bluuebunny/crossref_metadata_2025 huggingface dataset:
Skin‐sparing mastectomy
Authors: Bleicher Richard J. , Hansen Nora M. , Giuliano Armando E.
Published: November 2003

BACKGROUND

Skin‐sparing mastectomy (SSM) is a variation of modified radical mastectomy (MRM) optimized for reconstruction. The authors attempted to determine SSM attitudes and biases within different specialties and countries throughout the world.

METHODS

The authors polled 11,485 individuals via e‐mail, including members of surgical, medical, and breast oncology societies, about SSM. Respondents were directed to a survey website where data were directly entered into a database.

RESULTS

Among 1027 respondents, 19 said their knowledge was insufficient to attempt the survey. Surveys were completed by 1008 respondents (8.8%) from 52 countries, comprising 436 (43.3%) surgeons, 376 (37.3%) medical oncologists, 146 (14.5%) radiation oncologists, and 50 (5.0%) individuals from other fields. Of the respondents, 61.9% stated that SSMs are performed at their institution. However 19.1% of these believed that SSM leaves the nipple and areola intact. This perception was higher outside the U.S. (P < 0.0001). Despite knowledge by 77.8% that SSM does not have a higher local disease recurrence rate than MRM, 25.3% of these individuals did not believe the literature. This was most prevalent among radiation oncologists (48.5%), as was the belief that SSM is contraindicated in patients with ductal carcinoma in situ and invasive breast carcinoma (23.3%).

CONCLUSIONS

Despite a developing body of literature, there was variation in opinion among specialties and a lack of understanding of SSM. Many physicians were not familiar with the literature. Among those who were, skepticism was highest among radiation oncologists. Although these results were indicative of only those responding, education about SSM is needed across specialties and in other countries if the procedure is to be widely accepted. Cancer 2003. © 2003 American Cancer Society.
Disease‐specific symptoms and general quality of life of patients with prostate carcinoma before and after primary three‐dimensional conformal radiotherapy
Authors: Staff Ilene , Salner Andrew , Bohannon Richard , Panatieri Pauline , Maljanian Rose
Published: November 2003

BACKGROUND

Approximately 189,000 men are diagnosed with prostate carcinoma each year and more than 1 million are living with the disease. Good prognoses and undesirable sequelae accompany each of several available primary and adjuvant treatment options. The current study explored the effects of primary three‐dimensional conformal radiotherapy with or without neoadjuvant hormonal therapy on urinary, bowel, and sexual symptoms and health‐related quality of life (HRQOL).

METHODS

A prospective, repeated‐measures design study included 100 patients. Data from the Medical Outcomes Study Short Form Health Survey (a measure of general HRQOL) and a 12‐item symptom questionnaire were collected before the start of radiotherapy, approximately 1–3 months after completion of treatment, and again approximately 5–10 months after completion of treatment for follow‐up.

RESULTS

Patients reported few urinary symptoms after treatment. Bowel frequency and urgency were reported more frequently posttreatment and at follow‐up. Erectile difficulties, which were common pretreatment, were reported with increased frequency posttreatment and at follow‐up. General HRQOL scores were higher than age‐related general population norms for men at all three data collection times, but there were significant losses posttreatment for patients' physical functioning and vitality. At the 5–10‐month follow‐up, physical functioning remained lower but vitality scores regained some of the losses. A more extended follow‐up is needed. Neoadjuvant therapy, which was received before the pretreatment data collection, had a deleterious effect on erectile functioning but no interactive effects with the radiotherapy on symptoms or HRQOL.

CONCLUSIONS

Although patients with a diagnosis of prostate carcinoma experienced increased bowel and sexual dysfunction and decreased vitality after radiotherapy, their HRQOL scores remained at or above age‐related general population norms. Cancer 2003. © 2003 American Cancer Society.
Presence of the latent membrane protein 1 gene in nasopharyngeal swabs from patients with mucosal recurrent nasopharyngeal carcinoma
Authors: Tsang Ngan‐Ming , Chuang Chi‐Cheng , Tseng Chen‐Kan , Hao Sheng‐Po , Kuo Tseng‐Tong , Lin Chien‐Yu , Pai Ping‐Ching
Published: November 2003

BACKGROUND

Nasopharyngeal carcinoma (NPC) is the most common head and neck malignancy in southeastern China and Taiwan. Early detection of the local disease followed by timely and appropriate treatment is essential to increasing cure and survival rates. Detection of Epstein–Barr virus (EBV) genomic DNA, such as the latent membrane protein 1 gene (LMP‐1), in patients postirradiation during follow‐up may indicate mucosal recurrence.

METHODS

Seventy‐one patients with NPC underwent serial nasopharyngeal swabs for LMP‐1 polymerase chain reaction assay before, during, and after irradiation. All of patients achieved a complete disease remission of the LMP‐1 gene after irradiation that lasted for at least 6 months.

RESULTS

The median LMP‐1 disease remission time after the beginning of irradiation was 4.3 weeks. Patients with early LMP‐1 disease remission (≤ 4 weeks after the beginning of irradiation) and delayed LMP‐1 disease remission (> 4 weeks) had 3‐year local control rates of 93.5% and 76.9%, respectively (P = 0.0529). The LMP‐1 gene was detected again (reexpression of LMP‐1 [re‐LMP‐1]) in 10 patients after irradiation with at least 6 months of follow‐up. Nine of 10 patients (90%) in the re‐LMP‐1 positive group and 2 of 61 patients (3.3%) in the re‐LMP‐1 negative group developed local recurrence. Mucosal recurrence developed in nine patients, and all displayed re‐LMP‐1. By detecting re‐LMP‐1 using nasopharyngeal swabs, mucosal recurrence was diagnosed with a sensitivity of 100% (9 of 9 patients) and a specificity of 98.4% (61 of 62 patients). The 3‐year overall survival rate, the disease free survival rate for the entire group, and the estimated local mucosal control rates in the re‐LMP‐1 positive and re‐LMP‐1 negative groups were 86.5%, 76.5%, 19.4%, and 96.7%, respectively.

