bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Crystalloid versus Colloid and the α-2 Agonist Brimonidine versus Placebo on Intraocular Pressure during Prone Spine Surgery
Authors: Farag Ehab , Sessler Daniel I. , Kovaci Bledar , Wang Lu , Mascha Edward J. , Bell Gordon , Kalfas Iain , Rockwood Edward , Kurz Andrea
Published: February 2012

Background

Volume replacement with colloid solution and topical α-2 agonists may each moderate the progressive increase in intraocular pressure (IOP) during prone surgery. The authors tested the hypotheses that during prolonged prone surgery, IOP increases less with goal-directed intravenous administration of 5% albumin than with goal-directed administration of lactated Ringer's solution, and with topical α-2 agonist brimonidine than with placebo eye drops.

Methods

Patients having complex prone spine surgery were factorially randomized to albumin and topical placebo (n = 15); albumin and topical brimonidine (n = 16); lactated Ringer's solution and topical placebo (n = 13); and lactated Ringer's solution and topical brimonidine (n = 16). IOP was measured with a pneumotonometer. The primary outcome was time-weighted average intraoperative IOP.

Results

Prone positioning increased IOP a mean ± SD of 12 ± 6 mmHg. IOP increased to 38 ± 10 mmHg at the end of anesthesia (approximately 5.5 h). Time- weighted average intraoperative IOP in the brimonidine group was 4 (95% CI: 1, 8) mmHg lower than in the placebo group (P = 0.023), but no different in the crystalloid and albumin groups (mean difference (95% CI) of -2 (-5, 2) mmHg (P = 0.34). There was no interaction between the two randomized factors.

Conclusions

Brimonidine slightly reduced the primary outcome of intraoperative time-weighted average IOP, whereas there was no significant difference between goal-directed albumin or crystalloid administration. Brimonidine thus helps reduce IOP during spine surgery, but maintaining adequate blood pressure might play a more important role.
Genital human papillomavirus infections: current and prospective therapies
Authors: Stanley Margaret A.
Published: February 2012

Infection with human papillomaviruses (HPVs) is very common and associated with benign and malignant epithelial proliferations of skin and internal squamous mucosae. A subset of the mucosal HPVs are oncogenic and associated with 5 % of all cancers in men and women. There are two licensed prophylactic vaccines, both target HPV 16 and 18, the two most pathogenic, oncogenic types and one, additionally, targets HPV 6 and 11 the cause of genital warts. The approach of deliberate immunization with oncogenic HPV E6 and/or E7 proteins and the generation of antigen-specific cytotoxic T-cells as an immunotherapy for HPV-associated cancer and their high-grade pre-cancers has been tested with a wide array of potential vaccine delivery systems in Phase I/II trials with varying success. Understanding local viral and tumour immune evasion strategies is a prerequisite for the rational design of therapeutic vaccines for HPV-associated infection and disease, progress in this is discussed. There are no antiviral drugs for the treatment of HPV infection and disease. Current therapies are not targeted antiviral therapies, but either attempt physical removal of the lesion or induce inflammation and a bystander immune response. There has been recent progress in the identification and characterization of molecular targets for small molecule antagonists of the HPV proteins E1, E2 and E6 or their interactions with their cellular targets. Lead compounds that could disrupt E1–E2 protein–protein interactions have been discovered as have inhibitors of E6–E6-AP-binding interactions. Some of these compounds showed nanomolar affinities and high specificities and demonstrate the feasibility of this approach for HPV infections. These studies are, however, at an early phase and it is unlikely that any specific anti-HPV chemotherapeutic will be in the clinic within the next 10–20 years.
An influenza reassortant with polymerase of pH1N1 and NS gene of H3N2 influenza A virus is attenuated in vivo
Authors: Shelton Holly , Smith Matt , Hartgroves Lorian , Stilwell Peter , Roberts Kim , Johnson Ben , Barclay Wendy
Published: February 2012

Influenza viruses readily mutate by accumulating point mutations and also by reassortment in which they acquire whole gene segments from another virus in a co-infected host. The NS1 gene is a major virulence factor of influenza A virus. The effects of changes in NS1 sequence depend on the influenza polymerase constellation. Here, we investigated the consequences of a virus with the polymerase of pandemic H1N1 2009 acquiring an NS gene segment derived from a seasonal influenza A H3N2 virus, a combination that might arise during natural reassortment of viruses that currently circulate in humans. We generated recombinant influenza viruses with surface HA and NA genes and matrix M gene segment from A/PR/8/34 virus, but different combinations of polymerase and NS genes. Thus, any changes in phenotype were not due to differences in receptor use, entry, uncoating or virus release. In Madin–Darby canine kidney (MDCK) cells, the virus with the NS gene from the H3N2 parent showed enhanced replication, probably a result of increased control of the interferon response. However, in mice the same virus was attenuated in comparison with the virus containing homologous pH1N1 polymerase and NS genes. Levels of viral RNA during single-cycles of replication were lower for the virus with H3N2 NS, and this virus reached lower titres in the lungs of infected mice. Thus, virus with pH1N1 polymerase genes did not increase its virulence by acquiring the H3N2 NS gene segment, and MDCK cells were a poor predictor of the outcome of infection in vivo.
Strigolactones Suppress Adventitious Rooting in Arabidopsis and Pea
Authors: Rasmussen Amanda , Mason Michael Glenn , De Cuyper Carolien , Brewer Philip B. , Herold Silvia , Agusti Javier , Geelen Danny , Greb Thomas , Goormachtig Sofie , Beeckman Tom , Beveridge Christine Anne
Published: February 2012

