosomal regions, 4q32 (30.00%), 4q35 (27.27%), 9q21–22 (28.57%), and 9q22‐qter (35.71%), demonstrated a significative LOH (>20%), even if others show a borderline percentage (15–20%) of imbalance (1q32, 3p24, 10p22.1, and 17q21.3).

Conclusions:  Our findings suggest that a new chromosomal region mapping in the long arm of chromosome 4 could be involved in sporadic BCC carcinogenesis. Further analyses indicate that the minimal deleted region in 4q32–35 includes p33ING2/ING1L and SAP30, whose deletion could impair the G1‐phase checkpoint control and favor gene silencing, respectively.
Development of pemphigus herpetiformis in a patient with psoriasis receiving UV‐light treatment
Authors: Sanchez‐Palacios Carla , Chan Lawrence S.
Published: March 2004

Background:  Pemphigus is an autoimmune blistering disease of the skin and mucous membranes. Pemphigus herpetiformis, a rare variant of pemphigus, is characterized by erythematous, vesicular, bullous, or papular lesions in a herpetiform pattern, often associated with pruritus. Clinical cases documenting the development of pemphigus in patients with a history of psoriasis have been reported in the literature.

Methods:  We used immunological methods to study a case in which pemphigus herpetiformis occurred in a woman with a history of psoriasis, shortly after a course of ultraviolet B (UVB) therapy.

Results:  Histopathology revealed a subcorneal blister with prominent neutrophilic infiltration. Immunopathology detected in situ bound and circulating immunoglobulin G (IgG) autoantibodies to epithelial cell surfaces and circulating IgG autoantibodies against desmoglein 1. The patient was also found to have Hashimoto's thyroiditis.

Conclusions:  This case illuminates a possible role of UV therapy in the induction of pemphigus herpetiformis through an epitope‐spreading mechanism. The patient's autoimmune thyroiditis may also contribute to the predisposition for pemphigus development. The histopathological findings in pemphigus patients with a history of psoriasis may resemble Munro's microabscesses of psoriasis and should therefore alert pathologists and clinicians in considering additional diagnostic methods such as direct and indirect immunofluorescence.
Histological spectrum of cutaneous reactions to aspirin in chronic idiopathic urticaria
Authors: Zembowicz Artur , Mastalerz Lucyna , Setkowicz Malgorzata , Radziszewski Waldemar , Szczeklik Andrzej
Published: March 2004

Background:  During a clinical trial, we obtained 16 biopsies of skin eruptions induced by aspirin in patients with chronic idiopathic urticaria (CIU). In this setting, aspirin triggers skin eruptions through a well‐established non‐immunological mechanism involving the inhibition of cyclooxygenase type I. This presented the rare opportunity to evaluate histological features of a series of skin eruptions induced by a drug acting through a defined mechanism in a controlled experimantal setting.

Objective:  Histological analysis of 16 biopsies of skin eruptions induced by oral aspirin challenge in patients with CIU.

Design:  Microscopic analysis of tissue sections.

Patients:  16 patients with CIU.

Results:  Aspirin (up to 500 mg) induced a restricted range of histological responses with a classic pattern of urticarial tissue reaction occuring in the majority of (12 of 16) cases. Two biopsies showed an interstitial fibrohistiocytic (granuloma annulare‐like) reaction pattern. One case showed only a sparse perivascular lymphocytic infiltrate, and paucicellular dermal mucinosis was observed in one case.

Conclusions:  Polymorphism of histological patterns induced by aspirin suggests that in addition to the drug‐specific mechanisms triggering drug eruptions, individual factors also play a role in determining the ultimate histological phenotype of a drug response.
Preliminary Evidence on Wage Setting in Greek Manufacturing
Authors: Kapopoulos P. , Papadimitriou P.
Published: March 2004

