bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of PPAR‐γ and PTEN cascade participates in lovastatin‐mediated accelerated differentiation of oligodendrocyte progenitor cells
Authors: Paintlia Ajaib S. , Paintlia Manjeet K. , Singh Avtar K. , Orak John K. , Singh Inderjit
Published: June 2010

Previously, we and others documented that statins including‐lovastatin (LOV) promote the differentiation of oligodendrocyte progenitor cells (OPCs) and remyelination in experimental autoimmune encephalomyelitis (EAE), an multiple sclerosis (MS) model. Conversely, some recent studies demonstrated that statins negatively influence oligodendrocyte (OL) differentiation in vitro and remyelination in a cuprizone‐CNS demyelinating model. Therefore, herein, we first investigated the cause of impaired differentiation of OLs by statins in vitro settings. Our observations indicated that the depletion of cholesterol was detrimental to LOV treated OPCs under cholesterol/serum‐deprived culture conditions similar to that were used in conflicting studies. However, the depletion of geranylgeranyl‐pp under normal cholesterol homeostasis conditions enhanced the phenotypic commitment and differentiation of LOV‐treated OPCs ascribed to inhibition of RhoA‐Rho kinase. Interestingly, this effect of LOV was associated with increased activation and expression of both PPAR‐γ and PTEN in OPCs as confirmed by various pharmacological and molecular based approaches. Furthermore, PTEN was involved in an inhibition of OPCs proliferation via PI3K‐Akt inhibition and induction of cell cycle arrest at G1 phase, but without affecting their cell survival. These effects of LOV on OPCs in vitro were absent in the CNS of normal rats chronically treated with LOV concentrations used in EAE indicating that PPAR‐γ induction in normal brain may be tightly regulated‐providing evidences that statins are therapeutically safe for humans. Collectively, these data provide initial evidence that statin‐mediated activation of the PPAR‐γ‐PTEN cascade participates in OL differentiation, thus suggesting new therapeutic‐interventions for MS or related CNS‐demyelinating diseases. © 2010 Wiley‐Liss, Inc.
Challenges of Designing Hepatic Encephalopathy Treatment Trials
Authors: Sanaka Madhusudhan R. , Ong Janus P. , Mullen Kevin D.
Published: June 2010

Abstract

Background/Aims:

The efficacy and safety of rifaximin in comparison with lactitol in the treatment of hepatic encephalopathy was assessed in a prospective randomized, double–blind, double–dummy, controlled trial.

Methods:

A total of 103 patients with grade I–III acute hepatic encephalopathy were randomized to receive rifaximin (50 patients, 1200 mg/day) or lactitol (53 patients, 60 g/day) for 5–10 days. Changes in portal–systemic encephalopathy (PSE) index on entry and at the end of the study were used to evaluate the efficacy of the two therapies.

Results:

Both groups were comparable before treatment with regard to demographic data and characteristics of the hepatic encephalopathy episode. The global efficacy of both therapies was similar: 81.6% in the rifaximin group and 80.4% in the lactitol group showed improvement or total regression of the episode. A significantly better evolution of the PSE index was observed in the rifaximin group, due to a greater effect of rifaximin in two components of the index: EEG abnormalities and ammonia levels. No serious events related to either treatment were found during the study.

Conclusions:

Rifaximin may be considered a useful and safe alternative therapy to lactitol in the treatment of acute hepatic encephalopathy in cirrhosis.
The role of epigenetics in the acquisition and maintenance of effector function in virus‐specific CD8 T cells
Authors: Olson Matthew R. , Russ Brendan E. , Doherty Peter C. , Turner Stephen J.
Published: June 2010

CD8+ T cells are critical for protecting the body from infectious disease. To achieve this protection, CD8+ T cells must undergo a highly involved process of differentiation that involves the activation of naïve/quiescent cells followed by robust rounds of cell division and the acquisition of effector functions that mediate viral clearance. After the pathogen is eliminated, a small number of these cells survive into long‐lived memory and maintain the capacity to respond rapidly and reacquire effector function after secondary exposure to their cognate antigen. This review focuses on how CD8+ T cells acquire and regulate effector functions and how the capacity to produce effector molecules is maintained into memory. © 2010 IUBMB IUBMB Life 62(7): 519–526, 2010
Post‐hospitalization transitions: Examining the effects of timing of primary care provider follow‐up
Authors: Misky Gregory J. , Wald Heidi L. , Coleman Eric A.
Published: June 2010

BACKGROUND:

The transition between the inpatient and outpatient setting is a high‐risk period for patients. The presence and role of the primary care provider (PCP) is critical during this transition. This study evaluated characteristics and outcomes of discharged patients lacking timely PCP follow‐up, defined as within 4 weeks of discharge.

METHODS:

This prospective cohort enrolled 65 patients admitted to University of Colorado Hospital, an urban 425‐bed tertiary care center. We collected patient demographics, diagnosis, payer source and PCP information. Post‐discharge phone calls determined PCP follow‐up and readmission status. Thirty‐day readmission rate and hospital length of stay (LOS) were compared in patients with and without timely PCP follow‐up.

RESULTS:

The rate of timely PCP follow‐up was 49%. For a patient's same medical condition, the 30‐day readmission rate was 12%. Patients lacking timely PCP follow‐up were 10 times more likely to be readmitted (odds ratio [OR] = 9.9, P = 0.04): 21% in patients lacking timely PCP follow‐up vs. 3% in patients with timely PCP follow‐up, P = 0.03. Lack of insurance was associated with lower rates of timely PCP follow‐up: 29% vs. 56% (P = 0.06), but did not independently increase readmission rate or LOS (OR = 1.0, P = 0.96). Index hospital LOS was longer in patients lacking timely PCP follow‐up: 4.4 days vs. 6.3 days, P = 0.11.

