bluuebunny/crossref_metadata_2025 huggingface dataset:
Stromal cell‐derived factor‐1 and hepatocyte growth factor guide axon projections to the extraocular muscles
Authors: Lerner Oleg , Davenport Dominic , Patel Priya , Psatha Maria , Lieberam Ivo , Guthrie Sarah
Published: April 2010

Vertebrate eye movements depend on the co‐ordinated function of six extraocular muscles that are innervated by the oculomotor, trochlear, and abducens nerves. Here, we show that the diffusible factors, stromal cell‐derived factor‐1 (SDF‐1) and hepatocyte growth factor (HGF), guide the development of these axon projections. SDF‐1 is expressed in the mesenchyme around the oculomotor nerve exit point, and oculomotor axons fail to exit the neuroepithelium in mice mutant for the SDF‐1 receptor CXCR4. Both SDF‐1 and HGF are expressed in or around the ventral and dorsal oblique muscles, which are distal targets for the oculomotor and trochlear nerves, respectively, as well as in the muscles which are later targets for oculomotor axon branches. We find that in vitro SDF‐1 and HGF promote the growth of oculomotor and trochlear axons, whereas SDF‐1 also chemoattracts oculomotor axons. Oculomotor neurons show increased branching in the presence of SDF‐1 and HGF singly or together. HGF promotes the growth of trochlear axons more than that of oculomotor axons. Taken together, these data point to a role for both SDF‐1 and HGF in extraocular nerve projections and indicate that SDF‐1 functions specifically in the development of the oculomotor nerve, including oculomotor axon branch formation to secondary muscle targets. HGF shows some specificity in preferentially enhancing development of the trochlear nerve. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 549–564, 2010
From the intra‐desert ridges to the marine carbonate island chain: middle to late Permian (Upper Rotliegend–Lower Zechstein) of the Wolsztyn–Pogorzela high, west Poland
Authors: Kiersnowski Hubert , Peryt Tadeusz Marek , Buniak Arkadiusz , Mikołajewski Zbigniew
Published: April 2010

The tectonic Wolsztyn–Pogorzela palaeo‐High (WPH) is the south‐eastern termination of the Brandenburg–Wolsztyn High (western Poland), which during Late Permian times was an intra‐basin ridge surrounded by Upper Rotliegend sedimentary basins within the Southern Permian Basin. The geological history and structural framework of the WPH are complex. The High belongs to the Variscan Externides, consisting at present of strongly folded, faulted and eroded Viséan to Namurian flysch deposits capped by a thick cover of Upper Carboniferous–Lower Permian volcanic rocks. This sedimentary‐volcanic complex was strongly fragmented and vertically differentiated by tectonic movements and subsequently eroded, resulting in the deposition of coarse clastics surrounding uplifted tectonic blocks. During late Rotliegend time, arid climatic conditions significantly influenced occurrences of specific facies assemblages: alluvial, fluvial, aeolian and playa. Sedimentological study helped to recognize the interplay of tectonic and palaeoclimatic factors and to understand the phenomenon of aeolian sandstones interbedded with coarse deposits of alluvial cones close to fault scarps.

Subsequent tectonic and possible thermal subsidence of the studied area was synchronous with inundation by the Zechstein Sea. The rapid inundation process allowed for the preservation of an almost perfectly protected Uppermost Rotliegend landscape. Based on 3D seismic data from the base Zechstein reflector, a reconstruction of Rotliegend palaeogeomorphology was carried out, which shows examples of tectonic rejuvenation of particular tectonic blocks within the WPH area before inundation by the Zechstein Sea.

The inundation led to the deposition of the marine Kupferschiefer Shale followed by the Zechstein Limestone. In the deeper parts of the basin the latter is developed in thin basinal facies: in shallow parts (e.g. uplifted tectonic blocks forming in some cases islands), carbonate buildups were formed. The remarkable thickness of those buildups (bryozoan reefs) is interpreted as due to stable tectonic subsidence together with a rise of sea level. A detailed study of carbonate buildups has showed that their internal structure reflects changes in shallow marine environments and even emersion events, caused by sea‐level oscillations and tectonic movements of the reef substrate. Copyright © 2010 John Wiley & Sons, Ltd.
Association of diabetes mellitus with prostate cancer: Nested case–control study (Prostate testing for cancer and Treatment study)
Authors: Turner Emma L. , Lane Janet Athene , Donovan Jenny L. , Davis Michael J. , Metcalfe Chris , Neal David E. , Hamdy Freddie C. , Martin Richard M.
Published: April 2010

Observational studies suggest that diabetes is associated with a decreased risk of prostate cancer, but few are population based or have investigated associations with cancer stage or duration of diabetes. We report a case–control study nested within the population‐based Prostate testing for cancer and Treatment (ProtecT) study ISRCTN20141297. Men aged 50–69 years based around 9 UK cities were invited for a prostate‐specific antigen (PSA) test between June 2002 and November 2006. Amongst 55,215 PSA‐tested men, 1,966 had histologically confirmed prostate cancer; of these, 1,422 (72.3%) completed the questionnaire and 1,291 (65.7%) had complete data for analysis. We randomly selected 6,479 age‐ (within 5 years) and general practice‐matched controls. The prevalence of diabetes was 89/1,291 (6.9%) in cases and 555/6,479 (8.6%) in controls. Diabetes was associated with a reduced risk of prostate cancer (odds ratio = 0.78; 95% confidence interval: 0.61–0.99). There was weak evidence that the inverse association was greater for well‐ versus poorly differentiated cancers (p = 0.07). The magnitude of the inverse association did not change with increasing duration of diabetes (p for trend = 0.95). Diabetes is associated with a decreased risk of PSA‐detected prostate cancer. These data add to the evidence of the association of diabetes with prostate cancer in the PSA era.
Risk of cancer in a large cohort of U.S. veterans with diabetes
Authors: Atchison Elizabeth A. , Gridley Gloria , Carreon J. Daniel , Leitzmann Michael F. , McGlynn Katherine A.
Published: April 2010

