bluuebunny/crossref_metadata_2025 huggingface dataset:
Metastatic breast carcinoma involving the thyroid gland diagnosed by fine‐needle aspiration: A case report
Authors: Owens Christopher L. , Basaria Shezad , Nicol Theresa L.
Published: July 2005

Secondary involvement of the thyroid gland from a remote primary malignancy is uncommon. The distinction of metastatic carcinoma (MC) or sarcoma from a primary thyroid malignancy is important because the treatment is different. We discuss a case of a 64‐yr‐old female with a history of breast carcinoma, who presented with pain and swelling in her neck 5 yrs after being diagnosed with breast cancer. She had undergone mastectomy with subsequent chemotherapy and radiation for infiltrating mammary carcinoma. During the 5‐yr interval, she had been free of clinically evident metastatic disease. Subsequent work‐up revealed two distinct nodules in the left lobe of her thyroid gland as well as a subcutaneous mass in her right shoulder. A fine‐needle aspiration (FNA) of the larger thyroid nodule showed malignant epithelial cells with features consistent with breast carcinoma in a background of benign thyroid epithelial cells and colloid. The case was signed out as metastatic breast carcinoma. Subsequent FNA and biopsy of her right shoulder lesion also revealed metastatic breast carcinoma with similar morphology to the material in the thyroid FNA. Diagn. Cytopathol. 2005;33;110–115. © 2005 Wiley‐Liss, Inc.
HPV DNA testing in the triage of atypical squamous cells of undetermined significance (ASCUS): Cost comparison of two methods
Authors: Layfield Lester J. , Qureshi M. Nasar
Published: July 2005

Human papillomavirus (HPV) DNA testing for triage of cervical cytologies showing atypical squamous cells of undetermined significance (ASCUS) has become the standard of practice. Currently, Hybrid Capture II® (HCII®) is the preferred method for ASCUS triage. In situ hybridization for HPV represents an alternative to HCII and appears to have a superior specificity but is more expensive.

We compare the reimbursement rates of ASCUS triage (HPV high risk) using the methods of HCII and INFORM® (in situ hybridization for HPV) in a series of 431 ASCUS patients. The patients were followed for 1 yr, during which each patient had either colposcopic biopsy or follow‐up cervical cytology after ASCUS HPV DNA triage. Eighty‐nine patients were excluded from the analysis because of incomplete follow‐up. The HPV triage percentages, colposcopic biopsy positivity rates and cervical cytology positivity percentages were calculated for each method. The reimbursement rates of the tests/procedures used in the analysis were those in effect at the University of Utah in 2003. The total triage and follow‐up reimbursement costs were calculated for HCII and INFORM and compared.

HCII referred 19.9% of patients to colposcopy, with a biopsy positivity rate of 25.6% for dysplasia. INFORM referred 11.8% of patients to colposcopy, of whom 34% had a biopsy diagnosis of dysplasia. HCII negative cases revealed 19% to have ASCUS or higher on the follow‐up cervical cytology, while 19.9% of INFORM negative cases had a reading of ASCUS or higher at follow‐up cytologic examination. The 1‐yr HPV DNA triage and follow‐up reimbursements for HCII were $316,942.00 per 1,000 women, and for the INFORM methodology, the reimbursements were $369,484.00 per 1,000 women. The INFORM method was associated with higher specificity and sent fewer (41%) patients to colposcopy than did HCII. Although this smaller referral rate reduced reimbursement costs associated with colposcopy, the increased reimbursement paid for follow‐up cytologies and office visits of HPV DNA negative patient and the greater cost of the INFORM test results in higher overall reimbursement for INFORM.

Based on these costs and diagnostic accuracies, it appears that the INFORM HPV technology represents a viable option to HCII ASCUS triage. INFORM HPV appears to be 16% more expensive than HCII but has the advantage of sending 41% fewer women to colposcopy. Diagn. Cytopathol. 2005;33:138–143. © 2005 Wiley‐Liss, Inc.
Algorithm for cytological diagnosis of nonneoplastic lesions of the salivary glands
Authors: Malhotra Purnima , Arora Vinod K. , Singh Navjeevan , Bhatia Arati
Published: July 2005

The aim of this study was to formulate an algorithm for the cytologic diagnosis of nonneoplastic enlargements of the salivary gland.

Smear cellularity and cytological features such as presence of epithelial cells and types of inflammation were assessed in a retrospective study of 201 aspirates. One hundred and forty‐six were inflammatory, 19 were noninflammatory nonneoplastic, and 36 were cystic lesions.

Of the cystic lesions, cytological evidence of retention cyst was seen in seven, while two aspirates with only hemosiderin‐laden macrophages were hematomas. The remaining 27 defied subclassification. Noninflammatorynonneoplastic lesions included 5 fatty infiltrations, 2 sialadenosis, and 12 normal salivary glands. Forty‐two lesions were acute inflammations, 89 were chronic, and 15 were granulomatous. Cytomorphologic patterns identified in samples with acute inflammation were 9 abscesses, 29 acute obstructive sialadenitis, and 4 acute infective sialadenitis. Three aspirates with chronic inflammation were lymphoepithelial lesions, 82 chronic sialadenitis, and 4 lymph node in salivary gland. Fifteen granulomatous lesions were 10 tuberculosis, 3 sarcoidosis, and 2 foreign body granulomas. Using the proposed algorithmic approach, nonneoplastic salivary gland enlargement could be placed into distinct, clinically relevant diagnostic categories. Diagn. Cytopathol. 2005;33:90–94. © 2005 Wiley‐Liss, Inc.
Impact of a rock avalanche on a moraine‐dammed proglacial lake: Laguna Safuna Alta, Cordillera Blanca, Peru
Authors: Hubbard Bryn , Heald Andrew , Reynolds John M. , Quincey Duncan , Richardson Shaun D. , Luyo Marco Zapata , Portilla Nelson Santillan , Hambrey Michael J.
Published: July 2005

