bluuebunny/crossref_metadata_2025 huggingface dataset:
The Journal of Risk and Insurance: A 75‐Year Historical Perspective
Authors: Weiss Mary A. , Qiu Joseph
Published: May 2008

Abstract

This research provides a comprehensive historical analysis of articles published in The Journal of Risk and Insurance over the 75‐year period from 1932 to 2006. Historical statistics are provided including the number of articles, number of authors per article, geographic location of contributors, leading contributors, author affiliation (industry or academic), the proportion of articles that are theoretical and empirical, and topics covered. Statistics relating to the entire 75‐year period are provided as well as breakdowns by decade. The results indicate that the contributors to The Journal of Risk and Insurance have become more international over time, average article length and average number of authors per article have increased over time, and empirical articles appear more frequently than theoretical articles.
An Extension of Arrow's Result on Optimal Reinsurance Contract
Authors: Kaluszka Marek , Okolewski Andrzej
Published: May 2008

Abstract

We consider the problem of finding reinsurance policies that maximize the expected utility, the stability and the survival probability of the cedent for a fixed reinsurance premium calculated according to the maximal possible claims principle. We show that the limited stop loss and the truncated stop loss are the optimal contracts.
Explaining Low Annuity Demand: An Optimal Portfolio Application to Japan
Authors: Purcal Sachi , Piggott John
Published: May 2008

Abstract

Using an optimizing financial planning model in the tradition of Merton and Richard we explore how individuals should determine their life insurance and annuity choices, given uncertainty about investment returns and mortality. Both consumption and bequests appear as arguments in the individual's preference function. The model explicitly recognizes the existence of social security in retirement, and of loadings on insurance premiums, due to administration costs in the life insurance and annuities markets. The model sheds light on the reasons for the thinness of voluntary life annuity markets worldwide. The relative importance of pre‐existing annuitization through social security, the role of bequests, and premium loadings are quantitatively assessed within a single optimizing framework. Results are presented for a model specification calibrated to Japan.
Heart Rate Variability Measures During Sinus Rhythm Predict Cycle Length Entropy During Atrial Fibrillation
Authors: SEGERSON NATHAN M. , SMITH MICHAEL L. , WASMUND STEPHEN L. , LUX ROBERT L. , DACCARETT MARCOS , HAMDAN MOHAMED H.
Published: May 2008

Introduction:
Several noninvasive measures of cardiac risk such as heart rate variability (HRV) cannot be used in patients with atrial fibrillation (AF). One promising exception is the measure of ventricular cycle length entropy (VCLE) where initial data suggest that a reduction in VCLE portends an increased risk of cardiac death in patients with chronic AF. In this study, we hypothesized that measures of short‐term HRV during sinus rhythm would correlate with measures of cycle length entropy during paroxysms of AF.

Methods:
We tested 25 Holter recordings of paroxysmal AF from the Physionet AF Prediction Database. We calculated HRV parameters including standard deviation of all NN intervals (SDNN), the root mean square root of the differences between adjacent NN intervals (RMSSD), standard deviation of 5‐minute averages of NN intervals (SDANN), percentage of adjacent NN interval differences >50 ms (pNN50), and interbeat correlation coefficient (ICC) from 30 minutes of normal sinus rhythm, and entropy measures (the Shannon Informational Entropy [ShEn] and Average of Approximate Entropy [ApEn]) from 5 minutes of AF that occurred during the same 24‐hour monitor. Pairwise correlations were used to assess associations, as regression residuals were normally distributed.

Results:
The mean entropy measures during AF were: ShEn: 4.78 ± 0.82, ApEn: 0.198 ± 0.21. When assessed during the 30 minutes immediately preceding AF onset, ICC showed a significant negative correlation with both ShEn (r =–0.65, P < 0.001) and ApEn (r =–0.60, P < 0.01). RMSSD also correlated with both ShEn (r = 0.41, P = 0.04) and ApEn (r = 0.39, P = 0.05), but other HRV measures showed no correlation with VCLE during AF.

Conclusion: Reductions in RMSSD or increases in ICC, two short‐term HRV measures that are known to reflect parasympathetic function in sinus rhythm, are correlated with reductions in the entropy of ventricular response intervals during AF. Our findings suggest that entropy during AF may be modulated, in part, by vagal innervation.
Prospective Study of Atrial Fibrillation Termination During Ablation Guided by Automated Detection of Fractionated Electrograms
Authors: PORTER MICHAEL , SPEAR WILLIAM , AKAR JOSEPH G. , HELMS RAY , BRYSIEWICZ NEIL , SANTUCCI PETER , WILBER DAVID J.
Published: May 2008

Introduction: Complex fractionated atrial electrograms (CFAE) may identify critical sites for perpetuation of atrial fibrillation (AF) and provide useful targets for ablation. Current assessment of CFAE is subjective; automated detection algorithms may improve reproducibility, but their utility in guiding ablation has not been tested.

Methods and Results: In 67 patients presenting for initial AF ablation (42 paroxysmal, 25 persistent), LA and CS mapping were performed during induced or spontaneous AF. CFAE were identified by an online automated computer algorithm and displayed on electroanatomical maps. A mean of 28 ± 18 sites/patient were identified (20 ± 13% of mapped sites), and were more frequent during persistent AF. CFAE occurred most commonly within the CS, on the atrial septum, and around the pulmonary veins. Ablation initially targeting CFAE terminated AF in 88% of paroxysmal AF, but only 20% of persistent AF (P < 0.001). Subsequently, additional ablation was performed in all patients (PV isolation for paroxysmal AF, PV isolation + mitral and roof lines for persistent AF). Minimum follow‐up was 1 year. One‐year freedom from recurrent atrial arrhythmias without antiarrhythmic drug therapy after a single procedure was 90% for paroxysmal AF, and 68% for persistent AF.