Abstract.  The negotiating power of the unions and their role in wage determination depends on the level of centralization of the wage bargaining system as well as on other institutional arrangements. In this study, we estimate a set of wage equations in order to study the employment effects of different unions’ stances in wage determination as well as to investigate other characteristics of employment in Greek manufacturing. We discriminate between workers and employees (blue‐ and white‐collar workers) and between sectors in order to capture differences in the relative supply as well as differences in the negotiating power among the staff of the same industry. Empirical findings reveal that the persistence of unemployment arises as a result of the great bargaining power of the unions in negotiations at a sectoral level. White‐collar workers exhibit a stronger negotiating power compared with blue‐collar workers because of differences in the institutional framework.
Involvement of BREK, a serine/threonine kinase enriched in brain, in NGF signalling
Authors: Kawa Seiji , Fujimoto Jiro , Tezuka Tohru , Nakazawa Takanobu , Yamamoto Tadashi
Published: March 2004

We identified AATYK2 (Apoptosis‐Associated Tyrosine Kinase 2) through a database search as a kinase specifically expressed in the brain. After characterization, we renamed it BREK (Brain‐Enriched Kinase). Mouse BREK mRNA is expressed predominantly in brain, especially in olfactory bulb, olfactory tubercle, hippocampus, striatum, cerebellum, and cerebral cortex. Levels of expression and phosphorylation of BREK were high at 0–2 weeks after birth, suggesting that BREK is involved in neural development and functions during the early postnatal period. Phosphoamino acid analysis following in vitro kinase reaction revealed that BREK is a catalytically active, serine/threonine kinase. In PC12 cells, BREK was phosphorylated rapidly upon stimulation with nerve growth factor (NGF) in a protein kinase C‐dependent pathway. In differentiated PC12 cells, BREK was enriched in cell bodies and growth cones, and also present along neurites. Introduction of a kinase‐defective mutant of BREK into PC12 cells enhanced both ERK phosphorylation and neurite outgrowth in response to NGF, suggesting that BREK is a negative regulator of NGF‐induced neuronal differentiation. Thus, we conclude that BREK is a new member of the family of protein serine/threonine kinases and that it plays important roles in NGF‐TrkA signalling.
Cytoplasmic c‐Fos induced by the YXXQ‐derived STAT3 signal requires the co‐operative MEK/ERK signal for its nuclear translocation
Authors: Higashi Natsuko , Kunimoto Hiroyuki , Kaneko Shuhei , Sasaki Takanori , Ishii Masamitsu , Kojima Hirotada , Nakajima Koichi
Published: March 2004

A STAT3 (signal transducer and activator of transcription 3)‐ and a MEK/Erk‐mediated signal can be activated by cytokines, including IL‐6 (interleukin‐6), PDGF, and EGF. Recently, STAT3 and an ERK‐signal were shown to co‐operatively activate the c‐fos gene. Activation of a truncated form of the IL‐6 receptor subunit, gp130, that had only one YXXQ motif, induced both c‐Fos and JunB in NIH3T3 cells through STAT3 without an apparent increase in the AP‐1 (activator protein‐1) activity. In contrast, concomitant stimulation of the STAT3 signal and a MEK/Erk‐signal markedly increased AP‐1 activity with enhanced c‐Fos expression. Surprisingly, the c‐Fos induced by the YXXQ‐signal alone was localized to the cytoplasm, from which it translocated into the nucleus following TPA (12‐O‐tetradecanoyl‐phorbol 13‐acetate) treatment in a MEK/Erk‐dependent manner. c‐Fos that was expressed from a constitutive promoter localized to the nucleus and did not move into the cytoplasm in response to the YXXQ‐signal. Rather, the YXXQ‐signal was required during c‐Fos production for it to be retained in the cytoplasm. Thus, the YXXQ‐signal induces c‐Fos expression through STAT3 and anchors the new c‐Fos in the cytoplasm. In addition, the YXXQ‐signal and an Erk signal co‐operatively cause c‐Fos activation in the nucleus.
Distinct roles of DNA polymerases delta and epsilon at the replication fork inXenopusegg extracts
Authors: Fukui Tomoyuki , Yamauchi Kazumi , Muroya Taketo , Akiyama Masahiro , Maki Hisaji , Sugino Akio , Waga Shou
Published: March 2004

