bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors affecting calcium oxalate dihydrate fragmented calculi regrowth
Authors: Costa-Bauzá A , Perelló J , Isern B , Sanchis P , Grases F
Published: August 2006

Background

The use of extracorporeal shock wave lithotripsy (ESWL) to treat calcium oxalate dihydrate (COD) renal calculi gives excellent fragmentation results. However, the retention of post-ESWL fragments within the kidney remains an important health problem. This study examined the effect of various urinary conditions and crystallization inhibitors on the regrowth of spontaneously-passed post-ESWL COD calculi fragments.

Methods

Post-ESWL COD calculi fragments were incubated in chambers containing synthetic urine varying in pH and calcium concentration: pH = 5.5 normocalciuria (3.75 mM), pH = 5.5 hypercalciuria (6.25 mM), pH = 6.5 normocalciuria (3.75 mM) or pH = 6.5 hypercalciuria (6.25 mM). Fragment growth was evaluated by measuring increases in weight. Fragment growth was standardized by calculating the relative mass increase.

Results

Calcium oxalate monohydrate (COM) crystals formed on COD renal calculi fragments under all conditions. Under pH = 5.5 normocalciuria conditions, only COM crystals formed (growth rate = 0.22 ± 0.04 μg/mg·h). Under pH = 5.5 hypercalciuria and under pH = 6.5 normocalciuria conditions, COM crystals and a small number of new COD crystals formed (growth rate = 0.32 ± 0.03 μg/mg·h and 0.35 ± 0.05 μg/mg·h, respectively). Under pH = 6.5 hypercalciuria conditions, large amounts of COD, COM, hydroxyapatite and brushite crystals formed (growth rate = 3.87 ± 0. 34 μg/mg·h). A study of three crystallization inhibitors demonstrated that phytate completely inhibited fragment growth (2.27 μM at pH = 5.5 and 4.55 μM at pH = 6.5, both under hypercalciuria conditions), while 69.0 μM pyrophosphate caused an 87% reduction in mass under pH = 6.5 hypercalciuria conditions. In contrast, 5.29 mM citrate did not inhibit fragment mass increase under pH = 6.5 hypercalciuria conditions.

Conclusion

The growth rate of COD calculi fragments under pH = 6.5 hypercalciuria conditions was approximately ten times that observed under the other three conditions. This observation suggests COD calculi residual fragments in the kidneys together with hypercalciuria and high urinary pH values may be a risk factor for stone growth. The study also showed the effectiveness of specific crystallization inhibitors in slowing calculi fragment growth.
Generation of non-genomic oligonucleotide tag sequences for RNA template-specific PCR
Authors: Pinto Fernando Lopes , Svensson Håkan , Lindblad Peter
Published: August 2006

Background

In order to overcome genomic DNA contamination in transcriptional studies, reverse template-specific polymerase chain reaction, a modification of reverse transcriptase polymerase chain reaction, is used. The possibility of using tags whose sequences are not found in the genome further improves reverse specific polymerase chain reaction experiments. Given the absence of software available to produce genome suitable tags, a simple tool to fulfill such need was developed.

Results

The program was developed in Perl, with separate use of the basic local alignment search tool, making the tool platform independent (known to run on Windows XP and Linux). In order to test the performance of the generated tags, several molecular experiments were performed. The results show that Tagenerator is capable of generating tags with good priming properties, which will deliberately not result in PCR amplification of genomic DNA.

Conclusion

The program Tagenerator is capable of generating tag sequences that combine genome absence with good priming properties for RT-PCR based experiments, circumventing the effects of genomic DNA contamination in an RNA sample.
Occurrence of the leucine-to-phenylalanine knockdown resistance (kdr) mutation in Anopheles arabiensis populations in Tanzania, detected by a simplified high-throughput SSOP-ELISA method
Authors: Kulkarni Manisha A , Rowland Mark , Alifrangis Michael , Mosha Frank W , Matowo Johnson , Malima Robert , Peter Justin , Kweka Eliningaya , Lyimo Issa , Magesa Stephen , Salanti Ali , Rau Manfred E , Drakeley Chris
Published: August 2006

Background

Molecular markers of insecticide resistance can provide sensitive indicators of resistance development in malaria vector populations. Monitoring of insecticide resistance in vector populations is an important component of current malaria control programmes. Knockdown resistance (kdr) confers resistance to the pyrethroid class of insecticides with cross-resistance to DDT through single nucleotide polymorphisms (SNPs) in the voltage-gated sodium channel gene.

Methods

To enable detection of kdr mutations at low frequency a method was developed that uses polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA)-based technology, allowing rapid, reliable and cost-effective testing of large numbers of individual mosquitoes. This was used to assay mosquitoes from sites in lower Moshi, Tanzania.

Results

Sequence-specific oligonucleotide probes (SSOP) were used for simultaneous detection of both East and West African kdr mutations with high specificity and sensitivity. Application of the SSOP-ELISA method to 1,620 field-collected Anopheles arabiensis from Tanzania identified the West African leucine-phenylalanine kdr mutation in two heterozygous individuals, indicating the potential for resistance development that requires close monitoring.

