bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian Modeling of Complex Metabolic Pathways
Authors: Conti David V. , Cortessis Victoria , Molitor John , Thomas Duncan C.
Published: November 2003

Many chronic diseases are the result of a complex sequence of biochemical reactions involving exposures to various environmental agents, metabolized by a number of different genes. Routine epidemiologic analyses of such associations have tended to rely on standard contingency table or logistic regression methods, typically focusing on one variable at a time or pairwise combinations. We consider two statistical alternatives to this approach, one based on Bayesian model averaging, one based on pharmacokinetic modeling of the biochemical pathways. These approaches are illustrated using data from a case-control study of colorectal polyps in relation to tobacco smoking and consumption of well done red meat, both viewed as sources of heterocyclic amines and polycyclic aromatic hydrocarbons. The new analyses are structured in a manner that attempts to take advantage of prior knowledge of the metabolism of these classes of compounds and the various genes that regulate these pathways.
Heterogeneity in IBD Allele Sharing among Covariate-Defined Subgroups: Issues and Findings for Affected Relatives
Authors: Bull Shelley B. , Mirea Lucia , Briollais Laurent , Logan Alexander G.
Published: November 2003

Objectives: Modelling of variation in identical-by-descent (IBD) allele sharing using covariates can increase power to detect linkage, identify covariate-defined subgroups linked to particular marker regions, and improve the design of subsequent studies to localize genes and characterize their effects. In this report, we highlight issues that arise in studies of families with affected relatives. Methods: Mirea et al. [Genet Epidemiol 2003, in press] extended linear and exponential linkage likelihood models [Kong and Cox, Am J Hum Genet 1997;61: 1179–1188] to model variation in NPL scores among covariate-defined groups of families, and proposed likelihood ratio (LR) and t statistics to detect differences in allele sharing between groups defined by a binary covariate. Here we evaluate factors affecting the power of these tests analytically and by example, as well as effects of constraints, nuisance parameters, and incomplete data on test validity by simulation of locus heterogeneity in families with affected siblings or affected cousins. Results: Provided constraints on the parameters are avoided, these tests are particularly useful when one subgroup has less than expected IBD sharing. The distribution of the LR statistic depends on the extent of linkage, particularly in the presence of constraints. The t statistic may be biased by group differences in information content. Conclusions: We recommend that constraints be applied cautiously, and covariate effects in IBD allele sharing models interpreted with care.
Targeted Expression of Activated Rac3 in Mammary Epithelium Leads to Defective Postlactational Involution and Benign Mammary Gland Lesions
Authors: Leung Karen , Nagy Andre , Gonzalez-Gomez Ignacio , Groffen John , Heisterkamp Nora , Kaartinen Vesa
Published: November 2003

Rac3, a novel member of the Rho subfamily of the small GTPases, is frequently activated in cultured breast cancer cells and has been shown to mediate its effect via the p21-activated kinase (Pak) pathway. In order to evaluate these findings in vivo, we generated transgenic mice that express human constitutively active V12Rac under the control of the mouse mammary tumor virus (MMTV) promoter, which targets the transgene expression to the mammary epithelium. V12Rac3 expression could be detected during the first pregnancy, and the transgenic mammary gland tissues displayed an elevated Pak1 phosphorylation. Although milk proteins, β-casein and whey acidic protein were expressed and milk fat globules accumulated normally during pregnancy, 60% of transgenic mothers failed to nurse their pups. Surprisingly, although full lactational differentiation was never achieved in transgenic mice, gland involution was incomplete. For 5 days after weaning, involution was normal, but thereafter, epithelial islands characteristic of this early stage of involution persisted for months. The apoptotic index decreased after 5 days, and these glands were associated with increased p38 MAPK phosphorylation. Nine months postpartum, the transgenic mammary glands still demonstrated a large amount of persistent epithelial islands and abnormally large ducts with lymphocyte infiltration, whereas the tissues of non-transgenic controls had returned to their normal ‘virgin-like’ phenotype. These data show that sustained activation of Rac3 in the mammary epithelium leads to impaired mammary gland physiology and results in the formation of mammary gland lesions.
Prenatal Organization and Morphogenesis of the Sphenofrontal Suture in Humans
Authors: Captier G. , Cristol R. , Montoya P. , Prudhomme M. , Godlewski G.
Published: November 2003

Objective: The aim of this study was to describe the prenatal structure and morphogenesis of the sphenofrontal suture. Methods: Eleven human specimens, two embryos and nine fetuses, were prepared for light microscopy study of the sphenofrontal suture. Ten-micrometer sections were made with the microtome in the sagittal plane from the midline to the sphenoidal fontanelle. Results: At the end of the fetal period, the sphenofrontal suture had a five-layer structure like the cranial sutures, and was formed by two different morphogenetic unities. The orbitosphenofrontal suture was formed between the membranous ossification of the orbital part of the frontal bone and the endochondral ossification of the lesser wing of the sphenoid bone, i.e. the ala orbitalis. In the early stage, a transient sphenoethmoidal cartilage was inserted between these two ossifications. The second unit, the lateral sphenofrontal suture, was formed between the frontal bone and the greater wing of the sphenoid, and the ossification was membranous in this portion. It is formed like the cranial suture, directly from the mesenchyme. Conclusion: The sphenofrontal suture is a typical fibrous suture arising from two morphogenetic unities.
A Prospective Controlled Study of a Computer-Assisted Acenocoumarol Dosage Program
Authors: Marco Fernando , Sedano Carmen , Bermúdez Arancha , López-Duarte Mónica , Fernández-Fontecha Elena , Zubizarreta Alberto
Published: November 2003