Conclusions: Ablation guided by automated detection of CFAE proved feasible, and was associated with a high AF termination rate in paroxysmal, but not persistent AF. As an adjunct to conventional techniques, it was associated with excellent long‐term single procedure outcomes in both groups. Criteria for identifying optimal CFAE sites for ablation, and selection of patients most likely to benefit, require additional study.
Morphology and Molecular Phylogeny of Trimyema koreanum n. sp., a Ciliate from the Hypersaline Water of a Solar Saltern
Authors: CHO BYUNG CHEOL , PARK JONG SOO , XU KUIDONG , CHOI JOONG KI
Published: May 2008

ABSTRACT. A new ciliate, Trimyema koreanum n. sp., isolated from hypersaline water (salinity of 293‰) from a solar saltern in Korea, was investigated using live observation, protargol impregnation, and gene sequencing. Trimyema koreanum is about 30 × 13 μm in vivo, has usually 23 longitudinal ciliary rows forming two distinct ciliary girdles visible both in vivo and in protargol impregnation. A third indistinct ciliary girdle as well as a girdle of mucocysts is distinguishable only in impregnated cells. We suggest T. koreanum as a new species, differing from the most similar species, T. marinum, by the presence of two distinct ciliary girdles (T. marinum usually has six ciliary girdles clearly visible in living cells and three anterior spirals that encircle the cell completely). Although the number of known 18S rRNA sequences in the genus Trimyema was limited, the Trimyema group including T. koreanum forms a strong clade. The phylogenetic position confirms that the isolate belongs to the genus Trimyema and is different from previously sequenced species. Trimyema koreanum is able to consume both prokaryotes and small eukaryotes (specifically, the alga Dunaliella sp.).
A Phylogenetic Lineage of Closely Related Trypanosomes (Trypanosomatidae, Kinetoplastida) of Anurans and Sand Flies (Psychodidae, Diptera) Sharing the Same Ecotopes in Brazilian Amazonia1
Authors: FERREIRA ROBSON C. , DE SOUZA ADELSON A. , FREITAS RUI A. , CAMPANER MARTA , TAKATA CARMEM S. A. , BARRETT TOBY V. , SHAW JEFFREY J. , TEIXEIRA MARTA M. G.
Published: May 2008

ABSTRACT. Analysis of the phylogenetic relationships among trypanosomes from vertebrates and invertebrates disclosed a new lineage of trypanosomes circulating among anurans and sand flies that share the same ecotopes in Brazilian Amazonia. This assemblage of closely related trypanosomes was determined by comparing whole SSU rDNA sequences of anuran trypanosomes from the Brazilian biomes of Amazonia, the Pantanal, and the Atlantic Forest and from Europe, North America, and Africa, and from trypanosomes of sand flies from Amazonia. Phylogenetic trees based on maximum likelihood and parsimony corroborated the positioning of all new anuran trypanosomes in the aquatic clade but did not support the monophyly of anuran trypanosomes. However, all analyses always supported four major clades (An01‐04) of anuran trypanosomes. Clade An04 is composed of trypanosomes from exotic anurans. Isolates in clades An01 and An02 were from Brazilian frogs and toads captured in the three biomes studied, Amazonia, the Pantanal and the Atlantic Forest. Clade An01 contains mostly isolates from Hylidae whereas clade An02 comprises mostly isolates from Bufonidae; and clade An03 contains trypanosomes from sand flies and anurans of Bufonidae, Leptodactylidae, and Leiuperidae exclusively from Amazonia. To our knowledge, this is the first study describing morphological and growth features, and molecular phylogenetic affiliation of trypanosomes from anurans and phlebotomines, incriminating these flies as invertebrate hosts and probably also as important vectors of Amazonian terrestrial anuran trypanosomes.
Precipitation Coating of Rare‐Earth Orthophosphates on Woven Ceramic Fibers—Effect of Rare‐Earth Cation on Coating Morphology and Coated Fiber Strength
Authors: Fair Geoff E. , Hay Randall S. , Boakye Emmanuel E.
Published: May 2008

Monazite (La, Ce, Nd, and GdPO4) and xenotime (Tb, Dy, and YPO4) coatings were deposited on woven Nextel™610 and 720 fibers by heterogeneous precipitation from a rare‐earth citrate/phosphoric acid precursor. Coating phases and microstructure were characterized by SEM and TEM, and coated fiber strength was measured after heat treatment at 1200°C for 2 h. Coated fiber strength increased with decreasing ionic radius of the rare‐earth cation in the monazite and xenotime coatings, and correlates with the high‐temperature weight loss and the densification rate of the coatings. Dense coatings with trapped porosity and high weight loss at a high temperature degrade fiber strength the most. The degradation is consistent with stress corrosion driven by thermal residual stress from coating precursor decomposition products trapped in the coating at a high temperature.
Kinetics and Mechanism of Hot Corrosion of γ‐Y2Si2O7 in Thin‐Film Na2SO4 Molten Salt
Authors: Sun Ziqi , Li Meishuan , Zhou Yanchun
Published: May 2008