DNA polymerases δ and ɛ (Polδ and Polɛ) are widely thought to be the major DNA polymerases that function in elongation during DNA replication in eukaryotic cells. However, the precise roles of these polymerases are still unclear. Here we comparatively analysed DNA replication inXenopusegg extracts in which Polδ or Polɛ was immunodepleted. Depletion of either polymerase resulted in a significant decrease in DNA synthesis and accumulation of short nascent DNA products, indicating an elongation defect. Moreover, Polδ depletion caused a more severe defect in elongation, as shown by sustained accumulation of both short nascent DNA products and single‐stranded DNA gaps, and also by elevated chromatin binding of replication proteins that function more frequently during lagging strand synthesis. Therefore, our data strongly suggest the possibilities that Polδ is essential for lagging strand synthesis and that this function of Polδ cannot be substituted for by Polɛ.
The first CH domain of affixin activates Cdc42 and Rac1 through αPIX, a Cdc42/Rac1‐specific guanine nucleotide exchanging factor
Authors: Mishima Wataru , Suzuki Atsushi , Yamaji Satoshi , Yoshimi Ryusuke , Ueda Atsuhisa , Kaneko Takeshi , Tanaka Junko , Miwa Yoshihiro , Ohno Shigeo , Ishigatsubo Yoshiaki
Published: March 2004

Rho GTPases, Cdc42 and Rac1, play pivotal roles in cell migration by efficiently integrating cell‐substrate adhesion and actin polymerization. Although it has been suggested that integrins stimulate these Rho GTPases via some of integrin binding proteins such as focal adhesion kinase (FAK) and paxillin, the precise molecular mechanism is largely unknown. In this study, we showed that the over‐expression of RP1 corresponding to the first CH domain (CH1) of affixin, an integrin‐linked kinase (ILK)‐binding protein, induced a significant actin reorganization in MDCK cells by activating Cdc42/Rac1. Affixin full length and RP1 co‐immunoprecipitated with αPIX, a Cdc42/Rac1‐specific guanine nucleotide exchanging factor (GEF), and they co‐localized at the tips of lamellipodia in motile cells. The involvement of αPIX in the RP1‐induced Cdc42 activation was demonstrated by the significant dominant negative effect of a point mutant of αPIX, αPIX (L383R, L384S), lacking GEF activity. Our data strongly support that ILK and affixin provide a novel signalling pathway that links integrin signalling to Cdc42/Rac1 activation.
The pathogenic A4269G mutation in human mitochondrial tRNAIle alters the T‐stem structure and decreases the binding affinity for elongation factor Tu
Authors: Hino Narumi , Suzuki Tsutomu , Yasukawa Takehiro , Seio Kohji , Watanabe Kimitsuna , Ueda Takuya
Published: March 2004

The A4269G mutation in the human mitochondrial (mt) tRNAIle gene is associated with fatal cardiomyopathy. This mutation completely inhibits protein synthesis in mitochondria, thereby significantly reducing their respiratory activity. The steady‐state amount of tRNAIle in cells bearing the A4269G mutation is almost half that of control cells. We previously reported that this mutation causes tRNAIle to be unstable both in vivo and in vitro. To investigate whether the instability of the mutant tRNAIle is due to structural alterations, a nuclease‐probing experiment was performed with a mitochondrial enzymatic extract, which showed that the A4269G mutation destabilizes the T‐stem of the mutant tRNAIle. In addition, measurements of the binding affinity of the aminoacylated mutant tRNAIle for mt elongation factor Tu (EF‐Tu) showed that the mutant tRNAIle binds mt EF‐Tu less efficiently than the wild‐type does. This observation provides insight into the molecular pathology associated with tRNA dysfunction caused by this pathogenic point mutation.
Molecular mechanisms of DNA end‐loop formation by TRF2
Authors: Yoshimura Shige H. , Maruyama Hugo , Ishikawa Fuyuki , Ohki Rieko , Takeyasu Kunio
Published: March 2004

