bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct roles for the NF-κB1 and c-Rel transcription factors in the differentiation and survival of plasmacytoid and conventional dendritic cells activated by TLR-9 signals
Authors: O'Keeffe Meredith , Grumont Raelene J. , Hochrein Hubertus , Fuchsberger Martina , Gugasyan Raffi , Vremec David , Shortman Ken , Gerondakis Steve
Published: July 2005

Reticuloendotheliosis viral oncogene homolog/nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (Rel/NF-κB) activation is a ubiquitous outcome of engaging Toll-like receptors (TLRs), yet the cell-type–specific functions of this pathway in response to particular microbial signals remain poorly defined. Here we show that NF-κB1 and C-Rel, Rel/NF-κB proteins induced in conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) by cytosine-phosphate-guanosine (CpG) DNA, a TLR-9 ligand, serve markedly different functions in these DC subsets. With the exception of impaired interleukin-12 (IL-12) production, cultured Nfkb1–/–C-Rel–/– cDCs responded relatively normally to CpG DNA. In contrast, CpG-treated Nfkb1–/–C-Rel–/– pDCs, which were still able to produce type I interferon and regulated on activation normal T-cell expressed and secreted (RANTES), but not IL-6 or IL-12, failed to acquire an activated dendritic phenotype and underwent apoptosis. Although the TLR-9–mediated death of Nfkb1–/–C-Rel–/– pDCs, which coincided with a failure to up-regulate the prosurvival proteins B-cell lymphoma apoptosis regulator xL (Bcl-xL) and A1, was blocked by Bcl-2 transgene expression, this inhibition of apoptosis still failed to rescue the differentiation defects. This indicated that these NF-κB transcription factors independently regulate TLR-9–mediated pDC morphogenesis and survival. Collectively, these findings establish that NF-κB1 and c-Rel, while largely dispensable for TLR-9–induced cDC activation, are critical for regulating differentiation and survival programs during pDC activation.
Rank-invariant resampling based estimation of false discovery rate for analysis of small sample microarray data
Authors: Jain Nitin , Cho HyungJun , O'Connell Michael , Lee Jae K
Published: July 2005

Background

The evaluation of statistical significance has become a critical process in identifying differentially expressed genes in microarray studies. Classical p-value adjustment methods for multiple comparisons such as family-wise error rate (FWER) have been found to be too conservative in analyzing large-screening microarray data, and the False Discovery Rate (FDR), the expected proportion of false positives among all positives, has been recently suggested as an alternative for controlling false positives. Several statistical approaches have been used to estimate and control FDR, but these may not provide reliable FDR estimation when applied to microarray data sets with a small number of replicates.

Results

We propose a rank-invariant resampling (RIR) based approach to FDR evaluation. Our proposed method generates a biologically relevant null distribution, which maintains similar variability to observed microarray data. We compare the performance of our RIR-based FDR estimation with that of four other popular methods. Our approach outperforms the other methods both in simulated and real microarray data.

Conclusion

We found that the SAM's random shuffling and SPLOSH approaches were liberal and the other two theoretical methods were too conservative while our RIR approach provided more accurate FDR estimation than the other approaches.
Comparing independent microarray studies: the case of human embryonic stem cells
Authors: Suárez-Fariñas Mayte , Noggle Scott , Heke Michael , Hemmati-Brivanlou Ali , Magnasco Marcelo O
Published: July 2005

Background

Microarray studies of the same phenomenon in different labs often appear at variance because the published lists of regulated transcripts have disproportionately small intersections. We demonstrate that comparing studies by intersecting lists in this manner is methodologically flawed by reanalyzing three studies of the molecular signature of "stemness" in human embryonic stem cells. There are only 7 genes common to all three published lists, suggesting disagreement.

Results

Carefully reanalyzing all three together from the raw data we detect 111 genes upregulated and 95 downregulated in all three studies. The upregulated list was subject to rtRTPCR analysis and 75% of the genes were confirmed.

Conclusion

Our findings show that the three studies have a substantial core of common genes, which is missed if only the published lists are examined. Combined analysis of multiple experiments can be a powerful way to distil coherent conclusions.
Stimulus-dependent spatial patterns of response in SI cortex
Authors: Chiu Joannellyn S , Tommerdahl Mark , Whitsel Barry L , Favorov Oleg V
Published: July 2005

Background

Recently we reported that vibrotactile flutter stimulation of a skin locus at different amplitudes evokes an optical response confined to the same local region of the primary somatosensory cortex (SI), where its overall magnitude varies proportionally to the flutter amplitude. In this report, we characterize the impact of the flutter amplitude on the spatial patterns of activity evoked within the responding SI region.

Results

In order to characterize the spatial pattern of activity within the responding SI region, images of the flutter-evoked SI optical response were segmented and analyzed with spatial frequency analysis. The analysis revealed that: (1) dominant spatial frequencies in the optical intrinsic signal emerge within the responding SI region within 3–5 sec of stimulus onset; (2) the stimulus-evoked activity is spatially organized in a form of several roughly parallel, anterior-posteriorly extended waves, spaced 0.4–0.5 mm apart; (3) the waves themselves exhibit spatial periodicities along their long axis; and (4) depending on the flutter stimulus amplitude, these periodicities can range from fine 0.15 mm "ripples" at 50 μm amplitude to well-developed 0.5 mm fluctuations at the amplitude of 400 μm.