γ‐Y2Si2O7 is a promising candidate material both for high‐temperature structural applications and as an environmental/thermal barrier coating material due to its unique properties such as high melting point, machinability, thermal stability, low linear thermal expansion coefficient (3.9 × 10−6/K, 200°–1300°C), and low thermal conductivity (<3.0 W/m·K above 300°C). The hot corrosion behavior of γ‐Y2Si2O7 in thin‐film molten Na2SO4 at 850°–1000°C for 20 h in flowing air was investigated using a thermogravimetric analyzer (TGA) and a mass spectrometer (MS). γ‐Y2Si2O7 exhibited good resistance against Na2SO4 molten salt. The kinetic curves were well fitted by a paralinear equation: the linear part was caused by the evaporation of Na2SO4 and the parabolic part came from gas products evolved from the hotcorrosion reaction. A thin silica film formed under the corrosion scale was the key factor for retarding the hot corrosion. The apparent activation energy for the corrosion of γ‐Y2Si2O7 in Na2SO4 molten salt with flowing air was evaluated to be 255 kJ/mol.
Effect of irradiation on mating performance and mating ability in the West Indian sweetpotato weevil, Euscepes postfasciatus
Authors: Kumano Norikuni , Haraguchi Dai , Kohama Tsuguo
Published: May 2008

The sterile insect technique (SIT) is widely used for suppressing or eradicating target pest insect populations. The effectiveness of SIT depends on the ability of released sterile males to mate with and inseminate wild females. Irradiation not only damages the reproductive cells but the somatic cells as well. The mating behavior of irradiated males may be altered over time due to the depressed metabolic activity brought about by sterilization. In this study, we evaluated the mating behavior (copulation behavior, mating performance, and ability of sperm transfer) of irradiated males in Euscepes postfasciatus (Fairmaire) (Coleoptera: Curculionidae) for 16 days after irradiation in the laboratory. The mating performance of males irradiated with a 150 Gy dose, as currently used in the SIT program in Okinawa prefecture for E. postfasciatus, decreased compared to that of control after day 7. As a result, we considered that irradiation had no major effect on male mating behavior for approximately 1 week after irradiation.
Dihydroartemisinin induces apoptosis and sensitizes human ovarian cancer cells to carboplatin therapy
Authors: Chen Tao , Li Mian , Zhang Ruiwen , Wang Hui
Published: May 2008

The present study was designed to determine the effects of artemisinin (ARS) and its derivatives on human ovarian cancer cells, to evaluate their potential as novel chemotherapeutic agents used alone or in combination with a conventional cancer chemotherapeutic agent, and to investigate their underlying mechanisms of action. Human ovarian cancer cells (A2780 and OVCAR‐3), and immortalized non‐tumourigenic human ovarian surface epithelial cells (IOSE144), were exposed to four ARS compounds for cytotoxicity testing. The in vitro and in vivo antitumour effects and possible underlying mechanisms of action of dihydroartemisinin (DHA), the most effective compound, were further determined in ovarian cancer cells. ARS compounds exerted potent cytotoxicity to human ovarian carcinoma cells, with minimal effects on non‐tumourigenic ovarian surface epithelial (OSE) cells. DHA inhibited ovarian cancer cell growth when administered alone or in combination with carboplatin, presumably through the death receptor‐ and, mitochondrion‐mediated caspase‐dependent apoptotic pathway. These effects were also observed in in vivo ovarian A2780 and OVCAR‐3 xenograft tumour models. In conclusion, ARS derivatives, particularly DHA, exhibit significant anticancer activity against ovarian cancer cells in vitro and in vivo, with minimal toxicity to non‐tumourigenic human OSE cells, indicating that they may be promising therapeutic agents for ovarian cancer, either used alone or in combination with conventional chemotherapy.
Cyclooxygenase‐2 expression in dermatofibroma and dermatofibrosarcoma protuberans
Authors: Adler Neta , Tsabari Cochava , Sulkes Jaqueline , Ad‐El Dean , Feinmesser Meora
Published: May 2008

Background:  Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) occasionally resemble each other histologically but differ in histogenesis and biological behavior. This study sought to determine if these lesions can be differentiated by the quantity or quality of expression of cyclooxygenase‐2 (COX‐2), an enzyme associated with both reactive and neoplastic processes.

Patients and methods:  Formalin‐fixed and paraffin‐embedded samples from 20 DFs and 20 DFSPs were stained immunohistochemically with antibodies directed against COX‐2. Staining was evaluated semiquantitatively for percentage and intensity using a three‐tiered system. DFs were graded and analyzed by cellularity. Findings within the tumors were compared with fibrocyte staining in adjacent tissue. The results were analyzed.

Results:  Nineteen DFs (95%) and 15 DFSPs (75%) were immunopositive for COX‐2; this difference was not statistically significant. Highly cellular DFs showed more widespread (p = 0.0039; r = 0.614) and more intense (p = 0.0586; r = 0.429) staining than less cellular DFs and more prominent staining in adjacent fibroblasts (p = 0.044; r = 0.608).

Conclusions:  COX‐2 immunostaining does not distinguish DFs from DFSPs. However, the enzyme is expressed more widely and more intensely in more cellular, possibly younger, DFs. The prominent expression of COX‐2 in DFSP may have clinical implications for treatment with COX‐2 inhibitors in tumors that are not amenable to surgery.
Sebaceous carcinoma of the nipple
Authors: Cibull Thomas L. , Thomas Antoinette B. , Badve Sunil , Billings Steven D.
Published: May 2008

Sebaceous carcinoma (SC) is an uncommon neoplasm that usually presents as an ocular or extraocular cutaneous lesion of the head and neck. We report a case of an 83‐year‐old woman with SC of the nipple. To our knowledge, this is the first report of SC arising in the nipple.
UV‐induced DNA damage initiates release of MMP‐1 in human skin
Authors: Dong Kelly K. , Damaghi Niusha , Picart Stephanie D. , Markova Nelli G. , Obayashi Kei , Okano Yuri , Masaki Hitoshi , Grether‐Beck Susanne , Krutmann Jean , Smiles Kenneth A. , Yarosh Daniel B.
Published: May 2008