CONCLUSIONS

Expression of EBV LMP‐1 in nasopharyngeal swab specimens from patients with irradiated/treated NPC can provide a highly sensitive and specific method of forecasting mucosal recurrence. This investigation confirmed the reliability and feasibility of nasopharyngeal swabs in screening for mucosal recurrences in patients with NPC. Cancer 2003. © 2003 American Cancer Society.
Impact of race on outcome after definitive radiotherapy for squamous cell carcinoma of the head and neck
Authors: Al‐Othman Majid O. F. , Morris Christopher G. , Logan Henrietta L. , Hinerman Russell W. , Amdur Robert J. , Mendenhall William M.
Published: November 2003

BACKGROUND

The objective of the current study was to evaluate the impact of race (black vs. white) on the outcome of patients with invasive squamous cell carcinoma of the head and neck.

METHODS

Between 1983 and 1997, 686 patients completed definitive, twice‐daily radiotherapy (RT) alone or combined with a planned neck dissection; no patients received adjuvant chemotherapy. The minimum follow‐up was 2 years, and median follow‐up was 7 years for living patients. No patients were lost to follow‐up. Fifty‐five patients were black (8%).

RESULTS

Although the two groups had similar 5‐year local‐regional control rates (black patients vs. white patients: 70% vs. 76%, respectively;P= 0.275), black patients had double the risk for distant recurrence compared with white patients (27% vs. 13%;P= 0.012). The 5‐year cause‐specific and absolute survival rates were lower for black patients (52% vs. 74% [P= 0.001] and 29% vs. 52% [P< 0.001], respectively). Multivariate analyses revealed that race was an independent predictor of freedom from distant metastasis (P= 0.013), cause‐specific survival (P= 0.005), and absolute survival (P< 0.001).

CONCLUSIONS

Although equal local‐regional control rates can be achieved in black patients and white patients with squamous cell carcinoma of the head and neck, the risk of distant recurrence was significantly higher in black patients and resulted in decreased survival. Reevaluation of current strategies for pretreatment metastatic work‐ups and development of more effective systemic therapy will be key to improving the survival disparity in this group. Cancer 2003. © 2003 American Cancer Society.
Indole‐3‐carbinol induces a G1 cell cycle arrest and inhibits prostate‐specific antigen production in human LNCaP prostate carcinoma cells
Authors: Zhang Joann , Hsu B.A. Jocelyn C. , Kinseth B.A. Matthew A. , Bjeldanes Leonard F. , Firestone Gary L.
Published: November 2003

BACKGROUND

Indole‐3‐carbinol (I3C), a naturally occurring component of Brassica vegetables, such as cabbage, broccoli, and Brussels sprouts, is a promising anticancer agent for certain reproductive tumor cells. The objective of the current study was to characterize the cell cycle effects of I3C in human prostate carcinoma cells.

METHODS

The incorporation of [3H]thymidine and flow cytometry of propidium iodide–stained nuclei were used to monitor I3C‐regulated changes in prostate carcinoma cell proliferation and cell cycle progression. Western blotting was used to document expression changes in cell cycle components and prostate‐specific antigen (PSA) levels. The enzymatic activities of cyclin‐dependent kinases (CDK) were tested by in vitro protein kinase assays using the retinoblastoma protein as a substrate.

RESULTS

I3C suppressed the growth of LNCaP prostate carcinoma cells in a dose‐dependent manner by inducing a G1 block in cell cycle progression. I3C selectively inhibited the expression of CDK6 protein and transcripts and strongly stimulated the production of the p16 CDK inhibitor. In vitro protein kinase assays revealed the striking inhibition by I3C of immunoprecipitated CDK2 enzymatic activity and the relatively minor down‐regulation of CDK4 enzymatic activity. In LNCaP prostate carcinoma cells, I3C treatment inhibited production of PSA, whereas combinations of I3C and the androgen antagonist flutamide more effectively inhibited DNA synthesis and PSA levels compared with either agent alone.

CONCLUSIONS

The results of the current study demonstrated that I3C has a potent antiproliferative effect in LNCaP and other human prostate carcinoma cells. These findings implicate this dietary indole as a potential chemotherapeutic agent for controlling the growth of human prostate carcinoma cells. Cancer 2003. © 2003 American Cancer Society.
Dynamic‐window search for real‐time simulation of dynamic systems
Authors: Yoon Sugjoon , Kang Hyounjoo
Published: November 2003

1Various parameter values are provided in the form of tables, where data keys are ordered and unevenly spaced in general, for real‐time simulation of system components or dynamics of vehicles such as airplanes, automobiles, ships, and so on. The main purpose of this study is to compare conventional searching algorithms and to find or develop the most efficient searching method under constraint of real‐time simulation, especially hardware‐in‐the‐loop simulation. Since the real‐time constraint enforces use of a fixed step size in the integration of system differential equations because of the inherent nature of input from and output to real hardware, the worst case of iterated probes in searching algorithms is the key measure of comparison. If a parameter value has certain dynamics because of its relation with the state variables of the simulated system, the integration algorithm and the step size, a searching region at a given time frame can be reduced dramatically from the entire data table taking advantage of the information. The size of the reduced searching region, named dynamic‐searching window, varies and the window moves by its own dynamics as simulation time runs. Numerous numerical experiments were conducted with various data tables of different sizes and types, and yielded results compatible with relevant theories. In conclusion, whether bisection or interpolation or fast search is used in real‐time hardware‐in‐the‐loop simulation, the combination of dynamic‐window search guarantees a more stable and faster search of parameter values than using conventional algorithms alone. Copyright © 2003 John Wiley & Sons, Ltd.
Generation and characterization of the humoral immune response to DNA immunization with a chimeric β‐amyloid‐interleukin‐4 minigene
Authors: Ghochikyan Anahit , Vasilevko Vitaly , Petrushina Irina , Movsesyan Nina , Babikyan Davit , Tian Wenqiang , Sadzikava Nadya , Ross Ted M. , Head Elizabeth , Cribbs David H. , Agadjanyan Michael G.
Published: November 2003