The increase in oral anticoagulant (OA) treatment has led to development of new strategies for its control. We tested the efficacy of the GAO software (Dade Behring) in providing adequate acenocoumarol dosages for patients whose international normalised ratios (INRs) were no more than 0.5 points out of range. From December 1998 to August 1999, all outpatients in this setting were randomly assigned to receive computer-generated or traditionally fixed OA doses. Patients in their first 4 weeks of treatment were excluded. Overall, 8,352 dosages were calculated by the computer and 7,586 by the medical staff. The main endpoint of the study was the time spent in target INR range. The computer matched the traditional dosing, achieving a small but statistically significant greater efficacy in maintaining patients within the INR target range. The percentage of INR determinations over 5.5 was very low in both groups. Our results validate the computerised acenocoumarol dosing in our centre, achieving at least similar levels of effectiveness and safety compared with traditional dosage by medical staff.
Long-Term Hemostatic Effects of Cholesterol-Lowering Therapy with Atorvastatin
Authors: Trifiletti A. , Lasco A. , Scamardi R. , Pizzoleo M.A. , Gaudio A. , La Rocca R. , Morini E. , Frisina N.
Published: November 2003

This study assessed hemostatic effects of an HMC-CoA reductase inhibitor, atorvastatin, on different parameters in 32 hypercholesterolemic patients of both sexes. In the patients and in 25 control subjects, plasma levels of tissue-type plasminogen activator, plasminogen activator inhibitor (PAI-1), D-dimer, prothrombin fragment 1 + 2 (F1 + 2), total cholesterol, triglycerides and fibrinogen had been measured. All these parameters were evaluated in patients after 6 and 12 months of treatment with atorvastatin at a dosage of 20 mg/day. This treatment significantly lowered the total cholesterol level in all patients. Moreover, after 6 months of atorvastatin treatment, PAI-1 and F1 + 2, which were both increased at baseline, were significantly reduced. This reduction continued after 12 months. The present results show that a reduction of hemostatic abnormalities, which exist in hypercholesterolemia, may be another important effect of the atorvastatin therapy.
Reduction in Homocysteine by n–3 Polyunsaturated Fatty Acids after 1 Year in a Randomised Double-Blind Study following an Acute Myocardial Infarction: No Effect on Endothelial Adhesion Properties
Authors: Grundt Heidi , Nilsen Dennis W.T. , Mansoor Mohammad A. , Hetland Øyvind , Nordøy Arne
Published: November 2003

We hypothesized that n–3 polyunsaturated fatty acids (n–3 PUFAs) as compared to corn oil administered for 1 year following an acute myocardial infarction (MI) may reduce plasma total homocysteine (p-tHcy), ultrasensitive C-reactive protein (µCRP), and the adhesive properties of the endothelium, expressed as soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1). In a prospective, randomised, double-blind study, 300 acute MI patients were allocated to highly concentrated n–3 PUFAs (n = 150) or corn oil (n = 150). After 1 year on treatment there was an intergroup difference in p-tHcy in favour of the n–3 group (n = 118), p = 0.022. However, sE-selectin, sICAM-1 and µCRP were unaffected by the treatment. In conclusion, reduction of p-tHcy by long-term n–3 PUFAs treatment was not associated with demonstrable effects on markers of endothelial adhesion properties.
Effects of the Genetic Polymorphisms of the Renin-Angiotensin System on Focal Segmental Glomerulosclerosis
Authors: Luther Y. , Bantis C. , Ivens K. , Fehsel K. , Kolb-Bachhofen V. , Heering P.
Published: November 2003

Background/Aims: We analyzed the influence of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T and angiotensin-II-type-1 receptor (AT1R) A1166C genetic polymorphisms on the clinical course of focal segmental glomerulosclerosis (FSGS). Methods: This study consisted of 71 patients with nephrotic syndrome due to biopsy proven FSGS and 100 healthy controls. According to the slope of the reciprocal serum creatinine (1/Cr, ≧ or <–0.1 dl·mg–1· year–1) patients were classified into group A (slow progressors, n = 50) and group B (fast progressors, n = 21). Genotyping was performed using polymerase chain reaction (PCR). Results: There were no relevant differences in the allele frequencies of the investigated polymorphisms between patients with FSGS and controls. Patients carrying the T- allele of the AGT polymorphism required a larger number of antihypertensive agents (MM: 1.35 ± 1.0 vs. MT/TT: 2.0 ± 1.2, p < 0.05). The ACE-ID/DD genotypes were more frequently found in patients with fast progression (group A: II: 38.0%, ID/DD: 62.0% vs. group B: II: 14.3%, ID/DD: 85.7%, p < 0.05). The AT1R-A1166C polymorphism was not associated with any of the parameters studied. Conclusion: The course of FSGS is in part genetically determined by polymorphisms of the renin-angiotensin-system. The ACE-I/D polymorphism was shown to be a risk factor of progression of renal disease and the AGT-M235T polymorphism was associated with the severity of arterial hypertension.
Tissue Factor, Its Pathway Inhibitor, and Metabolic Disturbances in Long-Term Peritoneal Dialysis
Authors: Zemanová Pavlína , Opatrný Jr Karel , Opatrná Sylvie , Vít Ladislav , Šefrna František , Racek Jaroslav
Published: November 2003