Conclusion

The presence of the West African kdr mutation at low frequency in this East African population of An. arabiensis has implications for the spread of the kdr gene across the African continent.
Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix
Authors: Maheshwari Amita , Gupta Sudeep , Shet Tanuja , Wuntkal Rekha , Tongaonkar Hemant B
Published: August 2006

Background

Malignant mixed mullerian tumors (MMMT) are rare biphasic malignant neoplasm. The commonest site of their occurrence in female genital tract is body of the uterus. MMMT of the cervix is extremely rare.

Case presentation

We report the clinical, pathological and immunohistochemical profile and diagnostic difficulties in a case of giant MMMT of the cervix in a postmenopausal woman who presented with a large cervical mass. On microscopic examination, initially tumor appeared to be endometrial stromal sarcoma, however, immunohistochemical examination revealed the biphasic nature of the tumor. The malignant epithelial component was basaloid squamous carcinoma with homologous sarcomatous component. The patient was treated with surgery. However, she experienced vaginal vault recurrence four months after the initial treatment, which was successfully treated with pelvic radiotherapy.

Conclusion

Accurate diagnosis of cervical MMMT is important for appropriate treatment of the patient.
Novel missense mutations of the Deleted-in-AZoospermia-Like (DAZL) gene in infertile women and men
Authors: Tung Joyce Y , Rosen Mitchell P , Nelson Lawrence M , Turek Paul J , Witte John S , Cramer Daniel W , Cedars Marcelle I , Reijo-Pera Renee A
Published: August 2006

Background

The Deleted-in-AZoospermia-Like (DAZL) gene has homologs required for germ cell development in many organisms. Recently, we showed that there are several common polymorphisms within the DAZL gene that are associated with age at ovarian failure/menopause and sperm count.

Methods

Here we sought to identify rare mutations in DAZL and examine their phenotypes in men and women. We sequenced the DAZL gene in 519 individuals; sequences spanned the entire coding region of the gene.

Results

We report the identification of four putative missense mutations in DAZL. Three individuals that were heterozygous for a DAZL mutation reported having children, while two individuals that were homozygous reported no children. These mutations were found only in infertile men and women.

Conclusion

Given the strong data associating DAZL polymorphisms and deletions with fertility in humans and model organisms, we suggest that these mutations may be associated with age at menopause and/or sperm count and warrant further biochemical and genetic investigation.
Characterization of HIV-1 envelope gp41 genetic diversity and functional domains following perinatal transmission
Authors: Ramakrishnan Rajesh , Mehta Roshni , Sundaravaradan Vasudha , Davis Tiffany , Ahmad Nafees
Published: August 2006

Background

HIV-1 envelope gp41 is a transmembrane protein that promotes fusion of the virus with the plasma membrane of the host cells required for virus entry. In addition, gp41 is an important target for the immune response and development of antiviral and vaccine strategies, especially when targeting the highly variable envelope gp120 has not met with resounding success. Mutations in gp41 may affect HIV-1 entry, replication, pathogenesis, and transmission. We, therefore, characterized the molecular properties of gp41, including genetic diversity, functional motifs, and evolutionary dynamics from five mother-infant pairs following perinatal transmission.

Results

The gp41 open reading frame (ORF) was maintained with a frequency of 84.17% in five mother-infant pairs' sequences following perinatal transmission. There was a low degree of viral heterogeneity and estimates of genetic diversity in gp41 sequences. Both mother and infant gp41 sequences were under positive selection pressure, as determined by ratios of non-synonymous to synonymous substitutions. Phylogenetic analysis of 157 mother-infant gp41 sequences revealed distinct clusters for each mother-infant pair, suggesting that the epidemiologically linked mother-infant pairs were evolutionarily closer to each other as compared with epidemiologically unlinked sequences. The functional domains of gp41, including fusion peptide, heptad repeats, glycosylation sites and lentiviral lytic peptides were mostly conserved in gp41 sequences analyzed in this study. The CTL recognition epitopes and motifs recognized by fusion inhibitors were also conserved in the five mother-infant pairs.

Conclusion

The maintenance of an intact envelope gp41 ORF with conserved functional domains and a low degree of genetic variability as well as positive selection pressure for adaptive evolution following perinatal transmission is consistent with an indispensable role of envelope gp41 in HIV-1 replication and pathogenesis.
Number of risk genotypes is a risk factor for major depressive disorder: a case control study
Authors: Garriock Holly A , Delgado Pedro , Kling Mitchel A , Carpenter Linda L , Burke Michael , Burke William J , Schwartz Thomas , Marangell Lauren B , Husain Mustafa , Erickson Robert P , Moreno Francisco A
Published: August 2006

Background

The objective of the study was to determine the genetic basis of Major Depressive Disorder, and the capacity to respond to antidepressant treatment. An association study of 21 candidate polymorphisms relevant to monoamine function and the mechanism of antidepressant response was conducted in 3 phenotypically distinct samples: a group with chronic or recurrent depression unable to respond to antidepressants (non-responders) (n = 58), a group capable of symptomatic improvement with or without treatment (responders) (n = 39), and volunteer controls (n = 85). The responders and non-responders constituted a larger group of depressed subjects.

Methods

A candidate gene approach was employed to asses the genetics basis of Major Depressive Disorder. The genotypic frequencies of selected polymorphisms were compared between the controls and depressed subjects. To asses the genetics basis of the capacity to respond to antidepressant treatment, the responders were compared to the non-responders. Candidate genes were chosen based on functional studies and proximity to whole genome linkage findings in the literature. Risk genotypes were identified by previous functional studies and association studies.