Active immunization with fibrillar β–amyloid peptide (Aβ42) as well as passive transfer of anti‐Aβ antibodies significantly reduces Aβ plaque deposition, neuritic dystrophy, and astrogliosis in the brain of mutant amyloid precursor protein (APP)‐transgenic mice. Although the mechanism(s) of clearance of Aβ from the brain following active or passive immunization remains to be determined, it is clear that anti‐Aβ antibodies are critical for clearance. DNA immunization provides an attractive alternative to direct peptide and adjuvant approaches for inducing a humoral response to Aβ. We constructed a DNA minigene with Aβ fused to mouse interleukin‐4 (pAβ42‐IL‐4) as a molecular adjuvant to generate anti‐Aβ antibodies and enhance the Th2‐type of immune responses. Gene gun immunizations induced primarily IgG1 and IgG2b anti‐Aβ antibodies. Fine epitope analysis with overlapping peptides of the Aβ42 sequence identified the 1–15 region as a dominant B cell epitope. The DNA minigene‐induced anti‐Aβ antibodies bound to Aβ plaques in brain tissue from an Alzheimer's disease patient demonstrating functional activity of the antibodies and the potential for therapeutic efficacy.
Cutaneous lymphocyte antigen expression on human effector B cells depends on the site and on the nature of antigen encounter
Authors: Kantele Anu , Savilahti Erkki , Tiimonen Heidi , Iikkanen Katja , Autio Soile , Kantele Jussi M.
Published: November 2003

In contrast to T cells, information on skin‐homing B cells expressing the cutaneous lymphocyte antigen (CLA) is sparse. CLA expression on human B cells was investigated among circulating immunoglobulin‐secreting cells (ISC) and among antigen‐specific antibody‐secreting cells (ASC) elicited by parenteral, oral or rectal primary immunization, or by parenteral or oral secondary immunizationwith Salmonella typhi Ty21a. CLA expression was examined by combining cell sorting with an enzyme‐linked immunospot assay. Among all ISC, the proportion of CLA+ cells was 13–21%. Parenteral immunization induced antigen‐specific ASC of which 13% were CLA+, while oral and rectal immunizations were followed by only 1% of CLA+ ASC (p<0.001). Oral re‐immunization was followed by an up‐regulation of CLA (34–48%) regardless of the route of priming. Parenteral re‐immunization elicited ASC of which 9–14% were CLA+. In conclusion, the expression of CLA on human effector B cells depends on the site of antigen encounter: intestinal stimulation elicits cells with no CLA, while parenteral encounter elicits significant numbers of CLA+ cells. Even though primary antigen encounter in the intestine failed to stimulate CLA expression, up‐regulation of CLA was found upon intestinal antigen re‐encounter. These findings may be of relevance in the pathogenesis of some cutaneous disorders.
IL‐12 receptor deficiency revisited: IL‐23‐mediated signaling is also impaired in human genetic IL‐12 receptor β1 deficiency
Authors: Hoeve Marieke A. , de Boer Tjitske , Langenberg Dennis M. L. , Sanal Ozden , Verreck Frank A. W. , Ottenhoff Tom H. M.
Published: November 2003

IFN‐γ and IL‐12 are crucial cytokines for cell‐mediated immunity against intracellular pathogens. We have previously shown that human IL‐12Rβ1‐deficiency leads to impaired IL‐12 responsiveness and unusual susceptibility to infections due to mycobacteria and salmonellae. IL‐23 is a cytokine with functions that partially overlap with those of IL‐12. IL‐23 consists of IL‐12p40 and anovel p19 protein, and binds to a receptor complex comprising IL‐12Rβ1 and IL‐23R. Thus, IL‐12Rβ1‐deficiency may impair both IL‐12‐ and IL‐23 signaling, and both may contribute to the immunological phenotypes. To examine whether IL‐12Rβ1 is essential for IL‐23 signaling in human T cells, we have studied IL‐23 responsiveness of four IL‐12Rβ1‐deficient individuals. Whereas IL‐23promoted IFN‐γ production by CD4+ and CD8+ T cells in controls, IL‐12Rβ1‐deficient T cells lacked IL‐23‐induced IFN‐γ secretion, but responded normally to IL‐2, IL‐4, IL‐15 and IL‐18. We also show that induction of IFN‐γ production by IL‐23 depends upon TCR‐ligation and is enhanced by CD28‐costimulation. Furthermore, IL‐23 cooperates with IL‐12 and IL‐18 in promoting IFN‐γ production in controls, but not in patients. We conclude that IL‐12Rβ1‐deficiency impairs IL‐12‐ and IL‐23‐dependent signaling in human T cells. The syndrome caused by IL‐12Rβ1‐deficiency thus needs to be reinterpreted as resulting from defective IL‐12‐as well as IL‐23‐mediated immunity.
Mini‐review CD4 T cells are required for CD8 T cell memory generation
Authors: Bourgeois Christine , Tanchot Corinne
Published: November 2003