CONCLUSIONS:

Many patients discharged from this large urban academic hospital lacked timely outpatient PCP follow‐up resulting in higher rates of readmission and a non‐significant trend toward longer hospital LOS. Effective transitioning of care for vulnerable patients may require timely PCP follow‐up. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine.
Necrotizing fasciitis associated with acupuncture: A case report
Authors: Macuha Faustino , Ahn Andrew , Graham Robert
Published: June 2010

Infectious complications from acupuncture are extermely rare; we present a case of severe necrotizing Fasciitis (type 1) in an elderly nondiabetic male. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine.
FT‐Raman spectroscopic spectra on 3‐phenylpropylamine inclusion compounds
Authors: Ünal Arslan , Şentürk Şükrü , Şenyel Mustafa
Published: June 2010

Some new Hofmann‐3‐phenylpropylamine‐type clathrates with chemical formulae of M(3‐phenylpropylamine)2 Ni(CN)4. 2G (MNi or Co, G = 1,2‐dichlorobenzene or 1,3‐dichlorobenzene) have been prepared and their Fourier transform infrared(FT‐IR; 4000–400 cm−1), far‐infrared (600–100 cm−1) and FT‐Raman (4000–60 cm−1) spectra are reported. The ligand molecule, guest molecules, polymeric sheet and metal‐ligand bands of the clathrates are assigned in detail. The compounds are also characterized by thermal gravimetric analysis (TGA), differential thermal analysis (DTA), elemental analysis and magnetic susceptibility measurements. From the results, the monodentate 3‐phenylpropylamine ligand molecule bonds to the metal atom of |M‐Ni(CN)4 | ∞ polymeric layers in the trans‐gauche‐gauche (TGG) form, and 1,2‐dichlorobenzene or 1,3‐dichlorobenzene molecules are guested by this structure revealing the inclusion ability of the host complexes. Copyright © 2010 John Wiley & Sons, Ltd.
Pure component Raman spectral reconstruction from glazed and unglazed Yuan, Ming, and Qing shards: a combined Raman microscopy and BTEM study
Authors: Widjaja Effendi , Lim Geok Hong , Lim Qinyi , Mashadi Ahmad Bin , Garland Marc
Published: June 2010

Raman mapping measurements were performed on the glazed and unglazed surfaces of shards excavated from Yuan, Ming, and Qing dynasty strata. A number of areas on each surface were chosen. Circa 21 × 21 pixels were measured for each area using both 514 and 785‐nm laser as the Raman excitation. Data were collected from 100–3600 cm−1. Many sets of spectra exhibited very intense fluorescence. In spite of the intense fluorescence, the resulting sets of spectra were collated and analyzed together using the band‐target entropy minimization (BTEM) algorithm. Pure component spectral estimates of many of the major components were achieved, without the use of any a priori information such as spectral libraries. These include α‐silica quartz, carbon, anatase, cobalt oxides, hematite, glassy silicate, and lanthanide complexes. In addition, two further unidentified pure component spectra A and B were recovered as well as an interference pattern due to the microscopic texture of the shards (associated with small particle/thin layer domains). The carbon was primarily present in elemental form, i.e. mixture of amorphous and graphitic (unordered and ordered domains); however there is an evidence of some partial oxidation, i.e. formation of carboxylates. The interference patterns and the lanthanide complexes were only observed when using the longer wavelength red laser. The cobalt oxides and the anatase were only observed when using the green laser. In summary, the combination of Raman microscopy and BTEM has allowed the enumeration of many of the underlying spectral patterns present and hence unambiguous identification of the major individual components present in the archaeological samples. This approach would appear applicable to other classes of archaeological materials as well. Limitations and extensions of the present approach are discussed. Copyright © 2010 John Wiley & Sons, Ltd.
The increase in immunosuppression and its role in the development of malignant lesions
Authors: Cole Warren H.
Published: June 2010

The first evidence that a major operation results in immunosuppression appeared in 1957. A few years later, numerous articles appeared in the medical literature showing that the same effect took place in the human being. When kidney transplantation was begun, it was soon learned that immunosuppression was necessary to obtain good results. Soon after suppression was adopted it was noted that malignancies were being encountered. The same was true with cardiac transplantation. Within the many types of immunodeficiency's, malignant lesions are significantly encountered in only one‐AIDS.
Surgical oncology—theory and practice
Authors: Raven Ronald W.
Published: June 2010

In viewing the broad imagery of oncology, it is seen as a multidisciplinary subject, and attention is focused initially on oncology philosophy, indicating major problems for solution. The position of surgical oncology is clearly delineated in clinical oncology as a major discipline with well‐defined theory and practice, which is the main subject here. The foundations of the theory are the essential sciences for surgeons—surgical anatomy, physiology, and pathology, with surgical oncology now emerging as a multidisciplinary science. The basic sciences of surgical oncology, currently making valuable additions to oncology knowledge, are defined, and their relevance to the build‐up of the theory is described. There must be a constant feedback of theory and practice. Major surgical operations are central in the practice component; the latter can be epitomized as rehabilitation and continuing care. Rehabilitation begins with diagnosis. The performance of oncological operations requires sound surgical judgment and superb technical ability. The surgical oncologist has an important role in rehabilitation and continuing care programmes. Education and training courses in the theory and practice of surgical oncology are developing for graduates who desire a career in this discipline.
Inflammatory breast carcinoma: A distinct entity?
Authors: Kokal William A. , Hill L. Robert , Porudominsky David , Beatty J. David , Kemeny M. Margaret , Riihimaki Daniel U. , Terz Ose J.
Published: June 2010

