bluuebunny/crossref_metadata_2025 huggingface dataset:
Giant lipoma arising from deep lobe of the parotid gland
Authors: Wu Che-Wei , Chi Hung-Pin , Chiang Feng-Yu , Hsu Ying-Che , Chan Leong-Perng , Kuo Wen-Rei
Published: June 2006

Background

Lipomas are common benign soft tissue neoplasms but they are found very rarely in the deep lobe of parotid gland. Surgical intervention in these tumors is challenging because of the proximity of the facial nerve, and thus knowledge of the anatomy and meticulous surgical technique are essential.

Case presentation

A 71-year-old female presented with a large asymptomatic mass, which had occupied the left facial area for over the past fifteen years, and she requested surgical excision for a cosmetically better facial appearance. The computed tomography (CT) scan showed a well-defined giant lipoma arising from the left deep parotid gland. The lipoma was successfully enucleated after full exposure and mobilization of the overlying facial nerve branches. The surgical specimen measured 9 × 6 cm in size, and histopathology revealed fibrolipoma. The patient experienced an uneventful recovery, with a satisfying facial contour and intact facial nerve function.

Conclusion

Giant lipomas involving the deep parotid lobe are extremely rare. The high-resolution CT scan provides an accurate and cost-effective preoperative investigative method. Surgical management of deep lobe lipoma should be performed by experienced surgeons due to the need for meticulous dissection of the facial nerve branches. Superficial parotidectomy before deep lobe lipoma removal may be unnecessary in selected cases because preservation of the superficial lobe may contribute to a better aesthetic and functional result.
Ethnomedicine in Himalaya: a case study from Dolpa, Humla, Jumla and Mustang districts of Nepal
Authors: Kunwar Ripu M , Nepal Bal K , Kshhetri Hari B , Rai Sanjeev K , Bussmann Rainer W
Published: June 2006

Traditional plant use in Nepal has been documented for millennia. The importance of plants as medicine has not diminished in any way in recent times, and traditional medicines are still the most important health care source for the vast majority of the population.

This paper examines the ethnobotany and traditional use of plants extracted from the vulnerable alpine zone in the Dolpa, Humla, Jumla and Mustang districts of Nepal.

The results of this ethnobotanical study indicate that a very large number of plant species is used as traditional medicines. There were 107, 59, 44 and 166 species of ethnomedicinal importance in surveyed areas of Dolpa, Humla, Jumla and Mustang district respectively. Of these, 84 common species, used at least in two districts, were selected to enumerate their ethnomedicinal properties. The 84 species belonged to 75 genera and 39 families.

The commonest species in this pharmacopoeia were: Allium wallichii, Cordyceps sinensis, Dactylorhiza hatagirea, and Rheum australe. A total of 21 species were most common in three districts and 59 in two districts. The genera Aconitum, Allium, Arisaema, Berberis, Corydalis, Gentiana, Hippophae, Juniperus and Rhododendron each possessed two species with ethnomedicinal use. Labiatae was the most medicinally important family with five species used, followed by Araceae, Compositae, Liliaceae, Polygonaceae, Ranunculaceae, Scrophulariaceae and Umbelliferae, each contributing four species.
Overseas consultant psychiatrists moving into the NHS: initial experience
Authors: Shah Mitesh , Goswami Santanu , Singh Gagandeep , Brown Robert
Published: June 2006

Moving to a different country for work can be an interesting experience but can be demanding for healthcare professionals as the systems across countries are vastly different. At the same time, such an opportunity can enable professionals to broaden their skills and experiences. The National Health Service (NHS) provided such an opportunity by recruiting consultants from overseas under the International Fellowship Scheme. In this paper three psychiatrists (M.S., S.G. and G.S.) who moved to the UK under this scheme describe their initial experiences.
Oxygen Concentration Is an Important Factor for Modulating Progesterone Synthesis in Bovine Corpus Luteum
Authors: Nishimura Ryo , Sakumoto Ryosuke , Tatsukawa Yuko , Acosta Tomas J. , Okuda Kiyoshi
Published: June 2006

Oxygen deficiency caused by a decrease in the blood supply is known to induce various responses of cells. Because luteal blood flow has been shown to decrease during luteolysis, a low-oxygen condition seems to be an integral part of the environment during luteolysis. To determine whether a low-oxygen condition is associated with functional luteolysis, we examined the influence of reduced oxygen tension on the luteal progesterone (P4) generating system in cultured bovine midluteal cells. Luteal cells obtained from midcycle corpus luteum (d 8–12) were incubated under different O2 concentrations (20, 10, 5, 3% O2) with or without LH for 24 h. P4 production decreased with decreasing O2 concentration but was significantly stimulated by LH regardless of O2 concentration. After 8 h of culture, both basal and LH-stimulated P4 production was significantly lower under 3% O2 than under 20% O2. Low-oxygen condition also inhibited pregnenolone production. Cytochrome P450 side-chain cleavage enzyme (P450scc) mRNA expression, measured by quantitative PCR, decreased under low-oxygen condition in both non-LH-treated and LH-treated cells. Low-oxygen condition did not affect the expressions of steroidogenic acute regulatory protein mRNA or protein, whereas steroidogenic acute regulatory protein mRNA expression was stimulated by LH during 4 h of culture. Low-oxygen condition also did not affect 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase mRNA expression or the activity of the enzyme in the cells, regardless of the incubation period. The overall results indicate that a low-oxygen condition decreases P4 synthesis by attenuating P450scc production and P450scc activity in bovine luteal cells and suggest that oxygen deficiency is an essential condition for the progression of luteolysis in cattle.
Leptin Stimulates Proliferation and Inhibits Apoptosis in Barrett’s Esophageal Adenocarcinoma Cells by Cyclooxygenase-2-Dependent, Prostaglandin-E2-Mediated Transactivation of the Epidermal Growth Factor Receptor and c-Jun NH2-Terminal Kinase Activation
Authors: Ogunwobi Olorunseun , Mutungi Gabriel , Beales Ian L. P.
Published: June 2006