Adventitious root formation is essential for the propagation of many commercially important plant species and involves the formation of roots from nonroot tissues such as stems or leaves. Here, we demonstrate that the plant hormone strigolactone suppresses adventitious root formation in Arabidopsis (Arabidopsis thaliana) and pea (Pisum sativum). Strigolactone-deficient and response mutants of both species have enhanced adventitious rooting. CYCLIN B1 expression, an early marker for the initiation of adventitious root primordia in Arabidopsis, is enhanced in more axillary growth2 (max2), a strigolactone response mutant, suggesting that strigolactones restrain the number of adventitious roots by inhibiting the very first formative divisions of the founder cells. Strigolactones and cytokinins appear to act independently to suppress adventitious rooting, as cytokinin mutants are strigolactone responsive and strigolactone mutants are cytokinin responsive. In contrast, the interaction between the strigolactone and auxin signaling pathways in regulating adventitious rooting appears to be more complex. Strigolactone can at least partially revert the stimulatory effect of auxin on adventitious rooting, and auxin can further increase the number of adventitious roots in max mutants. We present a model depicting the interaction of strigolactones, cytokinins, and auxin in regulating adventitious root formation.
Immunological evaluation of personalized peptide vaccination in refractory small cell lung cancer
Authors: Terazaki Yasuhiro , Yoshiyama Koichi , Matsueda Satoko , Watanabe Noriko , Kawahara Akihiko , Naito Yoshiki , Suekane Shigetaka , Komatsu Nobukazu , Ioji Tetsuya , Yamada Akira , Mine Takashi , Terasaki Mizuhiko , Itoh Kyogo , Takamori Shinzo , Sasada Tetsuro
Published: February 2012

Since the prognosis of small cell lung cancer (SCLC) remains poor, development of new therapeutic approaches, including immunotherapies, would be desirable. In the current study, to evaluate immunological responses in refractory SCLC patients, we conducted a small scale phase II clinical trial of personalized peptide vaccination (PPV), in which vaccine antigens are selected based on pre‐existing host immunity. Ten refractory SCLC patients, who had failed to respond to chemo‐ and/or chemoradiotherapies (median number of regimens, 2.5; median duration, 20.5 months), were enrolled. A maximum of four human leukocyte antigen (HLA)‐matched peptides showing higher antigen‐specific humoral responses were subcutaneously administered (weekly for six consecutive weeks and then bi‐weekly thereafter). PPV was terminated before the 3rd administration in four patients because of rapid disease progression, whereas the remaining six patients completed at least one cycle (six times) of vaccinations. Peptide‐specific immunological boosting was observed in all of the six patients at the end of the first cycle of vaccinations, with their survival time of 25, 24.5 (alive), 10 (alive), 9.5, 6.5, and 6 months. Number of previous chemotherapy regimens and frequency of CD3+CD26+ cells in peripheral blood were potentially prognostic in the vaccinated patients (hazard ratio [HR] = 2.540, 95% confidence interval [CI] = 1.188–5.431, P = 0.016; HR = 0.941, 95% CI = 0.878–1.008, P = 0.084; respectively). Based on the feasible immune responses in refractory SCLC patients who received at least one cycle (six times) of vaccinations, PPV could be recommended for a next stage of larger‐scale, prospective clinical trials. (Cancer Sci 2012; 103: 638–644)
Pericellular pH homeostasis is a primary function of the Warburg effect: Inversion of metabolic systems to control lactate steady state in tumor cells
Authors: Mazzio Elizabeth A. , Boukli Nawal , Rivera Nery , Soliman Karam F. A.
Published: February 2012

The Warburg effect describes a heightened propensity of tumor cells to produce lactic acid in the presence or absence of O2. A generally held notion is that the Warburg effect is related to energy. Using whole‐genome, proteomic MALDI‐TOF‐MS and metabolite analysis, we investigated the Warburg effect in malignant neuroblastoma N2a cells. The findings show that the Warburg effect serves a functional role in regulating acidic pericellular pH (pHe), which is mediated by metabolic inversion or a fluctuating dominance between glycolytic‐rate substrate level phosphorylation (SLP) and mitochondrial (mt) oxidative phosphorylation (OXPHOS) to control lactic acid production. The results also show that an alkaline pHe caused an elevation in SLP/OXPHOS ratio (approximately 98% SLP/OXPHOS); while the ratio was approximately 56% at neutral pHe and approximately 93% in acidic pHe. Acidic pHe paralleled greater expression of mitochondrial biogenesis and OXPHOS genes, such as complex III–V (Uqcr10, Atp5 and Cox7c), mt Fmc1, Romo1, Tmem 173, Tomm6, aldehyde dehydrogenase, mt Sod2 mt biogenesis component PPAR‐γ co‐activator 1 adjunct to loss of mt fission (Mff). Moreover, acidic pHe corresponded to metabolic efficiency evidenced by a rise in mTOR nutrient sensor GβL, its downstream target (Eif4ebp1), insulin modulators (Trib3 and Fetub) and loss of catabolic (Hadhb, Bdh1 and Pygl)/glycolytic processes (aldolase C, pyruvate kinase, Nampt and aldose‐reductase). In contrast, alkaline pHe initiated loss of mitofusin 2, complex II–IV (Sdhaf1, Uqcrq, Cox4i2 and Aldh1l2), aconitase, mitochondrial carrier triple repeat 1 and mt biosynthetic (Coq2, Coq5 and Coq9). In conclusion, the Warburg effect might serve as a negative feedback loop that regulates the pHe toward a broad acidic range by altering lactic acid production through inversion of metabolic systems. These effects were independent of changes in O2 concentration or glucose supply. (Cancer Sci, 2012; 103: 422–432)
miR‐30c‐1* promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor HMBOX1
Authors: Gong Jiuyu , Liu Rongrong , Zhuang Ran , Zhang Yun , Fang Liang , Xu Zhuwei , Jin Liang , Wang Tao , Song Chaojun , Yang Kun , Wei Yuying , Yang Angang , Jin Boquan , Chen Lihua
Published: February 2012