Prior studies of cancer risk among diabetic men have reported inconsistent findings. The aim of this study was to assess the risk of cancer among a large cohort (n = 4,501,578) of black and white U.S. veterans admitted to Veterans Affairs hospitals. The cancer risk among men with diabetes (n = 594,815) was compared to the risk among men without diabetes (n = 3,906,763). Poisson regression was used to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs). Overall, men with diabetes had a significantly lower risk of cancer (RR = 0.93, 95%CI = 0.93–0.94). Men with diabetes, however, had increased risks of cancers of the liver (RR = 1.95, 95%CI = 1.82–2.09), pancreas (RR = 1.50, 95%CI = 1.42–1.59), biliary tract (RR = 1.41, 95%CI = 1.22–1.62), colon (RR = 1.20, 95%CI = 1.16–1.25), rectum (RR = 1.12, 95%CI = 1.07–1.18), and kidney (RR = 1.09, 95%CI = 1.03–1.16), as well as leukemia (RR = 1.14, 95%CI = 1.08–1.21) and melanoma (RR = 1.13, 95%CI = 1.03–1.24). In contrast, men with diabetes had decreased risks of cancers of the prostate (RR = 0.89, 95%CI = 0.87–0.91), brain (RR = 0.91, 95% CI = 0.82–0.99), buccal cavity (RR = 0.85, 95%CI = 0.82–0.89), lung (RR = 0.79, 95%CI = 0.77–0.80), esophagus (RR = 0.77, 95%CI = 0.72–0.82), and larynx (RR = 0.76, 95%CI = 0.71–0.80). These findings indicate that black and white men with diabetes are at significantly lower risk of total cancer and of two of the most common cancers among U.S. males; lung and prostate cancers. These decreased risks were offset, however, by increased risks of cancer at several sites. Hyperinsulinemia may explain the increased risks of the digestive cancers, while lower testosterone levels, in the case of prostate cancer, and higher BMI, in the case of lung cancer, may explain the decreased risks of those tumors.
Methylation patterns in cell‐free plasma DNA reflect removal of the primary tumor and drug treatment of breast cancer patients
Authors: Liggett Thomas E. , Melnikov Anatoliy A. , Marks Jeffrey R. , Levenson Victor V.
Published: April 2010

Abnormal DNA methylation is a feature of most types of cancer, which is reflected in cell‐free circulating DNA in plasma. It is, however, unknown whether surgical removal of the tumor and subsequent therapy induces changes in plasma DNA methylation, which can be used to monitor treatment. In this pilot study, methylation in cell‐free plasma DNA of 20 breast cancer patients was determined by the previously developed MethDet‐56 technique. Samples at three time points were analyzed—before surgery (baseline), after surgery (to evaluate the effects of resection) and after surgery on tamoxifen therapy (to determine the effects of treatment). Methylation patterns of healthy controls were used as a reference for all comparisons. Seven promoters were differentially methylated (p < 0.05) in at least one comparison; three changed after surgery; another one changed after beginning of tamoxifen treatment; and four were differentially methylated in baseline versus combined treatment samples. Increased methylation of PR PROX, MDGI, PAX 5 and RARβ2 at baseline (presurgery) diminished toward the healthy controls with the lowest methylation in the combined treatment group. Surgery alone decreased methylation in PAX 5 and RARβ2, whereas tamoxifen treatment changed methylation only in the B promoter of ESR1. Methylation patterns in cell‐free plasma DNA change after surgery and tamoxifen treatment, most significantly—after combined treatment. The baseline (presurgery) patterns become similar to those of healthy controls, suggesting that methylation patterns in cell‐free plasma DNA may be used to monitor treatment.
Promoter hypermethylation in Indian primary oral squamous cell carcinoma
Authors: Kaur Jatinder , Demokan Semra , Tripathi Satyendra Chandra , Macha Muzafar Ahmad , Begum Shahnaz , Califano Joseph A. , Ralhan Ranju
Published: April 2010

We evaluated promoter hypermethylation of a panel of tumor suppressor genes as a means to detect epigenetic alterations in oral squamous cell carcinomas (OSCC) of Indian‐origin and compare with North‐American head and neck squamous cell carcinomas (HNSCC). Quantitative‐methylation‐specific PCR was used to investigate the promoter methylation status of DCC, EDNRB, p16INK4a and KIF1A in 92 OSCC, and compared to 48 paired normal tissues and 30 saliva and sera samples from healthy control subjects. Aberrant methylation of at‐least one of these genes was detected in 74/92 (80.4%) OSCC; 72.8% at EDNRB, 71.7% at KIF1A, 47.8% at p16INK4a and 58.7% at DCC; and in 5 of 48 (10.4%) normal oral tissues. None of the saliva and sera samples from controls exhibited DNA methylation in these four target genes. Thirty‐two of 72 node positive cases harbored p16INK4a and DCC hypermethylation (p = 0.005). Thus, promoter hypermethylation in genes analyzed herein is a common event in Indian OSCC and may represent promising markers for the molecular staging of OSCC patients. We found higher frequency of p16INK4a methylation (47.8%) in this Indian cohort in comparison with a North‐American cohort (37.5%). In conclusion, aberrant methylation of EDNRB, KIF1A, DCC and p16INK4a genes is a common event in Indian OSCC, suggesting that epigenetic alterations of these genes warrant validation in larger studies for their potential use as biomarkers.
Extracting a robust US business cycle using a time‐varying multivariate model‐based bandpass filter
Authors: Creal Drew , Koopman Siem Jan , Zivot Eric
Published: April 2010