Obesity is an important risk factor for esophageal adenocarcinoma (EAC), and elevated serum leptin is characteristic of obesity. We hypothesized that leptin may have biological effects in promoting esophageal adenocarcinoma and examined the effects of leptin on the OE33 Barrett’s-derived EAC line. Proliferation was assessed by dimethylthiazoldiphenyltetra-zoliumbromide and 5-bromo-2′-deoxyuridine incorporation assays and apoptosis by ELISA of intracellular nucleosomes. Intracellular signaling was examined using specific pharmacological inhibitors and direct detection of phosphorylated active kinases. Expression of the long and short leptin receptors by OE33 cells was confirmed by RT-PCR, Western blotting and immunocytochemistry. Leptin stimulated OE33 cell proliferation in a dose-dependent manner and inhibited apoptosis. These effects were dependent on cyclooxygenase (COX)-2 and replicated by adding prostaglandin E2 (PGE2). The effects of PGE2 and leptin were abolished by the EP-4 antagonist AH23848. ERK, p38 MAPK, phosphatidylinositol 3′-kinase/Akt, and Janus tyrosine kinase (JAK)-2 were activated upstream of COX-2 induction, whereas the epidermal growth factor receptor and c-Jun NH2-terminal kinase (JNK) were downstream of COX-2. The activation of ERK and Akt but not p38 MAPK was JAK2 dependent. PGE2 stimulated phosphorylation of JNK in an EGF receptor-dependent manner, and activation of the epidermal growth factor receptor required protein kinase C, src, and matrix metalloproteinase activities. We conclude that leptin stimulates cell proliferation and inhibits apoptosis in OAC cells via ERK, p38 MAPK, phosphatidylinositol 3′-kinase/Akt, and JAK2-dependent activation of COX-2 and PGE2 production. Subsequent PGE2-mediated transactivation of the epidermal growth factor receptor and JNK activation are essential to the leptin effects. These effects may contribute to the greatly increased risk of esophageal adenocarcinoma in obesity.
Activin Inhibits the Human Pit-1 Gene Promoter through the p38 Kinase Pathway in a Smad-Independent Manner
Authors: de Guise Chantal , Lacerte Annie , Rafiei Shahrzad , Reynaud Rachel , Roy Melanie , Brue Thierry , Lebrun Jean-Jacques
Published: June 2006

The pituitary transcription factor Pit-1 regulates hormonal production from the anterior pituitary gland. However, the mechanisms by which Pit-1 gene expression is regulated in humans are poorly understood. Activin, a member of the TGFβ superfamily, acts as a negative regulator of cell growth and prolactin gene expression in lactotrope cells. In this study, we show that activin negatively regulates the human Pit-1 gene promoter. We defined a 117-bp element within the Pit-1 promoter that is sufficient to relay these inhibitory effects. We further investigated the signaling pathways that mediate activin-induced inhibition of Pit-1 gene promoter in pituitary lactotrope cells. We found that the activin effects on Pit-1 gene regulation are Smad independent and require the p38 MAPK pathway. Specifically, blocking p38 kinase activity reverses activin-mediated inhibition of the Pit-1 gene promoter. Together, our results highlight the p38 MAPK pathway as a key regulator of activin function in pituitary lactotrope cells and further emphasizes the critical role played by activin in regulating hormonal production in the pituitary gland.
The Mouse Testis Is the Source of Various Serine Proteases and Serine Proteinase Inhibitors (SERPINs): Serine Proteases and SERPINs Identified in Leydig Cells Are under Gonadotropin Regulation
Authors: Odet Fanny , Verot Adélie , Le Magueresse-Battistoni Brigitte
Published: June 2006

The occurrence of various serine proteinases and serine proteinases inhibitors (SERPINs) was investigated by RT-PCR in whole testes of 1-, 3-, and 8-wk-old mice in crude and enriched germ cell fractions, mouse Leydig tumor cells (mLTC-1), and primary cultures of 3- and 8-wk-old enriched fractions of Leydig cells and 3-wk-old Sertoli cells. New members were identified in the testis protease repertoire. Within the Leydig repertoire, a PCR product was found for plasminogen activators urokinase plasminogen activator (uPA) and tissue plasminogen activator (8-wk-old cells), matriptase-2 (mLTC-1), kallikrein-21, SERPINA5, SERPINB2 (primary cultures), and serine peptidase inhibitor Kunitz type 2 (SPINT2). The gonadotropin regulation was explored by semiquantitative RT-PCR, using steroidogenic acute regulatory protein (StAR) as a positive control. Matriptase-2, kallikrein-21, SPINT2, and SERPINA5 were down-regulated, whereas uPA and its receptor were up-regulated by human chorionic gonadotropin (hCG) via cAMP in the mLTC-1 cells. Positive effects were observed transiently after 1–8 h of hCG exposure, and negative effects, first evidenced after 6 h, lasted 48 h. The hCG-induced effects were confirmed in primary cultures. In addition, SERPINB2 was augmented by hCG in primary cultures. Addition of either trypsin or protease inhibitors did not alter the hCG-induced surge of StAR. Because hCG regulated proteases and SERPINs (whereas testosterone did not), it could alter the proteolytic balance of Leydig cells and consequently the metabolism of extracellular matrix components. Therefore, even though a direct interplay between the early hCG-induced surge of uPA and StAR is unlikely, our data together with the literature suggest that extracellular matrix proteins alter Leydig cell steroidogenesis.
The Role of Forkhead Box A2 to Restrict Androgen-Regulated Gene Expression of Lipocalin 5 in the Mouse Epididymis
Authors: Yu Xiuping , Suzuki Kichiya , Wang Yongqing , Gupta Aparna , Jin Renjie , Orgebin-Crist Marie-Claire , Matusik Robert
Published: June 2006