Abstract:  Destruction of collagen is a hallmark of photoaging. The major enzyme responsible for collagen 1 digestion, matrix metalloproteinase‐1 (MMP‐1), is induced by exposure to sunlight. To study the molecular trigger for this induction, human skin was ultraviolet‐B (UVB)‐irradiated and treated with liposome‐encapsulated DNA repair enzymes. The photolyase‐mediated DNA repair of epidermal UV damage was associated with a reduction of MMP‐1 mRNA and protein expression in both the epidermal and dermal compartments of the skin. The role of the epidermal cells in MMP‐1 induction in the fibroblasts was examined when human epidermal keratinocytes were irradiated with UVB and their media were transferred to unirradiated human dermal fibroblasts. Transfer of media from irradiated keratinocytes to unirradiated fibroblasts enhanced MMP‐1 mRNA and protein. Thus, UV damage to keratinocytes of the epidermis may participate in the destruction of collagen in the dermis by release of soluble mediators that signal fibroblasts to release MMP‐1. The MMP‐1 induction was reduced when the keratinocytes were treated with DNA repair enzymes T4 endonuclease V or UV endonuclease prior to transfer of the media to fibroblasts. This implies that UVB, which deposits most of its energy on the chromatin of the epidermal keratinocytes and to a lesser extent in the upper dermis, has a significant role in photoaging. DNA damage in the keratinocytes initiates one of the signals for MMP‐1 release, and enhancing DNA repair can reduce MMP‐1 expression in human skin cells and tissue.
Prevention of post‐operative nausea and vomiting in children – a prospective randomized double‐blind study
Authors: Sakellaris G , Georgogianaki P , Astyrakaki E , Michalakis M , Dede O , Alegakis A , Makatounaki K , Charissis G
Published: May 2008

Background/Purpose: Post‐operative nausea and vomiting (PONV) are common complications related to surgery and anaesthesia. The aim of this study was to assess whether sevoflurane, with or without the use of an antiemetic such as ondansetron, increases or not the incidence of PONV in children.

Methods: One hundred and ten children, 2 months to 14 years undergoing inguinal hernia, hypospadias and penile deformity repair, were randomly allocated into one of two groups, according to whether they received ondansetron or placebo (47 vs. 63). Induction and maintenance of anaesthesia was with Sevoflurane in both groups.

Regional anaesthesia was performed on all children (inguinal nerve, penile or caudal block). No opioids were used.

In post‐operative period, children were assessed for PONV, every 4 h for the first 24 h.

Results: Vomiting was very low in both groups (8 cases: 7.3%). No significant statistical difference of post‐operative nausea (p = 0.296) and vomiting (p = 0.462) (Fisher's exact test) was found between the group that received ondansetron and the placebo group.

Conclusion: We found that the use of ondansetron did not change the incidence of PONV, the avoidance of opioids and the adequate analgesia may contribute to this. Post‐operative oral intake of liquid, (within the first 4 h), increases the risk for PONV.
Effects of high protein levels in concentrate feed during the early fattening stage on physico‐chemical composition and sensory characteristics of M. longissimus in Japanese Black heifers
Authors: OKUMURA Toshiaki , SAITO Kaoru , NADE Toshihiro , MISUMI Satsuki , SAKUMA Hironori , NAKAYAMA Sachio , MASUDA Yasuhisa , FUJITA Kazuhisa , KAWAMURA Tadashi
Published: May 2008

ABSTRUCT

The effects that high levels of protein in concentrate feed has during the early fattening stage on physico‐chemical composition and sensory characteristics of M. longissimus in Japanese Black heifers were investigated. Four sets (8 head) of identical twins of Japanese Black heifers were divided into two groups: a group fed high levels of protein in concentrate feed in the early fattening stage (HCP); and a control group. Moisture, fat, protein, cooking loss, Warner‐Bratzler shear force and fatty acid composition of M. longissimus were similar in both groups. Levels of free amino acid (FAA), aspartic acid, glutamine, taurine and histidine were lower in the HCP group than in the control group (P < 0.05). Levels of glutamic acid, serine, asparagine, threonine and total FAA in the HCP group tended to be lower than in the control group (P < 0.1). There were no significant differences between the sensory characteristics (juiciness, tenderness, fattiness, flavor and overall acceptability) of the two groups. These results suggest that the use of high levels of protein in concentrate feed during the early fattening stage does not affect the sensory characteristics of Japanese Black beef, but does alter the FAA content.
Reduced dietary lysine enhances proportion of oxidative fibers in porcine skeletal muscle
Authors: KATSUMATA Masaya , MATSUMOTO Mitsuhito , KOBAYASHI Shu‐ichi , KAJI Yuji
Published: May 2008