Sixty‐four patients with the diagnosis of either inflammatory or locally advanced breast cancer were analyzed with respect to age, menopausal status, estrogen receptor protein (ERP) measurements, characteristics on clinical presentation, disease‐free interval (DFI), and overall survival. There were no significant differences between the two groups in the patients' clinical presentation, DFI, or overall survival time. Patients with inflammatory carcinoma were significantly younger as well as more likely to be pre‐ or perimenopausal than patients with locally advanced breast cancer. Of those patients who had ERP measurements performed, patients with inflammatory breast cancer had a significantly decreased incidence of ERP(+) tumors in comparison to patients with locally advanced breast cancer. These results suggest that inflammatory carcinoma of the breast behaves as an ERP(−) subtype of locally advanced breast carcinoma rather than a truly distinct entity.
Cole's precancerous hyperplasia of the breast
Authors: Humphrey P. , Humphrey L. , Humphrey L. J.
Published: June 2010

Due to his recognition as the discoverer of the first test for visualization of the gallbladder, his prolific research on dissemination of cancer and his stimulation and interest in stress and immunity, one of Warren Cole's most significant reports has not been accorded due recognition. In 1944, Cole presented data at the Southern Surgical Association Meeting which clearly identified the premalignant histologic change in the breast. In the published report, Cole and Rossiter [Ann Surg 119:573–590, 1944] presented a classification of benign breast histology: 1) adenofibrosis, 2) parenchymatous hyperplasia, 3) precancerous hyperplasia, and 4) cystic disease. Following the work of Warren in 1940 [Surg Gynecol Obstet 71:257–273], who stated that the chronic cystic mastitis had an incidence of breast cancer over 3 times the expected rate, this report of Cole and Rossiter focused on the worrisome lesion atypical epithelial hyperplasia.

Since then, Haagensen [“Diseases of the Breast,” Philadelphia: Saunders] has stressed that gross cystic disease is the lesion most associated with increased risk of cancer. In an attempt to resolve these seeming contraindications, we reviewed the charts of patients referred to a private breast clinic. With the advent of mammography, sonography, and thermography, the incidence and management of benign breast diseases has changed over the years. This study focuses on the current management of breast masses and reinforces the significance of Cole's classification.
Intravenous hyperalimentation as nutritional support for the cancer patient—an update
Authors: Rumley Thomas O. , Copeland Edward M.
Published: June 2010

Debilitating cancer cachexia is multifactorial, but many of the etiologies and most of the resulting effects are similar to those seen in malnourished patients without cancer. From the work in human beings and experimental animals, nutritional support of the tumor‐bearing host can replenish lean body mass, visceral protein components, and immunocompetence. This induction of anabolism, however, depends on time, content, the method of administration of hyperalimentation solutions; the initial and continuing catabolic response of the patient, as well as the degree of initial malnutrition; the energy expenditure of the patient required during oncologic therapy; and the expertise of the physician administering nutritional support. Increased tumor stimulation resulting from intravenous hyperalimentation (IVH) has never been observed in humans; the stimulatory effects of IVH on animal tumor systems have been identified only in previously depleted animals, and then growth rates have not been out of proportion to that of the host or to that of otherwise healthy animals. Animal data suggest that tumor growth characteristics can be affected by nutritional state and the exact substrates administered, ie, amino acids, carbohydrates, or fat. Further evidence suggests that the apparent enhanced tumor growth can be used to increase responsiveness to cell cycle‐specific chemotherapeutic agents during nutritional repletion. Current evidence supports the use of intravenous hyperalimentation in malnourished cancer patients who have effective oncologic therapeutic options; such patients should not be denied these options simply on the basis of severe nutritional cachexia.
Serum CA 12‐5 concentrations and CA 12‐5/CEA ratios in patients with epithelial ovarian cancer
Authors: Buamah Paul K. , Rake Mark O. , Drake Shirley R. , Skillen Andrew W.
Published: June 2010

In attempts to increase the specificity of the CA 12‐5 test the ratio of CA 12‐5 and CEA concentrations has been determined in 155 cancer patients, all of whom had an increased serum CA 12‐5. The patients included 47 with epithelial ovarian cancer, 38 with colorectal cancer, 24 with cervical cancer, 20 with lung cancer, 17 with gastric cancer, and 9 with pancreatic cancer. The CA 12‐5/CEA ratio in serum of patients with ovarian cancer ranged from 30 to 920 (mean 251), whereas in other types of cancer the highest ratio was 240 and the mean was 13. All 47 patients with ovarian cancer, but only 7 of the 108 patients with other types of cancer, showed a CA 12‐5/CEA ratio greater than 25. About 10% of the patients with gastric or colorectal cancer but none of those with other types of cancer showed an increased ratio. As the predictive value of a CA 12‐/CEA ratio of less than 25 excluding ovarian cancer is 100%, we recommend measuring the CEA concentration in all those with increased CA 12‐5 and calculation of the CA 12‐5/CEA ratio.
Effects of intra‐arterial chemotherapy with a new lipophilic anticancer agent, estradiol‐chlorambucil (KM2210), dissolved in lipiodol on experimental liver tumor in rats
Authors: Egawa Hiroto , Maki Atsuhiko , Mori Keiichiro , Yamamoto Yuzo , Mitsuhashi Satoshi , Bannai Kenji , Asano Kiro , Ozawa Kazue
Published: June 2010