Moraines that dam proglacial lakes pose an increasing hazard to communities in the Andes and other mountain ranges. The moraines are prone to failure through collapse, overtopping by lake waters or the effect of displacement waves resulting from ice and rock avalanches. Resulting floods have led to the loss of thousands of lives in the Cordillera Blanca mountains of Peru alone in the last 100 years. On 22 April 2002 a rock avalanche occurred immediately to the south‐west of Laguna Safuna Alta, in the Cordillera Blanca. The geomorphic evidence for the nature, magnitude and consequences of this event was investigated in August 2002. Field mapping indicated that the avalanche deposited 8–20 × 106 m3 of rock into the lake and onto the surface of the frontal region of Glaciar Pucajirca, which flows into the lake. Repeated bathymetric surveying indicated that ∼5 × 106 m3 of this material was deposited directly into the lake. The immediate effect of this event was to create a displacement wave that gained in height as it travelled along the lake basin, overtopping the impounding moraine at the lake's northern end. To achieve overtopping, the maximum wave height must have been greater than 100 m. This, and subsequent seiche waves, caused extensive erosion of both the proximal and distal faces of the impounding terminal moraine. Further deep gullying of the distal face of this moraine resulted from the supply of pressurized water to the face via a relief overflow tunnel constructed in 1978. Two‐dimensional, steady‐state analysis of the stability of the post‐avalanche moraine rampart indicates that its proximal face remains susceptible to major large‐scale rotational failure. Copyright © 2005 John Wiley & Sons, Ltd.
Elevated protein carbonylation in the brain white matter and gray matter of patients with multiple sclerosis
Authors: Bizzozero Oscar A. , DeJesus Gisela , Callahan Kelly , Pastuszyn Andrzej
Published: July 2005

Oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). Increased levels of reactive oxygen species (ROS) derived from infiltrating macrophages and microglial cells have been shown to reduce the levels of endogenous antioxidants and to cause the oxidation of various substrates within the MS plaque. To determine whether oxidative damage takes place beyond visible MS plaques, the occurrence of total carbonyls (TCOs) and protein carbonyls (PCOs) in the normal‐appearing white matter (NAWM) and gray matter (NAGM) of eight MS brains was assessed and compared with those of four control brains. The data show that most (7/8) of the MS‐WM samples contain increased amounts of PCOs as determined by reaction with 2,4‐dinitrophenylhydrazine and Western blot analysis. These samples also have high levels of glial fibrilary acidic protein (GFAP), suggesting that oxidative damage is related to the presence of small lesions. In contrast, we detected no evidence of protein thiolation (glutathionylation and cysteinylation) in the diseased tissue. To our surprise, MS‐NAGM specimens with high GFAP content also showed three times the concentration of TCOs and PCOs as the controls. The increase in PCOs is likely to be a consequence of reduced levels of antioxidants, in that the concentration of nonprotein thiols in both MS‐WM and ‐GM decreased by 30%. Overall, our data support the current view that both NAWM and ‐GM from MS brains contain considerable biochemical alterations. The involvement of GM in MS was also supported by the decrease in the levels of neurofilament light protein in all the specimens analyzed. To the best of our knowledge, this is the first study demonstrating the presence of increased protein carbonylation in post‐mortem WM and GM tissue of MS patients. © 2005 Wiley‐Liss, Inc.
Univariate and multivariate analysis of prognostic significance of betel quid chewing in squamous cell carcinoma of buccal mucosa in Taiwan
Authors: Lee Jang‐Jaer , Jeng Jiiang‐Huei , Wang Hsiao‐Mei , Chang Hao‐Hueng , Chiang Chun‐Pin , Kuo Ying‐Shiung , Lan Wan‐Hong , Kok Sang‐Heng
Published: July 2005

Background and Objectives

While betel quid (BQ) chewing is clearly the most avoidable risk factor of squamous cell carcinoma of buccal mucosa (BMSCC), little is known about the influence of this habit on the prognosis of BMSCC.

Methods

We surveyed 280 patients with BMSCC who were treated during an 8‐year period in a cohort study to assess the independent predictive value of pretreatment BQ chewing habit on the prognosis by univariate and multivariate analysis.

Results

We found by univariate analysis that sex, age, clinical stage, smoking, and BQ chewing significantly affected the patients' prognosis and only age, clinical stage, and BQ chewing had significant influence on prognosis by multivariate analysis (P < 0.05). Further analysis revealed that the prognostic effect of BQ chewing changed in a dose‐ and time‐dependent manner. The risk of death was 31.4‐fold higher in heavy user (duration >30 years, daily consumption >30 quids, age of start <20 years old) when compared to those who chewed BQ to a milder degree (duration <10 years, daily consumption <15 quids, age of start ≥20 years old ) (P < 0.001).