We develop a flexible business cycle indicator that accounts for potential time variation in macroeconomic variables. The coincident economic indicator is based on a multivariate trend cycle decomposition model and is constructed from a moderate set of US macroeconomic time series. In particular, we consider an unobserved components time series model with a common cycle that is shared across different time series but adjusted for phase shift and amplitude. The extracted cycle can be interpreted as a model‐based bandpass filter and is designed to emphasize the business cycle frequencies that are of interest to applied researchers and policymakers. Stochastic volatility processes and mixture distributions for the irregular components and the common cycle disturbances enable us to account for the heteroskedasticity present in the data. Forecasting results are presented for a set of different specifications. Point forecasts from the preferred model indicate a future recession with the uncertainty over the business cycle growing quickly as the forecast horizon increases. Copyright © 2010 John Wiley & Sons, Ltd.
Expression profile of genes identified in human spermatogonial stem cell‐like cells using suppression subtractive hybridization
Authors: Yoo Jung Ki , Lim Jung Jin , Ko Jung Jae , Lee Dong Ryul , Kim Jin Kyeoung
Published: April 2010

Spermatogenesis is the process by which testicular spermatogonial stem cells (SSCs) self‐renew and differentiate into mature sperm in the testis. Maintaining healthy spermatogenesis requires proper proliferation of SSCs. In this study, we sought to identify factors that regulate the proliferation of SSCs. Human SSC (hSSC)‐like cells were isolated from azoospermic patients by a modified culture method and propagated in vitro. After four to five passages, the SSC‐like cells spontaneously ceased proliferating in vitro, so we collected proliferating (P)‐hSSC‐like cells at passage two and senescent (S)‐hSSC‐like cells at passage five. Suppression subtractive hybridization (SSH) was used to identify genes that were differentially expressed between the P‐hSSC‐like and S‐hSSC‐like cells. We selected positive clones up‐regulated in P‐hSSC‐like cells using SSH and functionally characterized them by reference to public databases using NCBI BLAST tools. Expression levels of genes corresponding to subtracted clones were analyzed using RT‐PCR. Finally, we confirmed the differential expression of 128 genes in positive clones of P‐hSSC‐like cells compared with S‐hSSC‐like cells and selected 23 known and 39 unknown clones for further study. Known genes were associated with diverse functions; 22% were related to metabolism. Fifteen of the known genes and two of the unknown genes were down‐regulated after senescence of hSSC‐like cells. A comparison with previous reports further suggests that known genes selected, SPP1, may be related to germ cell biogenesis and cellular proliferation. Our findings identify several potential novel candidate biomarkers of proliferating‐ and senescencet‐hSSCs, and they provide potentially important insights into the function and characteristics of human SSCs. J. Cell. Biochem. 110: 752–762, 2010. © 2010 Wiley‐Liss, Inc.
Lyn kinase and ZAP70 are substrates of PTPROt in B‐cells: Lyn inactivation by PTPROt sensitizes leukemia cells to VEGF‐R inhibitor pazopanib
Authors: Motiwala Tasneem , Datta Jharna , Kutay Huban , Roy Satavisha , Jacob Samson T.
Published: April 2010

We have recently shown that the gene encoding the truncated form of protein tyrosine phosphatase receptor‐type O (PTPROt) expressed predominantly in hematopoietic cells is epigenetically silenced in human primary chronic lymphocytic leukemia (B‐CLL). To determine whether increased phosphorylation of the PTPROt substrates following PTPROt suppression alters signal transduction pathway(s) that impart a growth advantage to the leukemic lymphocytes, it is critical to discern the key substrates of PTPROt. Here, we used substrate‐trapping assay to identify two novel substrates of PTPROt, the tyrosine kinases Lyn and ZAP70. Both Lyn and ZAP70 were dephosphorylated by wild‐type PTPROt, but not by its catalytic site (CS) mutant. A critical phosphorylation site in Lyn, Y397, essential for its activity was dephosphorylated by PTPROt. Consequently, the activity of Lyn kinase was compromised when co‐expressed with PTPROt‐WT compared to vector control or upon co‐expression with PTPROt‐CS. Ectopic expression of PTPROt in Raji cells reduced phosphorylation of Lyn in the absence of any change in its protein levels. These results have revealed the physiological importance of PTPROt in regulating B‐cell receptor signaling at Lyn kinase. Further, ectopic expression of PTPROt also sensitized the cells to the VEGF‐R inhibitor Pazopanib. J. Cell. Biochem. 110: 846–856, 2010. © 2010 Wiley‐Liss, Inc.
The relationship between bone mechanical properties and ground reaction forces in normal and hypermuscular mice
Authors: Schmitt Daniel , Zumwalt Ann C. , Hamrick Mark W.
Published: April 2010

Understanding the relationship between external load and bone morphology is critical for understanding adaptations to load in extant animals and inferring behavior in extinct forms. Yet, the relationship between bony anatomy and load is poorly understood, with empirical studies often producing conflicting results. It is widely assumed in many ecological and paleontological studies that bone size and strength reflect the forces experienced by the bone in vivo. This study examines that assumption by providing preliminary data on gait mechanics in a hypermuscular myostatin‐deficient mouse model with highly mineralized and hypertrophied long bones. A small sample of hypermuscular and wild‐type mice was video recorded while walking freely across a force platform. Temporal gait parameters, peak vertical and transverse (mediolateral) ground reaction forces (GRFs), vertical impulse, and loading rates were measured. The only gait parameters that differed between the two groups were the speeds at which the animals traveled and the transverse forces on the hind limb. The myostatin‐deficient mice move relatively slowly and experienced the same magnitude of vertical forces on all limbs and transverse forces on the forelimb as the wild‐type mice; though the myostatin‐deficient mice did experience lower mediolateral forces on their hindlimbs compared with the wild‐type mice. These preliminary results call into question the hypothesis that skeletal hypertrophy observed in hypermuscular mice is a result of larger GRFs experienced by the animals' limbs during locomotion. This calls for further analysis and a cautious approach to inferences about locomotor behavior derived from bony morphology in extant and fossil species.J. Exp. Zool. 313A:339–351, 2010. © 2010 Wiley‐Liss, Inc.
Asymmetric [3H]‐labeling using ruthenium catalyzed transfer hydrogenation
Authors: Arns Steve , Moreau Anne , Young Robert N.
Published: April 2010