Results

A statistically significant difference in genotype frequency for theSLC6A4intron 2 VNTR was detected between the subjects with a history of depression and controls (p = 0.004). Surprisingly, a statistically significant difference was detected between responders and non-responders for theDRD4exon III VNTR genotype frequencies (p = 0.009). Furthermore, a difference between the controls and depressed subjects as well as between the controls and non-responders was detected for the number and distribution of risk genotypes in each group.

Conclusion

An association between several monoamine-related genes and Major Depressive Disorder is supported. The data suggest that the two depressive phenotypes are genetically different, inferring that the genetic basis for the capacity to respond to standard antidepressant treatment, and the genetic susceptibility to Major Depressive Disorder may be independent. In addition, a proof of concept is provided demonstrating that the number of risk genotypes may be an indication of susceptibility of major depressive disorder and the severity of the disorder.
Double blind randomized placebo-controlled trial on the effects of testosterone supplementation in elderly men with moderate to low testosterone levels: design and baseline characteristics [ISRCTN23688581]
Authors: Nakhai Pour Hamid Reza , Emmelot-Vonk Marielle H , Sukel-Helleman Marja , Verhaar Harald JJ , Grobbee Diederick E , van der Schouw Yvonne T
Published: August 2006

In ageing men testosterone levels decline, while cognitive function, muscle and bone mass, sexual hair growth, libido and sexual activity decline and the risk of cardiovascular diseases increase. We set up a double-blind, randomized placebo-controlled trial to investigate the effects of testosterone supplementation on functional mobility, quality of life, body composition, cognitive function, vascular function and risk factors, and bone mineral density in older hypogonadal men.

We recruited 237 men with serum testosterone levels below 13.7 nmol/L and ages 60–80 years. They were randomized to either four capsules of 40 mg testosterone undecanoate (TU) or placebo daily for 26 weeks. Primary endpoints are functional mobility and quality of life. Secondary endpoints are body composition, cognitive function, aortic stiffness and cardiovascular risk factors and bone mineral density. Effects on prostate, liver and hematological parameters will be studied with respect to safety.

Measure of effect will be the difference in change from baseline visit to final visit between TU and placebo. We will study whether the effect of TU differs across subgroups of baseline waist girth (< 100 cm vs. ≥ 100 cm; testosterone level (<12 versus ≥ 12 nmol/L), age (< median versus ≥ median), and level of outcome under study (< median versus ≥ median).

At baseline, mean age, BMI and testosterone levels were 67 years, 27 kg/m2and 10.72 nmol/L, respectively.
Flock-level risk factors for scrapie in Great Britain: analysis of a 2002 anonymous postal survey
Authors: McIntyre K Marie , Gubbins Simon , Sivam S Kumar , Baylis Matthew
Published: August 2006

Background

In November 2002, an anonymous postal survey of sheep farmers in Great Britain (GB) was conducted to identify factors associated with the flock-level occurrence of scrapie. This survey was undertaken to update an earlier postal survey in 1998, and was the first occasion in which a large-scale postal survey had been repeated.

Results

The results of the 2002 survey indicated that scrapie was more likely to occur in certain geographic regions; in purebred compared to commercial flocks; in larger flocks; in flocks which lambed in group pens compared to those which lambed in individual pens; in flocks which always lambed in the same location compared to those which did not; and in farms which kept certain breeds of sheep. In addition to these factors, the likelihood of the disease occurring in homebred animals was higher in flocks which bred a greater proportion of replacement animals or which bought-in lambs. Finally, within-flock transmission following exposure was more likely to occur in hill flocks compared to other farm types; in flocks which bred a greater proportion of replacement animals; and in farms which kept a certain crossbreed of ewe.

Conclusion

The risk factors identified from the 1998 and 2002 anonymous postal surveys in Great Britain were similar. However, differences between the surveys were identified in the influence of region and of purchasing behaviour on the risk of scrapie. These differences are most likely a consequence of changes in farmer awareness and the impact of the 2001 foot-and-mouth disease epidemic, respectively.
Explaining variation in GP referral rates for x-rays for back pain
Authors: Baker Rachel , Lecouturier Jan , Bond Senga
Published: August 2006

Background

Despite the availability of clinical guidelines for the management of low back pain (LBP), there continues to be wide variation in general practitioners' (GPs') referral rates for lumbar spine x-ray (LSX). This study aims to explain variation in GPs' referral rates for LSX from their accounts of the management of patients with low back pain.

Methods

Qualitative, semi-structured interviews with 29 GPs with high and low referral rates for LSX in North East England. Thematic analysis used constant comparative techniques.

Results

Common and divergent themes were identified among high- and low-users of LSX. Themes that were similar in both groups included an awareness of current guidelines for the use of LSX for patients with LBP and the pressure from patients and institutional factors to order a LSX. Differentiating themes for the high-user group included: a belief that LSX provides reassurance to patients that can outweigh risks, pessimism about the management options for LBP, and a belief that denying LSX would adversely affect doctor-patient relationships. Two specific differentiating themes are considered in more depth: GPs' awareness of their use of lumbar spine radiology relative to others, and the perceived risks associated with LSX radiation.