Natural killer (NK) cells play a critical role in antitumor immunity, and the activation of NK cells is regulated by a series of NK cell receptors. Here, we show that crosslinking CD226, an important NK cell receptor, with the anti‐CD226 mAb LeoA1 on NKL cells, regulated the expression of several microRNA and transmembrane tumor necrosis factor‐α. Among them, miR‐30c‐1* was noticed because overexpression of miR‐30c‐1* triggered upregulation of transmembrane tumor necrosis factor‐α expression and enhanced NK cell cytotoxicity against hepatoma cell lines SMMC‐7721 and HepG2. Furthermore, we proved that the inhibitory transcription factor HMBOX1, which depressed the activation of NK cells, was the direct target gene of miR‐30c‐1*. In conclusion, our results revealed a novel regulatory mechanism: miR‐30c‐1* promoted NK cell cytotoxicity against hepatoma cells by targeting HMBOX1. (Cancer Sci 2012; 103: 645–652)
Proteomic characterization of ovarian cancers identifying annexin‐A4, phosphoserine aminotransferase, cellular retinoic acid‐binding protein 2, and serpin B5 as histology‐specific biomarkers
Authors: Toyama Atsuhiko , Suzuki Atsushi , Shimada Takashi , Aoki Chikage , Aoki Yutaka , Umino Yukari , Nakamura Yusuke , Aoki Daisuke , Sato Taka‐Aki
Published: February 2012

Numerous studies have suggested that the different histological subtypes of ovarian carcinoma (i.e. clear cell, endometrioid, mucinous, and serous) have distinct clinical histories and characteristics; however, most studies that have aimed to determine biomarker have not performed comprehensive analyses based on subtype specificity. In the present study, we performed two‐dimensional gel electrophoresis‐based differential proteomic analysis of the different histological subtypes of ovarian carcinoma using tissue specimens from 39 patients. Seventy‐seven protein spots (55 unique proteins) were found to be up‐ or downregulated in a subtype‐specific manner. The most significant difference was observed for: (i) annexin‐A4 (ANXA4) and phosphoserine aminotransferase (PSAT1), which are expressed strongly in clear cell carcinoma; (ii) cellular retinoic acid‐binding protein 2 (CRABP2), which is expressed specifically in serous carcinoma; and (iii) serpin B5 (SPB5), which is upregulated in mucinous carcinoma. Validation of these candidates by western blotting using a 34 additional test sample set resulted in an expression pattern that was consistent with the screening and revealed that differential expression was independent of cancer stage or tumor grade within each subtype. Thus, the present study reinforces the notion that ovarian cancer subtypes can be clearly delineated on a molecular basis into four histopathological groups, and we propose that ANXA4, PSAT1, CRABP2, and SPB5 are candidate subtype‐specific biomarkers that can help define the basis of tumor histology at a molecular level. (Cancer Sci 2012; 103: 747–755)
GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER‐negative breast cancer
Authors: Miyake Tomohiro , Nakayama Takahiro , Naoi Yasuto , Yamamoto Noriaki , Otani Yoko , Kim Seung J. , Shimazu Kenzo , Shimomura Atsushi , Maruyama Naomi , Tamaki Yasuhiro , Noguchi Shinzaburo
Published: February 2012

The purpose of the present study was to investigate the association of glutathione S‐transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5‐fluorouracil/epirubicin/cyclophosphamide (P‐FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n = 123, stage II–III) treated with neoadjuvant P‐FEC were analyzed. Tumor samples were obtained by vacuum‐assisted core biopsy before P‐FEC. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1‐negative tumors (80.0%) than GSTP1‐positive tumors (30.6%) (P = 0.009) among estrogen receptor (ER)‐negative tumors but not among ER‐positive tumors (P = 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P = 0.013) among ER‐negative tumors. Luminal A, luminal B and HER2‐enriched tumors showed a significantly lower GSTP1 positivity than basal‐like tumors (P = 0.002, P < 0.001 and P = 0.009, respectively), while luminal A, luminal B and HER2‐enriched tumors showed a higher GSTP1 MI than basal‐like tumors (P = 0.076, P < 0.001 and P < 0.001, respectively). In conclusion, these results suggest the possibility that GSTP1 expression can predict pathological response to P‐FEC in ER‐negative tumors but not in ER‐positive tumors. Additionally, GSTP1 promoter hypermethylation might be implicated more importantly in the pathogenesis of luminal A, luminal B and HER2‐enriched tumors than basal‐like tumors. (Cancer Sci 2012; 103: 913–920)
Differential MyD88/IRAK4 requirements for cross‐priming and tumor rejection induced by heat shock protein 70‐model antigen fusion protein
Authors: Mizukami Shusaku , Kajiwara Chiaki , Tanaka Masato , Kaisho Tsuneyasu , Udono Heiichiro
Published: February 2012