Conclusions

Pretreatment BQ chewing habit worsens the prognosis of BMSCC in Taiwan. BQ chewing is a prognostic indicator that can be used in conjunction with clinical staging to help plan the treatment for the patients. J. Surg. Oncol. 2005;91:41–47. © 2005 Wiley‐Liss, Inc.
The significance of autophagy in cancer
Authors: Ng Grace , Huang Jingxiang
Published: July 2005

Autophagy, a vacuolar process of cytoplasmic degradation, is implicated in a form of programmed cell death distinct from apoptosis. The regulation of autophagy is complex and signalling pathways such as the target of rapamycin (Tor) kinase pathway, play important roles in tumourigenesis. Beclin 1, an autophagic protein, has been found to be a tumour suppressor. Conversely, cancer cells may exploit autophagy as a means to adapt to hypoxic and nutrient‐limiting environments. The relative importance of autophagic cell death and apoptosis in carcinogenesis remains to be established, and the Bcl‐2 family of proteins may be instrumental in coordinating the two pathways of programmed cell death. © 2005 Wiley‐Liss, Inc.
Is sphincter electromyography a helpful investigation in the diagnosis of multiple system atrophy? A retrospective study with pathological diagnosis
Authors: Paviour Dominic C. , Williams David , Fowler Clare J. , Quinn Niall P. , Lees Andrew J.
Published: July 2005

Sphincter electromyography (spEMG) is often used as an ancillary test when multiple system atrophy (MSA) is suspected. Our aim was to determine the clinical features associated with spEMG being performed, the influence of the result on the final clinical diagnosis, and its utility as a clinical investigation. A retrospective audit of all cases in the Queen Square Brain Bank between 1989 and 2002 was performed. The clinical features and diagnostic accuracy were compared between patients in whom spEMG was performed and those in whom it was not. From 845 sets of complete clinical records, we identified 37 (4.4%) cases that had been investigated with spEMG. Thirty of these cases had a pathological diagnosis of MSA. Of these 30, 24 had abnormal spEMGs, 5 had a borderline result, and only 1 had a normal spEMG. Sixty‐six cases had pathologically proven MSA but no spEMG. Those investigated with spEMG were younger at disease onset (P < 0.001), more frequently male (P = 0.03), and more likely to have had other investigations performed. They had a greater incidence of pyramidal tract signs at final clinical diagnosis, and the final clinical diagnostic accuracy was higher (P = 0.04). Due to the retrospective nature of the study, balanced populations for calculation of sensitivity and specificity were not available. In this selected series of pathologically confirmed cases, investigation with spEMG was one of several factors associated with improved clinical diagnostic accuracy. A normal spEMG is unlikely in pathologically proven MSA, at least in cases with a mean symptom duration of more than 5 years when the test is performed. © 2005 Movement Disorder Society
Corticobasal degeneration and Parkinson's disease assessed by HmPaO SPECT: The utility of factorial discriminant analysis
Authors: Kreisler Alexandre , Defebvre Luc , Lecouffe Pascal , Duhamel Alain , Charpentier Pierre , Steinling Marc , Destée Alain
Published: July 2005

The diagnosis of corticobasal degeneration (CBD) is difficult despite the existence of some typical clinical features. Single photon emission computerized tomography (SPECT) in CBD presents an original pattern (with asymmetric hypoperfusion in pre‐ and retrorolandic regions) that could facilitate the differential diagnosis of CBD relative to the other degenerative parkinsonian syndromes. The objective of our study was to compare the regional cerebral blood flow measurements studied by SPECT in both CBD and Parkinson's disease (PD) using a multivariate procedure. Twenty‐one patients with probable CBD and 20 patients with probable PD underwent brain 99mTc HmPaO SPECT. We used factorial discriminant analysis (FDA) to study the relative fixation of 26 regions of interest (ROIs) drawn on two transverse slices, together with the asymmetry indexes of 13 pairs of ROIs. FDA performed using the full set of parameters classified all the patients correctly. In order to classify the patients more easily, a predictive score using a selection of parameters was established. The most discriminating ROIs were the temporoinsular, temporoparietal, and frontal medial regions. We believe that this semiautomatic classification may be a precious tool for reinforcing the current clinical differential diagnosis of CBD and PD. © 2005 Movement Disorder Society
Nondopaminergic mechanisms in levodopa‐induced dyskinesia
Authors: Brotchie Jonathan M.
Published: July 2005

It has become increasingly apparent that Parkinson's disease involves many transmitter systems other than dopamine. This nondopaminergic involvement impacts on the generation of symptoms, on the neurodegenerative process, but, most tellingly, in the generation of side effects of current treatments, in particular, levodopa‐induced dyskinesia (LID). Such mechanisms contribute not only to the expression of LID once it has been established but also to the mechanisms responsible for the development, or priming, of the dyskinetic state and the subsequent maintenance of the brain in that primed state. Within the basal ganglia, abnormalities in different nondopaminergic components of the circuitry have been defined in LID. In particular, a role for enhanced inhibition of basal ganglia outputs by the GABAergic direct pathway has been suggested as a basic mechanism generating LID. We speculate that the external globus pallidus and subthalamic nucleus may play distinct roles in different forms of dyskinesia, e.g., chorea/dystonia; peak/diphasic/off. At the cellular level, an appreciation of abnormal signaling by, among others, glutamatergic (NMDA and AMPA receptors in particular), α2 adrenergic, serotonergic (5HT), cannabinoid and opioid mechanisms in both priming and expression of LID has begun to emerge over the last decade. This is being consolidated, though in many cases questions remain regarding the specific sites of such abnormality within the circuitry. Very recently, at the molecular level, mechanisms controlling neurotransmitter release and impacting on the ability of neurons to maintain particular forms of firing patterning and synchronization, e.g., SV2A, have been identified. This increased understanding has already delivered and will continue to define novel approaches to treatment that target both pre‐ and postsynaptic signaling molecules throughout the basal ganglia circuitry. © 2005 Movement Disorder Society
Adult polyglucosan body disease: A case report of a manifesting heterozygote
Authors: Ubogu Eroboghene E. , Hong Stacey Tay Kiat , Akman Hasan Orhan , Dimauro Salvatore , Katirji Bashar , Preston David C. , Shapiro Barbara E.
Published: July 2005