Conclusion

The observed spatiointensive fractionation on a sub-macrocolumnar scale of the SI response to skin stimulation might be the product of local competitive interactions within the stimulus-activated SI region and may be a feature that could yield novel insights into the functional interactions that take place in SI cortex.
A simplified search strategy for identifying randomised controlled trials for systematic reviews of health care interventions: a comparison with more exhaustive strategies
Authors: Royle Pamela , Waugh Norman
Published: July 2005

Background

It is generally believed that exhaustive searches of bibliographic databases are needed for systematic reviews of health care interventions. The CENTRAL database of controlled trials (RCTs) has been built up by exhaustive searching. The CONSORT statement aims to encourage better reporting, and hence indexing, of RCTs. Our aim was to assess whether developments in the CENTRAL database, and the CONSORT statement, mean that a simplified RCT search strategy for identifying RCTs now suffices for systematic reviews of health care interventions.

Methods

RCTs used in the Cochrane reviews were identified. A brief RCT search strategy (BRSS), consisting of a search of CENTRAL, and then for variants of the word random across all fields (random$.af.) in MEDLINE and EMBASE, was devised and run. Any trials included in the meta-analyses, but missed by the BRSS, were identified. The meta-analyses were then re-run, with and without the missed RCTs, and the differences quantified. The proportion of trials with variants of the word random in the title or abstract was calculated for each year. The number of RCTs retrieved by searching with "random$.af." was compared to the highly sensitive search strategy (HSSS).

Results

The BRSS had a sensitivity of 94%. It found all journal RCTs in 47 of the 57 reviews. The missing RCTs made some significant differences to a small proportion of the total outcomes in only five reviews, but no important differences in conclusions resulted. In the post-CONSORT years, 1997–2003, the percentage of RCTs with random in the title or abstract was 85%, a mean increase of 17% compared to the seven years pre-CONSORT (95% CI, 8.3% to 25.9%). The search using random$.af. reduced the MEDLINE retrieval by 84%, compared to the HSSS, thereby reducing the workload of checking retrievals.

Conclusion

A brief RCT search strategy is now sufficient to locate RCTs for systematic reviews in most cases. Exhaustive searching is no longer cost-effective, because in effect it has already been done for CENTRAL.
Testing the effectiveness of an innovative information package on practitioner reported behaviour and beliefs: The UK Chiropractors, Osteopaths and Musculoskeletal Physiotherapists Low back pain ManagemENT (COMPLeMENT) trial [ISRCTN77245761]
Authors: Evans David W , Foster Nadine E , Underwood Martin , Vogel Steven , Breen Alan C , Pincus Tamar
Published: July 2005

Background

Low back pain (LBP) is a common and costly problem. Initiatives designed to assist practitioner and patient decisions about appropriate healthcare for LBP include printed evidence-based clinical guidelines. The three professional groups of chiropractic, osteopathy and musculoskeletal physiotherapy in the UK share common ground with their approaches to managing LBP and are amongst those targeted by LBP guidelines. Even so, many seem unaware that such guidelines exist. Furthermore, the behaviour of at least some of these practitioners differs from that recommended in these guidelines.

Few randomised controlled trials evaluating printed information as an intervention to change practitioner behaviour have utilised a no-intervention control. All these trials have used a cluster design and most have methodological flaws. None specifically focus upon practitioner behaviour towards LBP patients. Studies that have investigated other strategies to change practitioner behaviour with LBP patients have produced conflicting results. Although numerous LBP guidelines have been developed worldwide, there is a paucity of data on whether their dissemination actually changes practitioner behaviour. Primarily because of its low unit cost, sending printed information to large numbers of practitioners is an attractive dissemination and implementation strategy. The effect size of such a strategy, at an individual practitioner level, is likely to be small. However, if large numbers of practitioners are targeted, this strategy might achieve meaningful changes at a population level.

Methods

The primary aim of this prospective, pragmatic randomised controlled trial is to test the short-term effectiveness (six-months following intervention) of a directly-posted information package on the reported clinical behaviour (primary outcome), attitudes and beliefs of UK chiropractors, osteopaths and musculoskeletal physiotherapists. We sought to randomly allocate a combined sample of 1,800 consenting practitioners to receive either the information package (intervention arm) or no information above that gained during normal practice (control arm). We collected questionnaire data at baseline and six-months post-intervention. The analysis of the primary outcome will assess between-arm differences of proportions of responses to questions on recommendations about activity, work and bed-rest, that fall within categories previously defined by an expert consensus exercise as either 'guideline-consistent' and 'guideline-inconsistent'.
An experimental study of sexual function improving effect of Myristica fragrans Houtt. (nutmeg)
Authors: Tajuddin  , Ahmad Shamshad , Latif Abdul , Qasmi Iqbal Ahmad , Amin Kunwar Mohammad Yusuf
Published: July 2005

Background

Myristica fragrans Houtt. (nutmeg) has been mentioned in Unani medicine to be of value in the management of male sexual disorders. The present study was undertaken to evaluate the aphrodisiac effect of 50% ethanolic extract of nutmeg along with its likely adverse effects and acute toxicity using various animal models.