Whereas the role of CD4 T cells in B cell memory generation is well established and unequivocal, the role that CD4 T cells play in CD8 responses was until recently far more elusive and controversial. A series of recent reports, however, have re‐assessed the role of CD4 help on CD8 responses and have given rise to surprisingly unambiguous conclusions. While studying very different systems, they demonstrated that CD4 T cells are absolutely required for the generation of bona fide CD8 memory cells; the reports allow, for the first time, strong analogies to be made between B and CD8 memory cell generation. These data invite us to drastically change our idea of CD4 help on CD8 responses because they show that the old dichotomy — Th‐dependent versus Th‐independentCD8 responses — is no longer accurate.
Selective Formation of Inter‐ and Intramolecular A‐D‐A π‐π Stacking: Solid‐State Structures of Bis(pyridiniopropyl)benzenes
Authors: Koizumi Take‐aki , Tsutsui Kanako , Tanaka Koji
Published: November 2003

The synthesis and molecular structures of bis(pyridiniopropyl)benzene derivatives, [1,4‐(4‐R‐C5H4N+CH2CH2CH2)2C6H4][X−]2 (1, R = H, X = I; 2, R = tBu, X = Br) have been investigated. Compound 1 adopts a linear structure in the solid state and the crystal packing geometry can be defined as isolated triplets formed by the phenylene ring of one molecule and two pyridinium rings of two neighboring molecules. In contrast, compound 2 has an S‐shaped arrangement, and an intramolecular acceptor−donor−acceptor triplet is formed among the central phenylene ring and two terminal pyridinium rings in the same molecule. Such a distinct difference in the crystal structures of 1 and 2 can be ascribed to the substituent on the pyridinium unit. The steric repulsion of the bulky tert‐butyl group hinders intermolecular A‐D‐A π‐π stacking. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
2‐Substituted (Azulen‐1‐yl)ethenes
Authors: Razus Alexandru C. , Nitu Carmen , Tecuceanu Victorita , Cimpeanu Valentin
Published: November 2003

An easy and efficient solvent‐free synthesis of 1‐(azulen‐1‐yl)‐2‐aryl‐ and heteroarylethenes is described. The reaction was performed simply by melting solid mixtures of azulenic Schiff bases and arylacetic acids, the crude products being purified by column chromatography. Limitations of the method were established by study of a large range of aryl and heteroarylacetic acids and also by examination of various azulenic Schiff bases. The same reaction was observed with other active methylene compounds, such as malonic acid and its derivatives or 1,3‐diketones. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Exploring Structural Opportunities: The Regioflexible Substitution of 1,3‐Difluorobenzene
Authors: Schlosser Manfred , Heiss Christophe
Published: November 2003

To demonstrate the superiority of modern organometallic methods, the inexpensive starting material 1,3‐difluorobenzene has been selectively converted into the three benzoic acids and all seven bromobenzoic acids containing the two fluorine atoms in homovicinal positions. The 2,6‐difluorobenzoic acid (1) was prepared in a one‐pot reaction consisting of direct metallation and carboxylation. The key step on the route to the bromobenzoic acid 4 was a deprotonation‐triggered bromine migration from the 2‐ to the 4‐position. All other products were attained through (2,6‐difluorophenyl)triethylsilane (11). Consecutive deprotonation of the sites adjacent to the fluorine atoms, followed by appropriate electrophilic substitution, provided not only the acid 7 but also the dibromo and iodobromo derivatives 13 and 23. These in turn gave the isomers 14 and 24 upon base‐mediated migration of the heaviest halogen, which made the acids 8 and 10 directly accessible. The regiocontrolled monodebromination of intermediate 14 afforded (4‐bromo‐2,6‐difluoro)triethylsilane (15), which opened the route to the acids 3 and 5 (by carboxylation and protodesilylation) and to acid 9 (by carboxylation and bromodesilylation). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Further Studies on the Synthesis of meso‐Tetraarylazuliporphyrins under Lindsey−Rothemund Reaction Conditions and Their Conversion into Benzocarbaporphyrins
Authors: Lash Timothy D. , Colby Denise A. , Ferrence Gregory M.
Published: November 2003

Azulene has been shown to react with pyrrole and a series of aromatic aldehydes in the presence of boron trifluoride etherate to give meso‐tetraarylazuliporphyrins 6. Good yields of azuliporphyrins were obtained for benzaldehyde, 4‐chlorobenzaldehyde, 4‐bromobenzaldehyde, and 4‐iodobenzaldehyde, and under dilute conditions p‐tolualdehyde gave respectable yields. In each case, substantial amounts of meso‐tetraarylporphyrins were also formed and a minor fraction of carbaporphyrin by‐products could be detected, but otherwise no other macrocyclic products could be identified. 4‐Nitrobenzaldehyde gave relatively poor yields of the corresponding azuliporphyrin, while p‐anisaldehyde only gave trace amounts of product. Pentafluorobenzaldehyde gave variable results, although in this case a large number of additional by‐products were identified including N‐fused pentaphyrin, hexaphyrin, and higher order porphyrinoids, but no expanded azulene‐containing macrocycles could be detected. Azuliporphyrins undergo reversible nucleophilic substitution on the seven‐membered ring with pyrrolidine, benzenethiol, hydrazine, or benzylamine to give carbaporphyrin adducts. This property appears to facilitate an oxidative ring contraction of azuliporphyrins 6 with tert‐butyl hydroperoxide in the presence of potassium hydroxide to produce mixtures of benzocarbaporphyrins 19 and 20. Tetraaryl‐benzocarbaporphyrins exhibit slightly reduced diatropic ring currents compared to their meso‐unsubstituted counterparts, although their UV/Vis spectra are very porphyrin‐like and exhibit strong Soret bands near 450 nm. The benzocarbaporphyrins undergo reversible protonation to give monocationic and dicationic species. The latter involves C‐protonation to generate an internal CH2 within the macrocyclic cavity. X‐ray crystallography of tetraphenylbenzocarbaporphyrin 19a confirms that the preferred tautomer has the two NHs on either side of the indene subunit, in agreement with previous theoretical and spectroscopic studies. In addition, the presence of phenyl substituents at the 5,20‐positions was found to tilt the indene moiety substantially by 27.4(1)° relative to the [18]annulene substructure. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Cover Picture: Studies in the Cycloproparene Series: Unexpected Products from Peterson Olefinations (Eur. J. Org. Chem. 23/2003)
Authors: Halton Brian , Boese Roland , Dixon Gareth M.
Published: November 2003

