bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients' and general practitioners' views of what constitutes appropriate hypertension management
Authors: Morecroft Charles , Cantrill Judy , Tully Mary
Published: April 2005

Objectives: To explore how patients and general practitioners (GPs) construct the concept of appropriateness in the context of hypertension management.

Method: Q-methodology was used. The study involved 120 patients and 12 GPs ranking 42 statements according to their degree of agreement or disagreement when considering appropriate hypertension management. The statements, comprising both clinical and non-clinical attributes, were developed from a qualitative study. Factor analysis of the data, using PQMethod computer software, determined if any patterns were discernible.

Results: Patients ( n = 92) and GPs ( n = 10) exclusively clustered to six factors (factor loadings ≥ 0.5, P <0.01), which accounted for 77% of the total variance. The findings indicated that patients and GPs consider appropriate hypertension management in different ways. The GPs indicated that they considered non-pharmacological measures highly important, whereas 72% of patients were ambivalent. The patients clustered to five appropriateness factors, which varied in the degree of involvement patients had, or wished to have, in their hypertension management. Of these five, two were chosen by 73 patients.

Conclusion: GPs' views differ from those of patients and there is variation between patients, which has important implications for patient-centred care. Further application of Q-methodology to explore patients' views of appropriateness of other medical conditions would be valuable.
Characteristics of Infants With Severe Retinopathy of Prematurity in Countries With Low, Moderate, and High Levels of Development: Implications for Screening Programs
Authors: Gilbert Clare , Fielder Alistair , Gordillo Luz , Quinn Graham , Semiglia Renato , Visintin Patricia , Zin Andrea ,   on behalf of the International NO-ROP Group
Published: April 2005

Objective. Retinopathy of prematurity (ROP) is a potentially avoidable cause of blindness in children. The proportion of blindness as a result of ROP varies greatly among countries depending on their level of development, being influenced by the availability of neonatal care, neonatal outcomes, and whether effective screening and treatment programs are in place. The objective of this study was to compare characteristics of premature infants who developed severe ROP between 1996 and 2002 in highly developed countries with less developed countries.

Methods. This was an observational study. A questionnaire was completed by ophthalmologists in countries with low, moderate, and high development rankings (3 highly developed countries and from 10 less well-developed countries) who screen for ROP in which they supplied birth weights and gestational ages (GAs) of infants who were treated for threshold ROP or identified with more advanced stages of the disease. Birth weights and GAs of infants with severe ROP were measured.

Results. The mean birth weights of infants from highly developed countries ranged from 737 to 763 g compared with values ranging from 903 to 1527 g in less developed countries. Mean GAs of infants from highly developed countries ranged from 25.3 to 25.6 weeks compared with 26.3 to 33.5 weeks in less developed countries. A total of 13.0% of 1091 infants from poorly developed countries exceeded United Kingdom screening criteria; 3.6% exceeded a criteria of <34 weeks’ GA and/or <1750 g birth weight.

Conclusions. These findings suggest that larger, more mature infants are developing severe ROP in countries with low/moderate levels of development compared with highly developed countries. ROP screening programs need to use criteria that are appropriate for their local population.
Naturally occurring changes in time spent watching television are inversely related to frequency of physical activity during early adolescence
Authors: Motl Robert W. , McAuley Edward , Birnbaum Amanda S. , Lytle Leslie A.
Published: April 2005

In this longitudinal study, we examined the relationship between changes in time spent watching television and playing video games with frequency of leisure‐time physical activity across a 2‐year period among adolescent boys and girls (). Latent growth modelling indicated that a decrease in time spent watching television was associated with an increase in frequency of leisure‐time physical activity. That relationship was strong in magnitude and independent of sex, socioeconomic status, smoking, and the value participants placed on health, appearance, and achievement. Our results encourage the design of interventions that reduce television watching as a possible means of increasing adolescent physical activity.
Local Excision Procedure for Warthin's Tumor of the Parotid Gland
Authors: Iwai Hiroshi , Yamashita Toshio
Published: April 2005

The aim of this work is to establish a local excision procedure (LEP) and indications of this procedure for Warthin's tumor. Seventy‐three patients (82 sides) with Warthin's tumor were studied. Point I was located 1 cm from the intertragal notch in the direction indicated by the notch. Point S was located 5 mm superior to the inferior end of the mandibular angle. The trunk of the facial nerve and the marginal mandibular branch run at the points I and S, respectively. In surgical maneuvers below the I‐S line, the marginal mandibular and colli branches may exist within the surgical field, but the trunk and other peripheral branches of the facial nerve will not be encountered. For Warthin's tumor estimated to be below the I‐S line (Group A), LEP was used, involving resection of the tumor after locating and dissecting the marginal mandibular and colli branches. For tumors not meeting these criteria (Group B), partial superficial parotidectomy was performed. Results indicated that mean volume of hemorrhage was significantly smaller, and that mean operation time was significantly shorter in Group A than in Group B. Conversely, no significant difference in tumor size or incidence of postoperative facial paresis was identified between the 2 groups. Recurrence has not yet been noted in either group. In conclusion, LEP is useful for Warthin's tumor below the I‐S line. This procedure seems applicable not only to Warthin's tumors, but also to other benign parotid tumors in the surgical field below the I‐S line, such as pleomorphic adenoma and lymphoepithelial cyst.
Bone Regeneration in the Rat Mandible with Bone Morphogenetic Protein‐2: A Comparison of Two Carriers
Authors: Arosarena Oneida A. , Collins Wesley L.
Published: April 2005

OBJECTIVE:

To compare mandibular bone regeneration with bone morphogenetic protein‐2 (BMP‐2) delivered with two carriers: a hyaluronic acid polymer (HY), and a collagen carrier complexed with calcium hydroxyapatite and tricalcium phosphate (collagen/HA/TCP).