Methods

The suspension of the extract was administered (100, 250 and 500 mg/kg, p.o.) to different groups of male rats daily for seven days. The female rats involved in mating were made receptive by hormonal treatment. The general mating behaviour, libido and potency were studied and compared with the standard reference drug sildenafil citrate. Likely adverse effects and acute toxicity of the extract were also evaluated.

Results

Oral administration of the extract at the dose of 500 mg/kg, produced significant augmentation of sexual activity in male rats. It significantly increased the Mounting Frequency, Intromission Frequency, Intromission Latency and caused significant reduction in the Mounting Latency and Post Ejaculatory Interval. It also significantly increased Mounting Frequency with penile anaesthetisation as well as Erections, Quick Flips, Long Flips and the aggregate of penile reflexes with penile stimulation. The extract was also observed to be devoid of any adverse effects and acute toxicity.

Conclusion

The resultant significant and sustained increase in the sexual activity of normal male rats without any conspicuous adverse effects indicates that the 50% ethanolic extract of nutmeg possesses aphrodisiac activity, increasing both libido and potency, which might be attributed to its nervous stimulating property. The present study thus provides a scientific rationale for the traditional use of nutmeg in the management of male sexual disorders.
Overcoming cisplatin resistance by mTOR inhibitor in lung cancer
Authors: Wu Chunjing , Wangpaichitr Medhi , Feun Lynn , Kuo Marcus Tien , Robles Carlos , Lampidis Theodore , Savaraj Niramol
Published: July 2005

Background

Cisplatin resistance is complex and involves several different mechanisms. Employing cDNA microarray analysis, we have found that cisplatin resistant cells share the common characteristic of increase in ribosomal proteins and elongation factors. We hypothesize that in order to survive cisplatin treatment, cells have to synthesize DNA repair proteins, antiapoptotic proteins and growth-stimulating proteins. Thus, by blocking the translation of these proteins, one should be able to restore cisplatin sensitivity. We have studied the role of CCI-779, an ester analog of rapamycin which is known to inhibit translation by disabling mTOR, in restoring cisplatin sensitivity in a panel of cisplatin resistant cell lines. We have also determined the role of CCI-779 in P-gp1 and MRP1 mediated resistance.

Results

Our data show that CCI-779 possess antiproliferative effects in both cisplatin sensitive and resistant cell lines, but shows no effect in P-gp1 and MRP1 overexpressing cell lines. Importantly, CCI-779 at 10 ng/ml (less that 10% of the growth inhibitory effect) can increase the growth inhibition of cisplatin by 2.5–6 fold. Moreover, CCI-779 also enhances the apoptotic effect of cisplatin in cisplatin resistant cell lines. In these resistant cells, adding CCI-779 decreases the amount of 4E-BP phosphorylation and p-70S6 kinase phosphorylation as well as lower the amount of elongation factor while cisplatin alone has no effect. However, CCI-779 can only reverse P-gp mediated drug resistance at a higher dose(1 ug/ml).

Conclusion

We conclude that CCI-779 is able to restore cisplatin sensitivity in small cell lung cancer cell lines selected for cisplatin resistance as well as cell lines derived from patients who failed cisplatin. These findings can be further explored for future clinical use. On the other hand, CCI-779 at achievable clinical concentration, has no growth inhibitory effect in P-gp1 or MRP1 overexpressing cells. Furthermore, CCI-779 also appears to be a weak MDR1 reversal agent. Thus, it is not a candidate to use in MDR1 or MRP1 overexpressing cells.
Management of renal cell carcinoma with solitary metastasis
Authors: Thyavihally Yuvaraja B , Mahantshetty Umesh , Chamarajanagar Ravichand S , Raibhattanavar Srinivas G , Tongaonkar Hemant B
Published: July 2005

Background

Distant metastasis are common in Renal cell carcinoma (RCC) nearly one forth of the patients have metastasis at presentation while another 50% develop metastasis during the follow-up. A small percentage of these are solitary metastasis. We describe survival after surgical excision or radiotherapy of solitary metastatic lesion from renal cell carcinoma

Patients and methods

Between 1988–2001, 43 patients with solitary metastasis to different sites from renal cell carcinoma underwent either surgical excision or radiotherapy were analyzed. The solitary nature of the lesions was confirmed by investigations. All patients have had radical nephrectomy for the primary lesion. Survival analysis was carried out by Kaplan Meier Method.

Results

All solitary metastatic lesions were treated with intent of cure either by excision or radiotherapy. Of these, 13 patients had solitary metastasis at the time of presentation in whom 3-year overall median survival was 26 months. The survival of those who developed solitary metastases during follow-up after nephrectomy for primary was 45 months. The patients with long interval between diagnosis and development of metastasis, early stage and low grade of the primary tumor had better prognosis.

Conclusion

Complete resection of either synchronous or metachronous solitary metastases from renal cell carcinoma is justified and can contribute to a long-term survival in this select group of patients.
Relevance similarity: an alternative means to monitor information retrieval systems
Authors: Dong Peng , Loh Marie , Mondry Adrian
Published: July 2005

Background

Relevance assessment is a major problem in the evaluation of information retrieval systems. The work presented here introduces a new parameter, "Relevance Similarity", for the measurement of the variation of relevance assessment. In a situation where individual assessment can be compared with a gold standard, this parameter is used to study the effect of such variation on the performance of a medical information retrieval system. In such a setting, Relevance Similarity is the ratio of assessors who rank a given document same as the gold standard over the total number of assessors in the group.