Murine epididymal retinoic acid-binding protein [or lipocalin 5 (Lcn5)] is synthesized and secreted by the principal cells of the mouse middle/distal caput epididymidis. A 5-kb promoter fragment of the Lcn5 gene can dictate androgen-dependent and epididymis region-specific gene expression in transgenic mice. Here, we reported that the 1.8-kb Lcn5 promoter confers epididymis region-specific gene expression in transgenic mice. To decipher the mechanism that directs transcription, 14 chimeric constructs that sequentially removed 100 bp of 1.8-kb Lcn5 promoter were generated and transfected into epididymal cells and nonepididymal cells. Transient transfection analysis revealed that 1.3 kb promoter fragment gave the strongest response to androgens. Between the 1.2-kb to 1.3-kb region, two androgen receptor (AR) binding sites were identified. Adjacent to AR binding sites, a Foxa2 [Fox (Forkhead box) subclass A] binding site was confirmed by gel shift assay. Similar Foxa binding sites were also found on the promoters of human and rat Lcn5, indicating the Foxa binding site is conserved among species. We previously reported that among the three members of Foxa family, Foxa1 and Foxa3 were absent in the epididymis whereas Foxa2 was detected in epididymal principal cells. Here, we report that Foxa2 displays a region-specific expression pattern along the epididymis: no staining observed in initial segment, light staining in proximal caput, gradiently heavier staining in middle and distal caput, and strongest staining in corpus and cauda, regions with little or no expression of Lcn5. In transient transfection experiments, Foxa2 expression inhibits AR induction of the Lcn5 promoter, which is consistent with the lack of expression of Lcn5 in the corpus and cauda. We conclude that Foxa2 functions as a repressor that restricts AR regulation of Lcn5 to a segment-specific pattern in the epididymis.
tRNA regulation of gene expression: Interactions of an mRNA 5′-UTR with a regulatory tRNA
Authors: Nelson Audrey R. , Henkin Tina M. , Agris Paul F.
Published: June 2006

Many genes encoding aminoacyl-tRNA synthetases and other amino acid–related products in Gram-positive bacteria, including important pathogens, are regulated through interaction of unacylated tRNA with the 5′-untranslated region (5′-UTR) of the mRNA. Each gene regulated by this mechanism responds specifically to the cognate tRNA, and specificity is determined by pairing of the anticodon of the tRNA with a codon sequence in the “Specifier Loop” of the 5′-UTR. For the 5′-UTR to function in gene regulation, the mRNA folding interactions must be sufficiently stable to present the codon sequence for productive binding to the anticodon of the matching tRNA. A model bimolecular system was developed in which the interaction between two half molecules (“Common” and “Specifier”) would reconstitute the Specifier Loop region of the 5′-UTR of the Bacillus subtilis glyQS gene, encoding GlyRS mRNA. Gel mobility shift analysis and fluorescence spectroscopy yielded experimental Kds of 27.6 ± 1.0 μM and 10.5 ± 0.7 μM, respectively, for complex formation between Common and Specifier half molecules. The reconstituted 5′-UTR of the glyQS mRNA bound the anticodon stem and loop of tRNAGly (ASLGlyGCC) specifically and with a significant affinity (Kd = 20.2 ± 1.4 μM). Thus, the bimolecular 5′-UTR and ASLGlyGCC models mimic the RNA–RNA interaction required for T box gene regulation in vivo.
Evolutionary conservation of a functionally important backbone phosphate group critical for aminoacylation of histidine tRNAs
Authors: Rosen Abbey E. , Brooks Bonnie S. , Guth Ethan , Francklyn Christopher S. , Musier-Forsyth Karin
Published: June 2006

All histidine tRNA molecules have an extra nucleotide, G-1, at the 5′ end of the acceptor stem. In bacteria, archaea, and eukaryotic organelles, G-1 base pairs with C73, while in eukaryotic cytoplasmic tRNAHis, G-1 is opposite A73. Previous studies of Escherichia coli histidyl-tRNA synthetase (HisRS) have demonstrated the importance of the G-1:C73 base pair to tRNAHis identity. Specifically, the 5′-monophosphate of G-1 and the major groove amine of C73 are recognized by E. coli HisRS; these individual atomic groups each contribute ∼4 kcal/mol to transition state stabilization. In this study, two chemically synthesized 24-nucleotide RNA microhelices, each of which recapitulates the acceptor stem of either E. coli or Saccharomyces cervisiae tRNAHis, were used to facilitate an atomic group “mutagenesis” study of the −1:73 base pair recognition by S. cerevisiae HisRS. Compared with E. coli HisRS, microhelixHis is a much poorer substrate relative to full-length tRNAHis for the yeast enzyme. However, the data presented here suggest that, similar to the E. coli system, the 5′ monophosphate of yeast tRNAHis is critical for aminoacylation by yeast HisRS and contributes ∼3 kcal/mol to transition state stability. The primary role of the unique −1:73 base pair of yeast tRNAHis appears to be to properly position the critical 5′ monophosphate for interaction with the yeast enzyme. Our data also suggest that the eukaryotic HisRS/tRNAHis interaction has coevolved to rely less on specific major groove interactions with base atomic groups than the bacterial system.
Carbon nanotubes by plasma-enhanced chemical vapor deposition
Authors: Bell Martin S. , Teo Kenneth B. K. , Lacerda Rodrigo G. , Milne W. I. , Hash David B. , Meyyappan M.
Published: June 2006