STUDY DESIGN:

Defects were created in the bilateral mandibular bodies of 16 Sprague‐Dawley rats. The defects were filled with the HY carrier, the HY carrier loaded with BMP‐2, the collagen/HA/TCP carrier, or the collagen/HA/TCP carrier loaded with BMP‐2. Animals were euthanatized after 6 weeks, and the hemi‐mandibles were analyzed histomorphologically.

RESULTS:

Specimens containing BMP‐2 had significantly larger new bone and marrow volumes than control specimens. Specimens in the hyaluronan/BMP‐2 group tended to have larger volumes of new bone and osteoid than collagen/HA/TCP/BMP‐2 specimens, though these differences were not statistically significant.

CONCLUSION:

The HY and collagen/HA/TCP carriers had comparable efficacy for bone healing with BMP‐2.

SIGNIFICANCE:

Bone morphogenetic proteins can be delivered with commercially available alloplasts as osteogenic bone substitutes for the repair of craniofacial bone defects. EBM rating: B‐2.
Safety Evaluation of Titanium Middle Ear Prostheses at 3.0 Tesla
Authors: Martin Angela D. , Driscoll Colin L. W. , Wood Christopher P. , Felmlee Joel P.
Published: April 2005

OBJECTIVE:

To assess the magnetic resonance imaging (MRI) safety of titanium middle ear prostheses at 3.0 tesla (T).

STUDY DESIGN AND SETTING:

Titanium middle ear prostheses from 3 commercial vendors were examined for magnetic field interactions at 3 T. Initially, ex vivo studies were performed to test for rotational motion and forward displacement (translational motion) of the prostheses in a static magnetic field. If movement was observed during this screening study, then the prosthesis was tested to determine the translational or rotational force acting upon the prosthesis. In addition to testing for prosthesis displacement, temperature changes of the prostheses were measured to assess for radiofrequency heating during imaging.

RESULTS:

Twenty‐one of the 24 titanium prostheses tested revealed no movement when tested in the 3 T static magnetic field. Three prostheses revealed minimal movement during the screening study. A translational force test (string test) was performed upon these 3 prostheses, and the measured angle of displacement was used to determine the force. This calculated force acting upon each prosthesis was essentially zero. Therefore, we conclude that the magnetic field interaction is negligible. A positive control with a ferromagnetic stainless steel prosthesis demonstrated obvious displacement during the screening study, as well as deflection of the prosthesis by 90° in the translational force test. Last, heating of the titanium prostheses did not occur in the 7 models tested.

CONCLUSIONS:

Middle ear prostheses made from titanium are safe, neither deflecting nor heating during magnetic resonance examinations conducted at 3 T. EBM rating: C‐1.
Expression of Interleukins in Patients with Nasal Polyposis
Authors: Voegels Richard Louis , De Pádua Francini Grecco Melo
Published: April 2005

OBJECTIVE:

To correlate the levels of interleukins 1 β, 3, 4, and 5 before and after surgery and compare the levels between patients with and without recurrence of nasal polyposis.

STUDY DESIGN AND SETTING:

Thirty‐nine patients with NP were selected, 13 of them allergic and 26 nonallergic. A control group of 11 individuals was also studied. The concentrations of interleukins were measured by enzyme‐linked immunosorbent assay.

RESULTS:

There was a higher incidence of NP after the fourth decade of life and among men. The clinical symptoms were similar in both groups of patients with nasal polyposis and characterized by nasal obstruction and anosmia. A significant reduction of all interleukins studied was observed after surgical treatment.

CONCLUSION:

Levels of interleukins 1β, 3, 4, and 5 were significantly reduced after surgery and the levels of interleukins 1β and 5 were significantly lower in patients without recurrence of nasal polyposis after surgery when compared to those with recurrence.
Endoscopic Surgery of Inverted Papillomas under Image Guidance—A Prospective Study of 42 Consecutive Cases at a Danish University Clinic
Authors: Von Buchwald Christian , Von Larsen Anders S.
Published: April 2005

BACKGROUND:

To evaluate the feasibility of endoscopic surgery with image guidance in the treatment of inverted papillomas.

STUDY DESIGN AND SETTING:

This prospective cohort study comprised 42 consecutive patients with biopsy‐confirmed inverted papillomas that were diagnosed between 1998 and 2003. All patients were treated by the first author (C.B.). Image guidance based on preacquired CT scans of the patients was used to assist the surgeon aiming at endoscopic resection of inverted papilloma. The success of the surgery was judged primarily by the recurrence rate and the treatment morbidity.

RESULTS:

The study group consisted of 30 males and 12 females with a median age of 61 years. The follow‐up period ranged from 9 months to 69 months (median, 37 months). The only additional procedure performed was the Caldwell‐Luc procedure (8 cases). Recurrence was diagnosed in 10 cases (24%), all in the original tumor site. Eight of these had undergone previous surgery for inverted papilloma. The recurrences were predominantly located in the maxillary or in the frontal sinus (8 cases). In 2 cases, the recurrence was simply removed endoscopically while performing the biopsy procedure. All recurrences were identified within the first 9 months. Associated malignancy was not shown. No severe complications occurred.

