bluuebunny/crossref_metadata_2025_split huggingface dataset:
[123/131I]Iodometomidate as a radioligand for functional diagnosis of adrenal disease: synthesis, structural requirements and biodistribution
Authors: Schirbel A. , Zolle I. , Hammerschmidt F. , Berger M. L. , Schiller D. , Kvaternik H. , Reiners Chr. 
Published: July 2004

Abstract
Metomidate [(R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid methyl ester] (MTO, 1, Fig. 1) is a potent and selective inhibitor of the cytochrome P-450 enzyme system in the adrenal cortex. Labelled in the 4-position with radioiodine, (R)-4-[131I]iodometomidate, 2, [131I]IMTO has been evaluated by in-vitro studies and also ex-vivo in rats. [131I]IMTO was synthesized by oxidative radioiododestannylation using a suitable precursor which was prepared by a new stereoselective synthesis. Optimization of the labelling reaction was performed by systematic variation of the most important reaction parameters. Under optimum reaction conditions, a labelling yield of 95% was obtained. In-vitro-stability of the tracer was studied over 8 days, indicating slow deiodination (0.27%/h). Displacement studies using [131I]IMTO and rat adrenal membranes revealed the structural requirements for high affinity binding, namely an intact ester group and (R)-configuration of the radioligand. Pharmacokinetic studies in rats showed fast accumulation of [131I]IMTO in the adrenals (approx. 10% ID/g tissue) with an activity plateau for 2 hours. Metabolic degradation was indicated by a steady increase of renal activity up to 4 hours post injection. Based on target to non-target ratios the highest contrast for imaging of the adrenals was observed between 30 and 60 min post injection of [131I]IMTO. We conclude that SPECT using [123I]IMTO will be a promising method for the characterization of adrenal incidentalomas.
Chemoselective pre-conjugate radiohalogenation of unprotected mono- and multimeric peptides via oxime formation
Authors: Poethko Thorsten , Schottelius Margret , Thumshirn Georgette , Herz Michael , Haubner Roland , Henriksen Gjermund , Kessler Horst , Schwaiger Markus , Wester Hans-Jürgen 
Published: July 2004

Abstract
As part of our ongoing efforts in the development of new 18F-labeled peptides for clinical PET imaging, a new two-step 18F-labeling methodology based on the chemoselective oxime formation between an unprotected aminooxy-functionalized peptide and a 18F-labeled aldehyde was investigated and optimized.
4-[18F]Fluorobenzaldehyde ([18F]FB-CHO) was prepared by direct n.c.a. fluorination of 4-formyl-N,N,N-trimethylanilinium triflate and purified by radio-HPLC or a strong-cation-exchange/reverse phase cartridge system. The aminooxyacetic acid (Aoa) modified model peptide LEF-NH2 (Leu-Glu-Phe-NH2) and monomeric, dimeric and tetrameric RGD-containing cyclopeptides were synthesized by solid phase peptide synthesis. Radiochemical yields of N-(4-[18F]fluorobenzylidene)-oxime-formation ([18F]FBOA) with the Aoa-modified unprotected peptides were investigated. Optimized reaction conditions (60 °C, 0.5 mM peptide, 15 min, aqueous solution, pH 2.5) resulted in 70%-90% conjugation yields for all unprotected peptides studied. Chemoselectivity was demonstrated in competition experiments with amino acid mixtures. Biodistribution in M21 melanoma bearing mice showed improved tumor uptake and excretion behaviour in the series c(RGDfE)HEG-Dpr-[18F]FBOA < (c(RGDfE)HEG)2K-Dpr-[18F]FBOA < ((c(RGDfE)HEG)2K)2K-Dpr-[18F]FBOA. Two hours p.i. the fraction of intact c(RGDfE)HEG-K-Dpr-[18F]FBOA in blood, liver, kidney and tumor was >90%, indicating high in vivo stability of the oxime linkage. Initial PET studies with ((c(RGDfE)HEG)2-K)2-K-Dpr-[18F]FBOA showed excellent imaging of M21-melanomas in mice.
In conclusion, the new two-step chemoselective 18F-labeling fulfills all requirements for large scale syntheses of peptides in clinical routine. This methodology is also adaptable to other radioisotopes (e.g. radiohalogenation in general) and will thus offer a broad field of application.
A rapid, almost quantitative conversion of [11C]carbon dioxide into [11C]carbon monoxide via [11C]formate and [11C]formyl chloride
Authors: Roeda Dirk , Crouzel Christian , Dollé Frédéric 
Published: July 2004