This paper presents the growth of vertically aligned carbon nanotubes by plasma-enhanced chemical vapor deposition (PECVD) using Ni catalyst and C2H2/NH3 feedstock. The role of plasma in aligning the carbon nanotubes during growth is investigated both experimentally and computationally, confirming that the field in the plasma sheath causes the nanotubes to be aligned. Experiments using a plasma analyzer show that C2H2 is the dominant precursor for carbon nanotube growth. The role of NH3 in the plasma chemistry is also investigated, and experimental results show how the interaction between NH3 and the C2H2 carbon feedstock in the gas phase explains the structural variation in deposited nanotubes for differing gas ratios. The effects of varying the plasma power during deposition on nanotube growth rate is also explored. Finally, the role of endothermic ion-molecule reactions in the plasma sheath is investigated by comparing measured data with simulation results.
Radical-surface interactions during film deposition: A sticky situation?
Authors: Liu Dongping , Martin Ina T. , Zhou Jie , Fisher Ellen R.
Published: June 2006

Our imaging of radicals interacting with surfaces (IRIS) method was used to investigate radical-surface reactions during low-temperature plasma-enhanced chemical vapor deposition (PECVD) processes. Special emphasis was placed on the analysis of surface reactivities for CH, SiH, CN, NH, NH2, CF2, and SiCl2 radicals during film growth. The effects of plasma parameters, such as radio frequency (rf) power and gas composition, substrate temperature, and substrate bias on radical-surface reactivity were analyzed. Different radicals exhibit different behavior at the surface of a depositing film. Specifically, CH, SiH, and CN are "sticky", with high surface reactivities. In contrast, other species such as NH, CF2, and SiCl2 do not stick to the surface of growing films and, in some cases are actually generated at the surface of the depositing film. Different plasma systems and parameters can have an effect on the stickiness of some of these species. Our IRIS measurements indicate a molecule's surface sticking probability may also be related to the molecule's electronic configuration and stability, with the most reactive species being molecules with a doublet electron configuration. In contrast, the singlet species examined here tend to be generated at the surface during film deposition. Our results also indicate that when a molecule scatters with greater than 100 % probability, it is likely to be strongly affected by energetic ion bombardment of the film surface.
Metal halide lamps: Gravitational influence on color separation
Authors: Stoffels W. W. , Flikweert A. J. , Nimalasuriya T. , van der Mullen J. J. A. M. , Kroesen G. M. W. , Haverlag M.
Published: June 2006

Metal halide lamps are very efficient light sources based on a Hg plasma arc with metal halide salt additions. In spite of their high efficiency, the lamps suffer from several problems, such as color separation and instabilities, which currently hinder large-scale use. These phenomena are caused by a complex interaction of convection and diffusion flows in the plasma. In order to unravel the various contributions, experiments under microgravity have been performed where convection is absent.

The experiments confirm the previously held qualitative views, but also provide absolute data on densities and temperatures that will be used to validate numerical models of these lamps.
Disparate LDL Phenotypic Classification among 4 Different Methods Assessing LDL Particle Characteristics
Authors: Ensign Wayne , Hill Nicole , Heward Christopher B
Published: June 2006

Background: Our study seeks to clarify the extent of differences in analytical results, from a clinical perspective, among 4 leading technologies currently used in clinical reference laboratories for the analysis of LDL subfractions: gradient gel electrophoresis (GGE), ultracentrifugation–vertical auto profile (VAP), nuclear magnetic resonance (NMR), and tube gel electrophoresis (TGE).

Methods: We collected 4 simultaneous blood samples from 40 persons (30 males and 10 females) to determine LDL subclasses in 4 different clinical reference laboratories using different methods for analysis. LDL subfractions were assessed according to LDL particle size and the results categorized according to LDL phenotype. We compared results obtained from the different technologies.

Results: We observed substantial heterogeneity of results and interpretations among the 4 methods. Complete agreement among methods with respect to LDL subclass phenotyping occurred in only 8% (n = 3) of the persons studied. NMR and GGE agreed most frequently at 70% (n = 28), whereas VAP matched least often.

Conclusions: As measurement of LDL subclasses becomes increasingly important, standardization of methods is needed. Variation among currently available methods renders them unreliable and limits their clinical usefulness.
Increased Plasma Concentrations of Activin A Predict Intraventricular Hemorrhage in Preterm Newborns
Authors: Florio Pasquale , Perrone Serafina , Luisi Stefano , Vezzosi Piero , Longini Mariangela , Marzocchi Barbara , Petraglia Felice , Buonocore Giuseppe
Published: June 2006

Background: Intraventricular hemorrhage (IVH) is a major cause of neurologic disabilities in preterm newborns. We evaluated the use of plasma activin A concentrations to predict the development of perinatal IVH.

Methods: We measured nucleated erythrocyte (NRBC) counts, plasma activin A, hypoxanthine (Hyp), and xanthine (Xan) in arterial blood samples obtained from 53 preterm infants during the first hour after birth. Cerebral ultrasound was performed within 48 h of birth and repeated at 5- or 6-day intervals until the age of 4 weeks.

Results: Grade I or II IVH was detected during the first 10 days of life in 11 of 53 patients (21%). Activin A, Hyp, and Xan concentrations and NRBC counts were higher in preterm newborns who subsequently developed IVH than in those who did not (P <0.0001, except P = 0.019 for Xan). Neonatal activin A was correlated (P <0.0001) with Hyp (r = 0.95), Xan (r = 0.90), and NRBC count (r = 0.90) in newborns without later IVH and in those who developed IVH (Hyp, r = 0.89, P = 0.0002; Xan, r = 0.95, P <0.0001; NRBC count, r = 0.90, P = 0.0002). At a cutoff of 0.8 μg/L activin A, the sensitivity and specificity were 100% [11 of 11; 95% confidence interval (CI), 71%–100%] and 93% (39 of 42; 95% CI, 81%–98%), and positive and negative predictive values were 79% (95% CI, 61%–100%) and 0% (95% CI, 0%–2%), respectively. The area under the ROC curve was 0.98.