Methods

The study was carried out on a collection of Critically Appraised Topics (CATs). Twelve volunteers were divided into two groups of people according to their domain knowledge. They assessed the relevance of retrieved topics obtained by querying a meta-search engine with ten keywords related to medical science. Their assessments were compared to the gold standard assessment, and Relevance Similarities were calculated as the ratio of positive concordance with the gold standard for each topic.

Results

The similarity comparison among groups showed that a higher degree of agreements exists among evaluators with more subject knowledge. The performance of the retrieval system was not significantly different as a result of the variations in relevance assessment in this particular query set.

Conclusion

In assessment situations where evaluators can be compared to a gold standard, Relevance Similarity provides an alternative evaluation technique to the commonly used kappa scores, which may give paradoxically low scores in highly biased situations such as document repositories containing large quantities of relevant data.
Anatomic and functional leg-length inequality: A review and recommendation for clinical decision-making. Part I, anatomic leg-length inequality: prevalence, magnitude, effects and clinical significance
Authors: Knutson Gary A
Published: July 2005

Background

Leg-length inequality is most often divided into two groups: anatomic and functional. Part I of this review analyses data collected on anatomic leg-length inequality relative to prevalence, magnitude, effects and clinical significance. Part II examines the functional "short leg" including anatomic-functional relationships, and provides an outline for clinical decision-making.

Methods

Online database – Medline, CINAHL and MANTIS – and library searches for the time frame of 1970–2005 were done using the term "leg-length inequality".

Results and Discussion

Using data on leg-length inequality obtained by accurate and reliable x-ray methods, the prevalence of anatomic inequality was found to be 90%, the mean magnitude of anatomic inequality was 5.2 mm (SD 4.1). The evidence suggests that, for most people, anatomic leg-length inequality does not appear to be clinically significant until the magnitude reaches ~ 20 mm (~3/4").

Conclusion

Anatomic leg-length inequality is near universal, but the average magnitude is small and not likely to be clinically significant.
Sex hormone modulation of cell growth and apoptosis of the human monocytic/macrophage cell line
Authors: Cutolo Maurizio , Capellino Silvia , Montagna Paola , Ghiorzo Paola , Sulli Alberto , Villaggio Barbara
Published: July 2005

Sex hormones seem to modulate the immune/inflammatory responses by different mechanisms in female and male rheumatoid arthritis patients. The effects of 17β-oestradiol and of testosterone were tested on the cultured human monocytic/macrophage cell line (THP-1) activated with IFN-γ in order to investigate their role in cell proliferation and apoptosis. Activated human THP-1 cells were cultured in the presence of 17β-oestradiol and testosterone (final concentration, 10 nM). The evaluation of markers of cell proliferation included the NF-κB DNA-binding assay, the NF-κB inhibition complex, the proliferating cell nuclear antigen expression and the methyl-tetrazolium salt test. Apoptosis was detected by the annexin V-propidium assay and by the cleaved poly-ADP ribose polymerase expression. Specific methods included flow analysis cytometry scatter analysis, immunocytochemistry and western blot analysis. Cell growth inhibition and increased apoptosis were observed in testosterone-treated THP-1 cells. Increased poly-ADP ribose polymerase-cleaved expression and decreased proliferating cell nuclear antigen expression, as well as an increase of IκB-α and a decrease of the IκB-α phosphorylated form (ser 32), were found in testosterone-treated THP-1 cells. However, the NF-κB DNA binding was found increased in 17β-oestradiol-treated THP-1 cells. The treatment with staurosporine (enhancer of apoptosis) induced decreased NF-κB DNA binding in all conditions, but particularly in testosterone-treated THP-1 cells. Treatment of THP-1 by sex hormones was found to influence cell proliferation and apoptosis. Androgens were found to increase the apoptosis, and oestrogens showed a protective trend on cell death – both acting as modulators of the NF-κB complex.
Genotypes and haplotypes of the methyl-CpG-binding domain 2 modify breast cancer risk dependent upon menopausal status
Authors: Zhu Yong , Brown Heather N , Zhang Yawei , Holford Theodore R , Zheng Tongzhang
Published: July 2005

Introduction

MBD2, the gene encoding methyl-CpG-binding domain (MBD)2, is a major methylation related gene and functions as a transcriptional repressor that can specifically bind to the methylated regions of other genes. MBD2 may also mediate gene activation because of its potential DNA demethylase activity. The present case-control study investigated associations between two single nucleotide polymorphisms (SNPs) in the MBD2 gene and breast cancer risk.

Methods

DNA samples from 393 Caucasian patients with breast cancer (cases) and 436 matched control individuals, collected in a recently completed breast cancer case–control study conducted in Connecticut, were included in the study. Because no coding SNPs were found in the MBD2 gene, one SNP in the noncoding exon (rs1259938) and another in the intron 3 (rs609791) were genotyped. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate cancer risk associated with the variant genotypes and the reconstructed haplotypes.