The present study was conducted to elucidate the effects of dietary lysine levels on the proportion of oxidative muscle fibers in porcine muscle. Two 6‐week‐old barrows from each of five litters were used. Each littermate was assigned to one of two diets, control (lysine content: 1.16%) or low lysine (LL) diet (lysine content: 0.73%). The diets were iso‐energetic and iso‐protein, and contained all essential amino acids (apart from lysine) in the recommended amounts. The pigs were fed these diets for 3 weeks. Citrate synthase (EC 4.1.3.4) activity in longissimus dorsi and rhomboideus muscles was higher in the LL group (P < 0.05). In both muscles, pigs fed the LL diet had a higher proportion of muscle fiber with activities of reduced nicotinic amide adenine dinucleotide dehydrogenase (EC 1.6.5.3,P < 0.01). The abundance of mRNA of peroxisome proliferator‐activated receptor γ coactivator 1α in rhomboideus muscle was higher in the LL group (P < 0.05), and those ofperoxisome proliferator‐activated receptor γ2were higher in both longissimus dorsi and rhomboideus muscles in the LL group (P < 0.05). We conclude that reduced intake of dietary lysine enhances proportion of oxidative muscle fiber, and hence oxidative capacity of porcine muscle.
Sprinkling coarse marble powder during the afternoon, toward the end of the laying period, may increase eggshell quality
Authors: ERENER Guray , OCAK Nuh , GARIPOGLU Ali Vaiz , OZTURK Ergin
Published: May 2008

The aim of this study was to investigate the effects of time, particle size (PS) and level of calcium supplementation above the requirements toward the end of the laying period on egg production and eggshell quality. A total of 675 Isa‐Brown layer hens were distributed in a completely randomized factorial arrangement of 3×3×3, using three sprinkling times (08.00, 12.00, 16.00 hours), PC (mash, granular and large size) and amounts (0 g control, 0.75 g/day/h, 1.50 g/day/h) of marble sprinkling as a calcium source. All hens were fed a commercial layer diet from 55 to 67 weeks of age. Sprinkling of 1.50 g marble reduced (P < 0.05) egg production compared to 0.75 g marble, and feed efficiency (FE) compared to that of 0 and 0.75 g marble. Sprinkling of 0.75 and 1.50 g marble increased (P < 0.01) eggshell weight, shell strength and shell thickness compared to that of 0 g marble. The interaction of sprinkling time‐by‐PS‐by–quantity of marble was significant for egg production (P < 0.05), FE and shell strength (P < 0.01). Results showed that sprinkling of coarse marble powder to complete diet increased shell strength without reduction in egg production and FE.
Differential expression of myostatin and its receptor in the porcine anterior pituitary gland
Authors: TAKETA Yoshikazu , NAGAI Yasuhiro , OGASAWARA Hideki , HAYASHI Shinichiro , MIYAKE Masato , TANAKA Sachi , WATANABE Kouichi , OHWADA Shyuichi , ASO Hisashi , YAMAGUCHI Takahiro
Published: May 2008

Myostatin (MSTN), known as growth and differentiation factor 8 (GDF‐8), is a member of the transforming growth factor β (TGF‐β) superfamily that negatively regulates skeletal muscle mass. Myostatin binds with high affinity to the receptor serine threonine kinase activin receptor type IIB (ActRIIB). Activins that also belong to the TGF‐β superfamily, stimulate follicle‐stimulating hormone production in gonadotrophs and suppress growth hormone and adrenocorticotropic hormone production in somatotrophs and corticotrophs, respectively. The aim of the present paper was therefore to clarify the endocrine action of MSTN in adenohypophysis. The present study details the expression and cellular localization of MSTN and ActRIIB in porcine anterior pituitary gland. The mRNA of MSTN and ActRIIB was consistently expressed in RT‐PCR. Immunohistochemistry of MSTN and specific hormones showed that MSTN localized in thyrotrophs and gonadotrophs, in which most of the MSTN immunoreactive cells were identified as thyrotrophs. The immunostaining of ActRIIB was restricted to corticotrophs. These results indicate that MSTN was mainly produced in thyrotrophs and its receptor, ActRIIB, was restrictively contained in corticotrophs. Interestingly, thyrotrophs immunoreactive for MSTN were frequently close to corticotrophs immunoreactive for ActRIIB. The present study suggests that MSTN from thyrotrophs may regulate corticotroph function as a paracrine mediator among the porcine anterior pituitary cells.
Effect of oral administration of 3,3′,4,4′,5‐pentachlorobiphyenl on the intestinal microbiota of Sprague–Dawley rats
Authors: YAMAZAKI Kaoru , SUZUKI Takehito , SHIRAI Mitsuyuki , TAKIZAWA Tatsuya , SHINODA Tadashi , MASAOKA Toshio , AKAHORI Fumiaki , MORITA Hidetoshi
Published: May 2008

The effect of the endocrine‐disrupting chemical 3,3′,4,4′,5‐pentachlorobiphyenl (PCB 126) on intestinal microbiota after oral administration, and the improvement of intestinal microbiota and feces quantity by the subsequent administration of Lactobacillus acidophilus or Lactobacillus reuteri was investigated. All the rats were given 100 μg/kg bodyweight of PCB 126. The changes in bacterial counts were confirmed using a culture method. The administration of PCB 126 tended to decrease the bacterial counts of lactobacilli (109.6−1010.2 to 108.8−109.2) and bifidobacteria (105.3−106.1 to 103.6−104.2), and to increase those of Enterobacteriaceae (108.2−109.1 to 109.4−1010.3) and staphylococci (106.6−107.4 to 107.2−108.4) compared to no PCB 126 administration. After administration of PCB 126, L. acidophilus or L. reuteri orally administered to rats caused Enterobacteriaceae and staphylococci counts to decrease, suggesting that the intestinal microbiota was improved by the lactobacilli. The administration of L. acidophilus and L. reuteri improved the balance of intestinal microbiota, and defecation volume returned to its normal level. L. acidophilus and L. reuteri have a remedial effect on intestinal microbiota affected by PCB 126 and can function to lessen accumulated PCB 126 volume.
Embryotoxicity of Ethanol and Acetaldehyde: Direct Effects of Mouse Embryo in Vitro
Authors: HIGUCHI Yoshiki , MATSUMOTO Nobuo
Published: May 2008