A 62‐year‐old man developed progressive gait instability, bladder dysfunction, proximal weakness, distal sensory loss, and mild cognitive impairment over 6 years. Neurologic examination revealed upper and lower motor neuron dysfunction in the lower extremities, with distal sensory loss. Electrodiagnostic studies, magnetic resonance imaging of the brain, and sural nerve biopsy were consistent with adult polyglucosan body disease. Biochemical and genetic analyses demonstrated reduced glycogen brancher enzyme levels associated with a heterozygous point mutation (Tyr329Ser or Y329S) in the glycogen brancher enzyme gene on chromosome 3. Mutational heterozygosity in the glycogen brancher enzyme gene has not been previously reported as a cause for this rare disease. A review of the clinical presentation, pathogenesis, etiology, and diagnosis of this disease is presented. Muscle Nerve, 2005
Molecular characterization of tumour heterogeneity and malignant mesothelioma cell differentiation by gene profiling
Authors: Sun Xiaojuan , Wei Lei , Lidén Johan , Hui Gao , Dahlman‐Wright Karin , Hjerpe Anders , Dobra Katalin
Published: July 2005

Malignant mesothelioma is an aggressive tumour, characterized by a variable differentiation pattern and poor prognosis. At present, the clinical outcome in patients with malignant mesothelioma is mainly predicted by the morphological phenotype of the tumour. However, this conventional clinicopathological parameter is of limited value, partly because of the biological heterogeneity of this tumour and poor understanding of the regulatory mechanisms underlying the various patterns of growth. To elucidate the intrinsic molecular programmes that determine tumour differentiation, oligonucleotide arrays were used in an in vitro model of mesothelioma differentiation. The analysis of 2059 genes detected 102 genes that were significantly deregulated. Clustering of these genes into functional categories showed distinctive patterns for the two phenotypes, namely epithelioid and sarcomatoid. The molecular fingerprint of the sarcomatoid tumour component indicates overrepresentation of growth factor receptors and growth factor binding proteins, whereas epithelioid mesothelioma cells express other tumour‐promoting factors involved in differentiation, metabolism, and regulation of apoptosis. These differences in the molecular phenotype may give a better basis for diagnosis and for designing novel therapies. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
cDNA expression profiling of chondrosarcomas: Ollier disease resembles solitary tumours and alteration in genes coding for components of energy metabolism occurs with increasing grade
Authors: Rozeman Leida B , Hameetman Liesbeth , van Wezel Tom , Taminiau Antonie HM , Cleton‐Jansen Anne Marie , Hogendoorn Pancras CW , Bovée Judith VMG
Published: July 2005

Conventional central chondrosarcomas are malignant cartilaginous tumours, occasionally arising secondary to either solitary or multiple (Ollier disease) enchondromas. Recurrences may have progressed in grade. The aims of the present study were to identify putative differences in gene expression between solitary and Ollier disease‐related tumours, and to elucidate signalling pathways involved in tumour progression by genome‐wide cDNA expression analysis. Arrays enriched for cartilage‐specific cDNAs and genes involved in general tumourigenesis were used to analyse enchondromas (n= 3, two with Ollier disease), chondrosarcomas of different grades (n= 19, three with Ollier disease), normal resting‐zone cartilage (n= 2), and chondrosarcoma cells in culture (n= 7). The arrays were analysed by unsupervised hierarchical clustering, significant analysis of microarray, andT‐tests. Confirmation of data was performed by immunohistochemistry and quantitative reverse transcriptase polymerase chain reaction (RT‐PCR). Ollier disease cases and solitary tumours revealed similar expression profiles, suggesting that the same signalling pathways are involved in tumourigenesis. Interestingly, JunB protein expression was significantly higher in grade I chondrosarcomas than in enchondromas (p= 0.009), which could be of diagnostic relevance. Upon chondrosarcoma progression, matrix‐associated genes are down‐regulated, reflecting the histology of high‐grade tumours. An increase in glycolysis‐associated, and a decrease in oxidative phosphorylation‐related, genes was found in high‐grade tumours. These findings suggest an adaptation in energy supply upon progression towards higher grade. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Patterns of treatment failure in infants with primitive neuroectodermal tumors who were treated on CCG‐921: A phase III combined modality study
Authors: Hong Theodore S. , Mehta Minesh P. , Boyett James M. , Donahue Bernadine , Rorke Lucy B. , Zeltzer Paul M.
Published: July 2005

Purpose

To analyze patterns of treatment failure in infants with primitive neuroectodermal tumors (PNETs) who were treated primarily with chemotherapy in a large multi‐institutional study.

Materials and Methods

Sixty‐five prospectively staged patients with PNET confirmed by central pathology review, who were 18 months or younger were treated on Children's Cancer Group Study 921 (CCG‐921) primarily with chemotherapy. Forty‐six patients had posterior fossa (PF) primary tumors and 19 patients had supratentorial (ST) primaries. Patterns of sites of initial treatment failure were analyzed and compared to failure patterns of 180 older children who had PF‐PNETs, and 44 older children with ST‐PNETs who were treated on the same protocol.