Priming of CD8+ T cells requires two signals, one produced by T‐cell receptor recognition of antigen, and a second that is often provided by the innate immune response. In this context, antigens non‐covalently or covalently associated with heat shock proteins (HSP) are internalized and processed in antigen‐presenting cells (APC) to be presented by MHC I molecules to CD8+ T cells, thus, signal 1 has been well characterized in this pathway of cross‐presentation. Signal 2 is not fully understood, although there are reports that Toll‐like receptors (TLRs) interact with HSP and activate APC. The ability of HSP to activate APC through TLRs is, however, controversial because of the possibility of endotoxin contamination. Using a variety of TLR KO mice, we present evidence that TLRs (TLR2, 3, 4, 7, and 9) and their adaptor molecules MyD88 and IRAK4 are dispensable in cross‐priming by a mycobacterial HSP70–antigen (ovalbumin as a model antigen) fusion protein; in contrast, MyD88/IRAK4, but not TLRs, are required for tumor rejection induced by the same reagent. Our results indicate that HSP‐mediated cross‐priming uses a second signal produced by mechanisms other than TLR cascades. We hypothesize that efficient cross‐priming by HSP70 alone is insufficient for tumor rejection and that MyD88/IRAK4‐dependent inflammatory stimulation, which might contribute to maintenance of the initially primed effector cells, is required to eradicate tumor burden. (Cancer Sci 2012; 103: 851–859)
A randomised, controlled trial comparing the Airtraq™ optical laryngoscope with conventional laryngoscopy in infants and children*
Authors: White M. C. , Marsh C. J. , Beringer R. M. , Nolan J. A. , Choi A. Y. S. , Medlock K. E. , Mason D. G.
Published: February 2012

The Airtraq™ optical laryngoscope became available in paediatric sizes in the UK in May 2008. We conducted a randomised, controlled trial comparing the Airtraq with conventional laryngoscopy during routine anaesthesia in children. We hypothesised that the Airtraq laryngoscope would perform as well as conventional laryngoscopy. Sixty patients (20 infants and 40 children) were recruited. The mean (SD) intubation time using the Airtraq was longer than conventional laryngoscopy overall (47.3 (32.6) vs 26.3 (11.5) s; p = 0.002), though the difference was only significant for children (p = 0.003) and not for infants (p = 0.29). The Airtraq provided a better view of the larynx compared with conventional laryngoscopy (in infants (percentage of glottic opening scores 100 (95–100 [90–100]) vs 77 (50–90 [40–100]), respectively; p = 0.001; visual analogue scores for field of view 9.2 (9.2–9.5 [8.2–10.0]) vs 6.8 (5.1–8.0 [4.7–10.0]), respectively; p = 0.001). In children, the Airtraq provided a similar view of the larynx (percentage of glottic opening scores 100 (100–100 [40–100]) vs 100 (90–100 [50–100]), respectively; visual analogue scores for field of view 9.2 (8.6–10.0 [7.0–10.0]) vs 9.2 (8.6–10.0 [5.6–10.0]), respectively; both p > 0.05), compared with conventional laryngoscopy.
Effect of forced‐air warming on the performance of operating theatre laminar flow ventilation*
Authors: Dasari K. B. , Albrecht M. , Harper M.
Published: February 2012

Forced‐air warming exhaust may disrupt operating theatre airflows via formation of convection currents, which depends upon differences in exhaust and operating room air temperatures. We investigated whether the floor‐to‐ceiling temperatures around a draped manikin in a laminar‐flow theatre differed when using three types of warming devices: a forced‐air warming blanket (Bair Hugger™); an over‐body conductive blanket (Hot Dog™); and an under‐body resistive mattress (Inditherm™). With forced‐air warming, mean (SD) temperatures were significantly elevated over the surgical site vs those measured with the conductive blanket (+2.73 (0.7) °C; p < 0.001) or resistive mattress (+3.63 (0.7) °C; p < 0.001). Air temperature differences were insignificant between devices at floor (p = 0.339), knee (p = 0.799) and head height levels (p = 0.573). We conclude that forced‐air warming generates convection current activity in the vicinity of the surgical site. The clinical concern is that these currents may disrupt ventilation airflows intended to clear airborne contaminants from the surgical site.
Tracheal intubation in morbidly obese patients: a comparison of the Intubating Laryngeal Mask Airway™ and Laryngeal Mask Airway CTrach™*
Authors: Arslan Z. I. , Özdamar D. , Yildiz T. S. , Solak Z. M. , Toker K.
Published: February 2012

The aim of this study was to evaluate the efficacy of the Intubating Laryngeal Mask Airway™ (ILMA) and Laryngeal Mask Airway CTrach™ (LMA CTrach) in facilitating tracheal intubation in morbidly obese patients. Eighty patients (body mass index > 40kg.m−2) were randomly allocated to the ILMA or the LMA CTrach. The median (IQR [range]) total time taken for tracheal intubation was shorter with the ILMA than with the LMA CTrach (78 (63–105 [40–265]) s vs 128 (98–221 [60–423]) s, respectively; p < 0.001). Significantly more manoeuvres were applied for the satisfactory ventilation and viewing of the glottis with the LMA CTrach (25% vs 55% with the ILMA; p = 0.006). During the postoperative period, there was more sore throat with the LMA CTrach (p < 0.02). We conclude that the ILMA results in shorter intubation times with fewer manoeuvres and sore throat compared with the LMA CTrach in the morbidly obese.
Difficult Airway Society Guidelines for the management of tracheal extubation
Authors:   Membership of the Difficult Airway Society Extubation Guidelines Group: M. Popat (Chairman), Mitchell V. , Dravid R. , Patel A. , Swampillai C. , Higgs A.
Published: February 2012