In the telomere region of human chromosomes, the (TTAGGG)n sequence stretches over several kilobases and forms a distinct higher‐order structure with various proteins. Telomere repeat binding factors (TRFs) bind specifically to this sequence and play critical roles in the maintenance of telomere structure and function. Here, we prepared a series of linear DNA carrying a stretch of telomeric sequence ((TTAGGG)n, ∼1.8 (kb) with different end‐structures and observed their higher‐order complexes with TRFs by atomic force microscopy. TRF2 molecules exclusively bound to the telomeric DNA region at several different places simultaneously mainly as a dimer, and often mediated DNA loop formation by forming a tetramer at the root. These multiple‐binding, multimerization and DNA loop formation by TRF2 were observed regardless of the DNA‐end structure (blunt, 3′‐overhanging, telomeric, non‐telomeric). However, when the DNA end carried the telomeric‐3′‐overhanging region, the loop was frequently formed at the end of the DNA. Namely, the TRF2‐mediated DNA loop formation is independent of the end‐structure and the 3′‐overhanging TTAGGG sequence is responsible for the stabilization of the loop. TRF1 also bound to the telomeric DNA as a dimer, but did not mediate DNA loop formation by itself. These results provide a new insight into the molecular mechanism of DNA end‐loop formation by TRFs.
The Sall3 locus is an epigenetic hotspot of aberrant DNA methylation associated with placentomegaly of cloned mice
Authors: Ohgane Jun , Wakayama Teruhiko , Senda Sho , Yamazaki Yukiko , Inoue Kimiko , Ogura Atsuo , Marh Joel , Tanaka Satoshi , Yanagimachi Ryuzo , Shiota Kunio
Published: March 2004

DNA methylation controls various developmental processes by silencing, switching and stabilizing genes as well as remodeling chromatin. Among various symptoms in cloned animals, placental hypertrophy is commonly observed. We identified the Spalt‐like gene3 (Sall3) locus as a hypermethylated region in the placental genome of cloned mice. The Sall3 locus has a CpG island containing a tissue‐dependent differentially methylated region (T‐DMR) specific to the trophoblast cell lineage. The T‐DMR sequence is also conserved in the human genome at the SALL3 locus of chromosome 18q23, which has been suggested to be involved in the 18q deletion syndrome. Intriguingly, larger placentas were more heavily methylated at the Sall3 locus in cloned mice. This epigenetic error was found in all cloned mice examined regardless of sex, mouse strain and the type of donor cells. In contrast, the placentas of in vitro fertilized (IVF) and intracytoplasmic sperm injected (ICSI) mice did not show such hypermethylation, suggesting that aberrant hypermethylation at the Sall3 locus is associated with abnormal placental development caused by nuclear transfer of somatic cells. We concluded that the Sall3 locus is the area with frequent epigenetic errors in cloned mice. These data suggest that there exists at least genetic locus that is highly susceptible to epigenetic error caused by nuclear transfer.
The endoplasmic reticulum stress response is stimulated through the continuous activation of transcription factors ATF6 and XBP1 in Ins2+/Akita pancreatic β cells
Authors: Nozaki Jun ichi , Kubota Hiroshi , Yoshida Hiderou , Naitoh Motoko , Goji Junko , Yoshinaga Takeo , Mori Kazutoshi , Koizumi Akio , Nagata Kazuhiro
Published: March 2004

The dominant C96Y mutation of one of the two murine insulin genes, Ins2, causes diabetes mellitus in ‘Akita’ mice. Here we established pancreatic islet β cell lines from heterozygous mice (Ins2+/Akita). Western blot analysis of endoplasmic reticulum (ER) molecular chaperones indicated that Grp78, Grp94 and Orp150 are significantly increased in Ins2+/Akita cells compared with wild‐type (Ins2+/+) cells. Reporter gene assays using the human GRP78 promoter with or without the ER stress response element (ERSE) showed that Ins2+/Akita cells exhibit significantly stronger ERSE‐dependent transcriptional activity than Ins2+/+ cells. Transient over‐expression of the Ins2 C96Y mutant in wild‐type β cells induces a stronger ERSE‐dependent stress response than does wild‐type Ins2 over‐expression. The ERSE‐binding transcription factor ATF6 is strongly activated in Ins2+/Akita cells. The activity of a reporter containing the specific binding sequence of another ERSE‐binding transcription factor, XBP1, is also enhanced in Ins2+/Akita cells. Levels of active forms of XBP1 mRNA and protein are both markedly elevated in Ins2+/Akita cells. These results indicate that this cell line is subject to continuous ER stress and that the Ins2 C96Y mutation induces the expression of ER chaperones through the activation of ATF6 and XBP1.
Feature
Authors: Rose Edward P. F.
Published: March 2004