Background/Aim: The tissue factor (TF) plays a key role in triggering the coagulation system in vivo. Our study was designed to determine whether or not the plasma levels of TF and its pathway inhibitor (TF pathway inhibitor; TFPI) in patients with chronic renal failure (CRF) treated by peritoneal dialysis (PD) (1) are pathologically altered; (2) differ between diabetics and nondiabetics, and (3) depend on the metabolic disorders associated with CRF and/or diabetes. Methods: Using ELISA, plasma TF and TFPI levels were measured once in 21 PD patients (10 with diabetes, 11 without diabetes) and in 21 healthy subjects. Results: As compared with healthy subjects (TF 282 pg/ml; TFPI 73 ng/ml), both TF and TFPI levels were significantly higher in PD patients with diabetes (485 pg/ml, p < 0.001, and 106 ng/ml, p < 0.01, respectively) and in PD patients without diabetes (480 pg/ml, p < 0,001, and 121 ng/ml, p < 0.001, respectively). The difference between diabetics and nondiabetics was not significant. In stepwise regression analysis, the TF levels depended on serum creatinine (partial correlation 0.39, p < 0.05), glycemia (0.43, p < 0.01), and insulin (–0.43, p < 0.05), and the TFPI levels depended on creatinine (partial correlation 0.67, p < 0.001), apolipoprotein B (0.46, p < 0.01), and plasma fibrinogen (0.43, p < 0.01). Conclusions: CRF patients on PD show increased plasma TF and TFPI levels. There is no difference between diabetics and nondiabetics. The TF and TFPI levels depend significantly on the renal function, as assessed by serum creatinine, and on some metabolic disorders. Elevated TF and TFPI levels may be related to thrombosis and atherosclerosis in CRF patients on PD.
Dissection of an inverted X(p21.3q27.1) chromosome associated with mental retardation
Authors: Leprêtre F. , Delannoy V. , Froguel P. , Vasseur F. , Montpellier C.
Published: November 2003

In a 6 year old boy referred for mental retardation, fragile X syndrome was ruled out by cytogenetic and molecular analyses. Cytogenetic investigations revealed an inverted X chromosome (p21.3q27.1). A similar chromosomal rearrangement was detected in his mildly mentally retarded mother. Fluorescence in situ hybridization (FISH), using a panel of ordered YAC clones, allowed the identification of YACs spanning both the Xp21.3 and Xq27.1 breakpoints, where many non-specific mental retardation loci have been reported so far. Further investigations by FISH showed that the IL1RAPL1 gene at Xp21.3 was disrupted by the X chromosome inversion and therefore its inactivation may be related to the mental retardation observed in our patients.
Molecular cloning, expression pattern and chromosomal mapping of pig CD9 antigen
Authors: Yubero N. , Jiménez-Marín A. , Yerle M. , Morera L. , Barbancho M.J. , Llanes D. , Garrido J.J.
Published: November 2003

CD9 is a member of the transmembrane-4 superfamily of surface molecules that seems to have a relevant role in cell migration and adhesion, as well as malignant progression. This work describes the isolation of the cDNA coding for the porcine CD9 molecule. Pig CD9 cDNA was isolated from a smooth muscle cDNA library and contains a 678-bp open reading frame with its predicted polypeptide sequence of 226 amino acids. The deduced amino acid sequence conserves the main characteristics of TM4 proteins, including the presence of four transmembrane domains. Like their homologous molecules from other species, pig CD9 has two extracellular regions of a different size with the minor loop bearing two possible glycosylation sites. The pig CD9 gene was localized to chromosome 5q25 by using a somatic cell hybrid panel. Analysis of CD9 expression in different porcine cells and tissues demonstrated that CD9 mRNA is ubiquitously expressed.
Molecular cloning and chromosomal assignment to SSC12p13→p11 of swine chemokine receptor CCR7
Authors: Shinkai H. , Muneta Y. , Eguchi T. , Suzuki K. , Awata T. , Uenishi H.
Published: November 2003

We cloned a gene encoding the swine chemokine (C-C motif) receptor 7 (CCR7) and clarified its genomic structure and chromosomal assignment. The ORF and deduced amino-acid sequence were highly conserved with human and mouse CCR7. The swine CCR7 gene was mapped to SSC12p13→p11 by FISH analysis. Stimulation of swine peripheral blood mononuclear cells by IL-12 and IL-18, considered potent inducers of Th1 cells from analyses in humans and mice, downregulated the expression of CCR7. This is the first report of the molecular cloning, chromosomal assignment and characterization of a chemokine receptor in swine.
Reptiles: a group of transition in the evolution of genome size and of the nucleotypic effect
Authors: Olmo E.
Published: November 2003

A comparison between genome size and some phenotypic parameters, such as developmental length and metabolic rate, showed in reptiles a nucleotypic correlation similar to the one observed in birds and mammals. Indeed, like homeotherms, reptiles exhibit a highly significant, inverse correlation of genome size with metabolic rate but unlike amphibians, no relationship with developmental length. Several lines of evidence suggest that these nucleotypic correlations are influenced by body temperature, which also affects the guanine + cytosine nuclear percentage, and that they play an important role in the adaptation of these amniotes. However, the reptilian suborders exhibit differences in the quantitative and compositional characters of the genome that do not completely correspond to differences in the phenotypic parameters commonly involved in the nucleotypic effect. Thus, additional factors could have influenced genome size in this class. These data could be explained with the model of Hartl and Petrov, who observed an inverse correlation between genome size, non-coding portion of the genome and rate of DNA loss and hypothesized a strong role for different spectra of spontaneous insertions and deletions (indels) in the variations of genome size. It is thus reasonable to surmise that variations in the reptilian genome were initially influenced by different indels spectra typical of the diverse lineages, possibly related to different chromosome compartmentalizations. The consequent size increases or decreases would have influenced various morphological and functional cell parameters, and through these some phenotypic characteristics of the whole organism, especially the metabolic rate, very important for environmental adaptation and thus subject to natural selection. Through this “nucleotypic” bond, natural selection would also have controlled genome size variations.
The temporal and spatial pattern of histone H3 phosphorylation at serine 28 and serine 10 is similar in plants but differs between mono- and polycentric chromosomes
Authors: Gernand D. , Demidov D. , Houben A.
Published: November 2003