Results

The entire cohort of younger patients fared much worse than those older than 18 months. Cumulative 5‐year relapse incidence (±SE) for younger patients with PF‐PNETs was 64.5 ± 8.9% for patients without metastases (M0) compared to 71.4 ± 13.4% for patients with metastases (M+). The cumulative 5‐year relapse incidences for younger patients with ST‐PNETs were 64.3 ± 13.7% for M0 patients compared to 100 ± 33.3% for M+ patients. Relapses in these patients occurred within 2 years. The overall treatment failure rate was significantly higher for younger compared to older patients with PF‐PNET and ST‐PNET. There was no statistically significant difference in relapse patterns between patients with PF primary tumors and ST primaries when stratified by stage. There was no statistically significant difference in relapse patterns between M0 and M+ patients. All patients had a high risk of recurrence at primary tumor site. Younger patients who had PF primary tumors without metastasis at presentation were significantly more likely to relapse in PF than older patients. Younger patients were at significant risk of relapse in the spine, but none had it as the sole site of first relapse.

Conclusions

Despite aggressive chemotherapy, younger children with PNETs have high rates of treatment failure and fare worse than high‐risk, older patients with PF‐PNETs, indicating the need to maximize local, regional, and systemic therapies. © 2005 Wiley‐Liss, Inc.
Use of two unrelated umbilical cord stem cell units in stem cell transplantation for Wiskott–Aldrich syndrome
Authors: Slatter M.A. , Bhattacharya A. , Flood T.J. , Abinun M. , Cant A.J. , Gennery A.R.
Published: July 2005

Wiskott–Aldrich syndrome, an X‐linked primary immunodeficiency can be cured by bone marrow transplantation. Umbilical cord haemopoietic stem cells are increasingly used as an alternative to bone marrow; advantages include ready availability, no risk to the donor, low rate of viral contamination, and low risk of graft versus host disease. Disadvantages include low stem cell dose for larger patients and lack of stem cells for boost infusions following the initial procedure. We report the case of a child with Wiskott–Aldrich syndrome who underwent cord blood stem cell transplantation with two separate cord blood units, 8 days apart. Pediatr Blood Cancer 2006;47:332–334. © 2005 Wiley‐Liss, Inc.
Essential erbB family phosphorylation in osteosarcoma as a target for CI‐1033 inhibition
Authors: Hughes Dennis P.M. , Thomas Dafydd G. , Giordano Thomas J. , McDonagh Kevin T. , Baker Laurence H.
Published: July 2005

Background

The role of erbB tyrosine kinases, especially Her‐2, in osteosarcoma has engendered intense debate. Some investigators identified an association between low‐level Her‐2 expression, compared to none, and poor patient outcome. Others questioned the importance of apparent cytoplasmic expression of Her‐2, since membranous overexpression is associated with poor outcome in carcinomas. We previously demonstrated that primary osteosarcoma cells express cell‐surface EGFR and Her‐2, with the p80 isoform of Her‐4 localized to the nucleus. We wished to determine if erbB kinases in osteosarcoma were phosphorylated, and if this was required for growth.

Procedures

We cultured early passage osteosarcoma cell lines in the presence or absence of the pan‐erbB inhibitor CI‐1033 and examined the phosphorylation status of EGFR, Her‐2, and Her‐4 by immunohistochemistry, cell‐based ELISA, flow cytometry and two dimensional Western blot. We also assessed the impact of CI‐1033 upon osteosarcoma growth and survival in vitro.

Results

EGFR, Her‐2, and Her‐4 were constitutively phosphorylated in early passage osteosarcoma cells cultured in vitro. CI‐1033 abrogated erbB receptor phosphorylation and caused growth inhibition and apoptosis in a titratible fashion with concentrations of 1 μM or more.

Conclusions

EGFR, Her‐2, and Her‐4 are constitutively phosphorylated in early passage osteosarcoma cells in tissue culture, and erbB signaling provides essential growth and anti‐apoptotic signals to osteosarcoma cells. This suggests that erbB overexpression is not required for erbB to promote malignancy, but rather that overexpression is one of several mechanisms that generate unregulated erbB signaling. © 2005 Wiley‐Liss, Inc.
Interferon alpha 2b treatment in an eleven‐year‐old boy with disseminated lymphangiomatosis
Authors: Timke Christian , Krause Martin F. , Oppermann Hans‐Conrad , Leuschner Ivo , Claviez Alexander
Published: July 2005

Disseminated lymphangiomatosis is a rare disease mostly observed in children and young adults. If no surgical removal can be achieved, the prognosis is poor, especially for patients with thoracic localization and pleural effusions. Next to pleural drainage, therapeutic options include radiotherapy, local, and systemic pharmacotherapy. An 11‐year‐old boy presented with disseminated lymphangiomatosis involving thorax with massive pleural effusions, retroperitoneum, and bones. In immunohistochemical analysis, the tissue biopsy stained positive for vascular endothelial growth factor‐receptor 3 (VEGFR‐3). The patient has been treated with interferon alpha 2b for 2 years, and achieved a good clinical and radiological response. Pediatr Blood Cancer 2007;48:108–111. © 2005 Wiley‐Liss, Inc.
Use of recombinant factor VIIa prior to lumbar puncture in pediatric patients with acute leukemia
Authors: Das Prabodh , Carcao Manuel , Hitzler Johann
Published: July 2005

The persistence of abnormal coagulation test results after standard treatment with fresh frozen plasma (FFP) poses significant problems in children with acute leukemia requiring a diagnostic lumbar puncture and intrathecal chemotherapy. We report the prophylactic use of a single dose of 90 µg/kg recombinant activated factor VII (rFVIIa) in three children and the rapid correction of abnormal coagulation test results previously not corrected by FFP. Administration of rFVIIa was useful in avoiding a delay of diagnostic lumbar punctures and intrathecal chemotherapy. Hemorrhagic complications and adverse effects of rFVIIa were not observed. Prospective evaluation of this indication and dose appears warranted. © 2005 Wiley‐Liss, Inc.
Measurement of cerebrovascular flow reserve in pediatric patients with sickle cell disease
Authors: Kedar Amos , Drane Walter E. , Shaeffer Douglas , Nicole Michael , Adams Caroline
Published: July 2005

Purpose

To report a method for determining absolute percentage change in cerebral blood flow (measurement of cerebrovascular reserve) before and after acetylazolamide (Diamox) administration in children with sickle cell anemia.