Conclusions: Activin A concentrations at birth are increased in preterm newborns who later develop IVH and may be useful for early identification of infants with hypoxic-ischemic brain insults who are at high risk for IVH.
The gating effect of calmodulin and calcium on the connexin50 hemichannel
Authors: Zhang Xianrong , Zou Tingting , Liu Yingle , Qi Yipeng
Published: June 2006

Gap junction channels formed by connexin50 (Cx50) are critical for the maintenance of eye lens transparency, which is sensitive to pH and external Ca2+concentration, but the mechanism is still not clear. In this study we performed dye uptake-leakage assays, patch clamping and confocal co-localization experiments to confirm the function of calmodulin (CaM) and Ca2+in the Cx50 hemichannel. Below pH 7.4, lucifer yellow (LY)-preloaded Cx50-HeLa cells allow dye to leak out when washed with Ca2+-free solution or incubated in solution containing 50 μg/ml W7 (CaM inhibitor) first, then washed in solution containing 2 mM Ca2+, whereas little or no dye leakage was observed when LY-preloaded Cx50-HeLa cells were incubated in solution containing 2 mM Ca2+. Moreover, in the absence of Ca2+, polarizing pulses applied to Cx50-HeLa activated outward transmembrane currents, which were inhibited by 2 mM external Ca2+. When Cx50-HeLa cells were incubated with 2 mM Ca2+and 50 μg/ml W7, the transmembrane currents were activated again. This indicates that Ca2+and CaM play a gating role in Cx50 hemichannels. Either the chelation of Ca2+or the inhibition of CaM increased the permeability of Cx50 hemichannels. The same phenomena were observed below pH 6.5. Furthermore, CaM could be localized in gap junctions formed by Cx50 below pH 6.5. Our results demonstrate that CaM and Ca2+can cooperate in the gating control of Cx50 hemichannels.
Insulin Pump Therapy in Youth With Type 1 Diabetes: A Retrospective Paired Study
Authors: Nimri Revital , Weintrob Naomi , Benzaquen Hadassa , Ofan Regina , Fayman Gila , Phillip Moshe
Published: June 2006

OBJECTIVE. To compare by age and glycemic control continuous subcutaneous insulin infusion with multiple daily injections in youth with type 1 diabetes.

METHODS. The files of 279 patients who had type 1 diabetes and switched from multiple daily injections to continuous subcutaneous insulin infusion between 1998 and 2003 were reviewed for glycemic control, body mass index standard deviation score, and adverse events. Patients were divided by age as follows: 23 prepubertal (median age: 5.4; range: 1.6–8.6 years), 127 adolescent (median age: 13.7; range 9–17 years), and 129 young adult (median age: 22.8; range: 17–40 years). The data were compared between the 12 months of multiple daily injections that preceded continuous subcutaneous insulin infusion and the period after the start of continuous subcutaneous insulin infusion for the whole cohort and by age group.

RESULTS. A significant decrease in hemoglobin A1c was demonstrated after the start of continuous subcutaneous insulin infusion use for the entire cohort (−0.51%) and for the prepubertal (−0.48%), adolescent (−0.26%), and young adult (−0.76%) groups. There was a significant interaction between the change in hemoglobin A1c level and hemoglobin A1c value at initiation of pump therapy (−1.7% for patients with hemoglobin A1c ≥10%; 0.2% for patients with hemoglobin A1c ≤7%). The rate of severe hypoglycemic episodes decreased significantly in the adolescent group, from 36.5 to 11.1 events per 100 patient-years, and in the young adult group, from 58.1 to 23.3. There was no significant change in the rate of diabetic ketoacidosis between the 2 periods. The young adults showed a significant decrease in body mass index standard deviation scores (−0.08 ± 0.37).

CONCLUSIONS. Continuous subcutaneous insulin infusion improves glycemic control in youth with type 1 diabetes, especially in those with a history of poor glycemic control. This improvement is associated with a decrease in the rate of severe hypoglycemia in the absence of weight gain.
The NR4A Subgroup: Immediate Early Response Genes with Pleiotropic Physiological Roles
Authors: Maxwell Megan A. , Muscat George E.O.
Published: June 2006

The nuclear hormone receptor (NR) superfamily includes the orphan NR4A subgroup, comprised of Nur77 (NR4A1), Nurr1 (NR4A2) and NOR-1 (NR4A3). These NRs are classified as early response genes, are induced by a diverse range of signals, including fatty acids, stress, growth factors, cytokines, peptide hormones, phorbol esters, neurotransmitters, and physical stimuli (for example magnetic fields, shear stress). The ability to sense and rapidly respond to changes in the cellular environment thus appears to be a hallmark of this subfamily. The members of the NR4A subgroup are well conserved in the DNA binding domain (∼91–95%) and the C-terminal ligand-binding domain (∼60%), but are divergent in the N-terminal AB region. These receptors bind as monomers, homodimers and heterodimers with RXRs (to mediate retinoid signaling) to different permutations of the canonical NR binding motif. The NR4A subgroup activates gene expression in a constitutive ligand-independent manner. NR4A-mediated trans-activation (LBD) involves unusually active N-terminal AF-1 domains that mediate coactivator recruitment. Moreover, the NR4A receptors encode atypical LBDs and AF-2 domains. For example, the LBDs contain no cavity due to bulky hydrophobic residue side chains, and lack the classical coactivator-binding cleft constituted by helices 3, 4 and 12. However, a hydrophobic patch exists between helices 11 and 12, that encodes a novel cofactor interface that modulates transcriptional activity. In line with the pleiotropic physiological stimuli that induce the NR4A subgroup, these orphan NRs have been implicated in cell cycle regulation (and apoptosis), neurological disease, steroidogenesis, inflammation, carcinogenesis and atherogenesis.
Nuclear Receptor Corepressors and PPARγ
Authors: Cohen Ronald N.
Published: June 2006