Conclusion

Several key factors differentiate the accounts of GPs who have high and low rates of referral for LSX, even though they are aware of clinical guideline recommendations. Intervention studies that aim to increase adherence to guideline recommendations on the use of LSX by changing the ordering behaviour of practitioners in primary care should focus on these factors.
Radiosensitization of colorectal carcinoma cell lines by histone deacetylase inhibition
Authors: Flatmark Kjersti , Nome Ragnhild V , Folkvord Sigurd , Bratland Åse , Rasmussen Heidi , Ellefsen Mali Strand , Fodstad Øystein , Ree Anne Hansen
Published: August 2006

Background

The tumor response to preoperative radiotherapy of locally advanced rectal cancer varies greatly, warranting the use of experimental models to assay the efficacy of molecular targeting agents in rectal cancer radiosensitization. Histone deacetylase (HDAC) inhibitors, agents that cause hyperacetylation of histone proteins and thereby remodeling of chromatin structure, may override cell cycle checkpoint responses to DNA damage and amplify radiation-induced tumor cell death.

Methods

Human colorectal carcinoma cell lines were exposed to ionizing radiation and HDAC inhibitors, and cell cycle profiles and regulatory factors, as well as clonogenicity, were analyzed.

Results

In addition to G2/M phase arrest following irradiation, the cell lines displayed cell cycle responses typical for either intact or defective p53 function (the presence or absence, respectively, of radiation-induced expression of the cell cycle inhibitor p21 and subsequent accumulation of G1 phase cells). In contrast, histone acetylation was associated with complete depletion of the G1 population of cells with functional p53 but accumulation of both G1 and G2/M populations of cells with defective p53. The cellular phenotypes upon HDAC inhibition were consistent with the observed repression of Polo-like kinase-1, a regulatory G2/M phase kinase. Following pre-treatment with HDAC inhibitors currently undergoing clinical investigation, the inhibitory effect of ionizing radiation on clonogenicity was significantly amplified.

Conclusion

In these experimental models, HDAC inhibition sensitized the tumor cells to ionizing radiation, which is in accordance with the concept of increased probability of tumor cell death when chromatin structure is modified.
Physiological routes from intra-uterine seminal contents to advancement of ovulation
Authors: Waberski Dagmar , Döhring Anke , Ardón Florencia , Ritter Nadine , Zerbe Holm , Schuberth Hans-Joachim , Hewicker-Trautwein Marion , Weitze Karl Fritz , Hunter Ronald HF
Published: August 2006

Whole boar semen or seminal plasma has been demonstrated to advance the time of ovulation in gilts. As a means of clarifying this influence, the contribution of uterine lymphatics and their white cell populations has been examined. After duct visualisation with Evan's blue, lymph was sampled from a mesometrial vessel in eight pre-ovulatory gilts whose uterine lumen was infused simultaneously with whole semen in one ligated horn and saline in the contralateral ligated horn. Lymph was collected from cannulated vessels for periods of up to four hours under general anaesthesia. Thereafter, mesometrial lymph nodes, utero-tubal junction and uterine wall tissues were sampled. The proportion of nucleated cells in the sampled lymph increased towards the end of the collection period, but erythrocytes were found in all instances preventing a meaningful differentiation and identification of leukocytes. Prominent uterine lymph nodes were present in the mesometrium on both sides of the reproductive tract in 7 of 10 gilts. Differences in cellular contents were demonstrated between the side of the tract infused with semen and that infused with saline control. Two of 4 gilts had lower values for CD4 (Cluster Differentiation) and 3 of 6 gilts higher values for MHC II (Major Histocompatibility Complex) markers on the side challenged with semen. In contrast, values remained constant for CD8 but ranged widely for CD18. Immunohistochemical analysis of uterine tissue samples for MHC II+ cells revealed significant differences (P < 0.05) between the control and semen-treated ligated portions of the horns, as well as between the tissue sample of uterine wall and that from the utero-tubal junction, but there were no significant differences for CD4+ cells. It therefore remains plausible that semen-induced cytokines in the uterine lymph undergo counter-current transfer to the ipsilateral ovary and accelerate the final maturation of pre-ovulatory Graafian follicles.
Familial, structural, and environmental correlates of MRI-defined bone marrow lesions: a sibpair study
Authors: Zhai Guangju , Stankovich James , Cicuttini Flavia , Ding Changhai , Jones Graeme
Published: August 2006

The aim of this study was to estimate the heritability and describe the correlates of bone marrow lesions in knee subchondral bone. A sibpair design was used. T2- and T1-weighted MRI scans were performed on the right knee to assess bone marrow lesions at lateral tibia and femora and medial tibia and femora, as well as chondral defects. A radiograph was taken on the same knee and scored for individual features of osteoarthritis (radiographic osteoarthritis; ROA) and alignment. Other variables measured included height, weight, knee pain, and lower-limb muscle strength. Heritability was estimated with the program SOLAR (Sequential Oligogenetic Linkage Analysis Routines). A total of 115 siblings (60 females and 55 males) from 48 families, representing 95 sib pairs, took part. The adjusted heritability estimates were 53 ± 28% (mean ± SEM; p = 0.03) and 65 ± 32% (p = 0.03) for severity of bone marrow lesions at lateral and medial compartments, respectively. The estimates were reduced by 8 to 9% after adjustment for chondral defects and ROA (but not alignment). The adjusted heritability estimate was 99% for prevalent bone marrow lesions at both lateral and medial compartments. Both lateral and medial bone marrow lesions were significantly correlated with age, chondral defects, and ROA of the knee (all p < 0.05). Medial bone marrow lesions were also more common in males and were correlated with body mass index (BMI). Thus, bone marrow lesions have a significant genetic component. They commonly coexist with chondral defects and ROA but only share common genetic mechanisms to a limited degree. They are also more common with increasing age, male sex, and increasing BMI.
Ventilator-associated pneumonia using a heated humidifier or a heat and moisture exchanger: a randomized controlled trial [ISRCTN88724583]
Authors: Lorente Leonardo , Lecuona María , Jiménez Alejandro , Mora María L , Sierra Antonio
Published: August 2006