Several geologists accompanied the army of Napoleon Bonaparte that landed in Egypt in 1798 – indicating that perception of the military value of geology is almost as old as Earth science itself.
The dentofacial features of Sanjad–Sakati syndrome: a case report
Authors: Al‐Malik M. I.
Published: March 2004

Summary. Sanjad–Sakati syndrome is an autosomal recessive disorder that was first reported by Sanjadet al. in 1988. It is characterized by congenital hypoparathyroidism, severe growth failure and dysmorphic features. The clinical features include deep set eyes, microcephaly, thin lips, depressed nasal bridge with beaked nose, external ear anomalies and learning difficulties. This report presents the case of a 4‐year‐old patient who was referred to our dental clinic because of pain in her mouth and poor dental health. Oral findings included micrognathic mandible and maxilla, microdontia, enamel hypoplasia as well as severely decayed teeth. Treatment was carried out under general anaesthesia to extract the most severely affected teeth and restore those which could be conserved. It was concluded that these patients have special dental needs; early diagnosis of the affected children is therefore important in order to commence preventive dental therapy and carry out appropriate dental treatment at the optimum time.
Periodontal management of an adolescent with Down's syndrome – a case report
Authors: Sasaki Y. , Sumi Y. , Miyazaki Y. , Hamachi T. , Nakata M.
Published: March 2004

Summary.  A case of periodontitis in a young adolescent Japanese girl with Down's syndrome is presented in this report. The patient received a monthly preventive course of dental care consisting of mechanical plaque control and oral hygiene instruction. After 2·5 years she recovered from progression of periodontal disease both clinically and microbiologically. The importance of clinical care for periodontitis in Down's syndrome patients is discussed.
Oral psoriasis in an 11‐year‐old child: a case report
Authors: Ariyawardana A. , Tilakaratne W. M. , Ranasinghe A. W. , Dissanayake M.
Published: March 2004

Summary.  Psoriasis is a chronic inflammatory dermatosis that very rarely involves the oral mucosa. There is no consistent pattern of clinical presentation in the oral cavity. Furthermore, manifestations of intraoral psoriasis in paediatric patients are extremely rare and only one case appeared to have been reported in the literature to date. In this paper we report a case of intraoral psoriasis in an 11‐year‐old child who had been previously diagnosed as having dermal psoriasis.
Dental caries experience in children with congenital heart disease: a case‐control study
Authors: Stecksén‐Blicks C. , Rydberg A. , Nyman L. , Asplund S. , Svanberg C.
Published: March 2004

Objectives.  To compare the dental health of a group of children with complex congenital heart disease with that of age and gender matched healthy controls.

Design.  Case‐control study.

Setting.  Faculty of Medicine and Odontology/Pediatric cardiology and Pedodontics, Umeå University, Sweden.

Sample and Methods.  All the cases and their controls lived in the county of Västerbotten in northern Sweden. Each group comprised 41 children with a mean age of 6·5 years. Data were collected from medical and dental records while all bitewing radiographs were read separately by one of the authors.