The cover picture shows the computed density potential (left) for the expected calicene from Peterson olefination of 1,1‐disilylcyclopropa[b]naphthalene with tetracyclone. The alcohol actually obtained from the reaction is shown on the right in its favoured conformation. Details are discussed in the article by B. Halton et al. on p. 4507 ff.
Electrochemical Studies of Thiol Self‐Assembled Monolayers at a Heated Gold‐Wire Microelectrode
Authors: Wang Jun , Gründler Peter
Published: November 2003

Mercaptoundecanoic acid (MUA) and glutathione (GSH) self‐assembled monolayers were prepared on gold‐ wire microelectrode. Cyclic voltammetry was used to investigate the influence of temperature on electrochemical behaviors of Fe(CN)63−/4− and Ru(NH3)63+/2+ at these SAMs modified electrodes in aqueous solution. It is found that temperature shows great influence on electron transfer (ET) and mass transport (MT) for the two SAMs modified electrodes and the influence of temperature depends on the charge properties of the redox couples and terminal groups of SAMs and the structure of the monolayer on gold surface. The temperature can greatly increase MT rate of Fe(CN)63−/4− at both MUA and GSH modified electrodes. However, the increased MT rate doesn't have any effect on the CV's for Fe(CN)63−/4− /MUA system. For Ru(NH3)63+/2+ , temperature can greatly improve the electrochemical reaction in both MUA and GSH modified electrodes, which is ascribed to temperature‐induced diffusion and convection and the electrostatic interaction between Ru(NH3)63+/2+ and negatively charged carboxyl groups on the electrode surface.
Extraction of rosemary essential oil by steam distillation and hydrodistillation
Authors: Boutekedjiret C. , Bentahar F. , Belabbes R. , Bessiere J. M.
Published: November 2003

Rosemary oil was extracted by both steam and hydrodistillations then analysed by gas chromatography and gas chromatography–mass spectrometry. The effect of time of extraction enabled us to follow the evolution of the yield and oil composition obtained by both processes. Copyright © 2003 John Wiley & Sons, Ltd.
Candidate gene association analysis for a quantitative trait, using parent‐offspring trios
Authors: Gauderman W. James
Published: November 2003

With the increasing availability of genetic data, many studies of quantitative traits focus on hypotheses related to candidate genes, and also gene‐environment (G×E) and gene‐gene (G×G) interactions. In a population‐based sample, estimates and tests of candidate gene effects can be biased by ethnic confounding, also known as population stratification bias. This paper demonstrates that even a modest degree of ethnic confounding can lead to unacceptably high type I error rates for tests of genetic effects. The parent‐offspring trio design is reviewed, and several forms of the quantitative transmission disequilibrium test (QTDT) are summarized. A variation of the QTDT (QTDTM) is described that is based on a linear regression model with multiple intercepts, one per parental mating type. This and other models are expanded to allow testing of G×E and G×G interactions. A method for computing required sample sizes using direct computations is described. Sample size requirements for tests of genetic main effects and G×E and G×G interactions are compared across various QTDT approaches to infer their efficiencies relative to one another. The QTDTM is found to meet or exceed the efficiency of other QTDT approaches. For example, the QTDTM is approximately 3% more efficient than the QTDT of Rabinowitz ([1997] Hum. Hered. 47:342–350) for testing a genetic main effect, but can be as much as twice as efficient for testing G×E interaction, and three times more efficient for testing G×G interaction. Genet Epidemiol 25:327–338, 2003. © 2003 Wiley‐Liss, Inc.
Score tests for epistasis models on quantitative traits using general pedigree data
Authors: Wang Kai
Published: November 2003

Efficient score tests for a two‐locus model for quantitative traits are proposed for general pedigrees. Two search strategies, simultaneous search and conditional search, are considered. These tests are attractive alternatives to the likelihood ratio test for their asymptotic equivalency to their respective likelihood ratio tests and efficiency in computation. The finite‐sample properties of these tests are investigated through simulations. Extensions to more complicated models and to other search strategies are discussed. Genet Epidemiol 25:314–326, 2003. © 2003 Wiley‐Liss, Inc.
Species and gender differences in the metabolism and distribution of tertiary amyl methyl ether in male and female rats and mice after inhalation exposure or gavage administration
Authors: Sumner Susan C. J. , Janszen Derek B. , Asgharian Bahman , Moore Timothy A. , Parkinson Horace D. , Fennell Timothy R.
Published: November 2003