The first general method for asymmetric tritiation using ruthenium catalyzed transfer hydrogenation and its application to the radiosynthesis of an exemplary prostaglandin EP4 receptor‐selective Prostaglandin E2 analog is described. The methodology should be of general utility for the enantioselective preparation of α‐tritiated chiral secondary alcohols. Copyright © 2010 John Wiley & Sons, Ltd.
Synapse loss in dementias
Authors: Clare Ryan , King Victoria G. , Wirenfeldt Martin , Vinters Harry V.
Published: April 2010

Synaptic transmission is essential for nervous system function, and its dysfunction is a known major contributing factor to Alzheimer's‐type dementia. Antigen‐specific immunochemical methods are able to characterize synapse loss in dementia through the quantification of various synaptic proteins involved in the synaptic cycle. These immunochemical methods applied to the study of Alzheimer's disease (AD) brain specimens have correlated synaptic loss with particularly toxic forms of amyloid‐β protein and have also established synapse loss as the best correlate of dementia severity. A significant but comparatively circumscribed amount of literature describes synaptic decline in other forms of dementia. Ischemic vascular dementia (IVD) is quite heterogeneous, and synapse loss in IVD seems to be variable among IVD subtypes, probably reflecting its variable neuropathologic correlates. Loss of synaptic protein has been identified in vascular dementia of the Binswanger type and Spatz‐Lindenberg's disease. Here we demonstrate a significant loss of synaptophysin density within the temporal lobe of frontotemporal dementia (FTD) patients. © 2010 Wiley‐Liss, Inc.
Enhanced adenoviral gene delivery to motor and dorsal root ganglion neurons following injection into demyelinated peripheral nerves
Authors: Zhang Yongjie , Zheng Yiyan , Zhang Yi Ping , Shields Lisa B.E. , Hu Xiaoling , Yu Panpan , Burke Darlene A. , Wang Heming , Jun Cai , Byers Jonathan , Whittemore Scott R. , Shields Christopher B.
Published: April 2010

Injection of viral vectors into peripheral nerves may transfer specific genes into their dorsal root ganglion (DRG) neurons and motoneurons. However, myelin sheaths of peripheral axons block the entry of viral particles into nerves. We studied whether mild, transient peripheral nerve demyelination prior to intraneural viral vector injection would enhance gene transfer to target DRG neurons and motoneurons. The right sciatic nerve of C57BL/6 mice was focally demyelinated with 1% lysolecithin, and the left sciatic nerve was similarly injected with saline (control). Five days after demyelination, 0.5 μl of Ad5‐GFP was injected into both sciatic nerves at the site of previous injection. The effectiveness of gene transfer was evaluated by counting GFP+ neurons in the DRGs and ventral horns. After peripheral nerve demyelination, there was a fivefold increase in the number of infected DRG neurons and almost a 15‐fold increase in the number of infected motoneurons compared with the control, nondemyelinated side. Focal demyelination reduced the myelin sheath barrier, allowing greater virus–axon contact. Increased CXADR expression on the demyelinated axons facilitated axoplasmic viral entry. No animals sustained any prolonged neurological deficits. Increased gene delivery into DRG neurons and motoneurons may provide effective treatment for amyotrophic lateral sclerosis, pain, and spinal cord injury. © 2010 Wiley‐Liss, Inc.
Impairment of nuclear factor‐κB activation increased glutamate excitotoxicity in a motoneuron–neuroblastoma hybrid cell line expressing mutant (G93A) Cu/Zn‐superoxide dismutase
Authors: Pyo Jung‐Soo , Ko Young San , Kim Woo Ho , Kim Manho , Lee Kwang‐Woo , Nam Seon Young , Chung Hee‐Yong , Cho Sung Jin , Baik Tai‐Kyoung , Lee Byung Lan
Published: April 2010

Mutations in the superoxide dismutase 1 (SOD1) gene are linked to glutamate excitotoxicity in familial amyotrophic lateral sclerosis (fALS), but the underlying mechanism remains unclear. We investigated whether nuclear factor‐κB (NF‐κB) activation is involved in glutamate excitotoxicity by using motor neuron–neuroblastoma hybrid cells that expressed a mutant (G93A) SOD1 (mtSOD1) or wild‐type SOD1 (wtSOD1). MtSOD1 cells were more vulnerable to glutamate excitotoxicity than wtSOD1 cells and showed higher NF‐κB activity, higher nuclear cRel expression, and lower nuclear RelA expression under basal conditions. Glutamate treatment increased NF‐κB activation along with nuclear expressions of RelA and cRel in wtSOD1 cells but induced only weak nuclear RelA expression in mtSOD1 cells. Suppression of NF‐κB activation using transfection of the superrepressive mutant form of IκBα (mIκBα) inhibited nuclear RelA expression in both types of SOD1 cells, which increased glutamate excitotoxicity in wtSOD1 cells but not in mtSOD1 cells. Furthermore, immunohistochemistry confirmed stronger RelA immunoreactivity in the nuclei of motor neurons of spinal cord in wild‐type SOD1 transgenic mice than in those in SOD1 G93A transgenic mice. In addition, we found that glutamate treatment decreased XIAP expression and increased caspase‐3 activity in mtSOD1 cells and mIκBα‐overexpressing wtSOD1 cells. Our results suggest that glutamate excitotoxicity in motor neurons of SOD1‐linked fALS is attributable, at least in part, to the impairment of IκBα‐dependent RelA activation and subsequent apoptosis mediated by XIAP inhibition and caspase‐3 activation. © 2010 Wiley‐Liss, Inc.
Prognostic indicators in node‐negative advanced gastric cancer patients
Authors: Saito Hiroaki , Kuroda Hirohiko , Matsunaga Tomoyuki , Fukuda Kenji , Tatebe Shigeru , Tsujitani Shunichi , Ikeguchi Masahide
Published: April 2010