Materials and Methods

Thirty‐six symptomatic sickle cell disease patients (48 studies) were evaluated. After the injection of either Tc‐99m bicisate ethyl cysteinate dimer (ECD) or hexamethyl propylene amine oxime (HMPAO), both whole body scans (with geometric mean correction) and single photon emission computed tomography (CT) were performed pre‐ and post‐Diamox administration with calculation of percentage brain uptake on the whole body images for both examinations and determination of cerebrovascular reserve (percentage change in brain uptake post‐Diamox). Evaluation for regional cerebral perfusion change was also performed.

Results

The cerebrovascular reserve measurement was 17.6% ± 43.5% (mean ± 1 SD). Thirty‐three of 48 studies (69%) showed an abnormal cerebrovascular reserve, while only 6 of 48 studies (12.5%) showed Diamox‐induced regional perfusion changes in the brain. No statistically significant relationship was found between the occurrence of a regional perfusion abnormality versus loss of cerebrovascular reserve (P = 0.75, Fisher exact test), suggesting that these are independent variables. The cerebrovascular reserve was reproducible, with an average standard deviation of ±0.54%.

Conclusion

A new, simple method for calculation of cerebrovascular reserve is presented; this method is reproducible and appears to be an independent variable in the evaluation of cerebrovascular status in sickle cell anemia patients. It should allow further characterization of this complex patient population, and possibly assist in detection of patients at risk for developing “silent” or overt stroke. © 2005 Wiley‐Liss, Inc.
Cholesterol‐imprinted polymer receptor prepared by a hybrid imprinting method
Authors: Wang Shaofeng , Xu Jianwei , Tong Yuejin , Wang Lin , He Chaobin
Published: July 2005

A novel cholesterol‐imprinted polymer (CMIP‐H) was prepared by a hybrid method of covalent imprinting and non‐covalent imprinting. This approach involves the copolymerization of a template‐containing monomer, cholesteryl 2‐hydroxyethyl methacrylate carbonate, and a cross‐linker, followed by hydrolysis to afford a flexible guest‐binding site accompanied with the easy and efficient removal of a ‘sacrificial spacer’. The effect of solvent on the binding capacity of CMIP‐H towards cholesterol was studied, indicating that a good binding capacity towards cholesterol could be achieved in a less‐polar solvent. The binding experiments of CMIP‐H towards a series of structural analogues of cholesterol, including cholesterol acetate, progesterone and stigmasterol, were carried out in hexane. The results showed that CMIP‐H almost did not bind cholesterol acetate at all because the hydrogen‐bonding site is blocked. It exhibited a similar binding towards both cholesterol and stigmasterol, but much higher binding towards progesterone. Copyright © 2005 Society of Chemical Industry
Tween 20‐modified poly(vinyl chloride) exhibits enhanced blood‐compatibility
Authors: Balakrishnan Biji , James Nirmala R , Jayakrishnan A
Published: July 2005

Poly(vinyl chloride) (PVC) resin was modified by grafting the non‐ionic surfactant poly(oxyethylene 20 sorbitan) monolaurate (Tween® 20) using isocyanate chemistry. PVC was aminated using ethylenediamine and coupled with hexamethylene diisocyanate. Tween 20 was then reacted with the polymer, resulting in the grafting of the surfactant. The polymer modification was confirmed using infrared and X‐ray photo‐electron spectroscopy. Films of modified polymer were cast from a solution of tetrahydrofuran. The surface of films prepared from the modified polymer showed increased hydrophilicity as evidenced by contact‐angle measurements. The solid/water free energy of the modified polymer surface was nearly a quarter of the energy of the bare PVC surface. Static platelet adhesion studies using platelet‐rich plasma demonstrated significantly reduced adhesion onto a modified PVC surface compared with unmodified PVC. Data obtained demonstrate that modification of polymers with Tween 20 may be an interesting way of imparting protein‐ and cell‐repelling characteristics to them, thereby improving their blood‐compatibility. Copyright © 2005 Society of Chemical Industry
Synthesis of gold–poly(methyl methacrylate) core–shell nanoparticles by surface‐confined atom transfer radical polymerization at elevated temperature
Authors: Kotal Atanu , Mandal Tarun K. , Walt David R.
Published: July 2005