Tracheal extubation is a high‐risk phase of anaesthesia. The majority of problems that occur during extubation and emergence are of a minor nature, but a small and significant number may result in injury or death. The need for a strategy incorporating extubation is mentioned in several international airway management guidelines, but the subject is not discussed in detail, and the emphasis has been on extubation of the patient with a difficult airway. The Difficult Airway Society has developed guidelines for the safe management of tracheal extubation in adult peri‐operative practice. The guidelines discuss the problems arising during extubation and recovery and promote a strategic, stepwise approach to extubation. They emphasise the importance of planning and preparation, and include practical techniques for use in clinical practice and recommendations for post‐extubation care.
High expression of CD98 alters epithelial barrier functions to promote induction of airway allergy
Authors: Liu T. , Ma J. , Li T.‐L. , Yang J.‐F. , Liang X. , Yang P.‐C.
Published: February 2012

Background

Epithelial barrier dysfunction is critical in the induction of allergy; the aetiology is to be further understood. A recent report indicates that CD98 plays a role in the intestinal epithelial barrier dysfunction.

Objectives

This study aimed to investigate the role of overexpression of CD98 in the induction of nasal allergy.

Methods

The nasal epithelium samples were collected from 30 patients with allergic rhinitis and 30 healthy subjects. The contents of CD98 and Staphylococcal enterotoxin B (SEB) in the nasal epithelium samples were evaluated by using Western blotting. The effect of SEB of inducing the expression of CD98 was evaluated with an airway epithelial cell line, the 16HBE14o cells. The epithelial barrier function was assessed with the indicators of transepithelial resistance (TER) and permeability to horseradish peroxidase (HRP). A mouse model was employed to evaluate the role of CD98 in the induction of nasal allergy.

Results

High levels of CD98 and SEB were detected in the nasal epithelium of patients with allergic rhinitis. A positive correlation was identified between CD98 and SEB in nasal epithelium samples. Exposure to SEB could induce the overexpression of CD98 in RPMI 2650 and 16HBE14o cells. The overexpression of CD98 down‐regulated TER and increased the permeability to HRP in 16HBE14o monolayers. Concurrent exposure to SEB and OVA induced nasal allergies in a mouse model that could be blocked by pre‐treatment with anti‐CD98 antibody.

Conclusions and Clinical Relevance

CD98 plays a critical role in compromising the airway epithelial barrier function that contributes to the induction of airway allergy.
Effects of growth hormone deficiency on body composition and biomarkers of cardiovascular risk after definitive therapy for acromegaly
Authors: Lin E. , Wexler T. L. , Nachtigall L. , Tritos N. , Swearingen B. , Hemphill L. , Loeffler J. , Biller B. M. K. , Klibanski A. , Miller K. K.
Published: February 2012

Background

Both growth hormone (GH) excess and GH deficiency are associated with abnormalities in body composition and biomarkers of cardiovascular risk in patients with pituitary disorders. However, the effects of developing GH deficiency after definitive treatment of acromegaly are largely unknown.

Objective

To determine whether development of GH deficiency after definitive therapy for acromegaly is associated with increased visceral adiposity and biomarkers of cardiovascular risk compared with GH sufficiency after definitive therapy for acromegaly.

Design

Cross‐sectional.

Patients

We studied three groups of subjects, all with a history of acromegaly (n = 76): subjects with subsequent GH deficiency (GHD; n = 31), subjects with subsequent GH sufficiency (GHS; n = 25) and subjects with active acromegaly (AA; n = 20). No study subjects were receiving somatostatin analogues, dopamine agonists or hGH.

Measurements

Body composition (by DXA), abdominal adipose tissue depots (by cross‐sectional CT), total body water (by bioimpedance analysis) and carotid intima‐media thickness (IMT) were measured. Fasting morning serum was collected for high‐sensitivity C‐reactive protein (hsCRP), lipids and lipoprotein levels. An oral glucose tolerance test was performed, and homoeostasis model of assessment‐insulin resistance (HOMA‐IR) was calculated.

Results

Abdominal visceral adipose tissue, total adipose tissue and total body fat were higher in subjects with GHD than GHS or AA (P < 0·05). Subcutaneous abdominal fat was higher, and fibrinogen and IMT were lower in GHD (but not GHS) than AA (P < 0·05). Patients with GHD had the highest hsCRP, followed by GHS, and hsCRP was lowest in AA (P < 0·05). Fasting glucose, 120‐min glucose, fasting insulin, HOMA‐IR and per cent total body water were lower in GHD and GHS than AA (P < 0·05). Triglycerides were higher in GHS than AA (P < 0·05). Lean body mass, mean arterial pressure, total cholesterol, HDL and LDL were comparable among groups.

Conclusions

Development of GHD after definitive treatment of acromegaly may adversely affect body composition and inflammatory biomarkers of cardiovascular risk but does not appear to adversely affect glucose homoeostasis, lipids and lipoproteins, or other cardiovascular risk markers.
Assessment of the human faecal microbiota: II. Reproducibility and associations of 16S rRNA pyrosequences
Authors: Flores Roberto , Shi Jianxin , Gail Mitchell H. , Gajer Pawel , Ravel Jacques , Goedert James J.
Published: February 2012

Eur J Clin Invest 2012;

Background:  We conducted a pilot study of reproducibility and associations of microbial diversity and composition in faecal microbial DNA.