Results

The variant genotypes at both SNP loci were significantly associated with reduced risk among premenopausal women (OR = 0.41 for rs1259938; OR = 0.54 for rs609791). Further haplotype analyses showed that the two rare haplotypes (A-C and A-G) were significantly associated with reduced breast cancer risk (OR = 0.40, 95% CI = 0.20–0.83 for A-C; OR = 0.47, 95% CI = 0.26–0.84 for A-G) in premenopausal women. No significant associations were detected in the postmenopausal women and the whole population.

Conclusion

Our results demonstrate a role for the MBD2 gene in breast carcinogenesis in premenopausal women. These findings suggest that genetic variations in methylation related genes may potentially serve as a biomarker in risk estimates for breast cancer.
Dendritic cells differentiated in the presence of IFN-β and IL-3 are potent inducers of an antigen-specific CD8+ T cell response
Authors: Breckpot Karine , Corthals Jurgen , Bonehill Aude , Michiels Annelies , Tuyaerts Sandra , Aerts Cindy , Heirman Carlo , Thielemans Kris
Published: July 2005

Dendritic cells (DC) are professional antigen-presenting cells that are used in vaccine approaches to cancer. Classically, mature monocyte-derived DC are generated in vitro in the presence of interleukin (IL)-4, granulocyte macrophage-colony stimulating factor, and inflammatory cytokines (G4-DC). Recently, it has been described that DC can also be generated in the presence of IL-3 and interferon (IFN)-β and that these DC are efficiently matured using polyriboinosinic polyribocytidylic acid (I3-DC). In this study, a series of in vitro experiments was performed to compare side-by-side I3-DC and G4-DC as vaccine adjuvants. Phenotypic characterization of the DC revealed differences in the expression of the monocyte marker CD14 and the maturation marker CD83. Low expression of CD14 and high expression of CD83 characterized G4-DC, whereas I3-DC displayed intermediate expression of CD14 and CD83. Both types of DC were as potent in the induction of allogeneic T cell proliferation. Upon CD40 ligation, G4-DC produced lower amounts of IFN-α and pulmonary and activation-regulated chemokine, similar amounts of IL-6, macrophage-inflammatory protein (MIP)-1α, and MIP-1β, and higher amounts of IL-12 p70, tumor necrosis factor α, and MIP-3β than I3-DC. We further evaluated whether the DC could be frozen/thawed without loss of cell number, viability, phenotype, and function. After freezing/thawing, 56.0% ± 9.0% of I3-DC and 77.0% ± 3.0% of G4-DC (n=9) were recovered as viable cells, displaying the same phenotype as their fresh counterparts. Finally, in vitro stimulations showed that fresh and frozen peptide-loaded I3-DC are more potent inducers of Melan-A-specific CD8+ T cell responses than G4-DC. The antigen-specific T cells were functional as shown in cytotoxicity and IFN-γ secretion assay.
Unrelated Donor Marrow Transplantation for B-Cell Chronic Lymphocytic Leukemia After Using Myeloablative Conditioning: Results From the Center for International Blood and Marrow Transplant Research
Authors: Pavletic Steven Z. , Khouri Issa F. , Haagenson Michael , King Roberta J. , Bierman Philip J. , Bishop Michael R. , Carston Michael , Giralt Sergio , Molina Arturo , Copelan Edward A. , Ringdén Olle , Roy Vivek , Ballen Karen , Adkins Douglas R. , McCarthy Philip , Weisdorf Daniel , Montserrat Emili , Anasetti Claudio
Published: July 2005

Purpose

To determine the role of myeloablative conditioning and unrelated donor (URD) bone marrow transplantation in the treatment of patients with advanced B-cell chronic lymphocytic leukemia (CLL).

Patients and Methods

A total of 38 CLL patients received a matched URD transplant using bone marrow procured by the National Marrow Donor Program. The median age was 45 years (range, 26 to 57 years), the median time from diagnosis was 51 months, and the median number of prior chemotherapy regimens was three. Fifty-five percent of patients were chemotherapy refractory and 89% had received fludarabine. Conditioning included total-body irradiation in 92% of patients. Graft-versus-host disease (GVHD) prophylaxis consisted of methotrexate with cyclosporine or tacrolimus for 82% of patients.

Results

Twenty-one patients (58%) achieved complete response and six (17%) achieved partial response. Incidences of grades 2 to 4 acute GVHD were 45% at 100 days and incidences of chronic GVHD were 85% at 5 years. Eleven patients are alive and disease free at a median of 6 years (range, 3.0 to 9.0 years). Five-year overall survival, failure-free survival, disease progression rates, and treatment-related mortality (TRM) were 33%, 30%, 32%, and 38% respectively.