Direct embryotoxic effects of ethanol (EtOH) and acetaldehyde (AcH) on mouse embryos during early organogenesis were studied using the whole embryo culture method. Mouse embryos (Jcl‐ICR) were cultured for 48 hours from day 8 & 1/2 to 10 & 1/2 (embryonic age; plug day = day 1) with EtOH‐ or AcH‐supplemented medium. Final concentrations of EtOH ranged from 5 mM to 1 M, whereas those of AcH ranged from 0.4 μM to 400 mM. Exposure to EtOH at 500 mM or more caused early death. Growth and development in EtOH‐exposed embryos were retarded as indicated by the dose‐dependent decrease measured by several embryonic growth parameters. The most common EtOH‐induced anomaly was exencephaly and it was observed remarkably in the 66 mM or more exposed group. Exposure to AcH at 40 μM or more caused early death. Growth and development in AcH‐treated embryos were retarded as a function of dosage. The most common AcH‐induced anomaly was the deformation complex of the neural tube such as transparent and prominent rhombencephalon and remarkable shortening of the posterior part of the body, with or without cyst formation. This deformation complex was observed remarkably in the 0.8 μM or more exposed group. It can be said by these results that AcH is approximately 10000 times more embryotoxic than EtOH in the early organogenetic period and both EtOH and AcH disturb the normal closure of the neural tube, but each compound affects the closure process in a different way and/or developmental stage.
Strain Differences of Postnatal Development of Righting Reflex, Traction and Motor‐Coordination, and Emotional Behavior in Rats
Authors: ASANO Yuzo , KOBAYASHI Takashi , HIGAKI Koh
Published: May 2008

Litters from the non‐treated dams in Sprague‐Dawley (SD) and Wistar rats which are used most frequently in reproduction studies were observed for strain differences concentrating on the behavioral development during the early postnatal stage. During the period before the eyelids open, the Wistar rats showed significantly earlier development of postural reflex and traction than the SD rats. However, during the period after eyelids open, the significant difference between these two strains disappeared. The numbers of fallings from a rotorod, ambulation, and rearing in the SD strain significantly increased as compared with those in the Wistar strain. These findings suggest that proper caution should be paid to the developmental period for observing the postural reflex and traction response for the particular strain.
Teratogenicity of Azosemide, a Loop Diuretic, in Rats, Mice and Rabbits
Authors: HAYASAKA Ikuo , UCHIYAMA Kaoru , MURAKAMI Kazuo , KATO Zenji , TAMAKI Fumikazu , SHIBATA Tadashi , SUGAWARA Tsutomu , HAYASHI Motohide
Published: May 2008

Teratogenic effects of azosemide, a loop diuretic, were investigated in rats, mice and rabbits. Azosemide was given orally to pregnant rats, mice and rabbits during organogenesis. The pregnant animals were killed at term and their fetuses were examined for external, visceral and skeletal abnormalities. In rats, azosemide at 10–30 mg/kg/day did not affect intrauterine growth, resorptions and rates of external and visceral malformations. Treatment with 90 mg/kg/day resulted in a significant increase in skeletal abnormalities such as wavy ribs, bent scapula and bent humerus. However, the skeletal abnormalities observed in term fetuses could not be found in adult offspring, indicating that they were temporary. In mice, 1250 mg/kg/day of azosemide caused maternal death, abortion, and retarded maternal and fetal weight. Treatment with 200–500 mg/kg/day did not induce fetal mortalities, external and visceral malformations. Skeletal abnormalities increased in dose‐dependent fashion. The type of abnormalities was identical to that encountered in rat fetuses. Furosemide as a positive control also produced similar types of skeletal abnormalities in mouse fetuses. In rabbits, azosemide did not have embryolethal or teratogenic effects even at the highest dose (6 mg/kg/ day), which caused maternal death.

Treatment for a different 3‐day period and then a different day during organogenesis in rats and mice showed that the sensitive period was days 15–17 of gestation with a peak on day 16 in rats, and days 12–15 with a peak on day 13 in mice.
Immunological Defects in a Bis(dichloroacetyl) diamine Induced Malformation Complex in Rats Closely Resembling the DiGeorge Syndrome
Authors: OKISHIMA Takahiro , EIZURU Yoshito , MINAMISHIMA Yoichi , OHDO Shozo , HAYAKAWA Kunio
Published: May 2008

ABSTRACT: Spleen cells from newborn rats with bisdiamine‐induced congenital malformation were examined for subpopulation of lymphocytes and responsiveness of the lymphocytes to phytohemagglutinin (PHA), concanavalin A (ConA) and lipopolysaccharide (LPS). T cells, but not B cells, were significantly diminished in the drug‐treated newborn rats. Proliferative response of the lymphocytes to PHA and ConA, but not to LPS, was significantly depressed in the drug‐treated newborns. Thus a defect in cell‐mediated immunity was suggested to be associated with the congenital anomaly.

It is tempting to consider that this bisdiamine‐induced malformation can be another animal model for the DiGeorge syndrome.
The Production of Cardiovascular Malformations with Combined Use of Antisera to Kidney and Fetal Heart
Authors: MIYATA Koichiro , YAMAMOTO Eiji , TAKESUE Tetsuo , MUNAKATA Shuzo , NINOMIYA Makoto , ONO Seigo
Published: May 2008

ABSTRACT: Wistar rats were administered rabbit anti‐fetal‐rat‐heart serum (AFHS) alone on day 9 of gestation or in combination with sub‐teratogenic doses of rabbit anti‐rat‐kidney serum (AKS).