Surface‐confined atom transfer radical polymerization was used to prepare gold nanoparticle–poly(methyl methacrylate) core–shell particles at elevated temperature. First, gold nanoparticles were prepared by the one‐pot borohydride reduction of tetrachloroaurate in the presence of 11‐mercapto‐1‐undecanol (MUD). MUD‐capped gold nanoparticles were then exchanged with 3‐mercaptopropyltrimethoxysilane (MPS) to prepare a self‐assembled monolayer (SAM) of MPS on the gold nanoparticle surfaces and subsequently hydrolyzed with hydrochloric acid. The extent of exchange of MUD with MPS was determined by NMR. The resulting crosslinked silica‐primer layer stabilized the SAM of MPS and was allowed to react with the initiator [(chloromethyl)phenylethyl] trimethoxysilane. Atom transfer radical polymerization was conducted on the Cl‐terminated gold nanoparticles with the CuCl/2,2′‐bipyridyl catalyst system at elevated temperature. The rates of polymerization with the initiator‐modified gold nanoparticles exhibited first‐order kinetics with respect to the monomer, and the number‐average molecular weight of the cleaved graft polymer increased linearly with the monomer conversion. The presence of the polymer on the gold nanoparticle surface was identified by Fourier transform infrared spectroscopy and transmission electron microscopy. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 3631–3642, 2005
Design of combinatorial protein libraries of optimal size
Authors: Saraf Manish C. , Gupta Anshuman , Maranas Costas D.
Published: July 2005

In this article we introduce a computational procedure, OPTCOMB (Optimal Pattern of Tiling for COMBinatorial library design), for designing protein hybrid libraries that optimally balance library size with quality. The proposed procedure is directly applicable to oligonucleotide ligation‐based protocols such as GeneReassembly, DHR, SISDC, and many more. Given a set of parental sequences and the size ranges of the parental sequence fragments, OPTCOMB determines the optimal junction points (i.e., crossover positions) and the fragment contributing parental sequences at each one of the junction points. By rationally selecting the junction points and the contributing parental sequences, the number of clashes (i.e., unfavorable interactions) in the library is systematically minimized with the aim of improving the overall library quality. Using OPTCOMB, hybrid libraries containing fragments from three different dihydrofolate reductase sequences (Escherichia coli, Bacillus subtilis, and Lactobacillus casei) are computationally designed. Notably, we find that there exists an optimal library size when both the number of clashes between the fragments composing the library and the average number of clashes per hybrid in the library are minimized. Results reveal that the best library designs typically involve complex tiling patterns of parental segments of unequal size hard to infer without relying on computational means. Proteins 2005. © 2005 Wiley‐Liss, Inc.
The βαβαβ elementary supersecondary structure of the Rossmann fold from porcine lactate dehydrogenase exhibits characteristics of a molten globule
Authors: Coinçon Mathieu , Heitz Annie , Chiche Laurent , Derreumaux Philippe
Published: July 2005

Protein classifications show that the Rossmann fold, which consists of two βαβαβ motifs (BABAB) related by a rough twofold axis, is the most populated αβ fold, and that the βαβ submotif (BAB) is a widespread elementary structural arrangement. Herein, we report MD simulations, circular dichroism and NMR analyses on BAB and BABAB from porcine lactate dehydrogenase to evaluate their intrinsic stability. Our results demonstrate that BAB is not stable in solution and is not a folding nucleus. We also find that BABAB, despite its appearance of a functional and structural unit, is not an independent and thermodynamically stable folding unit. Rather, we show that BABAB retains most native secondary structure but very little tertiary structure, thus displaying characteristics of a molten globule. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Benzene crystallization risks in the LIQUEFIN liquefied natural gas process
Authors: de Hemptinne J.‐C.
Published: July 2005

In liquefied natural gas (LNG) processes, the gas feed is cooled to very low temperatures (−160° C). The presence of traces of heavy hydrocarbon components may therefore result in crystallization, and thus equipment plugging. The present work investigates the solid–liquid–vapor equilibria and proposes a way to predict the risks of crystallization.

In the first section, the phase diagrams that may be encountered with natural gas mixtures at these very low temperatures are presented. A literature review shows that few data are available for operating conditions of LNG processes.

In the second section, the crystallization model based on a cubic equation of state, coupled with a Huron–Vidal mixing rule and combined with a solid‐phase model is presented. This model requires the crystallization heat capacity of pure components, which must be determined using the few data points available. Nevertheless, it appears that the resulting model is rather predictive when compared to data that were not used in the regression.

Finally, the model is applied in different zones of the LIQUEFIN process, commercialized by AXENS. The results have been used to improve the design of this LNG plant. © 2005 American Institute of Chemical Engineers Process Saf Prog, 2005
Two heating rates as a method for calculating the kinetic parameters of crystallization in a glassy system
Authors: Rasheedy M. S.
Published: July 2005

Various experimental methods are currently employed for determining the kinetic parameters of crystallization in a glassy system. These parameters include the activation energy E(kJ/mol), the Avrami exponent or the reaction order (n) and the frequency factor K0 (s–1). In the present work, a new method is derived from Johnson–Mehl–Avrami (JMA) equation to calculate the kinetic parameters of crystallization. The method starts with determining the activation energy E. The method depends on obtaining the same vol‐ume fraction of crystallization x(t) at two heating rates. Next, the reaction order n and the frequency factor K0 are determined successively. The present method is straightforward and involves no assumptions in addition to those involved in obtaining JMA equation. The new technique has successfully predicted the crystallization parameters of Ge10Te35As55 glasses during non‐isothermal annealing. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Quantitative Structure‐Activity Relationship (QSAR) Study of the Antioxidant Activity of Flavonoids
Authors: Rasulev Bakhtiyor F. , Abdullaev Nasrulla D. , Syrov Vladimir N. , Leszczynski Jerzy
Published: July 2005