Background and Objectives

Despite carrying better overall prognoses, some node‐negative gastric cancer patients die from recurrent malignancies. Identifying factors associated with disease‐specific survival in adequately staged node‐negative gastric cancer is important, as these patients are presumably free of microscopic regional metastases and may derive significant benefit from existing or future adjuvant strategies.

Methods

To investigate significant prognostic indicators in node‐negative advanced gastric cancer patients, we reviewed 777 advanced gastric cancer patients who had undergone curative gastrectomies.

Results

The 5‐year survival rate of node‐negative advanced gastric cancer patients is 84.9%, which is significantly better than that of patients with lymph node metastasis. Multivariate analysis indicated that tumor size, histology, and depth of invasion are independent prognostic factors. The 5‐year survival rate of patients with larger tumors (≥7 cm), poorly differentiated adenocarcinoma, and serosal invasion was 49.1%, which was significantly worse that of patients with fewer or none of these factors.

Conclusions

Tumor size, histology, and the presence of serosal invasion are strong indicators of poor prognosis in node‐negative advanced gastric cancer patients. J. Surg. Oncol. 2010; 101:622–625. © 2010 Wiley‐Liss, Inc.
Abductor paralysis after botox injection for adductor spasmodic dysphonia
Authors: Venkatesan Naren N. , Johns Michael M. , Hapner Edie R. , DelGaudio John M.
Published: April 2010

Objectives/Hypothesis:

Botulinum toxin (Botox) injections into the thyroarytenoid muscles are the current standard of care for adductor spasmodic dysphonia (ADSD). Reported adverse effects include a period of breathiness, throat pain, and difficulty with swallowing liquids. Here we report multiple cases of bilateral abductor paralysis following Botox injections for ADSD, a complication previously unreported.

Study Design:

Retrospective case series.

Methods:

Patients that received Botox injections for spasmodic dysphonia between January 2000 and October 2009 were evaluated. Patients with ADSD were identified. The number of treatments received and adverse effects were noted. For patients with bilateral abductor paralysis, age, sex, paralytic Botox dose, prior Botox dose, and course following paralysis were noted.

Results:

From a database of 452 patients receiving Botox, 352 patients had been diagnosed with ADSD. Of these 352 patients, eight patients suffered bilateral abductor paralysis, and two suffered this complication twice. All affected patients were females over the age of 50 years. Most patients had received treatments prior to abductor paralysis and continued receiving after paralysis. Seven patients recovered after a brief period of activity restrictions, and one underwent a tracheotomy. The incidence of abductor paralysis after Botox injection for ADSD was 0.34%.

Conclusions:

Bilateral abductor paralysis is a rare complication of Botox injections for ADSD, causing difficulty with breathing upon exertion. The likely mechanism of paralysis is diffusion of Botox around the muscular process of the arytenoid to the posterior cricoarytenoid muscles. The paralysis is temporary, and watchful waiting with restriction of activity is the recommended management. Laryngoscope, 2010
A corrosion study of nickel–copper and nickel–copper–palladium welding filler metals
Authors: Liang D. , Sowards J. W. , Frankel G. S. , Alexandrov B. T. , Lippold J. C.
Published: April 2010

In an effort to reduce the release of fumes containing carcinogenic Cr6+ during arc welding of stainless steel, Cr‐free filler metals for welding of SS304 have been developed. Corrosion studies were carried out on 304L stainless steel samples welded with these Cr‐free consumables. The corrosion properties of gas tungsten arc (GTA) and shielded metal arc (SMA) welds fabricated with NiCu and NiCuPd consumables were found to be comparable to those of welds fabricated with SS308L, the standard filler metal used with SS304. Although the breakdown potentials of the welds made using both welding processes were lower than that of the SS308L GTA weld, the repassivation potentials of these welds were much higher. Generally, the repassivation potential is a more conservative measure of susceptibility to localized corrosion. Accordingly, the NiCu and NiCuPd welds were more resistant to crevice corrosion than SS308L welds. The addition of a small amount of Pd improved the corrosion resistance relative to NiCu welds, which is consistent with previous studies from specially‐prepared button samples and bead‐on‐plate samples. Other corrosion studies such as creviced and uncreviced long time immersion, atmospheric exposure, and slow strain rate testing suggest that NiCuPd filler metal can be a potential replacement for the conventional SS308L filler metal for joining SS304.
Choline kinase overexpression increases invasiveness and drug resistance of human breast cancer cells
Authors: Shah Tariq , Wildes Flonne , Penet Marie‐France , Winnard Paul T. , Glunde Kristine , Artemov Dmitri , Ackerstaff Ellen , Gimi Barjor , Kakkad Samata , Raman Venu , Bhujwalla Zaver M.
Published: April 2010