Abstract
[11C]Formic acid can be produced from no-carrier-added [11C]carbon dioxide reliably and instantaneously in almost quantitative radiochemical yield using lithium triethylborohydride in THF. It can react, either on a solid support or as its non-hydrolysed LiEt3B-adduct, with a complex formed from hexachloroacetone and triphenylphosphine in THF at room temperature to give, again almost quantitatively, [11C]formyl chloride. The latter decomposes instantaneously to give [11C]carbon monoxide, providing an interesting alternative for current methods of [11C]carbon monoxide production in radiopharmaceutical chemistry. [11C]Formyl chloride has also potential in low-temperature N-formylation.
Determination of reaction parameters for the synthesis of the serotonin transporter ligand [11C]DASB: Application to a remotely controlled high yield synthesis
Authors: Solbach C. , Reischl G. , Machulla H.-J. 
Published: July 2004

Abstract
The synthesis of [11C]DASB is known to be performed by reacting the demethyl-DASB precursor with [11C]methyl iodide but the necessary reaction parameters had hitherto not been determined. In this work the dependence of the labelling yield on reaction temperature, reaction time, precursor concentration and type of solvent was investigated. Best results were found when methylation was carried out at 100 °C within 2 min using 4 mg/ml demethyl precursor in DMSO. With respect to [11C]methyl iodide a radiochemical yield of 74%±3% [11C]DASB was achieved. In addition, the synthesis was transferred to a remotely controlled module. A carbon-11 production for 1 h at 50 μA resulted in 3800-4300 MBq [11C]DASB with a specific activity of 152-211 GBq/μmol (4.1-5.7 Ci/μmol) (EOS) and a radiochemical purity of >95% in a sterile solution ready for injection. The total synthesis time was 45 min after EOB.
Synthesis of 4-([18F]fluoromethyl)-2-chlorophenylisothiocyanate: A novel bifunctional 18F-labelling agent
Authors: Wüst F. , Müller M. , Bergmann R. 
Published: July 2004

Abstract
The one-step radiosynthesis of 4-([18F]fluoromethyl)-2-chlorophenylisothiocyanate 18F-7 as a novel bifunctional 18F-labelling agent is described. Optimised reaction conditions in a remotely controlled synthesis module gave isothiocyanate 18F-7 in radiochemical yields of 45% (decay-corrected) within 40 min and high radiochemical purity of >95% after solid-phase-extraction. Coupling of compound 18F-7 with the primary amine benzylamine as a model reaction afforded the corresponding ((4-[18F]fluoromethyl)-2-chloro-phenyl)-benzyl thiourea 18F-8 in a high radiochemical yield of >90%. Stability studies of thiourea 18F-8 in terms of radiodefluorination showed appreciable buffer stability at pH 7.4, whereas significant radiodefluorination was observed when 18F-8 was incubated in buffers at pH 3.6 and pH 9.4. Preliminary dynamic PET studies with thiourea 18F-8 in male Wistar rats showed high bone accumulation, indicative of high in vivo radiodefluorination.
A new technique for radiolabelling of humic substances
Authors: Franke K. , Patt J. T. , Patt M. , Kupsch H. , Steinbach J. 
Published: July 2004

AbstractA new method of radiolabelling of humic substances (HS) in the aqueous phase has been developed. Radiolabelling with the short-lived positron-emitter18F was carried outviadiazonium coupling to electron-rich aromatic residues of the humic substances. Labelling yields of up to 75% were obtained after optimization of the synthetic procedure. Introductory experimental steps were performed for testing the labelling stability of the humic substances with ultrafiltration, electrophoretic and chromatographic methods.
Clinical presentation of 13 patients with subtelomeric rearrangements and a review of the literature
Authors: Roberts Amy E. , Cox Gerald F. , Kimonis Virginia , Lamb Allen , Irons Mira 
Published: July 2004