Conclusion

These data demonstrate that lasting remissions can be achieved after URD transplantation in patients with advanced CLL. High TRM suggest that myeloablative conditioning and HLA-mismatched donors should be avoided in future protocols, and it is mandatory to investigate transplant strategies with a lower morbidity and mortality, including the use of nonmyeloablative regimens.
Cervical radiculopathy due to intra-arterial infusion of cisplatin
Authors: Nishimura Toshiro , Sanada Jun-Ichiro , Furukawa Mitsuru
Published: July 2005

A 55-year-old man with cervical radiculopathy (C5–C8) was referred to us following intra-arterial infusion of cisplatin (CDDP) because of a recurrent neck mass of laryngeal cancer. Three hours after the CDDP infusion, he had noticed general weakness of the left upper extremity and hypoaesthesia of the lateral side of the upper and lower arm. The next day he was diagnosed with left cervical radiculopathy of C5 to C8, which improved gradually and had resolved completely six months after the infusion. Even with proper positioning of the infusion catheter to minimize potential complications, for anatomical reasons there are always some risks of neural injury with intra-arterial infusion from branches of the subclavian artery. This procedure should be carefully indicated in the case of a large neck tumour that is perfused from the major branches of the subclavian artery.
Fulminant post-tonsillectomy haemorrhage caused by aberrant course of the external carotid artery
Authors: Hofman Rutger , Zeebregts Clark J , Dikkers Frederik G
Published: July 2005

Haemorrhage, throat pain and otalgia are common complications following tonsillectomy. Haemorrhage is rarely life-threatening but in this paper we describe a fulminant secondary haemorrhage due to an aberrant external carotid artery in an eight-year-old boy. Acute surgical intervention with ligation of the external carotid artery was needed to control the bleeding.
Complications of paediatric cochlear implantation: experience in Izmir
Authors: Kandogan Tolga , Levent Olgun , Gurol Gultekin
Published: July 2005

Surgery for cochlear implantation (CI) bears the risks of complication associated with all major surgery, in addition to the particular risks associated with implanting a foreign body into the peripheral auditory system. Here we present a retrospective study involving 227 cochlear implant operations in 205 children to evaluate the rate of intra- and post-operative complications.

Complications were defined as major complications, requiring explantation of the device or further operation, causing a significant medical problem, or leading to any degree of facial paralysis or requiring additional hospitalization for treatment; or defined as minor complications, namely those that settled spontaneously, with conservative treatment, with local care and/or with medication alone.

In our study there were 15 (6.6 per cent) minor and 28 (12.33 per cent) major complications. The most frequent minor complication was dizziness and vomiting (3.08 per cent), followed by transient hemifacial oedema (1.76 per cent), head pain (1.32 per cent) and mild ataxia (0.4 per cent). The most frequent major complication was trauma to the device (9.69 per cent), followed by cerebrospinal fluid (CSF) gusher (2.2 per cent) and facial paresis (0.4 per cent). All of the device trauma cases were re-implanted. There were neither any life-threatening complications nor any facial nerve paralysis in our implanted children.

This study confirms that CI is relatively safe and that major complications are few and within acceptable limits.
DNA Sequencing by Indexer Walking
Authors: Gromek Katarzyna , Kaczorowski Tadeusz
Published: July 2005

Background: There is a need for DNA sequencing methods that are faster, more accurate, and less expensive than existing techniques. Here we present a new method for DNA analysis by means of indexer walking.

Methods: For DNA sequencing by indexer walking, we ligated double-stranded synthetic oligonucleotides (indexers) to DNA fragments that were produced by type IIS restriction endonucleases, which generate nonidentical 4-nucleotide 5′ overhangs. The subsequent amplification (30 thermal cycles) of indexed DNA provided a template for automated DNA sequencing with fluorescent dideoxy terminators. The data gathered in the first sequencing reaction permitted further movement into the unknown nucleotide sequence by digestion of analyzed DNA with selected type IIS restriction endonuclease followed by ligation of the next indexer. A library of presynthesized indexers consisting of 256 oligonucleotides was used for bidirectional analysis of DNA molecules and provided universal primers for sequencing.

Results: The proposed protocol was successfully applied to sequencing of cryptic plasmids isolated from pathogenic strains of Escherichia coli. The overall error rate for base-calling was 0.5%, with a mean read length of 550 nucleotides. Approximately 1000 nucleotides of high-quality sequence could be obtained per day from a single clone.

Conclusions: Indexer walking can be used as a low-cost procedure for nucleotide sequence determination of DNA molecules, such as natural plasmids, cDNA clones, and longer DNA fragments. It can also serve as an alternative method for gap filling at the final stage of genome sequencing projects.
Effects of Crude and Partially Purified Extracts from UV‐B–irradiated Rice Leaves on Helicoverpa armigera (Hübner)‡
Authors: Caasi‐Lit Merdelyn T.
Published: July 2005

The effect of crude and partially purified extracts from ultraviolet‐B (UV‐B)–irradiated rice (Oryza sativa L.) leaves on the growth and development of corn earworm, Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae), was investigated. Fifty μL droplets of a liquid diet containing different concentrations of the crude and partially purified extracts were fed to H. armigera neonates to determine possible short‐term toxicity effects. A choice test using a solid artificial diet was also performed to determine larval feeding preferences and antifeedant effects. To study effects on the life history of the insect, different concentrations of the crude and partially purified extracts were also incorporated in the artificial diet and fed to individually confined neonates of H. armigera. The neonates were reared up to the adult stage. Results showed that crude and partially purified extracts of UV‐B–irradiated rice leaves demonstrated antifeedant, growth‐inhibitory and antibiotic properties against H. armigera. At high concentrations, the extract initially stimulated larval feeding; however, there were subsequent negative effects on pupal and adult traits, thereby reducing the reproductive potential of adults. These partially purified extracts appeared to have an antifertility effect because adults laid fewer eggs and, of those eggs laid, viability was lower. These results suggest that the accumulated flavonoids or other phenolics in UV‐B–irradiated leaves, extracted from UV‐B–resistant rice cultivar ‘M202,’ affected the growth, development and reproduction of H. armigera, a polyphagous insect pest.
Evaluation of organochlorine compounds in peregrine falcon (falco peregrinus) and their main prey (columba livia) inhabiting central spain
Authors: Merino Rubén , Bordajandi Luisa R. , Abad Esteban , Rivera Josep , Jiménez Begoña
Published: July 2005