Immunolabeling using site-specific antibodies against phosphorylated histone H3 at serine 10 or serine 28 revealed in plants an almost similar temporal and spatial pattern of both post-translational modification sites at mitosis and meiosis. During the first meiotic division the entire chromosomes are highly H3 phosphorylated. In the second meiotic division, like in mitosis, the chromosomes contain high phosphorylation levels in the pericentromeric region and very little H3 phosphorylation along the arms of monocentric species. In the polycentric plant Luzula luzuloides phosphorylation at both serine positions occurs along the whole chromosomes, whereas in monocentric species, only the pericentromeric regions showed strong signals from mitotic prophase to telophase. No phosphorylated serine 10 or serine 28 was detectable on single chromatids at anaphase II resulting from equational segregation of rye B chromosome univalents during the preceding anaphase I. In addition, we found a high level of serine 28 as well as of serine 10 phosphorylation along the entire mitotic monocentric chromosomes after treatment of mitotic cells using the phosphatase inhibitor cantharidin. These observations suggest that histone H3 phosphorylation at serine 10 and 28 is an evolutionarily conserved event and both sites are likely to be involved in the same process, such as sister chromatid cohesion.
Effect of Steroids on Intestinal Lipid Uptake in Rats Is Enhanced by a Saturated Fatty Acid Diet
Authors: Thiesen Aducio , Keelan Monika , Wild Gary , Clandinin M. Tom , Agellon L.B. , Thomson Alan B.R.
Published: November 2003

Glucocorticosteroids enhance sugar digestive and absorptive functions of the intestine, but their effect on lipid uptake is unknown. Modifications in dietary lipids alter the nutrient transport properties of the intestine. The influence of 4 weeks’ treatment with budesonide (BUD), prednisone (PRED), or control vehicle in weanling rats fed either an isocaloric semisynthetic saturated fatty acid diet (SFA) or a polyunsaturated fatty acid diet (PUFA), on the uptake of lipids was assessed using everted gut rings. PRED and BUD increased the uptake of several fatty acids, and this was higher when the animals were fed SFA rather than PUFA. Changes in expression of the mRNAs for L-FABP (liver fatty acid binding protein) and ILBP (ileal lipid binding protein) did not explain these alterations in lipid uptake. Dietary lipid signalling of this adaptive response may involve proglucagon, c-jun, TNF-α and IL-10, whereas steroid signalling may involve proglucagon. In summary, steroids increase the absorption of lipids by a process which can be enhanced by the substitution of saturated for polyunsaturated lipids in the diet, and which is not explained by alterations in the expression of the mRNAs of L-FABP or ILBP.
No Effect of Angiotensin-Converting Enzyme Gene Polymorphism on Disease Progression and Left Ventricular Hypertrophy in Autosomal Dominant Polycystic Kidney Disease
Authors: Ecder Tevfik , McFann Kimberly K. , Raynolds Mary V. , Schrier Robert W.
Published: November 2003

Background: Autosomal dominant polycystic kidney disease (ADPKD) shows a variable clinical course suggesting that genetic modifiers might play a role. There are conflicting results about the effect of angiotensin-converting enzyme (ACE) gene polymorphism on the progression of renal failure in ADPKD. Also, the association between ACE gene polymorphism and the occurrence of left ventricular hypertrophy (LVH) has not been investigated in patients with ADPKD. Methods: ACE genotype analysis was performed in 409 Caucasian patients (137 male, 272 female) with ADPKD. Echocardiographic examination was done in 164 of these patients. Results: There were no significant differences between different ACE genotypes regarding renal function, renal volume, urinary protein excretion, blood pressure, the rate of hypertension, the age at diagnosis of hypertension, the rate of LVH and the incidence of end-stage renal disease (ESRD). Conclusion: ACE gene polymorphism does not have a significant effect on the development of ESRD and the prevalence of LVH in patients with ADPKD.
A Possible Genetic Factor in the Pathogenesis of Ovarian Dermoid Cysts
Authors: Caspi B. , Lerner-Geva L. , Dahan M. , Chetrit A. , Modan B. , Hagay Z. , Appelman Z.
Published: November 2003

This study was undertaken in order to evaluate a possible genetic influence on the pathogenesis of ovarian dermoid cysts. We have performed a case-control study comparing the prevalence of a history of dermoid cysts in first-degree relatives of women with dermoid cysts and among first-degree relatives of women without dermoid cysts. The study group included 285 women with an established diagnosis of ovarian dermoid cysts. The control group included 378 women with sonographically normal ovaries. To assess the relationship between a first-degree family history of dermoid cysts and the diagnosis of ovarian dermoid cysts, a multivariate stepwise logistic regression model was applied. In 28 families of the study group (9.8%), a dermoid cyst was found in at least 1 first-degree relative as compared with only eight families (2%) among the controls (adjusted odds ratio –5.60; 95% CI 2.24–14.2). The data suggest a genetic predisposition towards dermoid cysts which merits further exploration.
Pregnancy after Limb-Sparing Hemipelvectomy for Ewing’s Sarcoma
Authors: Chihara Izumi Goto , Osada Hisao , Iitsuka Yoshinori , Masuda Kentaro , Sekiya Souei
Published: November 2003