Anticancer effects and biodistribution of a new lipophilic anticancer agent, estradiol‐chlorambucil (KM2210), dissolved in lipiodol (LPD) were investigated as an intra‐arterial chemotherapy (IAC) on Walker 256 carcinosarcoma grown in the liver of 136 Wistar rats. All rats treated with KM2210 (10 mg)‐LPD survived for 90 days after administration, whereas none of the rats with LPD alone were alive for more than 19 days. Histological examination revealed that there was no viable tumor cell in the encapsulated necrotic tumor at 21 days after administration. There was no significant liver dysfunction or leukopenia due to KM2210. The biodistribution study using [l4C,3H]KM2210‐LPD solution showed that KM2210 accumulated selectively in tumor and that the tumor‐to‐normal‐liver and tumor‐to‐blood ratios were 10 and 1,000, respectively, at 21 days after administration. These results suggest that KM2210 has potential clinical application in the treatment of human liver cancer.
Synchronous, bilateral mastectomy
Authors: Staren Edgar D. , Robinson David A. , Witt Thomas R. , Economou Steven G.
Published: June 2010

Sixty‐four patients (mean age, 51 years) had mastectomies which were synchronous and bilateral. Sixty‐one premastectomy biopsies (bilateral, 34 and unilateral, 27) demonstrated the following: invasive carcinoma, 17; noninvasive carcinoma, 24; combination of above, 10; and benign disease, 10. Twenty‐two patients had bilateral mastectomy because of bilateral positive biopsy. Twenty‐nine patients with unilateral carcinoma on biopsy had bilateral mastectomy. Thirteen patients had bilateral mastectomy despite benign disease only on biopsy (10) or no biopsy (3). Ten unexpected carcinomas (34%) were found in the contralateral breast in the 29 patients with carcinoma diagnosed on unilateral biopsy. The biopsy pathology of these 10 spicemens was invasive ductal carcinoma in 1 and multifocal, noninvasive carcinoma(ductal, 3 and lobular, 6) in 9.

An unexpected carcinoma may be found in the contralateral breast in a significant number of patients who are selected for bilateral mastectomy, particularly if the selection is on the basis of a noninvasive, lobular histology. Bilateral mastectomy may be appropriate for such patients, particularly when complicated by a strong family history and breasts which are difficult to assess by physical or mammographic examination.
Flow cytometric analysis of the dna content in primary and metastatic lesions of colorectal cancer
Authors: Tomoda Hirotsugu , Inoue Tetsuya
Published: June 2010

We investigated and compared the DNA content between primary and metastatic lesions from 30 colorectal cancer cases. The findings were only diploid in 2 cases (6.7%) and only aneuploid in 18 cases (60.0%). On the whole, the DNA ploidy agreed in 20 cases (66.7%) between both lesions. In the 18 cases with only aneuploid tumors in both lesions, the DNA index tended to be larger in the metastatic lesions than in the primary lesions. In contrast, a variation in the DNA ploidy was observed in 10 cases (33.3%). These findings show that DNA ploidy tends to remain stable during metastasis in many cases of colorectal cancer, although the DNA index did tend to be larger in metastatic lesions than in primary lesions. The existence of intertumoral heterogeneity in the DNA ploidy also shows that specimens should be investigated from both lesions in order to obtain more accurate information on the tumor and its biological behavior.
Pulmonary metastasectomy for soft tissue sarcomas: Is it justified?
Authors: Frost Daniel B.
Published: June 2010

The role of pulmonary metastasectomy for metastatic soft tissue sarcomas is examined by reviewing the recent (1978‐1994) English language literature. There are no prospective studies that contain an appropriate control group, and only one retrospective study contains a matched control group. In those few studies that provide greater than 5‐year survival data, the survival curve still has a steep slope and few patients are alive at 7 years. In most studies only one or two patients are at risk at 5 years or more. Projected survival is therefore statistically questionable. It is currently impossible to know what is the impact of the surgical procedure over and above the natural history (biology) of the tumor. A randomized, prospective study, as suggested a decade ago, is still needed. While there may be some merit to pulmonary metastasectomy in highly selected patients, aggressive pulmonary metastasectomy does not seem justified by the available data.
Endoscopic injection sclerotherapy for esophageal varices associated with concomintant portal venous thrombus of hepatocellular carcinoma
Authors: Ohta Masayuki , Hashizume Makoto , Tomikawa Morimasa , Kamakura Tatsuro , Akazawa Kouhei , Ueno Kiichiro , Yamaga Hirohiko , Kitano Seigo , Tanoue Kazuo , Matsumata Takashi , Sugimachi Keizo
Published: June 2010

Between 1983 and 1994, we treated 51 patients with esophageal varices and portal trunk and main branch invasion of hepatocellular carcinoma, using endoscopic injection sclerotherapy. Variceal bleeding was controlled in 28 of 29 patients (96.6%), esophageal varices were completely eradicated in 28 (54.9%), and only 2 of 28 (7.1%) bled from small, dilated, venous vessels after eradication. The cumulative nonbleeding rate at 3 years was 87.5%. Death caused by hepatocellular carcinoma accounted for 89.4% of the patients, whereas the rate of bleeding from esophageal varices was 4.3%. Variables significantly associated with the duration of survival were Okuda's clinical stage, alpha‐fetoprotein, eradication of esophageal varices by sclerotherapy, and treatment of hepatocellular carcinoma, as determined in a univariate analysis. Multivariate analysis showed that eradication of esophageal varices by sclerotherapy, Okuda's clinical stage, and age were independent factors which significantly influenced survival time. We propose that complete eradication of esophageal varices and close follow‐up using endoscopy may lead to a reduction in bleeding from esophageal varices, and hence may reduce mortality rates related to this bleeding.
Concomitant sclerosing mesenteritis and inflammatory pseudotumor simulating gastric lymphoma or linitis plastica
Authors: Gincherman Yevgeniy , Langer Jille E. , Miller Leonard
Published: June 2010