The population of peregrine falcon (Falco peregrinus sbs. brookei) inhabiting the Regional Park of southeastern Madrid (RPSM), Spain, has experienced an increase of unsuccessful pairs (from 15% among a total of 20 pairs in 1995 to 55% among a total of 18 pairs in 2001). Traditionally, this area has been known to be contaminated with organochlorine compounds and toxic metals, which are known to be deleterious to the reproductive system of birds. During the breeding seasons of 2000 and 2001, contaminant residues were measured in unhatched eggs of peregrine falcons and liver of their main prey, to determine if they could be affecting the survival of the population. The most abundant contaminants were ortho-polychlorinated biphenyls (ortho-PCBs), ranging from 202.56 to 3,335.16 ng/g (wet wt) in falcon eggs and from 10.25 to 53.51 ng/g (wet wt) in pigeon livers. In all samples, the 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) were detected, although these levels never exceeded 20 pg/g (wet wt). The major contributor to total toxic equivalent quantities (TEQs) were non-ortho-PCBs. Organochlorine levels found in this study may contribute to the entire suite of stressors that are negatively affecting the peregrine population.
Approaches for linking whole-body fish tissue residues of mercury or DDT to biological effects thresholds
Authors: Beckvar Nancy , Dillon Tom M. , Read Lorraine B.
Published: July 2005

A variety of methods have been used by numerous investigators attempting to link tissue concentrations with observed adverse biological effects. This paper is the first to evaluate in a systematic way different approaches for deriving protective (i.e., unlikely to have adverse effects) tissue residue-effect concentrations in fish using the same datasets. Guidelines for screening papers and a set of decision rules were formulated to provide guidance on selecting studies and obtaining data in a consistent manner. Paired no-effect (NER) and low-effect (LER) whole-body residue concentrations in fish were identified for mercury and DDT from the published literature. Four analytical approaches of increasing complexity were evaluated for deriving protective tissue residues. The four methods were: Simple ranking, empirical percentile, tissue threshold-effect level (t-TEL), and cumulative distribution function (CDF). The CDF approach did not yield reasonable tissue residue thresholds based on comparisons to synoptic control concentrations. Of the four methods evaluated, the t-TEL approach best represented the underlying data. A whole-body mercury t-TEL of 0.2 mg/kg wet weight, based largely on sublethal endpoints (growth, reproduction, development, behavior), was calculated to be protective of juvenile and adult fish. For DDT, protective whole-body concentrations of 0.6 mg/kg wet weight in juvenile and adult fish, and 0.7 mg/kg wet weight for early life-stage fish were calculated. However, these DDT concentrations are considered provisional for reasons discussed in this paper (e.g., paucity of sublethal studies).
Comet assay with the fish cell line rainbow trout gonad-2 for in vitro genotoxicity testing of xenobiotics and surface waters
Authors: Nehls Sebastian , Segner Helmut
Published: July 2005

The present study examines the potential of the comet assay using the rainbow trout gonad cell line-2 (RTG-2) as an in vitro indicator test for genotoxicity assessment of aquatic contaminants and native surface waters. Initially, the comet assay protocol was adapted to the RTG-2 cell line. An exposure period of 2 h was found to be optimal, because DNA damage decreased when exposure was prolonged. Then, the sensitivity of the comet assay with RTG-2 cells toward six genotoxic reference substances was evaluated. The lowest-observed-effect concentration values for the directly acting genotoxins, 4-nitroquinoline-N-oxide and N-methyl-N-nitro-N-nitrosoguanidine, were in the low nanomolar range. The RTG-2 test system clearly was less sensitive for the indirectly acting genotoxins benzo[a]pyrene, nitrofurantoin, 2-acetylaminofluorene, and dimethylnitrosamine, despite the presence of xenobiotic metabolic capacities in RTG-2 cells. The two effect endpoints used, tail length (TL) and tail moment (TM), did not differ with respect to sensitivity, but the linearity of the concentration-response curve was better with TM than with TL. The overall reproducibility of the assay results was good. Finally, the applicability of the comet assay with RTG-2 cells for genotoxicity screening of native surface water samples was studied. The assay tolerated the use of nonsterile water samples and was able to detect genotoxic potentials in native water samples; that is, extraction and concentration of the samples were not needed. The results of the present study indicate the suitability of the comet assay with the fish cell line, RTG-2, as in vitro screen for detecting genotoxic potencies of xenobiotics and environmental samples.
Use of Xenopus laevis as a model for investigating in vitro and in vivo endocrine disruption in amphibians
Authors: Huang Yue-wern , Matthews Jason B. , Fertuck Kirsten C. , Zacharewski Tim R.
Published: July 2005