Ewing’s sarcoma of the bone is a malignant bone tumor occurring mostly in adolescence and was considered to have poor prognosis. With recent advances in multi-agent combined chemotherapy, prognosis has improved, and more patients with primary lesions in the pelvis opt for limb-saving surgeries. In the present case, Ewing’s sarcoma in the left pelvis was diagnosed at the age of 11 and the patient underwent multi-agent chemotherapy combined with limb-sparing hemipelvectomy. She became pregnant at the age of 22. After an uneventful pregnancy, she delivered a healthy child at 37 weeks of gestation by cesarean section because of pelvic distortion. This is the first reported case of pregnancy and delivery after limb-sparing hemipelvectomy due to Ewing’s sarcoma. Since the multi-modality treatment improves survival, the number of women with Ewing’s sarcoma who desire pregnancy is expected to increase in the future. This is a valuable case that will provide useful information for such patients.
Remission of HHV-8 and HIV-associated multicentric Castleman disease with ganciclovir treatment
Authors: Casper Corey , Nichols W. Garrett , Huang Meei-Li , Corey Lawrence , Wald Anna
Published: November 2003

Multicentric Castleman disease (MCD) is a lymphoproliferative disorder associated with human herpesvirus 8 (HHV-8) infection among persons with human immunodeficiency virus (HIV) infection. Treatment often includes chemotherapy, and progression to non-Hodgkin lymphoma frequently occurs. MCD is characterized in part by active HHV-8 replication, and many of the symptoms of MCD may be attributable to viral gene products. We describe the effect of ganciclovir on the clinical and virologic course of MCD in a series of 3 case reports. Two patients experienced a reduction in the frequency of episodic flares of MCD and detectable HHV-8 DNA with intravenous or oral ganciclovir, whereas the third patient recovered from an acute episode of renal and respiratory failure with intravenous ganciclovir therapy. These data provide in vivo evidence for the utility of antiviral agents against HHV-8 in the management of MCD.
Total Synthesis of Bioactive Tricyclic Marine Alkaloids, Lepadiformine and Related Compounds
Authors: Kibayashi Chihiro , Aoyagi Sakae , Abe Hideki
Published: November 2003

The first total synthesis of tricyclic marine alkaloids (±)-fasicularin (2) and (±)-lepadiformine (5) has been accomplished. The key common strategic element for the synthesis is the stereocontrolled intramolecular hetero-Diels–Alder reaction of an N-acylnitroso moiety with an exocyclic diene with or without bromine substitution to control the syn-facial or anti-facial selectivity, respectively. This reaction leads to the trans- or cis-fused decahydroquinoline ring systems 13 or 23 involving the simultaneous introduction of the nitrogenated quaternary center in a single step. On further elaboration of the six-membered or five-membered ring A, the trans-fused adduct 13 provided either (±)-fasicularin (2) or (±)-lepadiformine (5). The hydrochloride salt of synthetic (±)-5 was found to be identical with the isolated natural sample of lepadiformine, however, the tricyclic amino alcohol 4 that has the proposed structure of lepadiformine in a non-zwitterionic form, derived from the cis-fused adduct 23, was found to be different from lepadiformine by spectral comparison. These results thus unambiguously established the relative stereochemistry of lepadiformine, formerly assigned incorrectly, as shown by 5. The synthesis of natural (−)-enantiomer of lepadiformine was then undertaken using a highly efficient protocol involving a new variant of the N-acyliminium ion-initiated intramolecular spirocyclization in which a conjugated diene was exploited as a π nucleophile. Thus, the synthesis is accomplished in nine steps with 31.4% overall yield, making this the most selective and shortest synthesis of lepadiformine to date. Direct comparison of chiral HPLC analysis of synthetic (−)-lepadiformine and the natural product allowed to assign the absolute configuration of natural lepadiformine to be 3R,5S,7aR,11aR.
Photochemical Transformations of Quintet m-Phenylenedinitrenes
Authors: Chapyshev Sergei Victorovich , Tomioka Hideo
Published: November 2003

Photochemical transformations of quintet dinitrenes have been studied for the first time by FTIR spectroscopy during the photolysis of 1,3-diazidobenzene and its 2-methyl- and 2,4,6-trimethyl-substituted derivatives in solid argon at 13 K. The reactions involve two competitive processes. In the first one, the intramolecular insertion of the nitrene unit into the 1,6-aromatic bond induces ring-opening, which leads to the formation of aminoacetylenes. The second process involves the intramolecular addition of the nitrene unit to the 1,2-aromatic bond followed by ring-opening to form 4(2H-azirin-2-ylidene)-2-butenenitrile derivatives. Methyl groups in ortho-positions to the nitrene units of quintet dinitrenes efficiently protect their aromatic ring from nitrene attacks, substantially increasing the photochemical stability of such species. However, even quintet 2,4,6-trimethylphenylene-1,3-dinitrene decomposes to ring-opened products on extended irradiation. This indicates that quintet dinitrenes are much more photochemically reactive species than triplet nitrenes. Undesirable photochemical rearrangements of the latter at early stages of the photolysis of 1,3-diazidobenzenes are suppressed on introducing the methyl group in position 2 of these azides.
Mixed-Valence States of 1′,1″′-Bis(2-phenylbutyl)-1,1″-biferrocenium(1+) Triiodides: Effects of the Cation Symmetry and Counter Anion on the Electron-Transfer Rate
Authors: Oda Takashi , Nakashima Satoru , Okuda Tsutomu
Published: November 2003