Introduction

Some guidelines to prevent ventilator-associated pneumonia (VAP) do not establish a recommendation for the preferential use of either heat and moisture exchangers (HMEs) or heated humidifiers (HHs), while other guidelines clearly advocate the use of HMEs. The aim of this study was to determine the incidence of VAP associated with HHs or HMEs.

Methods

A randomized study was conducted in the intensive care unit of a university hospital involving patients expected to require mechanical ventilation for >5 days. Patients were assigned to two groups; one group received HH and the other group received HME. Tracheal aspirate samples were obtained on endotracheal intubation, then twice a week, and finally on extubation, in order to diagnose VAP. Throat swabs were taken on admission to the intensive care unit, then twice a week, and finally at discharge from the intensive care unit in order to classify VAP as primary endogenous, secondary endogenous, or exogenous.

Results

A total of 120 patients were assigned to HMEs (60 patients) and HHs (60 patients); 16 patients received mechanical ventilation for less than five days and were excluded from the analysis. Data analysis of the remaining 104 patients (53 HMEs and 51 HHs) showed no significant differences between groups regarding sex, age, Acute Physiology and Chronic Health Evaluation II score, pre-VAP use of antibiotics, days on mechanical ventilation, and diagnosis group. VAP was found in eight of 51 (15.69%) patients in the HH group and in 21 of 53 (39.62%) patients in the HME group (P = 0.006). The median time free of VAP was 20 days (95% confidence interval, 13.34–26.66) for the HH group and was 42 days (95% confidence interval, 35.62–48.37) for the HME group (P < 0.001). Cox regression analysis showed the HME as a risk factor for VAP (hazard rate, 16.2; 95% confidence interval, 4.54–58.04; P < 0.001).

Conclusion

The patients mechanically ventilated for more than five days developed a lower incidence of VAP with a HH than with a HME.
T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa
Authors: Goldmann Jana , Kwidzinski Erik , Brandt Christine , Mahlo Jacqueline , Richter Daniel , Bechmann Ingo
Published: August 2006

Although drainage pathways of soluble antigens from brain to cervical lymph nodes have been well established, there is no direct evidence for similar routes of leukocytes leaving the central nervous system. We developed a protocol allowing the cross-sectioning of an entire head-neck preparation while preserving the signal of the GFP. We monitored how GFP-expressing CD4 T lymphocytes injected into the entorhinal cortex after lesion or the lateral ventricle of unlesioned C57/bl6 mice reach cervical lymph nodes. Irrespective of the injection site, we demonstrate their passage through the cribroid plate, appearance in the nasal mucosa, and specific accumulation in one of the cervical lymph nodes.
Cellular reprogramming by gram-positive bacterial components: a review
Authors: Buckley Julliette M , Wang Jiang Huai , Redmond H Paul
Published: August 2006

LPS tolerance has been the focus of extensive scientific and clinical research over the last several decades in an attempt to elucidate the sequence of changes that occur at a molecular level in tolerized cells. Tolerance to components of gram-positive bacterial cell walls such as bacterial lipoprotein and lipoteichoic acid is a much lesser studied, although equally important, phenomenon. This review will focus on cellular reprogramming by gram-positive bacterial components and examines the alterations in cell surface receptor expression, changes in intracellular signaling, gene expression and cytokine production, and the phenomenon of cross-tolerance.
Granulocyte macrophage colony-stimulating factor enhances retinoic acid-induced gene expression
Authors: Shimizu Takahisa , Esaki Lisa , Mizuno Hiroko , Takeda Ken
Published: August 2006

We reported previously that treatment of human myeloblastic leukemia ML-1 cells with all-trans retinoic acid (ATRA) in combination with GM-CSF enhances the granulocytic differentiation, which is induced only slightly by ATRA alone. To investigate the mechanism underlying this differentiation and the synergistic effect of ATRA and GM-CSF, we used cDNA microarray to examine gene expression profiles of ML-1 cells treated with ATRA and/or GM-CSF. We identified 22 up-regulated genes in ML-1 cells treated with both reagents and examined the expression of these genes in cells treated with ATRA and/or GM-CSF by Northen blot analysis. Comparison of cells treated with both reagents and cells treated with ATRA or GM-CSF alone revealed that expression of nine of the 19 genes was induced synergistically by combined treatment with ATRA and GM-CSF. Expression of most of these genes was increased only slightly by ATRA alone, and this induction was enhanced by the addition of GM-CSF. These results indicate that GM-CSF enhances ATRA-induced gene expression. Moreover, studies with inhibitors of signaling molecules suggested that activation of JAK2 is associated with the synergistic induction of several genes by ATRA and GM-CSF. JAK2 inhibitor suppressed induction of NBT-reducing activity in ML-1 cells treated with both reagents. It is likely that the enhancer effect of GM-CSF on ATRA-induced gene expression leads to the differentiation induced synergistically by ATRA combined with GM-CSF. Further studies of the mechanism underlying this effect may identify better approaches for the treatment of RA-insensitive leukemia.
Signal transduction induced by apoptotic cells inhibits HIV transcription in monocytes/macrophages
Authors: Gekonge Bethsebah N , Schiralli Gillian , Schlegel Robert A , Henderson Andrew J
Published: August 2006