A Quantitative Structure‐Activity Relationship (QSAR) study has been carried out for 27 flavonoids belonging to four different groups (isoflavons, flavons, flavonols, flavanons) to correlate and predict the inhibition of lipids peroxidation effects (antioxidant activity). The genetic algorithm (GA) and multiple linear regression analysis (MLRA) were used to select the descriptors and to generate the correlation models that relate the structural features to the biological activities. The obtained equations consist of one to four descriptors calculated from the characteristics of the molecular structures with use of DRAGON software and quantum‐chemical methods. A number of molecular descriptors was obtained from the density functional theory (DFT) B3LYP/6‐31G(d, p) level optimized geometries (quantum‐chemical descriptors). The results of the GA‐MLRA analysis show that the position of the OH groups, the magnitude of dipole moment and the shape of the molecule play an important role in inhibition of lipids peroxidation by flavonoids. The significant QSAR models were obtained with r value of 0.935 and 0.933 for basic models. The q2 (cross validation r2) values and scrambling/randomization experiments also confirms the statistical significance of our models. These models are expected to be useful for screening of flavonoid antioxidants.
Predicting Anti‐HIV‐1 Activities of HEPT‐analog Compounds by Using Support Vector Classification
Authors: Lu Wencong , Dong Ning , Náray‐Szabó Gábor
Published: July 2005

The support vector classification (SVC), as a novel approach, was employed to make a distinction within a class of non‐nucleoside reverse transcriptase inhibitors. 1‐[(2‐hydroxyethoxy) methyl]‐6‐(phenyl thio)‐thymine (HEPT) derivatives with high anti‐HIV‐1 activities and those with low anti‐HIV‐1 activities were compared on the basis of the following molecular descriptors: net atomic charge on atom 4, molecular volume, partition coefficient, molecular refractivity, molecular polarisability and molecular weight. By using the SVC, a mathematical model was constructed, which can predict the anti‐HIV‐1 activities of the HEPT‐analogue compounds, with an accuracy of 100% as calculated on the basis of the leave‐one‐out cross‐validation (LOOCV) test. The results indicate that the performance of the SVC model exceeds that of the stepwise discriminant analysis (SDA) model, for which a prediction accuracy of 94% was reported.
Ab initio quantum chemical studies of fullerene molecules with substitutes C59X [XSi, Ge, Sn], C59X− [XB, Al, Ga, In], and C59X [XN, P, As, Sb]
Authors: Simeon Tomekia M. , Yanov Ilya , Leszczynski Jerzy
Published: July 2005

This article presents the results of systematic ab initio quantum chemical study of charged and neutral analogues of fullerene molecules: C59X[XSi, Ge, Sn], C59X− [XB, Al, Ga, In], and C59X+ [XN, P, As, Sb]. Hartree–Fock (HF) and density functional theory (DFT) levels of theory with Stuttgart–Dresden basis set were used to investigate the structure and properties of substituted fullerene molecules. A replacement of fullerene carbon atom with a heteroatom results in a unique chemical site on the fullerene surface, which may be used as a reactive center or to modify the electronic properties. We show the possibility of utilization of substituted fullerenes as atom‐like building units. Heteroatom substitution allows the tuning of the physical and chemical properties of original molecule for different material science and nanotechnology applications. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005
Bayesian sample‐size determination for inference on two binomial populations with no gold standard classifier
Authors: Stamey James D. , Seaman John W. , Young Dean M.
Published: July 2005

We consider the impact of test properties on the required sample size for the Bayesian design problem for comparing two proportions with error‐prone data. Specifically, we examine four cases: a single diagnostic test and two independent diagnostic tests, both when the test properties are identical across populations and when they differ. Interval‐based and moment‐based sample‐size determination criteria are contrasted using Monte Carlo simulation methods. We consider an application in which Strongyloides infections are compared in two populations. Copyright © 2005 John Wiley & Sons, Ltd.
Procedures for testing the homogeneity of relative difference in sparse data
Authors: Lui Kung‐Jong
Published: July 2005

To quantify the excess effect of an experimental treatment over a placebo group in clinical trials, we often consider use of the relative difference, defined as the proportion of patients who would respond to the experimental treatment among those who would not otherwise if they were assigned to the placebo group. To control the effects due to confounders on the response of interest, we frequently employ stratified analysis in practice. Before obtaining a summary estimate of the relative difference, it is desirable to assess whether this measure is constant across strata. Based on the beta–binomial model, we develop simple procedures for testing the homogeneity of relative difference for sparse data in which we have many strata but few patients per stratum. Using Monte Carlo simulations, we demonstrate that the proposed test procedures can generally perform well with respect to type I error in a variety of situations. We further evaluate and study the power of these test procedures. Finally, we note some robustness in using the test procedures proposed here. Copyright © 2005 John Wiley & Sons, Ltd.
Afternoon mid-latitude current system and low-latitude geomagnetic field asymmetry during geomagnetic storms
Authors: Grafe A. , Bespalov P. A. , Trakhtengerts V. Y. , Demekhov A. G.
Published: July 2005

Abstract. For four geomagnetic storms of middle intensity the relationship between the low-latitude magnetic field asymmetry using ASY indices and the intensity of the auroral eastward and westward electrojet was considered. It was asked whether there exists a connection between ASY and the eastward electrojet. To answer this question equivalent current systems were estimated in mid-latitudes. It was found that the observations obviously show no correlative relationship between the low-latitude magnetic-field asymmetry and the eastward electrojet, whereas one exists between ASY and the westward electrojet. To explain the generally accepted common three-dimensional current system between the partial ring current and the eastward electrojet, a condensor model of the three-dimensional current system was developed. It could be shown that the short periodic variations of the partial ring current are shielded by the condensor and cannot influence the eastward-electrojet current.