The effects of cation symmetry and packing on the mixed-valence state of binuclear ferrocene derivatives are discussed by using chiral isomers and the racemic modification of 1′,1″′-bis(2-phenylbutyl)-1,1″-biferrocenium(1+) triiodide. Although the three chiral isomers showed trapped-valence states at 78 K, only the (R,S) isomer showed a perfect detrapped-valence state at room temperature in the three isomers. The racemic modification consisted of the (R,R) and the (S,S) isomers showed a perfect detrapped-valence state at room temperature. This shows that the packing effect overcomes the effect of cation asymmetry. The electron-transfer rate for each pentaiodide salt was faster than that of the corresponding triiodide salt. A comparison between the (S,S) triiodide and the (S,S) pentaiodide salts reveals an important packing effect. The polymeric pentaiodide skeleton forced the (S,S) cation to have pseudo-inversion center.
Generation of Sulfur Ylides from Sulfonium Salts and Their Reactions. Comparative Study of Electrochemical Reduction with the Base Method and Mechanism Elucidation by the MO Method
Authors: Okazaki Yuichi , Ando Fumio , Koketsu Jugo
Published: November 2003

The cathodic reduction of sulfonium salts in acetonitrile in the presence and absence of benzaldehyde was carried out. Results were compared with results of the base method. In the presence of benzaldehyde, the electrochemical reduction gave epoxides as a result of the Corey–Chaykovsky reaction, thus confirming ylide formation. The electrochemical reduction of sulfonium salts without benzaldehyde yielded rearrangement products in high yield. On the contrary, upon base treatment of sulfonium salts without benzaldehyde, symmetrical epoxides derived from the benzyl group of the sulfonium salt are obtained as main products as a result of the auto oxidation of the sulfur ylide. The reaction mechanisms were elucidated based on the results obtained by a semi-empirical molecular orbital method.
Titanocene-Catalyzed Alkylation of Aryl-Substituted Alkenes with Alkyl Halides
Authors: Terao Jun , Watabe Hiroyasu , Miyamoto Masako , Kambe Nobuaki
Published: November 2003

Aryl-substituted alkenes (ArHC=CH2) react with alkyl halides (R–X, X = Br or Cl) in the presence of a catalytic amount of [Cp2TiCl2] and nBuMgCl in Et2O to give alkylated alkenes (ArHC=CHR). This reaction proceeds regio- and stereoselectively under mild conditions to afford E-olefins. Primary and secondary alkyl bromides and secondary alkyl chlorides can be used as suitable alkylating reagents. The reactions of aliphatic alkenes, such as 1-octene and internal alkenes, were sluggish. When t-alkyl halides are employed, alkylative dimerization of alkenes proceeds exclusively to give symmetrical vic-diarylalkanes. These reactions involve addition of alkyl radicals to arylalkenes to form benzyl radicals as a carbon–carbon bond-forming step. Dimerization of thus formed benzyl radicals affords symmetrical alkanes and β-hydrogen elimination from benzyltitanocene intermediates gives alkylated alkenes. A possibility that titanocene activates alkenes as radical accepters was also proposed.
Selective Selenate Adsorption on Cationated Amino-Functionalized MCM-41
Authors: Yokoi Toshiyuki , Tatsumi Takashi , Yoshitake Hideaki
Published: November 2003

A large distribution coefficient and large sorption capacity were observed during selenate adsorption by cation (Fe3+, Cu2+, and H+)-anchored diamino-functionalized MCM-41. Moreover, these synthetic adsorption media showed excellent selectivity for selenate sorption in the presence of other anions. In a pure potassium selenate solution, the distribution coefficients, Kd, exceeded 200000 when [selenate] < 25 mg in 1 g of these adsorbents (i.e., when the coverage of selenate < 0.4). The adsorption capacities of these three adsorption media were 117, 83.0, and 123 mg (g-adsorbent)−1, respectively, with the Fe and Cu centers having the capacity to bind 1.5 and 1.1 selenate anions on average. Tests on mono- (N-), di- (NN-), and triamino- (NNN-) functionalized MCM-41 showed that the diamino-functionalized varieties exhibited the largest value for Kd when cationated by Fe3+ and Cu2+. In the case of Fe/NN-MCM-41, diamino-functionalized MCM-41 cationated by Fe3+, the degree of inhibition caused by coexisting SO42− was much lower than the value reported for aluminum oxide. Cu/NN-MCM-41 showed the largest resistance to inhibition by Cl−. For the adsorbents that we tested, the effects of coexisting nitrate were smallest for these three anions. The local structure of the adsorption center in Fe/NN-MCM-41 was analyzed by EXAFS spectroscopy.
Soft Carbon-coated Hard Carbon Beads as a Lithium-ion Battery Anode Material
Authors: Yoshio Masaki , Wang Hongyu , Fukuda Kenji , Abe Takeshi , Ogumi Zempachi
Published: November 2003

Thermal vapor decomposition (TVD) process has been applied to coat soft carbon onto the surface of hard carbon beads. The resultant spherical hard–soft carbon composites with “core-shell” structure demonstrate better electrochemical performance than the starting hard carbon beads as anode materials in lithium-ion batteries. The effect of TVD-carbon shell on the electrochemical performance was correlated with some physical properties.
Microwave-polyol Preparation of Single-crystalline Gold Nanorods and Nanowires
Authors: Zhu Ying-Jie , Hu Xian-Luo
Published: November 2003