A direct correlation exists between increased choline kinase (Chk) expression, and the resulting increase of phosphocholine levels, and histological tumor grade. To better understand the function of Chk and choline phospholipid metabolism in breast cancer we have stably overexpressed one of the two isoforms of Chk‐α known to be upregulated in malignant cells, in non‐invasive MCF‐7 human breast cancer cells. Dynamic tracking of cell invasion and cell metabolism were studied with a magnetic resonance (MR) compatible cell perfusion assay. The MR based invasion assay demonstrated that MCF‐7 cells overexpressing Chk‐α (MCF‐7‐Chk) exhibited an increase of invasion relative to control MCF‐7 cells (0.84 vs 0.3). Proton MR spectroscopy studies showed significantly higher phosphocholine and elevated triglyceride signals in Chk overexpressing clones compared to control cells. A test of drug resistance in MCF‐7‐Chk cells revealed that these cells had an increased resistance to 5‐fluorouracil and higher expression of thymidylate synthase compared to control MCF‐7 cells. To further characterize increased drug resistance in these cells, we performed rhodamine‐123 efflux studies to evaluate drug efflux pumps. MCF‐7‐Chk cells effluxed twice as much rhodamine‐123 compared to MCF‐7 cells. Chk‐α overexpression resulted in MCF‐7 human breast cancer cells acquiring an increasingly aggressive phenotype, supporting the role of Chk‐α in mediating invasion and drug resistance, and the use of phosphocholine as a biomarker of aggressive breast cancers. Copyright © 2010 John Wiley & Sons, Ltd.
Four‐dimensional echocardiography with B‐flow imaging and spatiotemporal image correlation in the assessment of congenital heart defects
Authors: Zhang Ming , Pu Da‐Rong , Zhou Qi‐Chang , Peng Qing‐Hai , Tian Lei‐Qi
Published: April 2010

Objective

The objective of the present study was to evaluate the role of four‐dimensional ultrasound with B‐flow imaging and spatiotemporal image correlation (STIC) in the detection of congenital heart defects.

Methods

Automated longitudinal and transverse sweeping of the fetal chest was utilized to obtain the volume datasets of the heart. Among the fetuses recruited in the study, 20 were normal and 13 were fetuses with congenital heart anomalies. Reconstructed images of abnormal hearts were compared with those of normal fetuses.

Results

Of the 20 normal fetuses, all extracardiac vessels such as aorta, pulmonary artery, ductus artery, inferior vena cava, and ductus venosus could be detected on reconstructed images of 16 fetuses. In five normal cases, a four‐dimensional image was recorded to allow simultaneous visualization of all four pulmonary veins. In the 13 fetuses with cardiac anomalies, four‐dimensional sonography with B‐flow imaging and STIC detected the ‘digital casts’ of the outflow tracts, great arteries, and veins draining into the heart. These results demonstrate spatial relationship among these structures which provide important anatomical information.

Conclusions

The use of four‐dimensional ultrasound examination with B‐flow imaging and STIC is a very useful technique in identifying anatomical features of different congenital cardiac anomalies. Copyright © 2010 John Wiley & Sons, Ltd.
Assessing self‐efficacy for coping with cancer: development and psychometric analysis of the brief version of the Cancer Behavior Inventory (CBI‐B)
Authors: Heitzmann Carolyn A. , Merluzzi Thomas V. , Jean‐Pierre Pascal , Roscoe Joseph A. , Kirsh Kenneth L. , Passik Steven D.
Published: April 2010

Objective: The Cancer Behavior Inventory‐Brief Version (CBI‐B), a 12‐item measure of self‐efficacy for coping with cancer derived from the longer 33‐item version, was subjected to psychometric analysis.

Method: Participants consisted of three samples: 735 cancer patients from a multicenter CCOP study, 199 from central Indiana, and 370 from a national sample. Samples were mixed with respect to initial cancer diagnosis. Participants completed the CBI‐B and measures of quality of life, optimism, life satisfaction, depression, and sickness impact.

Results: Exploratory Factor Analysis with oblique rotation yielded four factors in the first sample: (1) Maintaining Independence and Positive Attitude; (2) Participating in Medical Care; (3) Coping and Stress Management; and (4) Managing Affect, which were confirmed in subsequent samples. Cronbach α coefficient for the 12‐item CBI‐B ranged from 0.84 to 0.88. Validity of the CBI‐B was demonstrated by positive correlations with measures of quality of life and optimism, and negative correlations with measures of depression and sickness impact.

Conclusion: The CBI‐B is a valid brief measure of self‐efficacy for coping that could be easily integrated into clinical oncology research and practice, and also used in screening patients. Copyright © 2010 John Wiley & Sons, Ltd.
The supportive care needs survey for partners and caregivers of cancer survivors: development and psychometric evaluation
Authors: Girgis Afaf , Lambert Sylvie , Lecathelinais Christophe
Published: April 2010

Objective: Begin to test the psychometric properties of a measure designed to capture the multi‐dimensional supportive care needs of cancer caregivers: the Supportive Care Needs Survey—Partners and Caregivers (SCNS‐P&C).

Methods: Draft SCNS‐P&C items were developed with reference to the literature and existing instruments and reviewed for face and content validity. The final SCNS‐P&C was then completed by 547 cancer caregivers. Psychometric analyses conducted included principal factor analysis, internal consistency, and construct validity through the known‐group approach.

Results: Factor analysis revealed four domains of needs: Health Care Service Needs, Psychological and Emotional Needs, Work and Social Needs, and Information Needs, with Cronbach's α coefficients ranging from 0.88 to 0.94. Construct validity of the SCNS‐P&C was partially supported. Across all domains, individuals with anxiety or depression were more likely to report at least one unmet moderate or high need in comparison to non‐anxious or non‐depressed participants. A greater proportion of younger participants experienced at least one unmet moderate or high need within the Psychological and Emotional Needs and Work and Social Needs domains. Proportion of reported unmet needs varied across cancer types for the Health Care Service Needs and Information Needs domains.