Tertiary amyl methyl ether (TAME) is a gasoline fuel additive used to reduce emissions. Understanding the metabolism and distribution of TAME is needed to assess potential human health issues. The effect of dose level, duration of exposure and route of administration on the metabolism and distribution of TAME were investigated in male and female F344 rats and CD‐1 mice following inhalation or gavage administration. By 48 h after exposure, >96% of the administered radioactivity was expired in air (16–71%) or eliminated in urine and feces (28–72%). Following inhalation exposure, mice had a two‐ to threefold greater relative uptake of [14C]TAME compared with rats. Metabolites were excreted in urine of rats and mice that are formed by glucuronide conjugation of tertiary amyl alcohol (TAA), oxidation of TAA to 2,3‐dihydroxy‐2‐methylbutane and glucuronide conjugation of 2,3‐dihydroxy‐2‐methylbutane. A saturation in the uptake and metabolism of TAME with increased exposure concentration was indicated by a decreased relative uptake of total [14C]TAME equivalents and an increase in the percentage expired as volatiles. A saturation of P‐450 oxidation of TAA was indicated by a disproportional decrease of 2,3‐dihydroxy‐2‐methylbutane and its glucuronide conjugate with increased exposure concentration. Copyright © 2003 John Wiley & Sons, Ltd.
In vitro protection of red blood cell acetylcholinesterase by metoclopramide from inhibition by organophosphates (paraoxon and mipafox)
Authors: Petroianu Georg , Arafat Kholoud , Kosanovic Melita , Saleh Ayman , Camasamudram Vijayasarathy , Hasan Mohamed Y.
Published: November 2003

Metoclopramide (MCP) is a dopamine receptor antagonist and serotonin receptor agonist widely used as an antiemetic and gastric prokinetic drug. In addition, MCP is a reversible inhibitor of cholinesterases from the human central nervous system and blood, and may have a red blood cell (RBC) acetylcholinesterase (AChE) protective effect against inhibition by organophosphates.

The purpose of the study was to quantify ‘in vitro’, by means of the IC50 shift, the extent of MCP conferred protection, by using paraoxon (POX) and mipafox (MPFX) as inhibitors. Paraoxon is a widely used non‐neuropathic organophospate responsible for a large number of accidental or suicidal exposures. Mipafox is a neuropathic organophospate.

Red blood cell AChE activities in human plasma were measured photometrically in the presence of different POX, MPFX and MCP concentrations and the IC50 was calculated. Determinations were repeated in the presence of increasing MCP concentrations. It appears that the IC50 shift induced by the presence of MCP increases with the MCP concentration in a linear manner.

The protective effect of MCP on cholinesterases could be of practical relevance in the treatment of POX and MPFX poisoning. We conclude that in vivo testing of MCP as an organophosphate protective agent is warranted. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis of [13C2]nifedipine
Authors: Ohtaka Kuniaki , Kajiwara Masahiro
Published: November 2003

[13C2]Nifedipine (3) was synthesized from [13C]methanol (&1macr;) in two steps. Copyright © 2003 John Wiley & Sons, Ltd.
The first enzymatic method for C–18F bond formation: the synthesis of 5′‐[18F]‐fluoro‐5′‐deoxyadenosine for imaging with PET
Authors: Martarello Laurent , Schaffrath Christoph , Deng Hai , Gee Antony D , Lockhart Andrew , O'Hagan David
Published: November 2003

The use of the key enzyme involved in carbon–fluorine bond formation in Streptomyces cattleya catalysing the formation of 5′‐fluoro‐5′‐deoxyadenosine (5′‐FDA) from fluoride ion and S‐adenosyl‐l‐methionine (SAM) was explored for its potential application in fluorine‐18 labelling of the adenosine derivative. Enzymatic radiolabelling of [18F]‐5′‐FDA was successfully carried out starting from SAM and [18F]HF when the concentration of the enzyme preparation was increased from sub‐mg/ml values to mg/ml values. The purity of the enzyme had no measurable effect on the radiochemical yield of the reaction and the radiochemical purity of [18F]‐5′‐FDA. Copyright © 2003 John Wiley & Sons, Ltd.
Fast, high‐resolution in vivo cine magnetic resonance imaging in normal and failing mouse hearts on a vertical 11.7 T system
Authors: Schneider Jürgen E. , Cassidy Paul J. , Lygate Craig , Tyler Damian J. , Wiesmann Frank , Grieve Stuart M. , Hulbert Karen , Clarke Kieran , Neubauer Stefan
Published: November 2003

Purpose

To establish fast, high‐resolution in vivo cine magnetic resonance imaging (cine‐MRI) on a vertical 11.7‐T MR system and to investigate the stability of normal and failing mouse hearts in the vertical position.

Materials and Methods

To optimize the method on a high‐field system, various MR‐related parameters, such as relaxation times and the need for respiratory gating, were quantitatively investigated. High‐resolution cine‐MRI was applied to normal mice and to a murine heart failure model. Cardiac functional parameters were compared to matched mice imaged previously on a horizontal MR system.

Results

A T1 of 1.10 ± 0.27 seconds and a T2 of 18.5 ± 3.9 msec were measured for murine myocardial tissue. A quantitative analysis also proved respiratory gating to be essential for obtaining artifact‐free cine images in the vertical position at this field strength. Cardiac functional parameters of mice, obtained within one hour, agreed well with those from previous studies of mice in the horizontal position.

Conclusion

This work shows that MR systems with a vertical bore design can be used to accurately measure cardiac function in both normal and chronically failing mouse hearts within one hour. The increased signal‐to‐noise ratio (SNR) due to the higher field strength could be exploited to obtain higher temporal and spatial resolution compared to previous studies that were performed on horizontal systems with lower field strengths. J. Magn. Reson. Imaging 2003;18:691–701. © 2003 Wiley‐Liss, Inc.
Application of the keyhole technique to T1ρ relaxation mapping
Authors: Wheaton Andrew J. , Borthakur Arijitt , Reddy Ravinder
Published: November 2003

Purpose

To demonstrate the feasibility of using the keyhole technique to minimize error in a least squares regression estimation of T1ρ from magnetic resonance (MR) image data.

Materials and Methods

The keyhole method of partial k‐space acquisition was simulated using data from a virtual phantom and MR images of ex vivo bovine and in vivo human cartilage. T1ρ maps were reconstructed from partial k‐space (keyhole) image data using linear regression, and error was measured with relation to T1ρ maps created from the full k‐space images. An error model was created based on statistical theory and fitted to the error measurements.