Results.  Children with congenital heart disease had significantly more caries in their primary teeth than the control group. The mean dmfs‐value was 5·2 ± 7·0 in the cardiac group compared to 2·2 ± 3·5 in the control group (P < 0·05). Twenty‐six of the children had all four 6‐year‐molars, and their mean DMFS‐values were 0·9 ± 1·9 in the cardiac group compared to 0·3 ± 0·6 in the control group (P > 0·05). The children with congenital heart disease had received more caries prevention based on the use of fluorides than the control group. There was a significant correlation between the number of fluoride varnish treatments and the dmfs value of the child (r = 0·411, P < 0·01). Fifty‐two per cent of the children in the cardiac group had been prescribed fluoride tablets on one or more occasions compared to 17% in the control group (P < 0·01). Number of months on digoxin medication and the dmfs‐value had a significant correlation (r = 0·368, P < 0·05). Ten of the children had been on digoxin medication between 6 and 87 months; this subgroup had a mean dmfs‐value of 10·1 ± 8·5.

Conclusion.  Swedish children with complex congenital heart disease have poorer dental health than healthy age and gender matched controls in spite of intensive preventive efforts. In many cases, intervention had been given when caries were present. A closer cooperation between paediatric cardiology and paediatric dentistry is needed.
Prevalence of early childhood caries among First Nations children, District of Manitoulin, Ontario
Authors: Peressini S. , Leake J. L. , Mayhall J. T. , Maar M. , Trudeau R.
Published: March 2004

Background.  Epidemiological studies of Aboriginal communities in Canada and Native American populations in the United States have reported that early childhood caries (ECC) is highly prevalent. The purpose of this study was to determine the prevalence of ECC and dental caries in the First Nations population of 3‐ and 5‐year‐old children in the District of Manitoulin, Ontario to assist in developing effective dental health promotion strategies.

Methods.  All 3‐ and 5‐year‐old children in elementary schools and day‐care centres in seven First Nation communities were eligible for the survey examination. Three‐year‐old children at home and 5‐year‐old children attending school off‐reserve in six of the communities were also eligible for epidemiological survey examination of oral health status including caries, gingival and soft tissue conditions. Cases of ECC were defined as children with caries or restorations on two or more primary maxillary incisors or canines or those having a total decayed, missing, filled primary teeth (dmft) score of 4 or greater.

Results.  A total of 87 children (59% 5 years old, 54% females) were examined. Seventy‐four per cent of children had one or more carious lesions. Forty‐five cases of ECC were found, a prevalence of 52%. The mean dmft score for cases was 7·5 (95% CI 6·5–8·4) and 0·8 (95% CI 0·5–1·1) for non‐cases (P < 0·001). Boys in both age groups were more likely to be affected by ECC than girls.

Conclusion.  Our results indicate that dental caries and ECC are highly prevalent in this population, with ECC cases having 6.7 more dmft than non‐cases.
Attitudes towards the use of hand over mouth (HOM) and physical restraint amongst paediatric specialist practitioners in the UK
Authors: Newton J. T. , Patel H. , Shah S. , Sturmey P.
Published: March 2004

Purpose.  To assess the views of paediatric specialist dental practitioners in the United Kingdom of the use of the hand over mouth technique and physical restraint.

Methods.  Questionnaire survey of all specialist dental practitioners in paediatric dentistry in the United Kingdom (n = 216). Replies were received from 179 individuals (82·8%).

Results.  The majority of the sample (over 80%) described HOM as having three components, broadly mirroring the description of the technique in clinical textbooks. Approximately 60% of the respondents reported that HOM should never be used (106 individuals, 59·2%). Those who endorsed the use of HOM suggested it should be used with cases of hysterical, tantrum behaviour (57 respondents, 32%). The use of physical restraint was endorsed for certain disabled patients by 110 individuals (62%); for very young patients by 69 respondents (39%); premedicated patients by 35 respondents (20%); physically resistive patients by 25 respondents (14%). Forty‐three respondents (24%) felt there were no psychological consequences of the use of HOM or physical restraint; 91 (51%) felt that HOM would result in the child fearing dental treatment.

Conclusions.  Specialist paediatric dental practitioners in the UK are familiar with the technique of HOM although they also feel that this technique should never be used. A large proportion of practitioners felt that the use of physical restraint was appropriate with certain disabled patients. The most commonly anticipated psychological sequeala which may accompany the use of these techniques was subsequent fear of dental treatment.
Oral health and caries related microflora in children during the first three months following renal transplantation
Authors: Al Nowaiser A. , Lucas V. S. , Wilson M. , Roberts G. J. , Trompeter R. S.
Published: March 2004

There is little information on the oral health of children undergoing renal transplantation during the early transplant period.