CONCLUSIONS:

A treatment based on endoscopic resection with image guidance appears to offer a safe treatment modality of inverted papilloma with insignificant morbidity. Predominantly cases with nonmedial involvement of the maxillary sinus still require a supplement with the Caldwell Luc procedure. Although all the recurrences were found within 9 months postoperatively, later recurrences cannot be excluded. Long‐term follow‐up is recommended.
Measuring Quality of Life in Preschool Children with Sore Throats and Otitis Media Using the Tapqol Questionnaire
Authors: Kubba Haytham , Swan Iain R. C. , Gatehouse Stuart
Published: April 2005

OBJECTIVES:

TNO‐AZL Preschool Quality of Life Questionnaire (TAPQOL) is one of the few instruments designed to assess health‐related quality of life in preschool children but its applicability to otolaryngology is unknown.

STUDY DESIGN AND SETTING:

We studied a consecutive series of children aged 1 to 5 years referred to hospital with recurrent sore throats, recurrent acute otitis media, or otitis media with effusion.

RESULTS:

TAPQOL domain scores were not influenced by age, sex, or socio‐economic class, but correlated with markers of disease severity (frequency of sore throat or pyrexia, time off school), ear‐related handicap (assessed with the OM6 questionnaire), and other measures of health‐related quality of life (visual analogue scale, 5‐point rating scale and the Health Utilities Index mark III). Comparison with published data from healthy children suggests that these common otolaryngologic problems have a large impact on a child's quality of life.

CONCLUSIONS:

TAPQOL seems to be appropriate for use in this context. Marked ceiling effects in some domains, however, may limit their sensitivity.
Late Quaternary climatic control on erosion and weathering in the eastern Tibetan Plateau and the Mekong Basin
Authors: Liu Zhifei , Colin Christophe , Trentesaux Alain , Siani Giuseppe , Frank Norbert , Blamart Dominique , Farid Segueni
Published: April 2005

High-resolution siliciclastic grain size and bulk mineralogy combined with clay mineralogy, rubidium, strontium, and neodymium isotopes of Core MD01-2393 collected off the Mekong River estuary in the southwestern South China Sea reveals a monsoon-controlled chemical weathering and physical erosion history during the last 190,000 yr in the eastern Tibetan Plateau and the Mekong Basin. The ranges of isotopic composition are limited throughout sedimentary records:87Sr/86Sr = 0.7206–0.7240 andεNd(0) = −11.1 to −12.1. These values match well to those of Mekong River sediments and they are considered to reflect this source region. Smectites/(illite + chlorite) and smectites/kaolinite ratios are used as indices of chemical weathering rates, whereas the bulk kaolinite/quartz ratio is used as an index of physical erosion rates in the eastern Tibetan Plateau and the Mekong Basin. Furthermore, the 2.5–6.5 μm/15–55 μm siliciclastic grain size population ratio represents the intensity of sediment discharge of the Mekong River and in turn, the East Asian summer monsoon intensity. Strengthened chemical weathering corresponds to increased sediment discharge and weakened physical erosion during interglacial periods. In contrast, weakened chemical weathering associated with reduced sediment discharge and intensified physical erosion during glacial periods. Such strong glacial–interglacial correlations between chemical weathering/erosion and sediment discharge imply the monsoon-controlled weathering and erosion.
Middle Pleistocene climate and habitat change at Zhoukoudian, China, from the carbon and oxygen isotopic record from herbivore tooth enamel
Authors: Gaboardi Mabry , Deng Tao , Wang Yang
Published: April 2005

The Pleistocene deposits at Zhoukoudian, often referred to as the “Peking Man” site, contain dental remains from a diverse group of herbivores, including Equus sanmeniensis, Cervus elaphus, Cervus nippon, Megaloceros pachyosteus, Sus lydekkeri, and Dicerorhinus choukoutienensis. The carbon and oxygen isotopic compositions of structural carbonate within the enamel of these teeth are used to reconstruct the paleodiet and paleoenvironment of the mammals. The δ13C values of enamel from Zhoukoudian range from −2.3‰ to −13.0‰, indicating that these mammals consumed between ∼25% and 100% C3 plants. The presence of significant amounts of C4 plants in the diets of some herbivore species indicates that at the onset of the Middle Pleistocene local habitats included mixed C3/C4 vegetation. By approximately 470,000 yr ago, C3 plants dominated the diets of herbivores studied, suggesting that the abundance of C4 flora had decreased in the area. For all deer analyzed in this study, the values of δ13C and δ18O decrease substantially from about 720,000 to 470,000 yr ago. This trend may be due to a strengthening of the winter monsoon during the Middle Pleistocene.
Eolian quartz flux variations in Cheju Island, Korea, during the last 6500 yr and a possible Sun–monsoon linkage
Authors: Lim Jaesoo , Matsumoto Eiji , Kitagawa Hiroyuki
Published: April 2005

We have obtained a high-resolution sedimentary record covering the last 6500 yr from a maar in Cheju Island, Korea, in order to reconstruct the history of variations in the eolian quartz flux (EQF) and hence Asian dust. The long-term variation of EQF reveals three intervals: a period of high EQF (4000–2000 cal yr B.P.) and two periods of low EQF (6500–4000 cal yr B.P. and 2000 cal yr B.P. to present), which have been affected by the East Asian monsoon due to insolation change and the cold air activity in high latitudes correlated with polar high-pressure systems. This long-term variation is superimposed by millennial- and centennial-scale fluctuations with periodicities of 1137, 739, 214, 162, 137, 127, and 111 yr, implying drier conditions in the source areas in China. The detrended EQF record correlates visually and statistically (cross-spectral analysis) with the atmospheric Δ14C record (solar proxy). The centennial-scale variability in EQF may be affected by the solar activity through the Sun–East Asian monsoon linkage.
Decreased plasma cholesterol and hypersensitivity to statins in mice lacking
Pcsk9
Authors: Rashid Shirya , Curtis David E. , Garuti Rita , Anderson Norma N. , Bashmakov Yuriy , Ho Y. K. , Hammer Robert E. , Moon Young-Ah , Horton Jay D.
Published: April 2005