The primary targets of HIV are CD4+ T cells and macrophages. HIV infection is associated with an increase in apoptosis of infected and uninfected CD4+ T cells, and these infected cells undergo apoptosis and produce HIV virions with phosphatidylserine (PS) on their surface. During phagocytosis of apoptotic cells, macrophages, using an array of receptors, are able to perceive various surface changes on apoptotic cells. The engagement of phagocytic receptors by ligands on the apoptotic cell surface results in the activation of signaling cascades, which facilitate engulfment. In this study, we examined how PS associated with virions and apoptotic cells influences HIV replication. We demonstrate that virus-associated PS is required for HIV infection of macrophages at a step prior to integration but following strong-stop, indicating that PS-initiated signals alter the establishment of HIV provirus. Conversely, apoptotic cells inhibited HIV transcription in infected macrophages, although this ability to suppress transcription was independent of PS. Furthermore, we show that ELMO, a key signaling molecule that participates in the phagocytosis of apoptotic cells, inhibited HIV transcription; however, knocking down endogenous ELMO expression in infected U937 cells rescued HIV transcription when these cells were coincubated with apoptotic targets. Taken together, these data show that apoptotic cells and the signals, which they initiate upon recognition by macrophages, influence the successful establishment of HIV infection and provirus transcription.
First steps in membrane oxygenation and prolonged extracorporeal perfusion in Duesseldorf using the Bramson membrane lung
Authors: Schulte Hagen D
Published: August 2006

After a shortened history of conventional closed and open heart surgery, including hypothermia by surface cooling and extracorporeal circulation, the first application of a new membrane oxygenator developed by ML Bramson with an integrated temperature exchange system and a heart-lung machine (HLM) was reported in 1972. The aim was to have an efficient oxygenating and gas exchange artificial lung that allowed prolonged perfusions in patients with cardiogenic shock or acute respiratory insufficiency. After in vitro closed recirculation studies comparing different bubble, vertical screen, and the new membrane oxygenators, the Bramson HLM was used in dog experiments before starting clinical cardiac surgery with routine interventions (closure of an atrial septal defect). The first clinically prolonged support for more than three hours after a double valve replacement in a NYHA class IV patient failed. A partial venoarterial prolonged perfusion for 42 hours and 43 minutes in a 10-year-old girl after surgical correction of a partial av canal defect and postoperative development of consistent lung edema caused by myocardial failure after an ischemic time of 43 minutes was the first successful long-term perfusion case in Europe. These first experiences with the Bramson membrane lung formed the basis, in our group, for further investigations of different perfusion routes and cannulations in animal experiments. Also, scanning electron microscopy studies could be performed with experimentally and clinically used membranes. The development of disposable membrane lung devices, for instance, Lande - Edwards, Kolobow Scimed, and General Electric Peirce membrane lungs, ameliorated and improved the use of these devices considerably. Also, BRAMSON had developed a disposable membrane lung device that had proved to be very effective in animal experiments by 1972, but, unfortunately, this device did not become commercially available.
Leukocyte filtration and aprotinin: synergistic anti-inflammatory protection
Authors: Olivencia-Yurvati Albert H , Wallace Neil , Ford Sheila , Mallet Robert T
Published: August 2006

Cardiopulmonary bypass activates an array of cellular and humoral inflammatory mechanisms that culminate in diverse or organ-specific injury. A manifestation of inflammatory injury to the heart, atrial fibrillation ranks among the most frequent and potentially life-threatening postsurgical complications. Pulmonary manifestations of the inflammatory response are also of major concern. Neutrophils activated by passage through the extracorporeal circuit inflict local injury and provoke the inflammatory cascade by producing oxyradicals and proinflammatory factors. This study tested if a combination of leukocyte depletion and aprotinin suppression of neutrophils could minimize postbypass atrial fibrillation and pulmonary dysfunction. In part one, two randomized groups of 90 patients undergoing primary coronary artery bypass grafting received full Hammersmith aprotinin alone (control group) or combined with leukofiltration (study group) and were prospectively examined. The dual treatment decreased the incidence of postoperative atrial fibrillation (7 of 90, 7.8%) by 67% versus aprotinin alone (21 of 90, 23.3%). Respiratory gas exchange in these patients was assessed from pulmonary shunt fraction. In the first two hours postbypass, pulmonary shunt fraction in the dual treatment group increased 40% less than in the group receiving aprotinin alone (p = 0.002), and subsided more quickly and completely over the next six hours. In part two, the cardiopulmonary bypass group receiving aprotinin+leukofiltration was retrospectively compared with 45 patients undergoing off-pump coronary revascularization. A strong, albeit not statistically significant trend (p= 0.08) toward a lower incidence of atrial fibrillation was found in the dual treatment group versus the off-pump group (8 of 45, 17.8%). These findings suggest that combining mechanical and pharmacologic suppression of the systemic inflammatory response could mitigate its deleterious arrhythmic and pulmonary complications.
The inflammatory response to cardiopulmonary bypass: a therapeutic overview
Authors: Rubens F D , Mesana T
Published: August 2006