Single-crystalline gold (Au) nanorods and nanowires have been successfully prepared in liquid phase by one-step, seedless and template-free microwave-polyol method. Ethylene glycol (EG) reduced HAuCl4 to form Au by microwave heating at 160 °C. Single-crystalline Au with other morphologies was also produced.
A Novel and Convenient Synthetic Route to a 9-Phosphatriptycene and Systematic Comparisons of 9-Phosphatriptycene Derivatives
Authors: Kobayashi Junji , Agou Tomohiro , Kawashima Takayuki
Published: November 2003

A novel synthetic route to a 9-phosphatriptycene was developed by utilizing ortho-lithiation of a triarylphosphine oxide as a key step. Systematic comparisons of the NMR spectra of 9-phosphatriptycene derivatives indicated the large s character of the lone pair orbital or the phosphorus–chalcogen bonds of the 9-phosphatriptycene derivatives.
Preparation of Iron Oxide Nanoparticles via Successive Reduction–Oxidation in Reverse Micelles
Authors: Nakanishi Takuya , Iida Hironori , Osaka Tetsuya
Published: November 2003

Nanometer-size particles of iron oxide were prepared by a successive reduction–oxidation of ferric or ferrous ions within reverse micelles. Nanoparticles of iron oxide were collected from reverse micellar solution as precipitates by adding modifier molecules. The X-ray diffraction patterns and magnetic properties of thus-prepared samples suggested the formation of nanocrystalline phase of maghemite, γ-Fe2O3.
Ethnic variation of the P53 codon 72 polymorphism, HPV persistence, and cervical cancer risk
Authors: Inserra P , Abrahamsen M , Papenfuss M , Giuliano A R
Published: November 2003

Association between the p53 codon 72 polymorphism and cervical cancer remains unresolved. We determined the association between the polymorphism and risk of human papillomavirus (HPV) persistence. The polymorphism was detected by restriction enzyme digestion following p53 amplification and HPV detection by the PGMY 09/11 primer set followed by reverse line blot hybridization: 3371 samples were analysed. HPV persistence was assessed on a subset of samples collected at baseline, four and 10 months ( n =442). Highly significant differences were observed between ethnic groups ( P <0.005). No associations were found between P53 arginine and cytological grade in women infected with any HPV or any oncogenic HPV, despite adjustment for ethnicity. These results were sustained even when HPV-negative women were used as controls. Persistence for any or oncogenic HPV infection was not associated with the polymorphism, irrespective or ethnicity adjustment. Our findings do not support a role for this polymorphism conferring elevated risk for HPV-related disease.
The emergence of AIDS in Guatemala: inpatient experience at the Hospital General San Juan de Dios
Authors: Samayoa Blanca , Arathoon Eduardo , Anderson Matthew , Rodriguez Jose , Quattrini Evelyn , Gordillo Claudia , Cotton Lucy
Published: November 2003

Little is known about the effect of human immunodeficiency virus (HIV) infection on the Central American healthcare system. We describe HIV-related admissions in a Guatemalan medical service. The study was conducted at Guatemala City's largest public hospital. Data were derived from standardized data collection sheets maintained by the HIV testing service and by HIV clinic physicians. Data were collected for 295 medicine admissions of 257 HIV-infected adults during an 18-month period in 1999 and 2000; 30% of the patients were women. Average age was 33 years. Only 12.5% of the patients had been diagnosed with HIV infection prior to 1999 and nearly all had symptomatic AIDS. 60.3% of the patients were diagnosed with HIV infection during their hospitalization. The most common discharge diagnoses were tuberculosis (13.9%), toxoplasmosis, diarrhoea, candida and other fungal infections, and meningitis. Mean length of stay for HIV-positive patients was 17 days. 23.7% of the patients died during their hospitalization; this was double the mortality of non-HIV patients. HIV-infected patients represented 5.8% of the total admissions of the general medical wards. In a country where HIV prevalence is thought to be less than 1%, AIDS is now responsible for over 5% of admissions to a large medical service at a cost of $500,000 per year. These findings underline the importance of HIV infection in Central America and demonstrate the utility of tracking hospital admission data as a method of surveillance.
Cervical human papillomavirus infections in commercial sex workers—risk factors and behaviours
Authors: Tideman R L , Thompson C , Rose B , Gilmour S , Marks C , van Beek I , Berry G , O'Connor C , Mindel A
Published: November 2003

We have investigated the prevalence of, and risk factors for, cervical human papillomavirus (HPV) infection in commercial sex workers (CSWs) and controls attending the same sexual health clinics in Sydney. A self-administered 'risk factor' questionnaire was completed and a Pap smear and a specimen for HPV detection and typing were taken. Results from the 288 CSWs and 266 controls were assessed by univariate and multivariate analyses. No significant difference in the rates of cervical HPV infection in CSWs (31.6%) and controls (24.4%) was found but HPV related cytological abnormalities were more common on the CSWs ( P <0.05). In both groups, factors independently associated with HPV infection were the use of non-barrier contraception, cytological abnormalities, age under 36 and the number of non-paying sexual partners. A risk factor for CSWs only was sex-work in Japan. A detailed 'work' history from CSWs may be useful to identify unsafe practices or work in countries where safer sex may be less acceptable.
Synthesis of adenosine derivatives as transcription initiators and preparation of 5′ fluorescein- and biotin-labeled RNA through one-step in vitro transcription
Authors: HUANG FAQING , WANG GUOCAN , COLEMAN TRICIA , LI NA
Published: November 2003