PCSK9
encodes proprotein convertase subtilisin/kexin type 9a (PCSK9), a member of the proteinase K subfamily of subtilases. Missense mutations in
PCSK9
cause an autosomal dominant form of hypercholesterolemia in humans, likely due to a gain-of-function mechanism because overexpression of either WT or mutant PCSK9 reduces hepatic LDL receptor protein (LDLR) in mice. Here, we show that livers of knockout mice lacking PCSK9 manifest increased LDLR protein but not mRNA. Increased LDLR protein led to increased clearance of circulating lipoproteins and decreased plasma cholesterol levels (46 mg/dl in
Pcsk9
–/–
mice versus 96 mg/dl in WT mice). Statins, a class of drugs that inhibit cholesterol synthesis, increase expression of sterol regulatory element-binding protein-2 (SREBP-2), a transcription factor that activates both the
Ldlr
and
Pcsk9
genes. Statin administration to
Pcsk9
–/–
mice produced an exaggerated increase in LDLRs in liver and enhanced LDL clearance from plasma. These data demonstrate that PCSK9 regulates the amount of LDLR protein in liver and suggest that inhibitors of PCSK9 may act synergistically with statins to enhance LDLRs and reduce plasma cholesterol.
Plakoglobin suppresses keratinocyte motility through both cell–cell adhesion-dependent and -independent mechanisms
Authors: Yin Taofei , Getsios Spiro , Caldelari Reto , Kowalczyk Andrew P. , Müller Eliane J. , Jones Jonathan C. R. , Green Kathleen J.
Published: April 2005

Plakoglobin (PG) is a member of the Armadillo family of adhesion/signaling proteins and has been shown to play a critical role in the organization of desmosomes and tissue integrity. Because dissolution of intercellular junctions is frequently an initial step in the onset of epithelial cell migration, we examined whether loss of PG promotes cell motility by compromising adhesive strength. Keratinocyte cultures established from PG–/–mice exhibited weakened adhesion and increased motility in transwell migration assays; both were restored by reintroducing PG through adenoviral infection. Interestingly, single PG–/– cells also exhibited increased motility, which was suppressed by reintroducing PG, but not the closely related β-catenin. Whereas both N- and C-terminally truncated PG deletion mutants restored adhesion, only N-terminally deleted PG, but not C-terminally deleted PG, suppressed single-cell migration. Furthermore, both the chemical inhibitor PP2 and dominant-negative Src tyrosine kinase inhibited single-cell motility in PG–/– cells, whereas constitutively active Src overcame the inhibitory effect of PG. These data demonstrate that PG strengthens adhesion and suppresses motility in mouse keratinocytes, through both intercellular adhesion-dependent and -independent mechanisms, the latter of which may involve suppression of Src signaling through a mechanism requiring the PG C terminus.
Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes
Authors: Darnell Jennifer C. , Fraser Claire E. , Mostovetsky Olga , Stefani Giovanni , Jones Thomas A. , Eddy Sean R. , Darnell Robert B.
Published: April 2005

Fragile-X mental retardation is caused by loss of function of a single gene encoding the Fragile-X mental retardation protein, FMRP, an RNA-binding protein that harbors two KH-type and one RGG-type RNA-binding domains. Previous studies identified intramolecular G-quartet RNAs as high-affinity targets for the RGG box, but the relationship of RNA binding to FMRP function and mental retardation remains unclear. One severely affected patient harbors a missense mutation (I304N) within the second KH domain (KH2), and some evidence suggests this domain may be involved in the proposed role of FMRP in translational regulation. We now identify the RNA target for the KH2 domain as a sequence-specific element within a complex tertiary structure termed the FMRP kissing complex. We demonstrate that the association of FMRP with brain polyribosomes is abrogated by competition with the FMRP kissing complex RNA, but not by high-affinity G-quartet RNAs. We conclude that mental retardation associated with the I304N mutation, and likely the Fragile-X syndrome more generally, may relate to a crucial role for RNAs harboring the kissing complex motif as targets for FMRP translational regulation.
The nucleolus as a stress sensor: JNK2 inactivates the transcription factor TIF-IA and down-regulates rRNA synthesis
Authors: Mayer Christine , Bierhoff Holger , Grummt Ingrid
Published: April 2005

Cells respond to a variety of extracellular and intracellular forms of stress by down-regulating rRNA synthesis. We have investigated the mechanism underlying stress-dependent inhibition of RNA polymerase I (Pol I) transcription and show that the Pol I-specific transcription factor TIF-IA is inactivated upon stress. Inactivation is due to phosphorylation of TIF-IA by c-Jun N-terminal kinase (JNK) at a single threonine residue (Thr 200). Phosphorylation at Thr 200 impairs the interaction of TIF-IA with Pol I and the TBP-containing factor TIF-IB/SL1, thereby abrogating initiation complex formation. Moreover, TIF-IA is translocated from the nucleolus into the nucleoplasm. Substitution of Thr 200 by valine as well as knock-out of Jnk2 prevent inactivation and translocation of TIF-IA, leading to stress-resistance of Pol I transcription. Our data identify TIF-IA as a downstream target of the JNK pathway and suggest a critical role of JNK2 to protect rRNA synthesis against the harmful consequences of cellular stress.
O-Acetylserine and the Regulation of Expression of Genes Encoding Components for Sulfate Uptake and Assimilation in Potato
Authors: Hopkins Laura , Parmar Saroj , Błaszczyk Anna , Hesse Holger , Hoefgen Rainer , Hawkesford Malcolm J.
Published: April 2005