Conclusions: The SCNS‐P&C has the potential to comprehensively assess the range of caregivers' supportive care needs, across the illness trajectory. Analyses supported the tool's internal consistency and construct validity. The SCNS‐P&C can be used by researchers and clinicians to determine caregivers' unmet needs, prioritise health‐care resources, and tailor supportive cancer care services accordingly. Copyright © 2010 John Wiley & Sons, Ltd.
Tracheostomy in children: A population‐based experience over 17 years
Authors: Al‐Samri Mohammed , Mitchell Ian , Drummond Derek S. , Bjornson Candice
Published: April 2010

Introduction

Tracheostomy is a lifesaving intervention with numerous complications.

Objectives

We describe the natural history of tracheostomy in children in a defined geographical area over a 17‐year period. Our primary aim is to stress the need for a consensus on pediatric tracheostomy care.

Methods

This retrospective study reviewed the charts of 72 children who had tracheostomy between January 1990 and January 2007. Indications for the procedure were divided into 3 groups: (1) upper airway obstruction at a well‐defined anatomic site (32 patients); (2) upper airway obstruction with a complex medical condition (24 patients); and (3) need for an access to the lower airway for long‐term ventilation and pulmonary care with normal airway anatomy (16 patients).

Results

The most common indication for tracheostomy was upper airway obstruction due to subglottic stenosis (15 patients, 21%) or as part of a complex craniofacial syndrome (15 patients, 21%). The duration of intubation prior to tracheostomy and the duration of hospitalization after tracheostomy varied markedly. Tracheocutaneous fistulae complicated 15 of the 38 (37%) decannulated patients. Tracheostomy infection occurred in 90% of the patients and tracheal granulation in 56%. Eleven (15%) deaths occurred, 10 were due to the underlying medical illness and 1 to a mucous plug.

Conclusion

The complications of tracheostomy in children are substantial. Surveillance and prompt interventions are necessary to overcome life‐threatening sequelae. A multidisciplinary (medical–surgical) approach provides better care for these highly vulnerable children. A consensus on pediatric tracheostomy care is needed. Pediatr Pulmonol. 2010; 45:487–493. © 2010 Wiley‐Liss, Inc.
Long‐term results of disodium etidronate treatment in pulmonary alveolar microlithiasis
Authors: Ozcelik Ugur , Yalcin Ebru , Arıyurek Macit , Ersoz Deniz Dogru , Cinel Guzin , Gulhan Bora , Kiper Nural
Published: April 2010

Pulmonary alveolar microlithiasis (PAM) is a rare disease with alveolar microliths mainly composed of calcium phosphate. The gene responsible for the disease is SLC34A2, which encodes a type‐IIb sodium phosphate cotransporter, has been described recently. Treatment of this disease is not clearly defined. Disodium etidronate is a member of bisphonates and it has been administered in these patients due to its inhibitory effect on the precipitation of hydroxyapatite microcrystals. Here, clinical and radiological improvement of two patients with PAM who were treated with disodium etidronate for 9 and 11 years, respectively, are presented. The pathogenetic mechanism of this treatment on the genetic basis of disease is discussed. Pediatr Pulmonol. 2010; 45:514–517. © 2010 Wiley‐Liss, Inc.
Antiproliferative and apoptotic effects of the herbal agent Pygeum africanum on cultured prostate stromal cells from patients with benign prostatic hyperplasia (BPH)
Authors: Quiles Maria T. , Arbós Maria A. , Fraga Antònia , de Torres Inés M. , Reventós Jaume , Morote Juan
Published: April 2010

BACKGROUND

Previous reports show that the herbal agent Pygeum africanum (PA) used to treat benign prostatic hyperplasia (BPH) inhibits proliferation of prostate stromal cells from BPH tissues. To determine underlying mechanisms, we compared proliferative and apoptotic responses to PA between BPH and non‐BPH prostate stromal cells with a focus on the specific reaction displayed by stromal cell subsets. An interaction of PA with growth factors and hormones was also investigated.

METHODS

Primary prostate stromal cells from BPH/LUTS patients undergoing open prostatectomy (n = 3) and patients without benign prostatic hyperplasia (BPH) undergoing cystectomy (n = 3) were treated with PA. Cells were characterized by immunofluorescence. Sensitivity to PA was determined using proliferation assays. Apoptosis, transforming growth factor B1 (TGFB1), fibroblast growth factor 2 (FGF2), vimentin, α smooth muscle actin (αSMA), and smoothelin expression were examined after PA treatment. Cell immunophenotype and proliferation were tested after incubating cells with PA plus either FGF2, TGFB1, vascular endothelial growth factor (VEGF), dihydrotestosterone (DHT) or 17β‐estradiol (E2).

RESULTS

Antiproliferative potency and apoptosis induced by PA on stromal cells were increased in BPH versus non‐BPH cells. Apoptosis targeted αSMA+ cells, more abundant in BPH cells. Downregulation of TGFB1 expression was induced by PA. FGF2 increased cells sensitivity to PA. Incubation with other mitogenic factors like VEGF, DHT, and E2 decreased sensitivity to PA. Both TGFB1 and E2 blocked the antiproliferative activity of PA.

CONCLUSIONS

Results suggest that PA is antiproliferative and apoptotic on proliferative prostate fibroblasts and myofibroblasts but not on smooth muscle cells. Mechanisms of action include TGFB1 downregulation and inhibition of FGF2 specific signaling. Prostate 70: 1044–1053, 2010. © 2010 Wiley‐Liss, Inc.
Androgens regulate adenylate cyclase activity and intracellular calcium in stromal cells derived from human prostate
Authors: Oliver Victoria L. , Anderson Carrie , Ventura Sabatino , Haynes John M.
Published: April 2010

BACKGROUND

Increased smooth muscle tone is a significant component of benign prostatic hyperplasia, the onset of which correlates with age and declining serum testosterone levels. This study investigates the effects of androgens on key regulators of smooth muscle tone: intracellular calcium ([Ca2+]i) and cyclic adenosine monophosphate (cAMP) in human cultured prostatic stromal cells (HCPSC).