The results showed that the incidence of cardiovascular malformation was low (4.3%) when AFHS alone was administered. However, the incidence markedly increased to 42.4% when a small dose (O.lml/lOOg) of AKS was given on day 9 followed by 0.9ml/lOOg of AFHS on day 10. Ventricular septal defects, aortic arch anomalies, and double outlet right ventricle were the most common cardiovascular malformations observed. These results were similar to our previous finding using adult rat heart antiserum, and suggest that AFHS alone is not teratogenic, but when combined with a sub‐teratogenic dose of AKS it becomes teratogenic and organ specific.
Comparative Study of Phenotypic Expression of Mice Trisomy 16 by Different Female Strains: Attempt at an Animal Model for Human Trisomy 21
Authors: MIYABARA Shinichi , SUGIHARA Hajime , YONEMITSU Nobuhisa , YUN Kankatsu
Published: May 2008

ABSTRACT  Mouse trisomy 16, which was induced by mating males of Rb(16.17)7 Bnr/Rb(9.16)9Rma with three different strains of female, C57BL/6, C57BL/10 and C3H/He, was examined in fetuses and newborns in terms of incidence of occurrence, malformations and sex ratio. The incidence of trisomies tended to be higher in C3H/He than in C57BL/6 and C57BL/10. Trisomies could not survive beyond term in C57BL/6, which was most thoroughly examined in the three strains. Trisomy‐associated generalized edema, beginning to appear on day 14 of pregnancy on fetus's back, reached the maximum on day 16 in all strains. On cardiovascular anomalies, persistent common atrioventricular canal was observed in virtually all trisomies from C57BL/10 and C57BL/6, while in about 80% from C3H/He. In conotruncal region, all trisomies from former two crossing exhibited double outlet right ventricle or persistent truncus arteriosus. In addition to these anomalies, riding aorta was found in C3H/He. Hydroureter and hydronephrosis developed from day 17 of pregnancy in trisomies other than those in C57BL/10. The histological study of gonads revealed that trisomy 16 tended to be predominant in males of each crossing. The anomalies encountered in mouse trisomy 16, such as edema, persistent common atrioventricular canal, and hydroureter and hydronephrosis appeared to be in common with human trisomy 21 embryos and fetuses. The tendency of predominance of mouse trisomies in males may provide further homology to human trisomy 21. It is supposed that genetic background by different female strains may affect phenotypic expression of malformations. The extremely high incidence of cardiovascular anomalies is regarded as suitable material for elucidation of pathogenesis.
Prospects of the Reproductive Toxicology: With Special Reference to the Developmental Hazards Due to the Treatment at the Stages from Prefertilization to Implantation*
Authors: TANIMURA Takashi
Published: May 2008

ABSTRACT  With the definition of teratogenicity was expanded in terms of developmental stages when the agent acts and types of developmental anomalies induced, the concept of reproductive toxicity or developmental toxicity has been established. These new terms are essentially the synonym; the former gives the prime emphasis on the parent generation while the latter on the longer phase of developmental stage of the offspring.

It has been generally stated that the environmental agents which act before the onset of organogenesis will bring the embryo either death or normal growth. However, some affect the preimplantation embryos with resultant congenital anomalies. Moreover, it has been demonstrated that various developmental defects can be induced by a premating treatment to males, some of which may have been caused by mechanisms other than mutagenicity. On the other hand, oogenesis in females takes a very long time and it is often difficult to determine when these environmental agents act before or after pregnancy. Recent episodes of herbicides (Agent Orange) and vaginal spermicides were introduced as examples.

Pharmaceutical drugs, chemicals given to humans intentionally at a relatively large amount in a limited duration, have been requested to be tested in laboratory animals on the possible developmental defects in offspring even when given prior to organogenesis. In Japan, at the test administered prior to and in the early stages of pregnancy (segment I study), it is recommended not only to examine fertility of the parent generation but also to observe the development of offspring as long as practically possible.

In the symposium held at the 24th Annual Meeting of the Japanese Teratology Society, significance of developmental failures of the offspring induced by environmental factors given to the parents and during the preimplantation period was critically discussed.
Cultrure and Transfer of Embryos as a Testing System for Embryo‐toxicity of Chemicals*
Authors: MATSUMOTO Nobuo , SPINDLE Akiko , KATAYAMA Susumu , KUBO Harumi
Published: May 2008

ABSTRACT  Culture system of mouse embryos from 2‐cell stage to early post‐implantation stage was established. To assess the growth and development of embryos, morphological, biochemical and cytogenetical endopoints were settled as follows:

1. Blastocysts formation (Day 4 of culture) after treatment of 2‐cell, 4 to 8‐cell and morula.

2. Retention of blastocoel fluid on Day 5 of culture after treatment of blastocysts on Day 4 of culture.

3. Formation of trophblast outgrowth, discrete inner cell masses (ICMs), and ICMs differentiating into the primary endoderm and ectoderm (two‐layer ICMs) on Day 9 of culture.

4. Inhibitory effects on incorporation of 3H‐thymidine into DNA and of L‐(35S) methionine into protein of embryonic cells after treatment with chemicals.

5. Induction of structural chromosome aberrations and sister chromatid exchanges (SCEs) after treatment of blastocysts.

6. Further development of the treated embryos after transfer of them into the uterine horns of foster mothers (Day 16.5).