cDNAs encoding a high-affinity sulfate transporter and an adenosine 5′-phosphosulfate reductase from potato (Solanum tuberosum L. cv Désirée) have been cloned and used to examine the hypothesis that sulfate uptake and assimilation is transcriptionally regulated and that this is mediated via intracellular O-acetylserine (OAS) pools. Gas chromotography coupled to mass spectrometry was used to quantify OAS and its derivative, N-acetylserine. Treatment with external OAS increased sulfate transporter and adenosine 5′-phosphosulfate reductase gene expression consistent with a model of transcriptional induction by OAS. To investigate this further, the Escherichia coli gene cysE (serine acetyltransferase EC 2.3.1.30), which synthesizes OAS, has been expressed in potato to modify internal metabolite pools. Transgenic lines, with increased cysteine and glutathione pools, particularly in the leaves, had increased sulfate transporter expression in the roots. However, the small increases in the OAS pools were not supportive of the hypothesis that this molecule is the signal of sulfur (S) nutritional status. In addition, although during S starvation the content of S-containing compounds decreased (consistent with derepression as a mechanism of regulation), OAS pools increased only following extended starvation, probably as a consequence of the S starvation. Taken together, expression of these genes may be induced by a demand-driven model, via a signal from the shoots, which is not OAS. Rather, the signal may be the depletion of intermediates of the sulfate assimilation pathway, such as sulfide, in the roots. Finally, sulfate transporter activity did not increase in parallel with transcript and protein abundance, indicating additional posttranslational regulatory mechanisms.
Betaxanthins as Substrates for Tyrosinase. An Approach to the Role of Tyrosinase in the Biosynthetic Pathway of Betalains
Authors: Gandía-Herrero Fernando , Escribano Josefa , García-Carmona Francisco
Published: April 2005

Tyrosinase or polyphenol oxidase (EC 1.14.18.1) is the key enzyme in melanin biosynthesis and in the enzymatic browning of fruits and vegetables. The role of tyrosinase in the secondary metabolism of plants still remains unclear, but its implication in betalain biosynthesis has been proposed. Betalains are an important class of water-soluble pigments, characteristic of plants belonging to the order Caryophyllales. In this article, the betaxanthins, tyrosine-betaxanthin (portulacaxanthin II) and dopaxanthin, are reported to be physiological substrates for tyrosinase. The direct activity of tyrosinase on selected betaxanthins is characterized in depth, and conversion of tyrosine-betaxanthin to dopaxanthin and its further oxidation to a series of compounds are described. Identity of the reaction products was studied by high-performance liquid chromatography and electrospray ionization-mass spectrometry. Masses determined for the reaction products were the same in all cases, 389 m/z ([M + H]+) and equal to that determined for betanidin. Data indicate that dopaxanthin-quinone is obtained and evolves to more stable species by intramolecular cyclization. Kinetic parameters for tyrosinase acting on dopaxanthin were evaluated, showing a high affinity for this substrate (K  m = 84.3 μ  m). The biosynthetic scheme of betalains is reviewed and a branch is proposed based on the description of physiological substrates for tyrosinase. Lampranthus productus, Glottiphylum oligocarpum, and Glottiphylum pigmaeum are described as sources of stereopure (2S/S)-dopaxanthin.
Antifreeze Proteins Modify the Freezing Process In Planta
Authors: Griffith Marilyn , Lumb Chelsey , Wiseman Steven B. , Wisniewski Michael , Johnson Robert W. , Marangoni Alejandro G.
Published: April 2005

During cold acclimation, winter rye (Secale cereale L. cv Musketeer) plants accumulate antifreeze proteins (AFPs) in the apoplast of leaves and crowns. The goal of this study was to determine whether these AFPs influence survival at subzero temperatures by modifying the freezing process or by acting as cryoprotectants. In order to inhibit the growth of ice, AFPs must be mobile so that they can bind to specific sites on the ice crystal lattice. Guttate obtained from cold-acclimated winter rye leaves exhibited antifreeze activity, indicating that the AFPs are free in solution. Infrared video thermography was used to observe freezing in winter rye leaves. In the absence of an ice nucleator, AFPs had no effect on the supercooling temperature of the leaves. However, in the presence of an ice nucleator, AFPs lowered the temperature at which the leaves froze by 0.3°C to 1.2°C. In vitro studies showed that apoplastic proteins extracted from cold-acclimated winter rye leaves inhibited the recrystallization of ice and also slowed the rate of migration of ice through solution-saturated filter paper. When we examined the possible role of winter rye AFPs in cryoprotection, we found that lactate dehydrogenase activity was higher after freezing in the presence of AFPs compared with buffer, but the same effect was obtained by adding bovine serum albumin. AFPs had no effect on unstacked thylakoid volume after freezing, but did inhibit stacking of the thylakoids, thus indicating a loss of thylakoid function. We conclude that rye AFPs have no specific cryoprotective activity; rather, they interact directly with ice in planta and reduce freezing injury by slowing the growth and recrystallization of ice.
ODORANT1Regulates Fragrance Biosynthesis in Petunia Flowers
Authors: Verdonk Julian C. , Haring Michel A. , van Tunen Arjen J. , Schuurink Robert C.
Published: April 2005