Results

T1ρ maps created from keyhole images of a human knee produced levels of error on the order of 1% while reducing standard image acquisition time approximately by half. The resultant errors were strongly correlated with expectations derived from statistical theory.

Conclusion

The error model can be used to analytically optimize the keyhole method in order to minimize the overall error in the estimation of the relaxation parameter of interest. The keyhole method can be generalized to significantly expedite all forms of relaxation mapping. J. Magn. Reson. Imaging 2003;18:745–749. © 2003 Wiley‐Liss, Inc.
Magnetic resonance imaging of the liver with ultrashort TE (UTE) pulse sequences
Authors: Chappell Karyn E. , Patel Nayna , Gatehouse Peter D. , Main Janice , Puri Basant K. , Taylor‐Robinson Simon D. , Bydder Graeme M.
Published: November 2003

Purpose

To assess the feasibility of imaging the liver in volunteers and patients with ultrashort echo time (UTE) pulse sequences.

Materials and Methods

Seven normal controls as well as 12 patients with biopsy‐proven generalized liver disease and three patients with focal disease were examined using pulse sequences with initial TEs of 0.08 msec followed by three later echoes, with or without frequency‐based fat suppression. T2* values were calculated from regions of interest in the liver.

Results

Good image quality was obtained in each subject. There was a highly significant difference in the mean T2* values between the normal controls and patients with generalized liver disease (P = 0.001). T2* was significantly decreased in hemochromatosis (P = 0.002) and increased in cirrhosis (P = 0.04), compared with controls. T2* also correlated with functional status assessed by Child's grade (P = 0.001). A hepatocellular carcinoma showed reduced short T2 components in the region of thermal ablation and evidence of a subcapsular hematoma which were not apparent with conventional imaging.

Conclusions

Imaging of the liver with UTE sequences showed good image quality and tolerance of abdominal motion. T2* was specifically correlated with the presence of hemochromatosis, cirrhosis, and functional grade. Imaging of short T2 relaxation components may provide useful information in disease. J. Magn. Reson. Imaging 2003;18:709–713. © 2003 Wiley‐Liss, Inc.
Eigenvalues in spectral gaps of a perturbed periodic manifold
Authors: Post Olaf
Published: November 2003

We consider a non‐compact Riemannian periodic manifold such that the corresponding Laplacian has a spectral gap. By continuously perturbing the periodic metric locally we can prove the existence of eigenvalues in a gap. A lower bound on the number of eigenvalue branches crossing a fixed level is established in terms of a discrete eigenvalue problem. Furthermore, we discuss examples of perturbations leading to infinitely many eigenvalue branches coming from above resp. finitely many branches coming from below. (© 2003 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Toric Fano varieties with divisorial contractions to curves
Authors: Sato Hiroshi
Published: November 2003

In this paper, we obtain a complete classification of smooth toric Fano varieties equipped with extremal contractions which contract divisors to curves for any dimension. As an application, we obtain a complete classification of smooth projective toric varieties which can be equivariantly blown‐up to Fano along curves. (© 2003 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Subthalamic somatosensory evoked potentials in Parkinson's disease
Authors: Pesenti Alessandra , Priori Alberto , Locatelli Marco , Egidi Marcello , Rampini Paolo , Tamma Filippo , Caputo Elena , Chiesa Valentina , Barbieri Sergio
Published: November 2003

Deep brain stimulation (DBS) of subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease. It also provides an opportunity to record neural activity from the human basal ganglia. In this study, to investigate the involvement of the human STN in sensory functions, we recorded somatosensory evoked potentials (SEPs) elicited by contralateral median‐nerve stimulation, from STN electrodes implanted for DBS in patients with Parkinson's disease. We suggest that the STN N18 component of SEPs in Parkinson's disease is a mainly local field potential elicited by muscle afferent input to the nucleus. © 2003 Movement Disorder Society
Coherence analysis in the myoclonus of corticobasal degeneration
Authors: Grosse Pascal , Kühn Andrea , Cordivari Carla , Brown Peter
Published: November 2003

We investigated whether myoclonus in corticobasal degeneration (CBD) is cortical or subcortical in origin. Many authors have suggested that the myoclonus in CBD is a subtype of cortical myoclonus, despite the fact that back‐averaging fails to detect a cortical correlate to spontaneous or action induced jerks and giant sensory evoked potentials are seldom found. Electroencephalographic–electromyographic (EEG–EMG) and EMG–EMG frequency analysis may be more sensitive to cortical drives when EMG bursts occur at a high frequency and at low amplitudes as in CBD. We evaluated EEG–EMG and EMG–EMG coherence and phase in 5 patients with clinically probable CBD and unilateral, action‐induced and stimulus‐sensitive myoclonus. We found negligible corticomuscular coherence despite a dramatically exaggerated EMG–EMG coherence. We conclude that an inflated EMG–EMG coherence is found in some patients with CBD and that this is unlikely to be due to an exaggerated cortical drive. © 2003 Movement Disorder Society
Survival time, mortality, and cause of death in elderly patients with Parkinson's disease. A 9‐year follow‐up
Authors: Fall Per‐Arne , Saleh Avin , Fredrickson Mats , Olsson Jan‐Edvin , Granérus Ann‐Kathrine
Published: November 2003