AbstractTo re‐examine the potential clinical indications for subtelomeric FISH testing and to provide additional cases to the growing literature on subtelomeric abnormalities and their genotype‐phenotype correlations, we present a single center case series of 13 patients with chromosomal abnormalities detected by subtelomeric FISH testing over a 21 month period. The most common abnormality involved chromosome 1p (23%). Partial monosomy was present in 69% of the patients, complex rearrangements in 23%, and partial trisomy in 8%. The mean time from first normal karyotype to positive subtelomeric FISH result was 3.8 years (n = 11, median 3.5 years, range: 6 months–10 years). One patient had an abnormal high resolution karyotype recognized retrospectively, and two other patients had abnormal karyotypes that were fully deciphered only after subtelomeric FISH analysis. Eighty five percent of cases occurred de novo. The subtelomeric FISH results were useful for adjusting the recurrence risks and helping to focus medical screening and monitoring. The results impacted family planning and satisfied families in search of a diagnosis. Our findings support the use of subtelomeric FISH analysis as a second tier test in patients suspected of having a chromosomal abnormality with a normal karyotype. Potential benefits of subtelomeric FISH testing include faster time to diagnosis, better informed patient prognosis, and more accurate genetic counseling. © 2004 Wiley‐Liss, Inc.
Genome‐wide linkage survey for genetic loci that affect the risk of suicide attempts in families with recurrent, early‐onset, major depression
Authors: Zubenko George S. , Maher Brion S. , Hughes Hugh B. , Zubenko Wendy N. , Scott Stiffler J. , Marazita Mary L. 
Published: July 2004

AbstractWe previously described the results of a genome‐wide linkage survey for genetic loci that influenced the development of unipolar mood disorders in 81 families identified by individuals with Recurrent, Early‐Onset, Major Depressive Disorder (RE‐MDD) [Zubenko et al. 2003b; Am J Med Genet (Neuropsychiatr Genet) 123B:1–18]. In the current study, we extended this linkage analysis by including the history of a suicide attempt as a covariate to identify chromosomal regions that harbor genes that influence the risk of this behavior in the context of mood disorders. This approach identified six linkage peaks with maximum multipoint ΔLOD scores that reached genome‐wide adjusted levels of significance (2p, 5q, 6q, 8p, 11q, and Xq). Four of these (2p, 6q, 8p, and Xq) exceeded the criterion for “highly‐significant linkage” (genome‐wide adjusted P < 0.001) recommended by Lander and Kruglyak [1995; Nat Genet 11:241–246]. The strongest evidence for linkage was observed in analyses employing affected relative pairs (ARPs) with the most severe and disabling Mood Disorders: Depression Spectrum Disorder and RE‐MDD. The highest ΔLOD score that emerged from this linkage analysis, 5.08, occurred for ARPs with Depression Spectrum Disorder at D8S1145 (37.0 cM, 18.2 Mbps, P < 0.0001) at cytogenetic location 8p22‐p21. Significant linkage results on Xq arose from analyses of ARPs with RE‐MDD at DXS1047 (143 cM, 127.8 Mbps, ΔLOD = 3.87, P < 0.0001), a finding that may contribute to the higher rate of suicide attempts among women than men. These findings provide evidence for suicide risk loci that are independent of susceptibility loci for Mood Disorders, and suggest that the capacity for suicide risk loci to affect the development of suicidal behavior depends on the psychiatric disorder or subtype with which they interact. © 2004 Wiley‐Liss, Inc.
Genetic conditions associated with intestinal juvenile polyps
Authors: Merg Anders , Howe James R. 
Published: July 2004

AbstractJuvenile polyps are hamartomatous polyps found primarily in infants and children, and in association with juvenile polyposis (JP; OMIM# 174900), Cowden syndrome (CS; OMIM# 158350), and Bannayan‐Riley‐Ruvalcaba syndrome (BRRS; OMIM# 153480). Although solitary juvenile polyps are benign lesions, when present in JP patients they may lead to gastrointestinal cancers. Germline mutations in MADH4 and BMPR1A predispose to JP, and both genes are involved in TGF‐β superfamily signaling pathways. In CS and BRRS, juvenile polyps are a less consistent feature, and CS patients are at risk for breast and thyroid cancers. Mutations of the tumor suppressor gene PTEN have been found in the germline of both CS and BRRS patients. Despite different underlying genetic mechanisms, these and other syndromes share the same phenotypic feature of juvenile polyps. © 2004 Wiley‐Liss, Inc.
Genetic insights into familial tumors of the nervous system
Authors: Melean German , Sestini Roberta , Ammannati Franco , Papi Laura 
Published: July 2004