Both inflammatory pseudotumours and sclerosing (retractile) mesenteritis are uncommon conditions of unknown origin. A number of authors have reported patients presenting with complaints that were attributed to one or the other of these entities. In our review of the literature, we were unable to find a single case report of mixed abdominal findings that could be explained by the presence of both conditions. We report a case of the patient presenting with abdominal mass that was identified as having features of both sclerosing mesenteritis and inflammatory pseudotumor on pathologic diagnosis.
Spindle cell tuor of the portal vein
Authors: Madariaga Juan R. , Nalesnik Michael A. , Iwatsuki Shunzaburo , Starzl Thomas E. , Fung John J.
Published: June 2010

The authors describe the first reported case of spindle cell tumor of the portal vein (SCTPV) surgically excised in a 28‐year‐old woman. The tumor had caused portal vein obstruction with extensive collaterals. A side‐to‐side mesocaval shunt was created to reduce portal hypertension. Six months later the SCTPV could be excised. Radiation therapy (4,500 cGY) was given 2 months later. Although the tumor recurred in the liver 4 years later, the patient is alive and free of symptoms 6 years after the initial diagnosis. © 1995 Wiley‐Liss, Inc.
Application of nanofiber‐packed SPE for determination of salivary‐free cortisol using fluorescence precolumn derivatization and HPLC detection
Authors: Chen Li‐Qin , Kang Xue‐Jun , Sun Jing , Deng Jian‐Jun , Gu Zhong‐Ze , Lu Zu‐Hong
Published: June 2010

Salivary cortisol has emerged as an easy‐to‐collect biologic marker of stress in many researches. In this study, we present a method for the determination of salivary‐free cortisol using HPLC method with fluorescence precolumn derivatization, which is based on a novel extraction from the strongly acidic medium (fluorescent derivatives of cortisol in sulfuric acid medium) by electrospun polystyrene nanofibers packed SPE. For high‐throughput sample extraction, an array pretreatment device based on nanofibers packed SPE micro‐column was designed. The LOD of cortisol was 0.01 μg/L (S/N=3). The RSDs (n=6) for all analytes were below 8.0%, and the recoveries were 110, 102.4, and 99.4% (n=3) for saliva spiked with 0.1, 10, and 20 μg/L of cortisol, respectively. The proposed method was then successfully applied in the determination of free cortisol in human saliva. The salivary cortisol concentrations in the real samples ranged from 0.22 to 7.45 μg/L. The nanofiber‐packed SPE overcame the low extraction recovery and bad clean‐up effect of the conventional methods, and increased the sensitivity and selectivity of the method.
Denaturing capillary electrophoresis for automated detection of L858R mutation in exon 21 of the epidermal growth factor receptor gene in prediction of the outcome of lung cancer therapy
Authors: Benesova Lucie , Pesek Milos , Belsanova Barbora , Sekerka Patrik , Minarik Marek
Published: June 2010

The presence of activating mutations within the tyrosine kinase domain of the epidermal growth factor receptor gene has been attributed to a positive response to biological therapy of lung cancer by small‐molecular tyrosine kinase inhibitors, gefitinib and erlotinib. Among the two most significant mutation types are deletions in exon 19 and a single point substitution in exon 21 (termed L858R). The exon 19 deletions can readily be examined by fragment analysis, due to the characteristic length difference between the normal and mutated PCR product. Analysis of the L858R point mutation, however, presents a greater challenge. The current paper is aimed at developing a sensitive, yet simple, low‐cost mutation detection assay directed at the L858R mutation using a method based on CE of heteroduplexes under partial denaturing conditions. We perform optimization of separation conditions on different commercial instruments including ones equipped with 8, 16 and 96 capillaries. We present normalized migration reproducibility in the range from 1 (8 and 16) to 5% (96) RSD. A reliable distinction of the R836R silent polymorphism from a potential presence of the L858R mutation is also demonstrated. In its implementation, the presented assay is just another application running on a conventional CE platform without the need of dedicated instrumentation.
HPLC‐PAD‐atmospheric pressure chemical ionization‐MS metabolite profiling of cytotoxic carotenoids from the echinoderm Marthasterias glacialis (spiny sea‐star)
Authors: Ferreres Federico , Pereira David M. , Gil‐Izquierdo Angel , Valentão Patrícia , Botelho João , Mouga Teresa , Andrade Paula B.
Published: June 2010