Floral scent is important to plant reproduction because it attracts pollinators to the sexual organs. Therefore, volatile emission is usually tuned to the foraging activity of the pollinators. In Petunia hybrida, volatile benzenoids determine the floral aroma. Although the pathways for benzenoid biosynthesis have been characterized, the enzymes involved are less well understood. How production and emission are regulated is unknown. By targeted transcriptome analyses, we identified ODORANT1 (ODO1), a member of the R2R3-type MYB family, as a candidate for the regulation of volatile benzenoids in Petunia hybrida cv W115 (Mitchell) flowers. These flowers are only fragrant in the evening and at night. Transcript levels of ODO1 increased before the onset of volatile emission and decreased when volatile emission declined. Downregulation of ODO1 in transgenic P. hybrida Mitchell plants strongly reduced volatile benzenoid levels through decreased synthesis of precursors from the shikimate pathway. The transcript levels of several genes in this pathway were reduced by suppression of ODO1 expression. Moreover, ODO1 could activate the promoter of the 5-enol-pyruvylshikimate-3-phosphate synthase gene. Flower pigmentation, which is furnished from the same shikimate precursors, was not influenced because color and scent biosynthesis occur at different developmental stages. Our studies identify ODO1 as a key regulator of floral scent biosynthesis.
DDM1 Binds Arabidopsis Methyl-CpG Binding Domain Proteins and Affects Their Subnuclear Localization
Authors: Zemach Assaf , Li Yan , Wayburn Bess , Ben-Meir Hagit , Kiss Vladimir , Avivi Yigal , Kalchenko Vyacheslav , Jacobsen Steven E. , Grafi Gideon
Published: April 2005

Methyl-CpG binding domain (MBD) proteins in Arabidopsis thaliana bind in vitro methylated CpG sites. Here, we aimed to characterize the binding properties of AtMBDs to chromatin in Arabidopsis nuclei. By expressing in wild-type cells AtMBDs fused to green fluorescent protein (GFP), we showed that AtMBD7 was evenly distributed at all chromocenters, whereas AtMBD5 and 6 showed preference for two perinucleolar chromocenters adjacent to nucleolar organizing regions. AtMBD2, previously shown to be incapable of binding in vitro–methylated CpG, was dispersed within the nucleus, excluding chromocenters and the nucleolus. Recruitment of AtMBD5, 6, and 7 to chromocenters was disrupted in ddm1 and met1 mutant cells, where a significant reduction in cytosine methylation occurs. In these mutant cells, however, AtMBD2 accumulated at chromocenters. No effect on localization was observed in the chromomethylase3 mutant showing reduced CpNpG methylation or in kyp-2 displaying a reduction in Lys 9 histone H3 methylation. Transient expression of DDM1 fused to GFP showed that DDM1 shares common sites with AtMBD proteins. Glutathione S-transferase pull-down assays demonstrated that AtMBDs bind DDM1; the MBD motif was sufficient for this interaction. Our results suggest that the subnuclear localization of AtMBD is not solely dependent on CpG methylation; DDM1 may facilitate localization of AtMBDs at specific nuclear domains.
ADHESION AND DE-ADHESION MECHANISMS AT POLYMER/METAL INTERFACES: Mechanistic Understanding Based on In Situ Studies of Buried Interfaces
Authors: Grundmeier G. , Stratmann M.
Published: April 2005

▪ Abstract  The review highlights the state-of-the-art research regarding the application of modern in situ spectroscopic, microscopic, and electrochemical techniques to improve the understanding of the interaction of organic molecules with metal surfaces. We also consider the chemical and electrochemical processes that lead to a de-adhesion of polymers from metal surfaces. Spectroscopic techniques such as surface-enhanced infrared or Raman spectroscopy provide molecular understanding of organic molecules and water at buried metal surfaces. This information is complementary to adhesion studies by means of atomic force microscopy and de-adhesion studies of polymer layers from metals by means of a scanning Kelvin probe. Adhesion and de-adhesion mechanisms are discussed, especially those involving humid and corrosive environments, which are the predominant and most important for metal/polymer composites in engineering applications.
CHEMICAL DESIGN AND IN SITU CHARACTERIZATION OF ACTIVE SURFACES FOR SELECTIVE CATALYSIS
Authors: Tada Mizuki , Iwasawa Yasuhiro
Published: April 2005

▪ Abstract  This review illustrates how catalytically active molecular structures are created on oxide surfaces by attachment of metal complexes with subsequent structural transformation and molecular imprinting on the surfaces. Also discussed is how the designed surfaces are characterized in situ by physical techniques including conventional and time-resolved X-ray absorption fine structure. The structural transformation and molecular imprinting for attached metal complexes can provide a new class of catalytic materials with a high complexity for selective catalysis including shape-selective and asymmetric catalysis.
REGULATION OF GENE TRANSCRIPTION BY BOTANICALS: Novel Regulatory Mechanisms
Authors: Shay Neil F. , Banz William J.
Published: April 2005

▪ Abstract  Early investigations of gene regulation revealed that nutrients could modulate gene expression, an example being the discovery of metal-regulated gene transcription ( 11 , 19 , 44 ). Only more recently have we focused on the ability of non-nutritional botanicals or functional food components to affect gene expression at the transcriptional level. Significant findings include the discovery that hyperforin is an active ingredient of the herbal remedy St. John's wort, and activates gene transcription of cytochrome p450-3A4, causing significant botanical-drug interactions. Recently, the lipid-regulating peroxisome proliferator-activated receptors have been studied as receptors activated by soy isoflavones, perhaps explaining the lipid-lowering effect of soy intake. Epigallocatechin gallate has been shown to be an inhibitor of the protealytic activity of the proteasome; this inhibition has a significant implication for cell proliferation and the stability of transcription factors in the nucleus. Very recently, the effects of botanicals have been studied as activators of sirtuins, important deacetylation enzymes that have been shown to enhance lifespan in a variety of organisms. Sirtuins have been implicated in the lifespan-enhancing effect of caloric restriction. Originally presumed to act mainly on compaction or accessibility of DNA, recent evidence shows important activity of sirtuins as controllers of transcriptional coactivator availability. This review focuses on novel mechanisms by which botanical products regulate cell function via gene transcription. Investigating these newly appreciated mechanisms will assist with the characterization and clarification of specific effects of botanicals on gene expression.
Phytophthora ramorum: Integrative Research and Management of an Emerging Pathogen in California and Oregon Forests
Authors: Rizzo David M. , Garbelotto Matteo , Hansen Everett M.
Published: April 2005