Mercuric chloride (MC), methylmercuric chloride (MMC), and 4‐Nitroquinoline 1‐oxide (4 NQO) were used for the experiment as model agents. The susceptibility of embryos to toxic effects of MMC changed as developmental stage progressed. The toxic effects of MC differed in manifestation from that of MMC. MMC was about 200 times as toxic to post‐implantation development as MC. These results were chiefly due to the difference between the compounds as regards the penetration of cell membrane and the distribution in living embryonic cells. As for the effects of 4NQO, structural chromosome aberrations and SCEs were induced at the concentration lower than the threshold value for the inhibition of morphological development. 4 NQO treated embryos which were transferred to the uterine horns of recipient mothers were implanted lower rate than control embryos. The embryos could not be implanted at all when treated with 10‐8M. The fetuses originated from the treated (10‐10M and 10‐9M 4NQO for 24 hr) blastocysts showed a remarkable decrease in their body weights without signs of external malformations.
A Review of Unilateral Cleft Lip and Palate Surgery*
Authors: FUKUDA Osamu
Published: May 2008

ABSTRACT  Operative techniques for unilateral cleft lip and palate have undergone continuous development, with improvement and modification, during the last three decades. The author's operation began with Tennison's method and gradually changed into a narrower and long triangular flap method. The edge of the orbicularis oris muscle on the cleft side is tucked under the center of the philtral dimple to obtain muscles linkage and a philtral ridge on the affected side. The longitudinal line is sutured with meticulous subcuticular stitches using 6–0 Nylon, resulting in a neat scar.

Relationship between vertical height of lip and width of triangular flap was examined in follow‐up studies. Flap width increased rapidly for one year after surgery and then slowed down to a pace proportionate with lip height. Although ratio of flap width to height increased from 27% to 40%, the balance of both sides of the lip did not, as had been thought might be possible, change. Correction of the cleft lip nose by the triangular flap method is rather difficult. It is considered natural for many surgeons to prefer a combination of the rotation‐advancement flap and small triangular flap.

Much remains to be discussed regarding cleft palate treatment. Author prefers closure of the hard palate using a vomer flap in the primary cleft lip operation because the most effective push‐back of the palate, without fistulae, is achieved. Underdevelopment of lip and maxilla should be evaluated from many aspects, and with a long‐term view.
Hyperadeninuria in a Patient with Congenital Deficiency of Adenine Phosphoribosyltransferase
Authors: NORO Tadao , KAMIKAWA Akira , SAMORI Tomoji
Published: May 2008

Abstract The authors have previously reported on the possibility of using the detection of crystalluria of 2, 8‐dihydroxyadenine as a screening test for the early discovery of congenital adenine phosphoribosytransferase deficiency.

Since the amount of adenine in urine was determined by high performance liquid chromatography and hyperadeninuria in a girl patient with this disease was definitely recognized, it is concluded that the detection of crystalluria of 2,8‐dihydroxyadenine as a primary screening test and the demonstration of hyperadeninuria as a secondary screening are helpful in an early detection of this disease.

The authors would like to propose this disease be designated a “Adenine‐body Urine Disease,” since adenine bodies such as adenine and 2,8‐dihydroxyadenine are excreted into the urine in large volumes.
Variation within Species in Response to Caffeine Teratologic Effects*
Authors: SULLIVAN F. M. , SMITH S. E. , McELHATTON P. R.
Published: May 2008

Abstract The most recent work from our own laboratory and also the. very large studies carried out by the FDA have clearly shown that caffeine has teratogenic effects in animals only when given in very high single daily doses. The doses necessary to produce teratogenic effects are of the order of one‐third the oral LD50 and usually produce other signs of severe maternal toxicity. Much larger daily doses if administered in divided doses or spread throughout the day in the drinking water, do not produce teratogenic effects. The teratogenic activity is dependent on the production of high peak blood levels probably around 60μg/ml or greater. Since such levels are never approached in humans even with high caffeine intakes, and on the basis of the available epidemiological evidence it would not appear that caffeine presents a teratogenic hazard for humans.

The available animal evidence suggests that high concentrations of caffeine in the embryo may cause haemorrhages which could be the mechanism of action whereby it causes the palatal and digital defects which have been observed.

Other actions of caffeine which have been observed in animal experiments have been reduction in fetal weight and associated retardation of ossification. These effects are seen with lower doses of caffeine than those causing teratogenic effects. The significance of these observations for humans is uncertain and is currently under investigation.
Introduction of a Cloned Gene into Fertilized Mouse Eggs and its Expression*
Authors: YAMAMURA Ken‐ichi
Published: May 2008

Abstract In order to analyze the role of enhancer sequence for the tissue‐specific and stage specific expression of immunoglobulin gene in normal diploid cells we have introduced cloned human y1 immunoglobulin genes into fertilized mouse eggs. Human y1 genes lacking enhancer sequence were not expressed in any tissues of transgenic mice. On the other hand human y1 genes containing enhancer sequence were expressed only in B lymphocytes. Levels of HIGI mRNA and percentage of human y chain producing cells in spleen cells were increased up to 50 times after treatment with lipopolysaccharide but not with Concanavalin A, suggesting B cell specific and regulated expression of HIGI gene. Human y chain producing cells were only found in the periphery of germinal center of the white pulp in histological section of the spleen suggesting stage‐specific expression. Human y chains appeared to be coupled with mouse light chains to form a complete IgG molecule and are secreted into cell supernatant. The production and secretion of endogenous immunoglobulin heavy and light chains in transgenic mice appeared to be the same as in normal mice. About one‐seventh of spleen cells that are producing endogenous mouse heavy chain produced human y1 chain at the same time. But no cell which produce only human y chain was observed. These results suggest that human γ chain expression had no effect on mouse immunoglobulin expression.