Methods.   Twenty‐four children undergoing renal transplantation aged 4–13·2 years and their matched controls were recruited. The dmfs, dmft, DMFS and DMFT, plaque, gingivitis and gingival enlargement scores were recorded. The oral microflora was sampled and cultured for S. mutans, Lactobacllus species and Candida species.

Results.   There was a significantly lower mean dmfs (0·3 ± 0·9; P = 0·03), dmft (0·3 ± 0·9; P = 0·03), DMFS (2·3 ± 5·3; P = 0·01) and DMFT (1·5 ± 2·6; P = 0·02), respectively, in the transplant group. There was a significantly greater mean plaque score (14·7 ± 11) for the permanent dentition, at baseline only, compared with 90 days post‐transplantation (9·4 ± 10·4; P = 0·02). There was a significantly greater gingival enlargement score (1·8 ± 1·4; P = 0·04) 90 days post‐transplantation compared with baseline. The S. mutans and Lactobacillus counts were significantly lower both at baseline (P = 0·0001 and P = 0·004) and 90 days post‐transplantation (P = 0·02; and P = 0·05), respectively, compared with the controls.

Conclusions.  The transplant children had less active dental disease than the controls although gingival enlargement needs careful monitoring.
A sensitive non‐destructive method for detecting IPNV carrier Atlantic salmon, Salmo salar L., by culture of virus from plastic adherent blood leucocytes
Authors: Munro E S , Gahlawat S K , Ellis A E
Published: March 2004

In populations of Atlantic salmon in sea water, infectious pancreatic necrosis virus (IPNV) could be detected by standard virological culture methods in sonicated kidney homogenates and in mucus samples (gill, skin and rectum) from 14 and nine of 25 fish, respectively, but all fish were positive by virus culture from lysates of kidney macrophages and adherent blood leucocytes. In fish which tested negative for IPNV by the standard method of detection, the virus could be detected using adherent blood leucocytes isolated on a Percoll gradient from as little as 10 μL of blood. The blood sample could be stored for at least 3 days in a heparinized tube on ice before preparing the plastic adherent leucocytes. Furthermore, the latter could be prepared without prior fractionation on Percoll simply by incubating whole blood (33 μL) in cell culture medium (66 μL) in 96‐well plates overnight and washing away the non‐adherent cells before lysing the adherent cells and inoculation of the lysate onto CHSE‐214 cells. This highly sensitive method for detecting IPNV‐carriers is therefore very suitable for non‐destructive sampling of fish in the field.
Immune responses and host protection of channel catfish, Ictalurus punctatus (Rafinesque), against Ichthyophthirius multifiliis after immunization with live theronts and sonicated trophonts
Authors: Xu D‐H , Klesius P H , Shelby R A
Published: March 2004

The humoral immune responses and host protection of channel catfish, Ictalurus punctatus (Rafinesque), against Ichthyophthirius multifiliis (Ich) were determined after immunization with live theronts and sonicated trophonts. Immunizations with live theronts or sonicated trophonts were carried out by both bath immersion and intraperitoneal (i.p.) injection. Cutaneous and serum immunoglobulin (Ig) levels and anti‐Ich antibodies were measured 12 and 21 days post‐immunization. The level of Ich infection and survival of catfish were determined after theront challenge. Cutaneous and serum anti‐Ich antibodies were significantly higher (P < 0.05) in fish immunized with live theronts by immersion or i.p. injection, or with sonicated trophonts administered by i.p. injection, than in fish immunized with sonicated trophonts by immersion, with bovine serum albumin by i.p. injection, or non‐immunized controls. Host protection was noted only in fish immunized with live theronts by immersion or i.p. injection or with sonicated trophonts by i.p. injection. There was a positive correlation between higher levels of anti‐Ich antibodies and host survival in the immunized fish.