Phytophthora ramorum, causal agent of sudden oak death, is an emerging plant pathogen first observed in North America associated with mortality of tanoak (Lithocarpus densiflorus) and coast live oak (Quercus agrifolia) in coastal forests of California during the mid-1990s. The pathogen is now known to occur in North America and Europe and have a host range of over 40 plant genera. Sudden oak death has become an example of unintended linkages between the horticultural industry and potential impacts on forest ecosystems. This paper examines the biology and ecology of P. ramorum in California and Oregon forests as well discussing research on the pathogen in a broader management context.
Oxidized LDL induces mitochondrially associated reactive oxygen/nitrogen species formation in endothelial cells
Authors: Zmijewski Jaroslaw W. , Moellering Douglas R. , Goffe Claire Le , Landar Aimee , Ramachandran Anup , Darley-Usmar Victor M.
Published: April 2005

Exposure of cells to complex mixtures of oxidized lipids such as those found in oxidized low-density lipoprotein (oxLDL) induce reactive oxygen and nitrogen species (ROS/RNS) formation. The source of the ROS/RNS within cells is unknown; it is thought they may be involved in redox cell signaling. Although this possibility was initially overlooked, it is becoming clear that mitochondria, which are a source of superoxide and hydrogen peroxide, may play a critical role in the response of cells on exposure to oxidized lipids. In this study, we tested the possibility that mitochondria are a potential source of oxLDL-dependent formation of ROS/RNS in endothelial cells. Using confocal microscopy, we demonstrated that a significant proportion of oxLDL-dependent dichlorodihydrofluorescein (DCF) fluorescence is colocalized to mitochondria. In support of this concept, rho0 endothelial cells showed a substantial decrease in ROS/RNS formation stimulated by oxLDL. In contrast, mostly nonmitochondrial DCF fluorescence was detected in cells exposed to an extracellular source of hydrogen peroxide. The exposure of cells to a nitric oxide synthase inhibitor and urate resulted in a decrease in oxLDL-induced DCF fluorescence that was restored by addition of nitric oxide donors to the medium. Taken together, these results suggest that oxLDL-dependent DCF fluorescence is mitochondrially associated and may be due to the formation of peroxynitrite.
Cardiomyocyte apoptosis induced by short-term diabetes requires mitochondrial GSH depletion
Authors: Ghosh Sanjoy , Pulinilkunnil Thomas , Yuen Gloria , Kewalramani Girish , An Ding , Qi Dake , Abrahani Ashraf , Rodrigues Brian
Published: April 2005

Oxidative stress due to excessive reactive oxygen species (ROS) and depleted antioxidants such as glutathione (GSH) can give rise to apoptotic cell death in acutely diabetic hearts and lead to heart disease. At present, the source of these cardiac ROS or the subcellular site of cardiac GSH loss [i.e., cytosolic (cGSH) or mitochondrial (mGSH) GSH] has not been completely elucidated. With the use of rotenone (an inhibitor of the electron transport chain) to decrease the excessive ROS in acute streptozotocin (STZ)-induced diabetic rat heart, the mitochondrial origin of ROS was established. Furthermore, mitochondrial damage, as evidenced by loss of membrane potential, increases in oxidative stress, and reduction in mGSH was associated with increased apoptosis via increases in caspase-9 and -3 activities in acutely diabetic hearts. To validate the role of mGSH in regulating cardiac apoptosis, l-buthionine-sulfoximine (BSO; 10 mmol/kg ip), which blocks GSH synthesis, or diethyl maleate (DEM; 4 mmol/kg ip), which inactivates preformed GSH, was administered in diabetic rats for 4 days after STZ administration. Although both BSO and DEM lowered cGSH, they were ineffective in reducing mGSH or augmenting cardiomyocyte apoptosis. To circumvent the lack of mGSH depletion, BSO and DEM were coadministered in diabetic rats. In this setting, mGSH was undetectable and cardiac apoptosis was further aggravated compared with the untreated diabetic group. In a separate group, GSH supplementation induced a robust amplification of mGSH in diabetic rat hearts and prevented apoptosis. Our data suggest for the first time that mGSH is crucial for modulating the cell suicide program in short-term diabetic rat hearts.
HIF-1 activation attenuates postischemic myocardial injury: role for heme oxygenase-1 in modulating microvascular chemokine generation
Authors: Ockaili Ramzi , Natarajan Ramesh , Salloum Fadi , Fisher Bernard J. , Jones Drew , Fowler Alpha A. , Kukreja Rakesh C.
Published: April 2005