An HPLC‐PAD‐atmospheric pressure chemical ionization‐MS metabolite profiling analysis was conducted on the marine echinoderm Marthasterias glacialis (spiny sea‐star). Bio‐guided purification of the methanolic extract led to the isolation of several carotenoids, namely zeaxanthin, astaxanthin and lutein. These compounds were characterized using both UV–Vis characteristics and MS spectra interpretation. No previous works addressed the MS analysis of carotenoids present in this organism. The purified carotenoid fraction displayed a strong cell proliferation inhibition against rat basophilic leukemia RBL‐2H3 (IC25=268 μg/mL) cancer cell line. Against healthy V79 (rat lung fibroblasts (IC25=411 μg/mL)) cell line, however, toxicity was lower, as it is desired for anti‐cancer molecules. This study suggests that M. glacialis may constitute a good source of bioactive compounds that can be used as lead compounds for the pharmaceutical industry.
Efficient isolation and purification of five products from microbial biotransformation of cinobufagin by high‐speed counter‐current chromatography
Authors: Ma Xiao‐Chi , Xin Xiulan , Zhang Bao‐jing , Deng Sha , Yao Ji‐hong , Wang Chang‐yuan , Cui Jian , Tian Yan , Liu Ke‐xin
Published: June 2010

An efficient separation method of using high‐speed counter‐current chromatography was successfully established to directly purify cytotoxic transformed products of cinobufagin byCordyceps militaris. The two‐phase solvent system composed ofn‐hexane–ethyl acetate–methanol–water (4:6:3:4, v/v) was used in high‐speed counter‐current chromatography. A total of 9 mg of 4β,12α‐dihydroxyl‐cinobufagin (1), 15 mg of 12β‐hydroxyl‐cinobufagin (2), 8 mg of 5β‐hydroxyl‐cinobufagin (3), 12 mg of deacetylcinobufagin (4) and 6 mg of 3‐keto‐cinobufagin (5) were obtained in a one‐step separation from 400 mg of the crude extract with purity of 98.7, 97.2, 90.6, 99.1 and 99.4%, respectively, as determined by HPLC. Their chemical structures were identified on the basis of1H‐NMR and13C‐NMR technology. All products (1–5) showed the potent activities against human carcinoma cervicis (Hela) and malignant melanoma (A375) cellsin vitro.
A technique for detecting GABA in the human brain with PRESS localization and optimized refocusing spectral editing radiofrequency pulses
Authors: Keltner John R. , Wald Lawrence L. , Christensen James D. , Maas Luis C. , Moore Constance M. , Cohen Bruce M. , Renshaw Perry F.
Published: June 2010

A proton magnetic resonance spectral editing technique is presented that uses PRESS excitation to achieve spatially localized measurements of brain gamma‐aminobutyric acid (GABA). The homonuclear difference spectroscopy technique employs a frequency selective inversion pulse to suppress the creatine resonance at 3.0 ppm. The timing of this pulse is optimized to maximize the suppression of creatine by minimizing the effect of the editing pulse on the 3.0 ppm resonances. The PRESS excitation achieves three dimensional spatial localization in a single acquisition making it less sensitive to patient motion than multiple acquisition techniques. The performance and utility of this technique were evaluated by phantom experiments and by in vivo measurements of brain GABA concentration in 10 normal subjects.
Comparison of k‐space sampling schemes for multidimensional MR spectroscopic imaging
Authors: Hugg James W. , Maudsley Andrew A. , Weiner Michael W. , Matson Gerald B.
Published: June 2010

For clinical 31P MR spectroscopic imaging (MRSI) studies, where signal averaging is necessary, some improvement of sensitivity and spatial response function may be achieved by acquiring data over a spherical k‐space volume and varying the number of averages acquired in proportion to the desired spatial filter. Eight different k‐space sampling schemes are compared through simulations that provide graphs of the spatial response functions (SRF), and tabulations of voxel volumes, relative signal‐to‐noise ratios (SNR), and relative data collection efficiencies (SNR per unit volume over the same time). All schemes were based on practical experiments, each of which could be implemented in the same length of time. The results show that in comparison with cubic k‐space sampling with the same number of signal averages at each point, spherical and acquisition‐weighted k‐space sampling can be used to achieve reduced Gibbs ringing along the principal axes directions, and thus reduced contamination from adjacent tissue in these directions, without degradation of voxel volume or SNR.
Power efficient on‐resonance saturation pulses for magnetization transfer in magnetic resonance imaging
Authors: Mao Jintong , Ballinger J. Ray
Published: June 2010

A family of new on‐resonance saturation pulses for magnetization transfer in MRI is proposed. These pulses can be represented as a product of a shaped function and a cosine function. The shaped function can have many different forms, one of which is a Gaussian function. The experimental results on a 1.0 T whole body scanner show that the new on‐resonance pulses are more efficient for magnetization transfer than either on‐resonance binomial sequence pulses or offresonance Gaussian pulses at the same power level.
Practical implementation of single‐voxel double‐quantum editing on a whole‐body NMR spectrometer: Localized monitoring of lactate in the human leg during and after exercise
Authors: Jouvensal Laurence , Carlier Pierre G. , Bloch Gilles
Published: June 2010

The classical double‐quantum editing sequence 90°x‐τ−180°y‐τ−90°x‐t1−90°x‐τ−180°y‐τ‐AQ (τ = 1/4J) was rendered volume selective, by making slice selective the first 90° pulse and the two 180° pulses. Using simple rules to ensure optimum radio frequency phase coherence, this single‐voxel editing sequence, reminiscent of a basic PRESS localization technique, was implemented on a whole‐body 3 T spectrometer, and in vitro editing of lactate methyl protons was demonstrated without any significant loss in intrinsic sensitivity. The effectiveness of the proposed approach in vivo was also illustrated through the localized monitoring of lactate in the human leg during and after exercise.
Reduction of errors in ASL cerebral perfusion and arterial transit time maps using image de‐noising
Authors: Wells Jack A. , Thomas David L. , King Martin D. , Connelly Alan , Lythgoe Mark F. , Calamante Fernando
Published: June 2010