Methods and results:  Participants (25 men and 26 women, aged 17–65 years) provided questionnaire data and multiple samples of one stool collected with two Polymedco and two Sarstedt devices preloaded with RNAlater. 16S rRNA genes in each faecal DNA aliquot were amplified, sequenced (Roche/454 Life Sciences) and assigned to taxa. Devices were compared for ease of use and reproducibility [intraclass correlation coefficient (ICC)] between duplicate aliquots on diversity and taxonomic assignment. Associations were tested by linear regression. Both collection devices were easy to use. Both alpha diversity (Shannon index) and beta diversity (UniFrac) were higher between than within duplicates (P ≤ 10−8) and did not differ significantly by device (P ≥ 0·62). Reproducibility was good (ICC≥0·77) for alpha diversity and taxonomic assignment to the most abundant phyla, Firmicutes and Bacteroidetes (71·5% and 25·0% of sequences, respectively), but reproducibility was low (ICC≤0·48) for less abundant taxa. Alpha diversity was lower with nonantibiotic prescription medication (P = 0·02), with younger age (P = 0·03) and marginally with higher body mass index (P = 0·08).

Conclusions:  With sampling from various parts of a stool, both devices provided good reproducibility on overall microbial diversity and classification for the major phyla, but not for minor phyla. Implementation of these methods should provide insights into how broad microbial parameters, but not necessarily rare microbes, affect risk of various conditions.
Assessment of the human faecal microbiota: I. Measurement and reproducibility of selected enzymatic activities
Authors: Flores Roberto , Shi Jianxin , Gail Mitchell H. , Ravel Jacques , Goedert James J.
Published: February 2012

Eur J Clin Invest 2012

Background  The intestinal microbial community has major effects on human health, but optimal research methods are unsettled. To facilitate epidemiologic and clinical research, we sought to optimize conditions and to assess reproducibility of selected core functions of the distal gut microbiota, β‐glucuronidase and β‐glucosidase bioactivities.

Methods and results  A colorimetric kinetic method was optimized and used to quantify activities of β‐glucuronidase and β‐glucosidase in human faeces. Enzyme detection was optimal with neutral pH, snap freezing in liquid nitrogen and rapid thawing to 37 °C before protein extraction. Enzymatic stability was assessed by delayed freezing for 2–48 h to mimic field settings. Activities decayed approximately 20% within 2 h and 40% within 4 h at room temperature. To formally assess reproducibility, 51 volunteers (25 men; mean age 39) used two devices to self‐collect and rapidly chill four replicates of a stool. Devices were compared for mean enzymatic activities and intraclass correlation coefficients (ICC) in paired replicates of the self‐collected specimens. Reproducibility was excellent with both devices for β‐glucuronidase (ICC 0·92). The larger collection device had significantly higher reproducibility for β‐glucosidase (ICC 0·92 vs. 0·76, P < 0·0001) and higher mean activities for both enzymes (P < 0·0001).

Conclusions  Optimal measurement of these core activities of the microbiota required a sufficient quantity of rapidly chilled or frozen specimens collected in phosphate buffered saline at pH7·0. Application of these methods to clinical and epidemiologic research could provide insights on how the intestinal microbiota affects human health.
Levels and patterns of expression of hypoxia‐inducible factor‐1α, vascular endothelial growth factor, glucose transporter‐1 and CD105 in adenoid cystic carcinomas with high‐grade transformation
Authors: Costa Ana F , Tasso Marcelo G , Mariano Fernanda V , Soares Andresa B , Chone Carlos T , Crespo Agricio N , Fresno Manuel F , Llorente Jose L , Suárez Carlos , de Araújo Vera C , Hermsen Mario , Altemani Albina
Published: February 2012

Costa A F, Tasso M G, Mariano F V, Soares A B, Chone C T, Crespo A N, Fresno M F, Llorente J L, Suárez C, de Araújo V C, Hermsen M & Altemani A  (2012) Histopathology 60, 816–837

Levels and patterns of expression of hypoxia‐inducible factor‐1α, vascular endothelial growth factor, glucose transporter‐1 and CD105 in adenoid cystic carcinomas with high‐grade transformation

Aims:  To compare the expression of proteins regulated by hypoxia between adenoid cystic carcinoma (ACC) with and without high‐grade transformation (HGT).

Methods and results:  In eight ACC–HGT and 18 ACC without HGT, expression of hypoxia‐inducible factor‐1 (HIF‐1α), vascular endothelial growth factor (VEGF), glucose transporter‐1 (GLUT‐1) and microvascular density (MVD) by CD105 (a hypoxia‐inducible protein expressed in angiogenic endothelial cells) was determined. Expression levels of HIF‐1α and VEGF as well as CD105‐MVD did not differ significantly between: (i) transformed and conventional areas (TA and CA, respectively) of ACC–HGT, (ii) CA and ordinary ACC. HIF‐1α was detected in 100% of cases and presented a diffuse expression pattern. No significant association was found between levels of HIF‐1α expression and tumour size, metastasis and recurrence. GLUT‐1 showed a prostromal expression pattern and was observed exclusively in TA (three of six cases) and in only three of 14 ACC.