This community‐based study of Parkinson's disease (PD) investigated age at death and cause of death in a cohort of 170 previously studied patients. The current study is a 9‐year follow‐up, and the results are compared to 510 sex‐ and age‐matched controls from the same area. A total of 170 patients were diagnosed with PD on August 31, 1989, within a defined area of Sweden. A control group of 510 persons from the same area and with the same age and sex distribution was also examined regarding age at death and cause of death. After 9.4 years, 121 cases (71.1%) and 229 controls (44.9%) were no longer alive. Thus, the mortality rate ratio was 1.6 (95% confidence interval [CI], 1.3–1.8) when comparing PD patients with controls. The all‐cause hazard ratio for cases compared to controls was 2.4 (95% CI, 1.9–3.0). The mean age at death for the cases was 81.9 (95% CI, 80.3–83.0) years and for the controls 82.9 (95% CI, 82.0–83.7) years. Survival analysis also showed a shorter survival time (P < 0.001) for PD patients. Only 53% of the death certificates for the deceased patients recorded PD as an underlying or contributory cause of death. Many PD patients reached a high age but had a shorter survival than the controls. There was a significant increase in deaths from pneumonia. © 2003 Movement Disorder Society
Psychogenic movement disorders in two children
Authors: Özekmekçi Sibel , Apaydin Hulya , Ekinci Burçak , Yalçinkaya Cengiz
Published: November 2003

Two schoolboys with diagnostic criteria for psychogenic movement disorder (PMD) are described: one with bizarre tremor of the right hand and a very slow and cautious gait, another with exaggerated trunk sway and collapses during standing and walking. © 2003 Movement Disorder Society
Transient ischemic attacks presenting as hemiballism
Authors: Kim Jae Woo , Choi Seoung‐Ho , Kim Wook‐Joo , Chun Sang‐Myung
Published: November 2003

Hemiballism is continuous, nonpatterned involuntary movement characterized by irregular, coarse, flinging movement involving the limbs on one side. Hemiballism is most commonly caused by stroke. However, very rarely a transient ischemic attack (TIA) presents as hemiballism. We describe 2 such patients with hemiballism presenting as TIA. © 2003 Movement Disorder Society
Complete NMR assignment of (+)‐10β,14‐dihydroxy‐allo‐aromadendrane
Authors: Vizzotto Lucinéia , Muzzi Rozanna Marques , de Lima Dênis Pires
Published: November 2003

The assignment of 1H and 13C NMR of the sesquiterpene (+)‐10β,14‐dihydroxy‐allo‐aromadendrane by means of two‐dimensional NMR is reported. Copyright © 2003 John Wiley & Sons, Ltd.
Conformational analysis of 14‐hydroxymodhephene by NMR, x‐ray diffraction and molecular modeling studies
Authors: Reyes‐Trejo Benito , Morales‐Ríos Martha S. , Alvarez‐Cisneros E. Celina , Joseph‐Nathan Pedro
Published: November 2003

The conformational state of the [3.3.3]propellane framework for 14‐hydroxymodhephene was determined by extensive application of one‐ and two‐dimensional 1H and 13C NMR spectroscopy combined with x‐ray diffraction studies of a synthesized derivative, spectral simulation and molecular modeling. The conformational rigidity of the molecule in solution, established at room temperature, revealed the existence of envelope conformers for both cyclopentane fragments, with C‐7 puckered endo and C‐10 exo with respect to the mean plane containing the B and C rings. Copyright © 2003 John Wiley & Sons, Ltd.
The refractory period of transmission is impaired in axonal Guillain–Barré syndrome
Authors: Kuwabara Satoshi , Bostock Hugh , Ogawara Kazue , Sung Jia‐Ying , Kanai Kazuaki , Mori Masahiro , Hattori Takamichi , Burke David
Published: November 2003

Guillain–Barré syndrome (GBS) is classified as acute motor axonal neuropathy (AMAN) or acute inflammatory demyelinating polyneuropathy (AIDP). Motor nerve conduction block is frequently found in both subtypes of GBS. To compare patterns of conduction block and the safety factor for impulse transmission in AMAN and AIDP, pairs of supramaximal stimuli at intervals of 1–5 ms were delivered to stimulate the median nerve at the wrist. At the 2‐ and 3‐ms intervals, compound muscle action potentials (CMAPs) to the second stimulus were significantly smaller in AMAN patients (n = 7) than in normal subjects (n = 10) and AIDP patients (n = 6). Over 4 weeks from onset, the amplitude of both conditioned and unconditioned CMAPs returned toward normal, consistent with improvement in the safety factor for impulse transmission. The refractory period of transmission is impaired in AMAN, and the site of transmission failure is likely to be the motor nerve terminals. In addition to axonal degeneration, the critically but reversibly reduced safety factor is important in the pathophysiology of AMAN, and consistent with the rapid resolution of distal conduction block often seen in AMAN patients. Muscle Nerve 28: 683–689, 2003
Prevalence and progression of mitochondrial diseases: A study of 50 patients
Authors: Arpa Javier , Cruz‐Martínez Antonio , Campos Yolanda , Gutiérrez‐Molina Manuel , García‐Rio Francisco , Pérez‐Conde Concepción , Martín Miguel A. , Rubio Juan C. , Del Hoyo Pilar , Arpa‐Fernández Ana , Arenas Joaquín
Published: November 2003

We report 50 patients with various clinical phenotypes of mitochondrial disease studied over the past 10 years in a large urban area (Madrid Health Area 5). The clinical phenotypes showed a large variety of abnormalities in molecular biology and biochemistry. The prevalence of mitochondrial diseases was found to be 5.7 per 100,000 in the population over 14 years of age. Clinical and electrophysiological assessment reveal signs of neuropathy in 10 patients. Electromyographic findings consistent with myopathy were obtained in 37 cases. Six patients died of medical complications. Disease phenotype influenced survival to some degree (P< 0.01). Age of onset and gender were not associated with differences in survival. Mitochondrial disease is thus far more common than expected and a common cause of chronic morbidity. Muscle Nerve 28: 690–695, 2003