In this work, the performance of image de‐noising techniques for reducing errors in arterial spin labeling cerebral blood flow and arterial transit time estimates is investigated. Simulations were used to show that the established arterial spin labeling cerebral blood flow quantification method exhibits the bias behavior common to nonlinear model estimates, and as a result, the reduction of random errors using image de‐noising can improve accuracy. To assess the effect on precision, multiple arterial spin labeling data sets acquired from the rat brain were processed using a variety of common de‐noising methods (Wiener filter, anisotropic diffusion filter, gaussian filter, wavelet decomposition, and independent component analyses). The various de‐noising schemes were also applied to human arterial spin labeling data to assess the possible extent of structure degradation due to excessive spatial smoothing. The animal experiments and simulated data show that noise reduction methods can suppress both random and systematic errors, improving both the precision and accuracy of cerebral blood flow measurements and the precision of transit time maps. A number of these methods (and particularly independent component analysis) were shown to achieve this aim without compromising image contrast. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
Three‐dimensional ultrasound in evaluating the fetus
Authors: Dückelmann Anna M. , Kalache Karim D.
Published: June 2010

In recent years three‐dimensional (3D) ultrasound has made a place in clinical practice and has become a major field of research in obstetrics. In this article we will review the diagnostic performance of the most widely used 3D ultrasound applications in the assessment of fetal anomalies, explain the technique to gain correct 3D images and offer some practical advice for their efficient use. Examples are given to demonstrate the applicability and vividness of 3D in daily routine. Copyright © 2010 John Wiley & Sons, Ltd.
NMR and crystallographic structures of the FK506 binding domain of human malarial parasite Plasmodium vivax FKBP35
Authors: Alag Reema , Qureshi Insaf A. , Bharatham Nagakumar , Shin Joon , Lescar Julien , Yoon Ho Sup
Published: June 2010

The emergence of drug‐resistant malaria parasites is the major threat to effective malaria control, prompting a search for novel compounds with mechanisms of action that are different from the traditionally used drugs. The immunosuppressive drug FK506 shows an antimalarial activity. The mechanism of the drug action involves the molecular interaction with the parasite target proteins PfFKBP35 and PvFKBP35, which are novel FK506 binding protein family (FKBP) members from Plasmodium falciparum and Plasmodium vivax, respectively. Currently, molecular mechanisms of the FKBP family proteins in the parasites still remain elusive. To understand their functions, here we have determined the structures of the FK506 binding domain of Plasmodium vivax (PvFKBD) in unliganded form by NMR spectroscopy and in complex with FK506 by X‐ray crystallography. We found out that PvFKBP35 exhibits a canonical FKBD fold and shares kinetic profiles similar to those of PfFKBP35, the homologous protein in P. falciparum, indicating that the parasite FKBP family members play similar biological roles in their life cycles. Despite the similarity, differences were observed in the ligand binding modes between PvFKBD and HsFKBP12, a human FKBP homolog, which could provide insightful information into designing selective antimalarial drug against the parasites.
Interaction of an ionic complementary peptide with a hydrophobic graphite surface
Authors: Sheng Yuebiao , Wang Wei , Chen P.
Published: June 2010

Protein adsorption on a surface plays an important role in biomaterial science and medicine. It is strongly related to the interaction between the protein residues and the surface. Here we report all‐atom molecular dynamics simulations of the adsorption of an ionic complementary peptide, EAK16‐II, to the hydrophobic highly ordered pyrolytic graphite surface. We find that, the hydrophobic interaction is the main force to govern the adsorption, and the peptide interchain electrostatic interaction affects the adsorption rate. Under neutral pH condition, the interchain electrostatic attraction facilitates the adsorption, whereas under acidic and basic conditions, because of the protonation and deprotonation of glutamic acid and lysine residues, respectively, the resulting electrostatic repulsion slows down the adsorption. We also found that under basic condition, during the adsorption peptide Chain II will be up against a choice to adsorb to the surface through the hydrophobic interaction or to form a temporary hydrophobic core with the deposited peptide Chain I. These results provide a basis for understanding some of the fundamental interactions governing peptide adsorption on the surface, which can shed new light on novel applications, such as the design of implant devices and drug delivery materials.
The Total Chemical Synthesis of Monocyte Chemotactic Protein‐1 (MCP‐1)
Authors: Brown Angus R. , Covington Maryanne , Newton Robert C. , Ramage Robert , Welch Patricia
Published: June 2010

The affinity‐based Nα‐amino protecting group tetrabenzo [a,c,g,i]fluorenyl‐17‐methoxycarbonyl (Tbfmoc) has been utilized as a hydrophobic probe to allow the simple, quick and highly effective isolation of a 76 residue cysteine‐containing protein (MCP‐1). The base‐labile Tbfmoc group can be removed under very mild conditions, which preserve the thiol‐con taining protein in the reduced state. Oxidative folding was then used to furnish the biologically active β‐chemokine MCP‐1.
310‐Helices, Helix Screw Sense and Screw Sense Reversal in the Dehydro‐peptide Boc‐Val‐ΔPhe‐Gly‐ΔPhe‐Val‐OMe
Authors: Tuzi Angela , Rosaria Ciajolo M. , Picone Delia , Crescenzi Orlando , Temussi Pier Andrea , Fissi Adriano , Pieroni Osvaldo
Published: June 2010