The CXC chemokine IL-8, which promotes adhesion, activation, and transmigration of polymorphonuclear neutrophils (PMN), has been associated with production of tissue injury in reperfused myocardium. Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric peptide that is a key regulator of genes such as heme oxygenase (HO)-1 expressed under hypoxic conditions. We hypothesized that HO-1 plays an important role in regulating proinflammatory mediator production under conditions of ischemia-reperfusion. HIF-1 was activated in the human microvascular endothelial cell line (HMEC-1) with the prolyl hydroxylase inhibitor dimethyloxalylglycine (DMOG). DMOG significantly attenuated cytokine-induced IL-8 promoter activity and protein secretion and cytokine-induced PMN migration across human microvascular endothelial cell line HMEC-1 monolayers. In vivo studies in a rabbit model of myocardial ischemia-reperfusion showed that rabbits pretreated with a 20 mg/kg DMOG infusion ( n = 6) 24 h before study exhibited a 21.58 ± 1.76% infarct size compared with 35.25 ± 2.06% in saline-treated ischemia-reperfusion animals ( n = 6, change in reduction = 39%; P < 0.001). In DMOG-pretreated (20 mg/kg) animals, plasma IL-8 levels at 3 h after onset of reperfusion were 405 ± 40 pg/ml vs. 790 ± 40 pg/ml in saline-treated ischemia-reperfusion animals ( P < 0.001). DMOG pretreatment reduced myocardial myeloperoxidase activity, expressed as number of PMN per gram of myocardium, to 1.43 ± 0.59 vs. 4.86 ± 1.1 ( P = 0.012) in saline-treated ischemia-reperfused hearts. Both in vitro and in vivo DMOG-attenuated IL-8 production was associated with robust HO-1 expression. Thus our data show that HIF-1 activation induces substantial HO-1 expression that is associated with attenuated proinflammatory chemokine production by microvascular endothelium in vitro and in vivo.
Transcription of the human and rodent SPAM1 / PH-20 genes initiates within an ancient endogenous retrovirus
Authors: Dunn Catherine A , Mager Dixie L
Published: April 2005

Background

Sperm adhesion molecule 1 (SPAM1) is the major mammalian testicular hyaluronidase and is expressed at high levels in sperm cells. SPAM1 protein is important for penetration of the cumulus cell layer surrounding the ovum, and is also involved in zona pellucida binding and sperm intracellular signalling. A previous study had identified SPAM1 as one of the many human genes that initiate within a transposable element.

Results

Examination of the human, mouse and rat SPAM1 loci revealed that transcripts initiate within the pol gene of an endogenous retrovirus (ERV) element. This is highly unusual, as all previously identified ERV-initiated cellular gene transcripts initiate within the viral long terminal repeat promoter. The SPAM1 locus therefore represents an example of the evolution of a promoter from protein-coding sequence. We have identified novel alternative promoter and splicing variants of human and murine SPAM1. We show that all transcript variants are expressed primarily in the testis and are predicted to encode identical proteins.

Conclusion

The testis-specific promoters of the human and mouse SPAM1 genes are derived from sequence that was originally part of an ERV pol gene. This represents the first known example of an ERV-derived promoter acting in a gender-specific manner.
Adequate symptom relief justifies hepatic resection for benign disease
Authors: Fioole Bram , Kokke Marike , van Hillegersberg Richard , Borel Rinkes Inne HM
Published: April 2005

Background

The purpose of this study was to evaluate the long-term results of partial liver resection for benign liver lesions.

Methods

All patients operated on for benign liver lesions from 1991 to 2002 were included. Information was retrieved from medical records, the hospital registration system and by a telephonic questionnaire.

Results

Twenty-eight patients with a median age of 41 years (17–71) were operated on (M/F ratio 5/23). The diagnosis was haemangioma in 8 patients, FNH in 6, HCA in 13 and angiomyolipoma in 1. Eight patients were known to have relevant co-morbidity. Median operating time was 207 minutes (45–360). The morbidity rate was 25% and no postoperative mortality was observed. Twenty-two patients (79%) had symptoms (mainly abdominal pain) prior to surgery. Twenty-five patients were reached for a questionnaire. The median follow up was 55 months (4–150). In 89% of patients preoperative symptoms had decreased or disappeared after surgery. Four patients developed late complications.

Conclusion

Long-term follow up after liver surgery for benign liver lesions shows considerable symptom relief and patient satisfaction. In addition to a correct indication these results justify major surgery with associated morbidity and mortality.
Capreomycin is active against non-replicating M. tuberculosis
Authors: Heifets Leonid , Simon Julie , Pham Van
Published: April 2005

Background

Latent tuberculosis infection (LTBI) is affecting one-third of the world population, and activation of LTBI is a substantial source of new cases of tuberculosis. LTBI is caused by tubercle bacilli in a state of non-replicating persistence (NRP), and the goal of this study was to evaluate the activity in vitro of various antimicrobial agents against non-replicating M. tuberculosis.

Methods

To achieve a state of NRP we placed broth cultures of M. tuberculosis (three strains) in anaerobic conditions, and in this model tested all known anti-TB drugs and some other antimicrobial agents (a total of 32 drugs). The potential effect was evaluated by plating samples from broth cultures for determining the number of viable bacteria (CFU/ml) during a prolonged period of cultivation. Besides drug-free controls we used metronidazole for positive controls, the only drug known so far to be effective against tubercle bacilli in anaerobic setting.

Results

On a background of non-replicating conditions in drug-free cultures and clear bactericidal effect of metronidazole none of the antimicrobial agents tested produced effect similar to that of metronidazole except capreomycin, which was as bactericidal at the same level as metronidazole.

Conclusion

The unique ability of capreomycin to be bactericidal in vitro among the anti-TB drugs against non-replicating tubercle bacilli may justify the search for other drugs among peptide antibiotics with similar activity. This phenomenon requires further studies on the mechanism of action of capreomycin, and evaluation of its activity in appropriate animal models.