Expanding our previous finding of an adenosine-initiated transcription system, we now demonstrate that either the 5′ site or the N6 site of adenosine nucleotides can be modified extensively without abolishing their ability to initiate transcription under the T7 [phis]2.5 promoter. Two series of amino derivatives of adenosine nucleotides were synthesized. Fluorescein and biotin groups were coupled to AMP derivatives through linkers of different sizes and hydrophobicities. Both fluorescein- and biotin-conjugated (at either the 5′ or N6 site) adenosine nucleotides can act as efficient transcription initiators, producing fluorescein- and biotin-labeled RNA at the specific 5′ end by a one-step transcription procedure, eliminating posttranscriptional modification. Furthermore, N6-modified adenosine derivative-initiated transcription synthesizes 5′ end modified RNA with a free phosphate group, providing the possibility for further derivatization. The current finding makes easily available a variety of site-specifically functionalized RNA, which may be used in nucleic acid detection, RNA structural and functional investigation, and generation and isolation of novel functional RNA.
Cic1p/Nsa3p is required for synthesis and nuclear export of 60S ribosomal subunits
Authors: FATICA ALESSANDRO , OEFFINGER MARLENE , TOLLERVEY DAVID , BOZZONI IRENE
Published: November 2003

Cic1p/Nsa3p was previously reported to be associated with the 26S proteasome and required for the degradation of specific substrates, but was also shown to be associated with early pre-60S particles and to be localized to the nucleolus. Here we report that Cic1p/Nsa3p is required for the synthesis of 60S ribosome subunits. A temperature-sensitive lethal cic1–2 point mutation inhibits synthesis of the mature 5.8S and 25S rRNAs. Release of the pre-60S particles from the nucleolus to the nucleoplasm was also inhibited as judged by the nuclear accumulation of an Rpl11b-GFP reporter construct. We suggest that Cic1p/Nsa3p associates early with nascent preribosomal particles and is required for correct processing and nuclear release of large ribosomal subunit precursors.
Identification of BHB splicing motifs in intron-containing tRNAs from 18 archaea: evolutionary implications
Authors: MARCK CHRISTIAN , GROSJEAN HENRI
Published: November 2003

Most introns of archaeal tRNA genes (tDNAs) are located in the anticodon loop, between nucleotides 37 and 38, the unique location of their eukaryotic counterparts. However, in several Archaea, mostly in Crenarchaeota, introns have been found at many other positions of the tDNAs. In the present work, we revisit and extend all previous findings concerning the identification, exact location, size, and possible fit to the proposed bulge-helix-bulge structural motif (BHB, now renamed hBHBh′) of the sequences spanning intron–exon junctions in intron-containing tRNAs of 18 archaea. A total of 103 introns were found located at the usual position 37/38 and 33 introns at 14 other different positions, that is, in the anticodon stem and loop, in the D-and T-loops, in the V-arm, or in the amino acid arm. For introns located at 37/38 and elsewhere in the pre-tRNA, canonical hBHBh′ motifs were not always found. Instead, a relaxed hBH or HBh′ motif including the constant central 4-bp helix H flanked by one helix (h or h′) on either side generating only one bulge could be disclosed. Also, for introns located elsewhere than at position 37/38, the hBHBh′ (or HBh′) structure competes with the three-dimensional structure of the mature tRNA, attesting to important structural rearrangements during the complex multistep maturation-splicing processes. A homotetramer-type of splicing endonuclease (like in all Crenarchaeota) instead of a homodimeric-type of enzyme (as in most Euryarchaeota) appears to best fit the requirement for splicing introns at relaxed hBH or HBh′ motifs, and may represent the most primitive form of this enzyme.
Demonstration of the role of the DnaK chaperone system in assembly of 30S ribosomal subunits using a purified in vitro system
Authors: MAKI JENNIFER A. , SOUTHWORTH DANIEL R. , CULVER GLORIA M.
Published: November 2003

Recently, there has been controversy regarding the ability of the DnaK chaperone system to facilitate Escherichia coli 30S subunit assembly at otherwise nonpermissive conditions. Here, we present additional data indicating that purified DnaK chaperone assembled 30S subunits are functional. Additionally, explanations for reported differences are discussed.
Evolutionary conservation of the U7 small nuclear ribonucleoprotein inDrosophila melanogaster
Authors: AZZOUZ TELDJA N. , SCHÜMPERLI DANIEL
Published: November 2003

The U7 snRNP involved in histone RNA 3′ end processing is related to but biochemically distinct from spliceosomal snRNPs. In vertebrates, the Sm core structure assembling around the noncanonical Sm-binding sequence of U7 snRNA contains only five of the seven standard Sm proteins. The missing Sm D1 and D2 subunits are replaced by U7-specific Sm-like proteins Lsm10 and Lsm11, at least the latter of which is important for histone RNA processing. So far, it was unknown if this special U7 snRNP composition is conserved in invertebrates. Here we describe several putative invertebrate Lsm10 and Lsm11 orthologs that display low but clear sequence similarity to their vertebrate counterparts. Immunoprecipitation studies inDrosophilaS2 cells indicate that theDrosophilaLsm10 and Lsm11 orthologs (dLsm10 and dLsm11) associate with each other and with Sm B, but not with Sm D1 and D2. Moreover, dLsm11 associates with the recently characterizedDrosophilaU7 snRNA and, indirectly, with histone H3 pre-mRNA. Furthermore, dLsm10 and dLsm11 can assemble into U7 snRNPs in mammalian cells. These experiments demonstrate a strong evolutionary conservation of the unique U7 snRNP composition, despite a high degree of primary sequence divergence of its constituents. Therefore,Drosophilaappears to be a suitable system for further genetic studies of the cell biology of U7 snRNPs.