Conclusions:  Both the absence of significant alterations in levels of expression of HIF‐1α, VEGF and CD105 and the patterns of expression of HIF‐1α and GLUT‐1 suggest that hypoxia may not play a key role in the process of high‐grade transformation of ACC. Although HIF‐1α expression is a common finding in ACC, it cannot be used as a marker of tumour aggressiveness.
Concordance of HER2 status assessed on needle core biopsy and surgical specimens of invasive carcinoma of the breast
Authors: Lee Andrew H S , Key Heather P , Bell Jane A , Hodi Zsolt , Ellis Ian O
Published: February 2012

Lee A H S, Key H P, Bell J A, Hodi Z & Ellis I O  (2012) Histopathology 60, 880–884

Concordance of HER2 status assessed on needle core biopsy and surgical specimens of invasive carcinoma of the breast

Aims:  Human epidermal growth factor receptor 2 (HER2) status of invasive breast cancers is vital for selection of patients for trastuzumab treatment. This study aimed to assess the level of agreement of HER2 status in core biopsy and excision specimens using immunohistochemistry, with in‐situ hybridisation for equivocal cases.

Methods and results:  300 consecutive invasive carcinomas with core biopsy and surgical specimens had HER2 assessed on both specimens. Immunohistochemistry was performed first. Fluorescence in‐situ hybridization (FISH) was automatically performed if the immunohistochemistry was scored as equivocal (2+). There was agreement between the HER2 status of the two specimens in 294 tumours (98%). In two carcinomas the core was negative and the excision specimen showed focal strong staining with amplification. In four carcinomas the core biopsy was negative and the excision showed 2+ staining with amplification in at least one block (although in three there was no amplification in a second block).

Conclusion:  There is excellent agreement between HER2 assessed in core biopsy and surgical specimens. Discrepancies arise most frequently due to focal amplification or levels of gene amplification around the cut‐off for defining positivity.
Recent progress toward understanding the physiological function of bone marrow mesenchymal stem cells
Authors: Shi Chao
Published: February 2012

Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as regenerative therapeutics. Cultured MSCs secrete various modulatory factors, which contribute to the immunosuppressive effects of transplanted MSCs as a therapy. Although the in vitro phenotype of MSCs has been well characterized, identification of MSCs in vivo is made difficult by the lack of specific markers. Current advances in murine MSC research provide valuable tools for studying the localization and function of MSCs in vivo. Recent findings suggest that MSCs exert diverse functions depending on tissue context and physiological conditions. This review focuses on bone marrow MSCs and their roles in haematopoiesis and immune responses.
Effect of fermented rice culture on the microbiological, biochemical and sensory characteristics of low‐salt douchi, a traditional Chinese fermented soybean condiment
Authors: Hu Huiping , Hao Jianxiong , Cheng Yongqiang , Yin Lijun , Ma Yanli , Yu Zhenwei , Li Lite
Published: February 2012

A low‐salt (4% NaCl, w/w) douchi supplemented with different concentration of fermented rice culture (FRC) of 0%, 5%, 10%, 15% and 20% (v/w) was produced, and the effect of FRC on microbiology, biochemistry and sensory quantity was investigated. Results indicated that FRC had a significant effect on low‐salt douchi. Compared with the control (added 0% FRC), in the other treatments, the counts of yeast and lactic acid bacteria increased by about 50%, whereas the moulds decreased by about 30%; the pH reduction was close to 4.7; total acid increased to about 1.300 g per 100 g; reducing sugar maintained a decrease to 21.07 mg per g; amino nitrogen increased to about 0.900 g per 100 g, but not above the control (1.013 g per 100 g). In general terms, total free amino acid contents and three organic acids were higher in low‐salt products than four commercial products. Sensory evaluation of products supplemented with 10% and 15% FRC revealed better overall acceptability compared with other treatments and a commercial product.
Enrichment of tocols from rice germ oil using supercritical carbon dioxide
Authors: Ko Soon‐Nam , Ha Tae‐Yeoul , In Hong Seung , Yoon Sung Won , Lee Junsoo , Kim Yangha , Kim In‐Hwan
Published: February 2012

An efficient process was developed for enrichment of tocols from rice germ oil (RGO) using supercritical carbon dioxide (SC‐CO2). Tocols were efficiently enriched in residue by removal of fatty acid methyl ester from the esterified RGO using SC‐CO2. The enrichment of tocols was carried out at an operating pressure of 12.4–15.8 MPa, an operating temperature of 40–60 °C and a carbon dioxide flow rate of 5.0 L min−1. The combination of 13.8 MPa pressure and 60 °C temperature was selected as the most suitable for efficient enrichment of tocols. The level of tocols (1270 mg/100 g) in the residue obtained at these operating conditions was six times higher than the tocols level (192 mg/100 g) of the starting material, namely esterified RGO. There were no significant differences in relative percentages of tocols homologues between esterified RGO and the residue obtained by SC‐CO2 extraction.
Efficiency of modified skimmed milk base media to achieve high exopolysaccharide/cell ratios by Lactobacillus delbrueckii subsp. bulgaricus SZ2 in optimised conditions defined by the response surface methodology
Authors: Abdi Reihaneh , Sheikh‐Zeinoddin Mahmoud , Soleimanian‐Zad Sabihe
Published: February 2012