The estrogenic activity of 17β-estradiol (E2), α-zearalenol (α-ZEA), genistein (GEN), and 4-t-octylphenol (4-t-OP) was investigated using Xenopus laevis-based assays. All test compounds competed with [3H]E2 for binding to a recombinant Xenopus estrogen receptor (xER) with the following relative affinities: E2 > α-ZEA > 4-t-OP > GEN. The ability of these compounds to induce xER-mediated reporter gene expression was then assessed in MCF-7 human breast cancer cells cotransfected with a Gal4-xERdef chimeric estrogen receptor and a Gal4-regulated luciferase reporter gene. Luciferase activity was increased 30- to 50-fold by 10 nM E2 relative to that in solvent control. Maximal reporter gene activity induced by 10 nM α-ZEA was 54% of that induced by E2; however, the activity did not increase following doses of up to 10 μM. A dose of 1 μM 4-t-OP induced 23% of the maximal reporter gene activity induced by E2, whereas 10 μM GEN induced activity to the same level as E2. A dose-dependent increase in vitellogenin (VTG) mRNA expression was observed in Xenopus treated intraperitoneally with E2 at 0.05 to 5 mg/kg/d for three consecutive days, with the maximal induction observed in the group receiving 1 mg/kg/d. The α-ZEA, GEN, and 4-t-OP also significantly induced VTG mRNA expression, although at higher doses. These results demonstrate the utility of X laevis as an amphibian model to assess the estrogenic activity of endocrine disruptors.
Contaminant accumulation and biomarker responses in caged fish exposed to effluents from anthropogenic sources in the karnaphuly river, bangladesh
Authors: Al-Arabi Syed A.M. , Adolfsson-Erici Margaretha , Waagbø Rune , Ali M. S. , Goksøyr Anders
Published: July 2005

The possible ecotoxicological effects of a paper and pulp mill effluent were investigated by measuring selected contaminants and biomarkers in caged Nile tilapia (Oreochromis niloticus) and sharptooth catfish (Clarias gariepinus) from the Karnaphuly River, Bangladesh. Fish were caged for 28 d at two upstream reference sites (2 and 4 km) and four downstream sites (3, 5, 8, and 12 km) from the effluent outlets. Organochlorine contaminants and bile biomarkers were bioaccumulated to higher levels at downstream polluted sites than at the reference sites, including hexachlorobenzene (HCB), hexachlorocyclohexane (HCH), polychlorinated biphenyls (PCBs) in liver, and chlorophenolic compounds like 2,4-dichlorophenol and 2,4,6-trichlorophenol in bile. Levels of glucose, protein, and aspartate aminotransferase were analyzed in plasma, whereas cytochrome P4501A (CYP1A) levels were determined in S-12 supernatants of liver. The results, including CYP1A induction and bile biomarkers, clearly indicated that, in addition to the paper and pulp mill effluents, the downstream sites appear to receive other inputs of contaminants. This field assessment in a Bangladeshi river demonstrates biomarker measurements in caged fish as a promising approach for evaluating accumulation and effects of industrial effluents in fish of developing countries.
A new biodegradation prediction model specific to petroleum hydrocarbons
Authors: Howard Philip , Meylan William , Aronson Dallas , Stiteler William , Tunkel Jay , Comber Michael , Parkerton Thomas F.
Published: July 2005

A new predictive model for determining quantitative primary biodegradation half-lives of individual petroleum hydrocarbons has been developed. This model uses a fragment-based approach similar to that of several other biodegradation models, such as those within the Biodegradation Probability Program (BIOWIN) estimation program. In the present study, a half-life in days is estimated using multiple linear regression against counts of 31 distinct molecular fragments. The model was developed using a data set consisting of 175 compounds with environmentally relevant experimental data that was divided into training and validation sets. The original fragments from the Ministry of International Trade and Industry BIOWIN model were used initially as structural descriptors and additional fragments were then added to better describe the ring systems found in petroleum hydrocarbons and to adjust for nonlinearity within the experimental data. The training and validation sets had r2 values of 0.91 and 0.81, respectively.
Sorbate size-dependent maximum capacities for adsorption of organic compounds in the slowly and very slowly desorbing domains of a sediment
Authors: van den Heuvel Henny , van Noort Paul
Published: July 2005

Maximum capacities were determined for adsorption of six polycyclic aromatic hydrocarbons, seven polychlorinated biphenyls, and five chlorobenzenes in both the slowly desorbing domain and the very slowly desorbing domain of a sediment. For separate compound classes in the two desorption domains, log-transformed maximum adsorption capacities were linearly related to the relative magnitude of the shadow of the sorbate on an imaginary planar surface. For planar compounds, the ratio of maximum adsorption capacities for the slowly desorbing domain and the very slowly desorbing domain was approximately two. This ratio was eightfold higher for strongly nonplanar polychlorinated biphenyls, which suggests that adsorption depends on sorbate thickness in the very slow desorption domain but not in the slow desorption domain. The rates of decrease of the log-transformed sum of maximum capacities for adsorption in the slow desorption domain and the very slow desorption domain with increasing relative magnitude of the shadow of the sorbate on a planar surface were similar to those derived from literature data regarding maximum capacities for adsorption onto a soil and a sediment. It is proposed that the rates of decrease for both the slow desorption domain and the very slow desorption domain may have general applicability to soils and sediments.