The demographic of cardiac surgery patients continues to evolve to include older, sicker candidates, all the while maintaining an expectation of excellent outcomes. These latter results can only be achieved by the parallel advancement and re-examination of the technology of cardiopulmonary bypass (CPB); the key tool used daily by surgical teams worldwide. In this review, we will provide an overview of integrated therapeutic strategies that can be utilized to minimize the complex and myriad changes related to inflammation after CPB with the understanding that this may abrogate the detrimental end-organ and systemic effects of blood activation. Therapeutic strategies specifically related to the technology can be classified into those targeting biomaterial dependent or independent processes. The former can be addressed by the utilization of currently available biocompatible surfaces such as with heparin-coated circuits, phosphorylcholine-coated circuits (‘biomembrane mimicry’) and circuits composed of copolymers containing surface-modifying additives. The most important strategies related to biomaterial independent activation include the modification of techniques related to cardiotomy blood management and blood filtration. Finally, all of these strategies must be integrated and tailored with complementary pharmacologic agents such as aprotinin and steroids to optimize anti-inflammatory synergism. Only if we are armed with a comprehensive knowledge of the molecular and cellular basis for these strategies will we be able to continue to evolve our treatment in parallel with our patients to achieve these goals.
Clinical significance of coated extracorporeal circuits: a review of novel technologies
Authors: Gunaydin Serdar
Published: August 2006

Coating of extracorporeal circuits may be a solution to prevent adverse effects induced by the contact of blood elements and proteins with foreign surfaces. This paper reviews the recent novel coating technologies and compares their documented in vitro and ex vivo advantages under the clinical setting. Data presented have also been supported by postclinical biomaterial research to verify biocompatibility and hemocompatibility.
Lung Injury after Cardiopulmonary Bypass
Authors: Clark Stephen C
Published: August 2006

Pulmonary injury during cardiopulmonary bypass is common as patient factors (smoking, pain, pneumonia) and the effects of cardiopulmonary bypass combine to compromise lung function after cardiac surgery. Lung injury follows the propagation of an inflammatory response involving cytokines, complement, neutrophils, monocytes, activated endothelial cells and platelets. Neutrophils sequester in the lung in response to chemo-tactic agents and release injurious oxygen free radicals and specific enzymes resulting in widespread pulmonary injury.

To alleviate this lung injury a number of possible interventions exist. Off pump surgery may reduce the degree of systemic inflammation but respiratory impairment still occurs and the clinical advantage is uncertain. The use of leukocyte filtration can attenuate the acute inflammatory response with encouraging though variable results. Aprotinin, Pentoxyfilline, Nitric oxide, Aspirin and other agents have shown benefits in lung function after cardiopulmonary bypass induced lung injury.

Given the magnitude and diversity of the inflammatory response to cardiopulmonary bypass many possible interventions exist to attenuate lung injury resulting from extracorporeal circulation. Immediate clinical benefits are likely to result from successful amelioration of the processes involved.
Rehabilitation for Parkinson's disease: a systematic review of available evidence
Authors: Gage Heather , Storey Lesley
Published: August 2006

Objective: To systematically review the available evidence on the effectiveness of nonpharmacological rehabilitation interventions for people with Parkinson's disease, and identify future research needs.

Design: Electronic searches of four databases (CINAHL, Cochrane Library, MEDLINE, PsychLIT) 1980-2002; examination of reference lists of relevant papers. Controlled trials and observational studies were included. Data extraction and quality assessment of papers by two independent reviewers. A narrative review.

Setting: Rehabilitation interventions delivered either in subjects' own homes, or in clinical settings as outpatients.

Subjects: Community-living adults with Parkinson's disease.

Interventions: Physiotherapy, occupational therapy, speech and language therapy, psychological counselling and support, and education.

Main measures: A range of outcomes: mobility, functional status, speech, swallowing, psychological well-being, as determined by the studies included in the review.

Results: Forty-four different studies (reported in 51 papers) were included (25 physiotherapy, 4 occupational therapy, 10 speech and language therapy, 3 psychological counselling, 1 educational, 1 multidisciplinary). All studies, except one, reported improvements on at least one outcome measure.

Conclusions: Findings may reflect publication bias, but suggest interventions can affect patients' lives for the better in a variety of ways. It is difficult to interpret the clinical importance of statistically significant improvements reported in most studies. There is a need for methodologically more robust research with meaningful follow-up periods, designed in a manner that separates specific and nonspecific effects. Cost-effectiveness evidence is required to provide clear guidance on service extensions.
Animal-assisted therapy for middle-aged schizophrenic patients living in a social institution. A pilot study
Authors: Kovács Zoltán , Kis Renáta , Rózsa Sándor , Rózsa Linda
Published: August 2006

Objectives: To determine whether animal-assisted therapy is effective in the rehabilitation of middle-aged schizophrenic patients living in a social institution.