Exopolysaccharide (EPS) production by Lactobacillus delbrueckii subsp. bulgaricus SZ2 was optimised in modified MRS (M‐MRS) using the response surface methodology (RSM). Maximum EPS production was 74.3 ± 2 mg/L, and the optimised values of the three variables predicted for maximum EPS production included a temperature of 38.7 °C, Bacto‐casitone and glucose concentrations of 24.5 and 29.6 g/L, respectively. To compare EPS production in MRS and skimmed milk (SM), the kinetics of EPS formation and growth were monitored in M‐MRS, SM, skimmed milk plus 2% additional sucrose (Suc‐SM) and skimmed milk containing Bacto‐casitone (20 g/L) and yeast nitrogen base (5 g/L) (BY‐SM). EPS production in all the media tested seemed to be growth‐related. The EPS/cell ratios were determined to be 3.12 × 10−10, 1.43 × 10−10, 4.42 × 10−11 and 3.16 × 10−11 mg/cell, in Suc‐SM, SM, M‐MRS and BY‐SM, respectively, clearly indicating the greater effect of C/N ratio when cell behaviour in EPS production is considered.
Physicochemical characterisation of the hydrocolloid from Brea tree (Cercidium praecox)
Authors: Bertuzzi María A. , Slavutsky Anibal M. , Armada Margarita
Published: February 2012

The Brea gum (BG) is a hydrocolloid obtained as phloematic exudate from Cercidium praecox. The exudate was purified by solution and subsequent drying. BG showed high solubility in water 28.3% at 25 °C that increased as temperature was raised. Viscosity of BG solutions increased with BG concentration increase and temperature decrease. Addition of acid or alkali produced changes in solution viscosity as the electrostatic charges on the macromolecule were altered. Solution density at 25 °C increased linearly with hydrocolloid concentration up to saturation. BG lowered the surface tension of water to 51.3 mN m−1 when BG concentration was 5%, remaining constant for higher concentrations. The diameter of oil droplets emulsified decreased and foamability increased with BG concentration increase up to 5% of BG. BG presents adequate functional characteristics for use as stabiliser in preparations with high content of insoluble solids and as stabiliser and emulsifier in emulsions and foams.
Reversal of multicentury tree growth improvements and loss of synchrony at mountain tree lines point to changes in key drivers
Authors: Fajardo Alex , McIntire Eliot J. B.
Published: February 2012

1. Altitudinal tree line ecotones (ATE) are among the most sensitive plant formations facing global warming as the altitudinal decrease in temperature is considered the driver controlling the upper elevation limit of tree lines world‐wide. In this study, we attempted to answer the following questions: (i) how have the conditions during the last 2–3 centuries affected ATE tree growth (physiology) and recruitment (demography)? and (ii) how strong is synchrony between these two processes at the ATEs?

2. We used spatial sampling grids at different ATEs in two ecosystems on two subcontinents: Nothofagus pumilio in the Andes of Chilean Patagonia (46° SL) and Pinus albicaulis in the Rockies of Western Montana, USA (46° NL). Basal increment cores were extracted from trees to estimate the growth and recruitment date. An annual detrended basal area increment was estimated for each tree and was modelled against elevation and time.

3. Tree growth improved over multiple centuries at all tree lines. Recently (c. 50 years), however, improvements are disappearing or reversing. The uppermost tree line trees showed moderate declines in Montana and incipient declines in Patagonia. The declines are most dramatic slightly below current tree line (c. 200 m). Tree recruitment patterns showed that tree lines have been moving uphill in both regions until at least 40–70 years ago. These movements occurred primarily through abrupt pulses upward with infilling occurring concurrently (Patagonia) or at some time thereafter (Montana).

4. Synchrony between growth and recruitment occurred in the 18th and 19th centuries in both regions. This synchrony was negative in Patagonia and positive in Montana, with varying lag periods. During the 20th century, these patterns of synchrony were lost at all sites. This loss of synchrony suggests that we could be entering a global period in which temperature is no longer the dominant driver of key features of tree lines.

5.
Synthesis. Our study shows that at two structurally different tree lines, recent and initial declines in growth and losses of long‐term synchrony are occurring in the latter part of the 20th century. These findings are opposite to simplistic expectations of global warming effects on tree line dynamics and call for a model reformulation that uncouples drivers of growth and recruitment.
Are existing measures of overall diet quality associated with peak bone mass in young premenopausal women?
Authors: Zagarins S. E. , Ronnenberg A. G. , Gehlbach S. H. , Lin R. , Bertone‐Johnson E. R.
Published: February 2012

How to cite this article
 Zagarins S.E., Ronnenberg A.G., Gehlbach S.H., Lin R. & Bertone‐Johnson E.R. (2012) Are existing measures of overall diet quality associated with peak bone mass in young premenopausal women? J Hum Nutr Diet.25, 172–179

Background:  Low peak bone mass in young adulthood is associated with an increased risk of osteoporosis and fracture after menopause, and an understanding of the modifiable factors that contribute to low peak bone mass is important for fracture prevention. Diet is an important modifiable factor linked to bone health and, although studies have examined the role of individual dietary components in bone health, bone growth and maintenance are complex processes, and such studies may not adequately represent the role of diet in these processes.

Methods:  To address this issue, a cross‐sectional analysis of 226 healthy, premenopausal women aged 18–30 years was conducted to determine whether existing indices of overall diet quality are associated with bone density in premenopausal women nearing peak bone mass. Bone density was measured using dual‐energy X‐ray absorptiometry and diet quality was measured using two overall diet scores based on current dietary guidelines: the Recommended Food Score and the Alternate Healthy Eating Index (AHEI).

Results:  In the multiple linear regression, bone density did not increase across quartiles of either diet quality score and was not associated with continuous diet quality variables. Furthermore, none of the individual AHEI components (e.g. fruit intake, vegetable intake) were associated with bone density.

Conclusions:  These findings suggest that existing diet quality scores are not appropriate for studies of peak bone mass, most likely because they do not give sufficient weight to foods and nutrients important to bone health. We recommend the development of a diet pattern index that better predicts bone mass measures.