The nuclear receptor corepressors NCoR and SMRT repress gene transcription by recruiting a histone deacetylase complex. Their roles in PPARγ action have been controversial. Recent evidence, however, suggests that NCoR and SMRT repress PPARγ-mediated transcriptional activity on specific promoters in the adipocyte. In addition, by repressing PPARγ action, these corepressors inhibit the ability of adipocyte differentiation to proceed. A further understanding of corepressor action in the adipocyte will provide insight into the balance of forces regulating adipogenesis, insulin sensitivity, and Type 2 diabetes mellitus.
Integrating nuclear receptor mobility in models of gene regulation
Authors: Gelman Laurent , Feige Jerome N. , Tudor Cicerone , Engelborghs Yves , Wahli Walter , Desvergne Beatrice
Published: June 2006

The mode of action of nuclear receptors in living cells is an actively investigated field but much remains hypothetical due to the lack, until recently, of methods allowing the assessment of molecular mechanisms in vivo. However, these last years, the development of fluorescence microscopy methods has allowed initiating the dissection of the molecular mechanisms underlying gene regulation by nuclear receptors directly in living cells or organisms. Following our analyses on peroxisome proliferator activated receptors (PPARs) in living cells, we discuss here the different models arising from the use of these tools, that attempt to link mobility, DNA binding or chromatin interaction, and transcriptional activity.
Conditions Affecting the Release of Phosphorus from Surface Lake Sediments
Authors: Christophoridis Christophoros , Fytianos Konstantinos
Published: June 2006

Laboratory studies were conducted to determine the effect of pH and redox conditions, as well as the effect of Fe, Mn, Ca, Al, and organic matter, on the release of ortho‐phosphates in lake sediments taken from Lakes Koronia and Volvi (Northern Greece). Results were evaluated in combination with experiments to determine P fractionation in the sediment. The study revealed the major effect of redox potential and pH on the release of P from lake sediments. Both lakes showed increased release rates under reductive conditions and high pH values. The fractionation experiments revealed increased mobility of the reductive P fraction as well as of the NaOH‐P fraction, indicating participation of both fractions in the overall release of sediment‐bound P, depending on the prevailing environmental conditions. The results were assessed in combination with the release patterns of Fe, Mn, Ca, Al, and organic matter, enabling the identification of more specific processes of P release for each lake. The basic release patterns included the redox induced reductive dissolution of P‐bearing metal oxides and the competitive exchange of phosphate anions with OH− at high pH values. The formation of an oxidized surface microlayer under oxic conditions acted as a protective film, preventing further P release from the sediments of Lake Volvi, while sediments from Lake Koronia exhibited a continuous and increased tendency to release P under various physicochemical conditions, acting as a constant source of internal P loading.
MCH−/− Mice Are Resistant to Aging-Associated Increases in Body Weight and Insulin Resistance
Authors: Jeon Justin Y. , Bradley Richard L. , Kokkotou Efi G. , Marino Francis E. , Wang Xiaomei , Pissios Pavlos , Maratos-Flier Eleftheria
Published: June 2006

Ablation of the hypothalamic peptide, melanin-concentrating hormone (MCH), leads to a lean phenotype and resistance to diet-induced obesity. Observation of MCH−/− mice at older ages suggested that these effects persist in mice >1 year old. Leanness secondary to caloric restriction is known to be associated with improved glucose tolerance as well as an overall increase in life span. Because the MCH−/− model represents leanness secondary to increased energy expenditure rather than caloric restriction, we were interested in determining whether this model of leanness would be associated with beneficial metabolic effects at older ages. To assess the effects of MCH ablation over a more prolonged period, we monitored male and female MCH−/− mice up to 19 months. The lean phenotype of MCH−/− mice persisted over the duration of the study. At 19 months, MCH−/− male and female mice weighed 23.4 and 30.8% less than their wild-type counterparts, a result of reduced fat mass in MCH−/− mice. Aged MCH−/− mice exhibited better glucose tolerance and were more insulin sensitive compared with wild-type controls. Aging-associated decreases in locomotor activity were also attenuated in MCH−/− mice. We also evaluated two molecules implicated in the pathophysiology of aging, p53 and silent inflammatory regulator 2 (Sir2). We found that expression of the tumor suppressor protein p53 was higher in MCH−/− mice at 9 and 19 months of age. In contrast, expression of Sir2 was unchanged. In aggregate, these findings suggest that MCH ablation improves the long-term outcome for several indicators of the aging process.
Retinal Vessel Diameters and Risk of Impaired Fasting Glucose or Diabetes
Authors: Ikram M. Kamran , Janssen Joop A.M.J.L. , Roos Anna M.E. , Rietveld Ingrid , Witteman Jacqueline C.M. , Breteler Monique M.B. , Hofman Albert , van Duijn Cornelia M. , de Jong Paulus T.V.M.
Published: June 2006

The association between a smaller retinal arteriolar-to-venular ratio (AVR) and incident diabetes may be due to arteriolar narrowing, venular dilatation, or both. We investigated associations between baseline vessel diameters and incident impaired fasting glucose or diabetes in a population-based cohort (aged ≥55 years). Baseline retinal vessel diameters (1990–1993) were measured on digitized images of 2,309 subjects with a normal glucose tolerance test (postload glucose <7.8 mmol/l). At follow-up (1997–1999), impaired fasting glucose was defined as 6.1–7.0 mmol/l and diabetes as ≥7.0 mmol/l and/or antidiabetic medication use. Odds ratios (ORs) per SD increase in venular diameters were 1.13 (95% CI 1.00–1.29) for impaired fasting glucose and 1.09 (0.90–1.33) for diabetes. ORs per SD decrease in arteriolar diameters were 1.12 (0.98–1.27) and 1.08 (0.89–1.31) and per SD decrease in AVR were 1.29 (1.13–1.46) and 1.19 (0.98–1.45). After adjustment for cardiovascular risk factors, the associations were unaltered for venules and disappeared for arterioles. After stratification on age, associations between venular dilatation and impaired fasting glucose (1.23 [1.02–1.47]) or diabetes (1.18 [0.89–1.56]) were mainly present in participants aged <70 years. In conclusion, in our study, the risk of impaired fasting glucose and diabetes with AVR was explained by venular dilatation rather than arteriolar narrowing, warranting more focus on the causes of this dilatation.
SGK1 Kinase Upregulates GLUT1 Activity and Plasma Membrane Expression
Authors: Palmada Monica , Boehmer Christoph , Akel Ahmad , Rajamanickam Jeyaganesh , Jeyaraj Sankarganesh , Keller Konrad , Lang Florian
Published: June 2006