Design: A before and after study with nine-month treatment period.

Setting: Social institute for psychiatric patients.

Subjects: Seven schizophrenic patients living in the social institute.

Interventions: Weekly sessions of animal-assisted therapy for a nine-month period, each therapeutic session lasting for 50 minutes.

Measures used: The Independent Living Skills Survey assessed by an independent rater.

Results: After the completion of the therapy significant improvement in the domestic and health activities occurred.

Conclusions: Animal-assisted therapy seems to be helpful in the rehabilitation of schizophrenic patients living in a social institution.
Differences in outcome of a multidisciplinary treatment between subgroups of chronic low back pain patients defined using two multiaxial assessment instruments: the Multidimensional Pain Inventory and lumbar dynamometry
Authors: Vollenbroek-Hutten Miriam MR , Hermens Hermie J , Wever Daniël , Gorter Michiel , Rinket Joost , IJzerman Maarten J
Published: August 2006

Objective: To investigate the effects of a multidisciplinary back school programme (Roessingh Back Rehabilitation Programme, RRP) compared with usual care, as well as differences in treatment outcome between subgroups defined using two multiaxial assessment instruments: the Multidimensional Pain Inventory (MPI-DLV) and lumbar dynamometry.

Design: Randomized controlled trial.

Setting: Rehabilitation.

Subjects: One hundred and sixty-three patients with chronic, aspecific low back pain.

Intervention: All subjects were randomly assigned either to a multidisciplinary, physically oriented group treatment or to their usual care.

Main outcome measures: The Roland Disability Questionnaire and health-related quality of life (EuroQol, EQ5-D) were measured as primary outcomes before randomization and after eight weeks and six months follow-up.

Result: Only 30-50% of the patients in the RRP group showed improvement and this number is not significantly different from the control group. Subgroup analyses give some first indications that multiaxial measurement instruments can be used to identify subgroups with differences in treatment effects.

Conclusion: The overall effect of a multidisciplinary treatment is disappointing, however multiaxial assessment before admission might be valuable in clinical practice, resulting in more effective treatments for patients with chronic low back pain.
Drunk and Disorderly: Alcohol, Urban Life and Public Space
Authors: Jayne Mark , Holloway Sarah L. , Valentine Gill
Published: August 2006

This paper shows that, despite receiving significant attention, the relationship between alcohol, drunkenness and public space has been undertheorized. We show that where drinking has been considered it has generally been as a peripheral concern of political-economy accounts that have sought to conceptualize the development of the modern city, or more recently the impact of global economic restructuring on urban life and public space. Moreover, such work has posited the relationship between drinking and the political, economic, social, cultural and spatial practices and processes bound up with, for example, social control in modern city or with contemporary gentrification, corporatization, fragmentation and regulation of the night-time economy, public space and revanchist urban policy in very general terms. While drawing on evidence from around the world, this paper focuses on the UK and highlights the need for a research agenda underpinned by a more specific consideration of urban drinking. We suggest that such a project must seek to unpack the connections and differences between supranational, national, regional and local drinking practices and related issues, and in particular pursue a more nuanced understanding of the social relations and cultural practices associated with the emergence of particular kinds of urban drinking spaces.
The Effect of Aspartame on Rat Brain Xenobiotic-Metabolizing Enzymes
Authors: Vences-Mejía A , Labra-Ruíz N , Hernández-Martínez N , Dorado-González V , Gómez-Garduño J , Pérez-López I , Nosti-Palacios R , Carranza R Camacho , Espinosa-Aguirre JJ
Published: August 2006

This study demonstrates that chronic aspartame (ASP) consumption leads to an increase of phase I metabolizing enzymes (cytochrome P450 (CYP)) in rat brain. Wistar rats were treated by gavage with ASP at daily doses of 75 and 125 mg/kg body weight for 30 days. Cerebrum and cerebellum were used to obtain microsomal fractions to analyse activity and protein levels of seven cytochrome P450 enzymes. Increases in activity were consistently found with the 75 mg/kg dose both in cerebrum and cerebellum for all seven enzymes, although not at the same levels: CYP 2E1-associated 4-nitrophenol hydroxylase (4-NPH) activity was increased 1.5-fold in cerebrum and 25-fold in cerebellum; likewise, CYP2B1-associated penthoxyresorufin O-dealkylase (PROD) activity increased 2.9- and 1.7-fold respectively, CYP2B2-associated benzyloxyresorufin O-dealkylase (BROD) 4.5- and 1.1- fold, CYP3A-associated erythromycin N-demethylase (END) 1.4- and 3.3-fold, CYP1A1-associated ethoxyresorufin O-deethylase (EROD) 5.5- and 2.8-fold, and CYP1A2- associated methoxyresorufin O-demethylase (MROD) 3.7- and 1.3-fold. Furthermore, the pattern of induction of CYP immunoreactive proteins by ASP paralleled that of 4-NHP-, PROD-, BROD-, END-, EROD- and MROD-related activities only in the cerebellum. Conversely, no differences in CYP concentration and activity were detected in hepatic microsomes of treated animals with respect to the controls, suggesting a brain-specific response to ASP treatment.