AbstractNervous system tumors represent unique neoplasms that arise within the central and peripheral nervous system. While the vast majority of nervous system neoplasm occur sporadically, most of the adult and pediatric forms have a hereditary equivalent. In a little over a decade, we have seen a tremendous increase in knowledge of the primary genetic basis of many of the familial cancer syndromes that involve the nervous system, syndromes that are mostly inherited as autosomal dominant traits. In this review, we discuss the most recent findings on the genetic basis of hereditary nervous system tumors. The identification of genes associated with familial cancer syndromes has in some families enabled a “molecular diagnosis” that complements clinical assessment and allows directed cancer surveillance for those individuals determined to be at‐risk for disease. © 2004 Wiley‐Liss, Inc.
Longitudinal analysis of deciduous tooth emergence: IV. Covariate effects in Japanese children
Authors: Holman Darryl J. , Yamaguchi Kyoko 
Published: July 2004

AbstractEmergence of the deciduous teeth is generally considered to be robust to moderate environmental insults, malnutrition, and disease. Consequently, deciduous tooth emergence has been used to assess growth and development and for age estimation in children. In this paper, we examine the way in which nutritional status and other covariates affect deciduous tooth emergence in a sample of 114 Japanese children born in Tokyo in 1914 and 1924. Parametric survival analysis was used to quantify the effects of nutritional status, breastfeeding behavior, and sex on the hazard of deciduous tooth emergence. Children of poor nutritional status exhibited significantly delayed emergence of all deciduous teeth, with effects that ranged from 14–29% increases in mean emergence times. Children of medium nutritional status exhibited increases in mean emergence times of 5–9% for the canines and lower molars, and 13–17% for the incisors. Partial breastfeeding had no effect on tooth emergence, but children who were not breastfed at all showed delayed emergence of the upper incisors. No significant sex differences in emergence were found. The findings contradict the idea that moderate malnutrition has little effect on deciduous tooth emergence. Furthermore, nutritional differences may account for some of the observed differences among populations in the timing of tooth emergence. Am J Phys Anthropol, 2004. © 2004 Wiley‐Liss, Inc.
Continuity or colonization in Anglo‐Saxon England? Isotope evidence for mobility, subsistence practice, and status at West Heslerton
Authors: Montgomery Janet , Evans Jane A. , Powlesland Dominic , Roberts Charlotte A. 
Published: July 2004

AbstractThe adventus Saxonum is a crucial event in English protohistory. Scholars from a range of disciplines dispute the scale and demographic profile of the purported colonizing population. The 5th–7th century burial ground at West Heslerton, North Yorkshire, is one of the few Anglian cemeteries where an associated settlement site has been identified and subjected to extensive multidisciplinary postexcavation study. Skeletal and grave good evidence has been used to indicate the presence of Scandinavian settlers. A small, preliminary study using lead and strontium isotope analysis of tooth enamel, mineralized in early childhood, from Neolithic/Early Bronze Age (n = 8), Iron Age (n = 2), and Early Anglo‐Saxon (n = 32) skeletons, was carried out to directly investigate this hypothesis. Results suggest that lead provides dissimilar types of information in different time periods. In post‐Roman England, it appears to reflect the level of exposure to circulated anthropogenic rather than natural geological lead, thus being a cultural rather than geographical marker. Consequently, only strontium provides mobility evidence among the Anglian population, whereas both isotope systems do so in pre‐Roman periods. Strontium data imply the presence of two groups: one of “local” and one of “nonlocal” origin, but more work is required to define the limits of local variation and identify immigrants with confidence. Correlations with traditional archaeological evidence are inconclusive. While the majority of juveniles and prehistoric individuals fall within the “local” group, both groups contain juveniles, and adults of both sexes. There is thus no clear support for the exclusively male, military‐elite invasion model at this site. Am J Phys Anthropol 126:123–138, 2005. © 2004 Wiley‐Liss, Inc.
Paleopathological study of hallux valgus
Authors: Mays S.A. 
Published: July 2004