Phosphatidylinositol 3-kinase (PI3 kinase) inhibition disrupts the ability of insulin to stimulate GLUT1 and GLUT4 translocation into the cell membrane and thus glucose transport. The effect on GLUT4 but not on GLUT1 is mediated by activation of protein kinase B (PKB). The serum- and glucocorticoid-inducible kinase SGK1, a further kinase downstream of PI3 kinase, regulates several transporters by enhancing their plasma membrane abundance. GLUT1 contains a consensus site (95Ser) for phosphorylation by SGK1. Thus, the present study investigated whether GLUT1 is regulated by the kinase. Tracer-flux studies in Xenopus oocytes and HEK-293 cells demonstrated that GLUT1 transport is enhanced by constitutively active S422DSGK1. The effect requires the kinase catalytical activity since the inactive mutant K127NSGK1 failed to modulate GLUT1. GLUT1 stimulation by S422DSGK1 is not due to de novo protein synthesis but rather to an increase of the transporter’s abundance in the plasma membrane. Kinetic analysis revealed that SGK1 enhances maximal transport rate without altering GLUT1 substrate affinity. These observations suggest that SGK1 regulates GLUT1 and may contribute to or account for the PI3 kinase–dependent but PKB-independent stimulation of GLUT1 by insulin.
Inhibition of p38MAPK Increases Adipogenesis From Embryonic to Adult Stages
Authors: Aouadi Myriam , Laurent Kathiane , Prot Matthieu , Le Marchand-Brustel Yannick , Binétruy Bernard , Bost Frédéric
Published: June 2006

Formation of new adipocytes from precursor cells contributes to adipose tissue expansion and obesity. In this study, we asked whether p38 mitogen-activated protein kinase (MAPK) pathway regulates normal and pathological adipogenesis. In both dietary and genetically (ob/ob) obese mice, adipose tissues displayed a marked decrease in p38MAPK activity compared with the same tissues from lean mice. Furthermore, p38MAPK activity was significantly higher in preadipocytes than in adipocytes, suggesting that p38MAPK activity decreases during adipocyte differentiation. In agreement with an inhibitory role of p38MAPK in this process, we found that in vitro inhibition of p38MAPK, with the specific inhibitor PD169316, increased the expression of adipocyte markers in several cellular models, from embryonic to adult stages. Importantly, the expression of adipocyte markers was higher in p38MAPKα knockout cells than in their wild-type counterparts. Phosphorylation of C/EBPβ, which enhances its transcriptional activity, is increased after p38MAPK inhibition. Finally, either inhibition or disruption of p38MAPK increased peroxisome proliferator–activated receptor (PPAR)γ expression and transactivation. Rescue of p38MAPK in knockout cells reduced PPARγ activity to the low basal level of wild-type cells. We demonstrate here, by using multipronged approaches involving p38 chemical inhibitor and p38MAPKα knockout cells, that p38MAPK plays a negative role in adipogenesis via inhibition of C/EBPβ and PPARγ transcriptional activities.
Angiotensin II Type 1 Receptor Blockade Improves β-Cell Function and Glucose Tolerance in a Mouse Model of Type 2 Diabetes
Authors: Chu Kwan Yi , Lau Tung , Carlsson Per-Ola , Leung Po Sing
Published: June 2006

We identified an angiotensin-generating system in pancreatic islets and found that exogenously administered angiotensin II, after binding to its receptors (angiotensin II type 1 receptor [AT1R]), inhibits insulin release in a manner associated with decreased islet blood flow and (pro)insulin biosynthesis. The present study tested the hypothesis that there is a change in AT1R expression in the pancreatic islets of the obesity-induced type 2 diabetes model, the db/db mouse, which enables endogenous levels of angiotensin II to impair islet function. Islets from 10-week-old db/db and control mice were isolated and investigated. In addition, the AT1R antagonist losartan was administered orally to 4-week-old db/db mice for an 8-week period. We found that AT1R mRNA was upregulated markedly in db/db islets and double immunolabeling confirmed that the AT1R was localized to β-cells. Losartan selectively improved glucose-induced insulin release and (pro)insulin biosynthesis in db/db islets. Oral losartan treatment delayed the onset of diabetes, and reduced hyperglycemia and glucose intolerance in db/db mice, but did not affect the insulin sensitivity of peripheral tissues. The present findings indicate that AT1R antagonism improves β-cell function and glucose tolerance in young type 2 diabetic mice. Whether islet AT1R activation plays a role in the pathogenesis of human type 2 diabetes remains to be determined.
Statins Prevent Dextrose-Induced Endothelial Barrier Dysfunction, Possibly Through Inhibition of Superoxide Formation
Authors: Haas Michael J. , Horani Mohamad H. , Parseghian Shant A. , Mooradian Arshag D.
Published: June 2006