METHODS

HCPSC were cultured in the absence or presence of dihydrotestosterone (DHT; 3, 30, and 300 nM) or testosterone (0.3–300 nM) alone or in the presence of flutamide (10 µM). Changes in [Ca2+]i were determined in FURA‐2AM (10 µM) loaded cells. Changes in cAMP were determined by Alpha Screen® assay.

RESULTS

Up to 32% of cultured cells exhibited spontaneous elevations of [Ca2+]i. The frequency of these elevations was reduced by nifedipine (10 µM), ryanodine (1 µM), and the adenylate cyclase inhibitor MDL 12,330A (20 µM). Compared to steroid‐free cells, a 3‐day incubation of cells with testosterone (only 3 nM) elevated basal, but not peak [Ca2+]i. In the presence of flutamide, all concentrations of testosterone tested elevated basal, but not peak [Ca2+]i. DHT (30 and 300, but not 3 nM) lowered peak and basal [Ca2+]i. Increased testosterone concentration dependently decreased resting cell cAMP (pIC50: 7.64 ± 0.29 nM).

CONCLUSIONS

These findings demonstrate that some HCPSC have the ability to spontaneously and transiently elevate [Ca2+]i. The magnitude of these [Ca2+]i peaks, along with resting levels of calcium and cAMP, appear to be regulated by androgens. Prostate 70: 1222–1232, 2010. © 2010 Wiley‐Liss, Inc.
Saporin toxin‐conjugated monoclonal antibody targeting prostate‐specific membrane antigen has potent anticancer activity
Authors: Kuroda Kenji , Liu He , Kim Sae , Guo Ming , Navarro Vincent , Bander Neil H.
Published: April 2010

BACKGROUND

Prostate‐specific membrane antigen (PSMA) provides an attractive target for monoclonal antibody targeted therapies in the treatment of prostate cancer (PC). In this study, we generated an immunotoxin by linking a humanized anti‐PSMA monoclonal antibody (hJ591) to the ribosome‐inactivating protein toxin saporin. The hJ591–saporin immunoconjugate was evaluated for antitumor activity against PC cells.

METHODS

PSMA‐positive cell lines, LNCaP and CWR22Rv1 and a PSMA‐negative cell line, PC‐3, were used in these experiments. The hJ591 was biotinylated and mixed with streptavidin–saporin (SAZAP). The binding ability of hJ591–SAZAP and the extent of internalization into the cells were tested. The viability of cells treated with hJ591–SAZAP was also examined and the apoptotic cells were measured. Lastly, the anticancer effect of hJ591–SAZAP was investigated in vivo.

RESULTS

The binding ability of hJ591–SAZAP to PSMA was equivalent to that of unconjugated J591. Internalization of hJ591–SAZAP was clearly detected in PSMA‐positive, but not in PSMA‐negative cell lines. IC50 of hJ591–SAZAP was 0.14 nM, 1.99 nM, and more than 100 nM in LNCaP, CWR22Rv1, and PC‐3 cells, respectively. After 72 hr of hJ591–SAZAP treatment, the percentage of apoptotic cells was 60.29% and 40.73% in LNCaP and CWR22Rv1 cells, respectively, compared to 4.70% in PC‐3 cells. The hJ591–SAZAP also had anticancer activity in a LNCaP xenograft model.

CONCLUSIONS

Our findings show that hJ591–SAZAP conjugate has potent and selective antitumor effects on PSMA‐positive PC cells in vitro and in vivo. This study supports development of PSMA antibody–toxin conjugates for therapy of PC. Prostate 70:1286–1294, 2010. © 2010 Wiley‐Liss, Inc.
The synthetic estrogen diethylstilbestrol (DES) inhibits the telomerase activity and gene expression of prostate cancer cells
Authors: Geier Rinat , Adler Shulamit , Rashid Gloria , Klein Ami
Published: April 2010

BACKGROUND

Telomerase, which lengthens telomeres, is normally down‐regulated in somatic cells and highly up‐regulated in dividing cells, such as malignant cells. Human prostate cancer is androgen dependent. Estrogens, including the synthetic estrogen diethylstilbestrol (DES), are used in prostate cancer treatment to reduce androgen levels via feedback inhibition of the hypothalamic release of luteinizing hormone releasing hormone (LH‐RH). DES has also direct anticancer activities, such as apoptosis induction. We investigated in vitro the effect of DES on telomerase activity and on gene expression in the presence and absence of androgens. We used two prostate cancer cell lines: LNCaP (androgen dependent) and PC3 (androgen independent).

METHODS

LNCaP and PC3 cells were treated with 0.1–1,000 nM testosterone or dihydrotestosterone (DHT) in the presence of DES (25 or 50 µM). Cell telomerase activity and gene expression (mRNA) were measured.

RESULTS

LNCaP: As expected, testosterone and DHT significantly increased telomerase activity and gene expression. However, these effects were inhibited by DES. Contrary to expectations, the combination of DES and testosterone functioned synergistically leading to complete inhibition of telomerase activity. PC3: Testosterone and DHT did not affect telomerase activity and gene expression, whereas DES, in the absence or presence of the androgens, significantly inhibited telomerase activity.

CONCLUSIONS

In the present study, we demonstrated the ability of DES to inhibit telomerase in prostate cancer cells. Androgens did not limit the inhibitory effect and even acted synergistically with DES in the LNCaP line. This phenomenon should be considered if telomerase inhibition is part of prostate cancer treatment. Prostate 70:1307–1312, 2010. © 2010 Wiley‐Liss, Inc.