AbstractHallux valgus is the abnormal lateral deviation of the great toe. The principal cause is biomechanical, specifically the habitual use of footwear which constricts the toes. In this study, descriptions of the anatomical changes of hallux valgus from published cadaveric and clinical studies were used to generate criteria for identifying the condition in ancient skeletal remains. The value of systematic scoring of hallux valgus in paleopathology is illustrated using two British skeletal series, one dating from the earlier and one from the later Medieval period. It was found that hallux valgus was restricted to later Medieval burials. This appears consistent with archaeological and historical evidence for a rise in popularity, during the late Medieval period (at least among the richer social classes), of narrow, pointed shoes which would have constricted the toes. Am J Phys Anthropol 126:139–149, 2005. © 2004 Wiley‐Liss, Inc.
Changing intracellular compartmentalization of β‐galactosidase in the ROSA26 reporter mouse during embryonic development: A light‐ and electron‐microscopic study
Authors: Aoyama Naoyoshi , Molin Daniel G.M. , Mentink Monica M.T. , Koerten Henk K. , de Ruiter Marco C. , Gittenberger‐de Groot Adriana C. , Poelmann Robert E. 
Published: July 2004

AbstractThe beta‐geo (LacZ) reporter gene encodes for β‐galactosidase (β‐gal) in all cells of the ROSA26 mouse during embryonic development. As such, β‐gal activity constitutes an excellent marker for in situ labeling of expressing cells. However, the intracellular distribution of β‐gal differs between cells, and changes during embryonic development. Therefore, we studied LacZ‐encoded β‐gal using light and electron microscopy in the heart, lung, liver, and small intestine on days 13 and 16 of gestation, and the kidney on day 16 of gestation in ROSA26 mice. The Bluo‐gal method was carried out under standardized conditions, including fixation, washing, and incubation procedures. Intracellular β‐gal staining is encountered in a combination of membranous compartments, including the nuclear envelope, the endoplasmic reticulum, and the plasma membrane. Its exact localization depends on the cell type and is regulated during development. Therefore, one must take the compartmental transition of intracellular β‐gal staining into consideration when interpreting results obtained from experiments using ROSA26 mice. © 2004 Wiley‐Liss, Inc.
Localization of estrogen and androgen receptors in male reproductive tissues of mice and rats
Authors: Yamashita Shuji 
Published: July 2004

AbstractUsing immunohistochemical methods, we studied the cell‐type‐ and species‐specific expressions of estrogen receptor (ER) isoforms (ERα and ERβ) and androgen receptors (ARs) in the male reproductive tract and accessory sex glands of mature mice and rats. ERα and ERβ showed cell‐type‐ and species‐specific distributions, respectively. In contrast, AR was localized in the epithelial and stroma cells of all tissues examined in this study, in both species. In mice, the epithelial cells of the ductuli efferentes showed a strong ERα‐immunoreaction, and those of the caput epididymis, coagulating glands, and prostate also exhibited a positive reaction. Stroma cells, except in the ductuli efferentes, showed a positive ERα‐immunostaining. In rats, ERα was detected in very few cell types: the epithelial cells of the ductuli efferentes showed a strong reaction, and the stroma cells of the ampullary and urethral glands exhibited a weak reaction. ERβ was localized in the epithelial cells of the prostate in mice, while the reaction was faint or negative in both the epithelial and stroma cells of other tissues. In rats, the ERβ‐immunoreaction was strongest in the epithelial cells of the ventral prostate. The epithelial cells of the corpus and cauda epididymis, ductus deferens, and urethral glands, and the stroma cells of the urethral glands were also positively ERβ‐immunostained. Almost the same AR distribution pattern was observed in both species. In particular, strong AR‐immunostaining was present in the epithelial cells of the caput and corpus epididymis, seminal vesicle, and ventral prostate. These results indicate that species and tissues differences should be taken into careful consideration in assessing the physiological and pharmacological effects of sex steroids (particularly estrogens) on the reproductive tissues of male rodents. © 2004 Wiley‐Liss, Inc.