Statins may have favorable effects on endothelial barrier function, possibly through reduction of oxidative stress and modulation of expression of vasoactive proteins. The permeability of human umbilical endothelial cells in culture to a group of fluorescein isothiocyanate dextrans of different molecular weights were studied under various experimental conditions. Superoxide anion production was measured with an ethidium bromide fluorescence method. Cellular endothelin 1 mRNA and endothelin 1 in culture media were measured with Northern blots and enzyme immunoassays, respectively. Rosuvastatin (10 nmol/l) normalized the 500 mg/dl dextrose–induced permeability changes. Superoxide anion production induced by 500 mg/dl dextrose was inhibited by therapeutic concentrations of rosuvastatin or simvastatin (10 nmol/l), whereas the increased levels of cellular endothelin 1 mRNA and endothelin 1 in culture media was inhibited by supratherapeutic concentrations of statins (≥0.1 μmol/l). In conclusion, 1) endothelial cell barrier dysfunction occurs in cells treated with high concentrations of dextrose, 2) statin treatment of endothelial cells normalizes barrier permeability, and 3) the favorable effects of statins may be attributed to the inhibition of the dextrose-induced increase in superoxide anions, whereas inhibition of endothelin expression was observed only at supratherapeutic concentrations.
Loss of Endothelial Glycocalyx During Acute Hyperglycemia Coincides With Endothelial Dysfunction and Coagulation Activation In Vivo
Authors: Nieuwdorp Max , van Haeften Timon W. , Gouverneur Mirella C.L.G. , Mooij Hans L. , van Lieshout Miriam H.P. , Levi Marcel , Meijers Joost C.M. , Holleman Frits , Hoekstra Joost B.L. , Vink Hans , Kastelein John J.P. , Stroes Erik S.G.
Published: June 2006

Hyperglycemia is associated with increased susceptibility to atherothrombotic stimuli. The glycocalyx, a layer of proteoglycans covering the endothelium, is involved in the protective capacity of the vessel wall. We therefore evaluated whether hyperglycemia affects the glycocalyx, thereby increasing vascular vulnerability. The systemic glycocalyx volume was estimated by comparing the distribution volume of a glycocalyx permeable tracer (dextran 40) with that of a glycocalyx impermeable tracer (labeled erythrocytes) in 10 healthy male subjects. Measurements were performed in random order on five occasions: two control measurements, two measurements during normoinsulinemic hyperglycemia with or without N-acetylcysteine (NAC) infusion, and one during mannitol infusion. Glycocalyx measurements were reproducible (1.7 ± 0.2 vs. 1.7 ± 0.3 l). Hyperglycemia reduced glycocalyx volume (to 0.8 ± 0.2 l; P < 0.05), and NAC was able to prevent the reduction (1.4 ± 0.2 l). Mannitol infusion had no effect on glycocalyx volume (1.6 ± 0.1 l). Hyperglycemia resulted in endothelial dysfunction, increased plasma hyaluronan levels (from 70 ± 6 to 112 ± 16 ng/ml; P < 0.05) and coagulation activation (prothrombin activation fragment 1 + 2: from 0.4 ± 0.1 to 1.1 ± 0.2 nmol/l; d-dimer: from 0.27 ± 0.1 to 0.55 ± 0.2 g/l; P < 0.05). Taken together, these data indicate a potential role for glycocalyx perturbation in mediating vascular dysfunction during hyperglycemia.
Oral administration of sucrose solutions and measurement of serum sucrose concentrations to evaluate gastric permeability in adult bottlenose dolphins (Tursiops truncatus)
Authors: Buddington Karyl K. , Holmes William E. , Clemons-Chevis Connie L. , Solangi Moby A. , Vanderpool Delphine , Buddington Randal K.
Published: June 2006

Objective—To measure concentrations of sucrose in the serum of captive dolphins after oral administration of a sucrose solution and determine the suitability of this method for use as a test to detect gastric ulcers.

Animals—8 adult captive bottlenose dolphins (Tursiops truncatus).

Procedures—Blood samples were collected from the ventral fluke vein of dolphins before and 45 minutes after oral administration of 500 mL of solution containing 25 or 50 g of sucrose; oral administration was achieved by use of gastric intubation. Serum was separated, diluted in a solution of 90% acetonitrile-to10% water that contained 10 ng of an internal standard (trichlormethiazide)/μL, mixed, and centrifuged. Supernatant was analyzed by use of liquid chromatography–mass spectrometry–mass spectrometry (LC-MS-MS).

Results—Serum sucrose concentrations of dolphins were at or less than the limits of detection before oral administration. Values after administration of sucrose solution varied among dolphins and were higher and more variable after administration of 50 g, compared with concentrations after administration of 25 g.

Conclusions and Clinical Relevance—Serum sucrose concentrations in samples collected during routine health evaluations of captive dolphins can be reliably measured by use of LC-MS-MS. Correlating serum sucrose concentrations with endoscopic observations of the gastric mucosa of dolphins will validate this approach for use in screening for the prevalence and severity of gastric ulcers and determining the efficacy of treatment regimens.
Helminths of Antarctic fishes: Life cycle biology, specificity and geographical distribution
Authors: Rocka Anna
Published: June 2006

Bony fishes (Teleostei) play an important role in the completion of life cycles of helminth parasites in the Antarctica. These fishes may be definitive, second intermediate or paratenic hosts of the helminths. The most species-rich taxon is Digenea. Virtually all of these digeneans use teleosts as definitive hosts. Only one species, Otodistomum cestoides, occurs as the adult stage in skates (Chondrichthyes), with teleosts as its second intermediate host. Among 14 cestode species maturing in fishes only one, Parabothriocephalus johnstoni, occurs in a bony fish, Macrourus whitsoni, whereas the others are parasites of Chondrichthyes (cartilaginous fishes). Antarctic Chondrichthyes are not infected with nematode and acanthocephalan species. Specificity to the intermediate and/or paratenic hosts of the majority of Antarctic helminths is wide, whereas that for definitive hosts is often narrower, restricted to one order or sometimes even to one or two host species. Almost all of 73 helminth species maturing in Antarctic fishes are endemics. Only 4 digenean and one nematode species are cosmopolitan or bipolar.