The pentapeptide Boc‐Val‐ΔPhe‐Gly‐ΔPhe‐Val‐OMe, containing two dehydro‐phenylalanine (ΔPhe) residues, has been synthesized and its structure investigated. In the crystalline state, the molecule adopts a right‐handed 310‐helical conformation stabilized by two intramolecular hydrogen bonds between CO of Val1 and NH of ΔPhe4, and between CO of ΔPhe2 and NH of Val5, respectively. NMR measurements are consistent with the presence of 310‐helical structures also in acetonitrile and dimethylsulphoxide solution: the distances between backbone protons estimated from NOE connectivities are in overall agreement with those observed in the solid state; the chemical shifts of the amide protons show the smaller temperature coefficients for the NHs that in solid state are involved in intramolecular hydrogen bonds. The CD spectra in acetonitrile, chloroform, methanol and dimethylsulphoxide display exciton couplets of bands corresponding to the ΔPhe electronic transition at 280nm; the sign of the bands is consistent with the presence of helical structures having a prevalent left‐handed screw sense. Addition of 1,1,1,3,3,3‐hexafluoro‐ propan‐2‐ol gives rise to the gradual appearance of a couplet of opposite sign, suggesting the helix reversal from left‐handed sense to right‐handed sense. The conformational behaviour is discussed on the basis of the specific sequence of the peptide.
Excitonic precursor states in ultrafast pump–probe spectroscopies of surface bands
Authors: Gumhalter Branko , Lazić Predrag , Došlić Nadja
Published: June 2010

We discuss the formation and evolution of transient coherent excitonic states induced by ultrashort laser irradiation of metal surfaces supporting the surface and image potential bands (typically the low index surfaces of Cu and Ag). These states, which evolve into the image potential states in the course of screening of primary optically excited electron–hole pair, may play the role of early intermediate states in pump–probe spectroscopies of surfaces (e.g. two‐photon‐photoemission or sum‐frequency generation) if the formation of image charge density proceeds on the time scale of the order of or longer than the pump–probe pulse duration and delay. In this regime a pump–probe experiment may yield information on the characteristics of such states rather than the states in relaxed image potential bands. Time scales of the various stages of these processes are estimated using an exactly solvable model of surface screening.
Influence of the Mn concentration on the electromechanical response d33 of Mn‐doped ZnO films
Authors: Luo J. T. , Zhu X. Y. , Chen G. , Zeng F. , Pan F.
Published: June 2010

The influence of Mn concentration on the electromechanical response d33 of Mn‐doped ZnO films has been investigated. It is found that d33 decreases slightly with the increase of Mn concentration until 4.8 at%, and then increases rapidly with Mn concentration increasing further. The maximum d33 value of ∼86 pC/N is obtained in Zn0.913Mn0.087O films. When the Mn concentration exceeds 8.7 at%, d33 turns to decrease. We suggest that Mn valence and ionic size in Mn‐doped ZnO films play important roles in the electromechanical response. The improved piezoelectric properties could make Mn‐doped ZnO a promising candidate for piezoelectric devices. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Neural network‐based adaptive dynamic surface control of uncertain nonlinear pure‐feedback systems
Authors: Wang Dan
Published: June 2010

In this paper, by incorporating the dynamic surface control technique into a neural network‐based adaptive control design framework, we have developed a backstepping‐based control design for a class of nonlinear systems in pure‐feedback form with arbitrary uncertainty. The circular design problem which may exist in pure‐feedback systems is overcome. In addition, our development is able to eliminate the problem of ‘explosion of complexity’ inherent in the existing backstepping‐based methods. A stability analysis is given, which shows that our control law can guarantee the semi‐global uniformly ultimate boundedness of the solution of the closed‐loop system, and makes the tracking error arbitrarily small. Moreover, the proposed control design scheme can also be directly applied to the strict‐feedback nonlinear systems with arbitrary uncertainty. Copyright © 2010 John Wiley & Sons, Ltd.
Closed‐loop input shaping control of vibration in flexible structures using discrete‐time sliding mode
Authors: Pai Ming‐Chang
Published: June 2010

Input shaping technique is widely used in reducing or eliminating residual vibration of flexible structures. It is easy to implement and achieve the exact elimination of the residual vibration if the dynamics of the system are known accurately. However, it is not very robust to parameter uncertainties and external disturbances. In this paper, a closed‐loop input shaping method is developed for reducing or eliminating residual vibration of flexible structure systems with parameter uncertainties and external disturbances. The algorithm is based on input shaping control and discrete‐time sliding mode control. It is shown that the proposed scheme guarantees closed‐loop system stability, and yields good performance and robustness in the presence of parameter uncertainties and external disturbances as well. The selection of switching surface and the existence of sliding mode are two important issues, which have been addressed. The knowledge of upper bound of uncertainties is not required. Furthermore, it is shown that increasing the robustness to parameter uncertainties does not lengthen the duration of the impulse sequence. Simulation results demonstrate the efficacy of the proposed closed‐loop input shaping control scheme. Copyright © 2010 John Wiley & Sons, Ltd.
First language acquisition
Authors: Goodluck Helen
Published: June 2010

This article reviews current approaches to first language acquisition, arguing in favor of the theory that attributes to the child an innate knowledge of universal grammar. Such knowledge can accommodate the systematic nature of children's non‐adult linguistic behaviors. The relationships between performance devices (mechanisms for comprehension and production of speech), non‐linguistic aspects of cognition, and child grammars are also discussed.WIREs Cogn Sci2011 2 47–54 DOI: 10.1002/wcs.95

This article is categorized under:

Linguistics > Language Acquisition