bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Value of Anti‐F‐Actin Antibodies in a French Multicenter Study
Authors: CHRETIEN‐LEPRINCE P , BALLOT E , ANDRE C , OLSSON N O , FABIEN N , ESCANDE A , OKSMAN F , DUBUQUOI S , JEGO S , GOETZ J , CHEVAILLER A , SANMARCO M , HUMBEL R L , JOHANET C
Published: July 2005

Abstract: According to international criteria, autoimmune hepatitis (AIH) type 1 is characterized by the presence of antinuclear or anti‐smooth muscle antibodies (SMA) with F‐actin specificity. SMA have been found in 85% of AIH patients, but are not specific to this disease, and anti‐F‐actin specificity is not always verified when SMA are detected. The objective of this study was to determine the diagnostic value of anti‐F‐actin antibodies in a large population. A multicenter study involving 12 clinical centers was performed. Patients were selected on the basis of the presence of F‐actin SMA detected by indirect immunofluorescence (IIF) on rat liver‐kidney‐stomach sections and was confirmed by IIF on Hep2 cells treated with colchicine, or F‐actin dot‐blot. The clinical status of patients was determined from their medical records. One hundred sixty‐eight patients were included: 76% women, 24% men; mean age of 45 years (range, 2–88 years), with a bimodal age distribution. Sixty percent had AIH type 1, and 40% had another disease. In the group of women younger than 25 years, 90% had AIH type 1. Other pathologies associated with antiactin were other liver diseases (19%), including viral hepatitis C (7%), and nonliver diseases (21%), including connective tissue diseases (12%). Antibody titers were higher in AIH than in other diseases. Antiactin antibodies are of major diagnostic value in AIH, especially in young women; they may be found in other disease settings, but mostly at low levels.
Paraneoplastic Neurological Antibodies: A Laboratory Experience
Authors: KARIM ABID R. , HUGHES RICHARD G. , WINER JOHN B. , WILLIAMS ADRIAN C. , BRADWELL ARTHUR R.
Published: July 2005

Abstract: Antineuronal antibodies are associated with rare paraneoplastic neurological syndromes, and their identification alerts clinicians to examine for the presence of a tumor. Presented here is laboratory experience (prevalence, difficulties, and procedures) and several interesting but inconclusive results. A total of 1045 samples were screened over a 2‐year period; 91 showed a degree of binding of antibodies to the cerebellum, and 22 of these 91 were confirmed, by Western blot, to have specific antineuronal antibodies. Thirteen of 22 were Hu‐positive, and 6 of these also had antinuclear antibodies. Six were Yo‐positive, 2 had anti‐Ma antibodies, and 1 was Tr‐positive. An additional 27 of 91 patients had cerebellar antibodies giving recognized staining patterns (Hu, Yo, and Ma). However, Western blot did not confirm these specificities, and hence they were reported as atypical. Six of 27 of these patients had neoplasms; 3 of the 6 gave nucleolar patterns (not Ma). Two appeared similar to Yo, and 1 similar to Hu. Antineuronal antibodies are rare, and in the absence of a specific etiology patients should be examined further for the possible presence of an underlying tumor. Methodical classification of the antibodies must be conducted to avoid incorrect reporting. Further criteria on the typing/reporting of atypical results may aid diagnosis of paraneoplastic neurological syndromes.
Determination of ANA Specificity Using the UltraPlex™ Platform
Authors: SMITH JODIE , ONLEY DAVID , GAREY CAROLINE , CROWTHER STUART , CAHIR NICHOLAS , JOHANSON ADAM , PAINTER SIANIE , HARRADENCE GRANT , DAVIS RICARDO , SWARBRICK PETER
Published: July 2005

Abstract: SmartBead Technologies has developed a multiplexed immunofluorescence assay, the UltraPlex ANA Profile, which determines nine antinuclear antibodies simultaneously. The UltraPlex assay platform uses bar‐coded microparticles to track analytes through assays. These bar‐coded microparticles were used to tag and track key ANA markers: Jo‐1, Scl‐70, Sm, SmRNP, SSA, SSB, U1RNP, Centromere B, dsDNA, and a blank control microparticle. The immunofluorescence assays are fully automated and are performed on a Perkin‐Elmer multiprobe II liquid handling system that performs all sera dilutions, additions of reagents, washes, and incubation steps. Results were determined by the automated UltraPlex plate reader. This fully automated multiplex antinuclear antibody (ANA) immunoassay was used to screen commercially available ANA‐positive sera and negative control samples. The UltraPlex ANA Profile enables the panels of samples to be screened simultaneously for nine ANA antoantibodies, requiring significantly less labor and fewer reagents, with performance equivalent to existing gold‐standard methods.
Clinical Utility of the Anti‐CCP Assay: Experiences with 700 Patients
Authors: SAUERLAND ULRICH , BECKER HEIDEMARIE , SEIDEL MATTHIAS , SCHOTTE HEIKO , WILLEKE PETER , SCHORAT ANNETTE , SCHLÜTER BERNHARD , DOMSCHKE WOLFRAM , GAUBITZ MARKUS
Published: July 2005

Abstract: Our objective was to determine the frequency of antibodies to cyclic citrullinated peptides (CCPs) in a series of patients with a variety of rheumatic diseases. Seven hundred consecutive serum samples from patients at an outpatient clinic were tested for the presence of rheumatoid factor (RF) and anti‐CCP. Clinical diagnosis, radiographic information, and other laboratory data were taken from patients' charts. The sensitivity and specificity of anti‐CCP reactivity for the diagnosis of rheumatoid arthritis (RA) were 74.0% and 94.5%, respectively; the corresponding results for RF were 69.7% sensitivity and 81.0% specificity. Highest rates of false‐positive RF tests were found in patients with SLE (18.3% vs. 12.7% CCP), Sjögren's syndrome (73.3% vs. 3.3% CCP), and a control group with chronic hepatitis (24.7% vs. 1.3% CCP). The detection of anti‐CCP is useful for the diagnosis of RA because of its similar sensitivity but higher specificity compared with RF. Anti‐CCP also helps to diagnose other inflammatory and noninflammatory diseases (especially connective tissue diseases) by reducing the rate of false‐positive results in comparison with RF.
Antinuclear Antibodies in Domestic Animals
Authors: GERSHWIN LAUREL J.
Published: July 2005

Abstract: Antinuclear antibodies in domestic animal species have been commonly detected for many years, with the greatest frequency occurring in dogs as well as horses and cats. Most commonly, the assay used in diagnostic laboratories is indirect immunofluorescence on HEP‐2 cells, similar to that used in human medicine, but with the exception that species‐specific antiglobulin reagents are used instead of antihuman immunoglobulin. To a lesser extent, the Crithidia luciliae test for antibodies to double‐stranded DNA has been used. Several research groups have used other assays.
Autoimmunity and Coxsackievirus Infection in Primary Sjögren's Syndrome
Authors: TRIANTAFYLLOPOULOU ANTIGONI , MOUTSOPOULOS HARALAMPOS M.
Published: July 2005

Abstract: Exocrine gland epithelial cells are the target of autoimmune pathology in primary Sjögren's syndrome (pSS). Their activated phenotype has incited the notion that they are infected by a virus. We recently presented evidence that coxsackieviruses may persistently infect the salivary glands of pSS patients. We hypothesize that coxsackieviruses may play a permissive role for the perpetuation and possibly the induction of autoimmune disease in pSS.
Human and Nonhuman Primate Lentiviral Infection and Autoimmunity
Authors: ONLAMOON NATTAWAT , PATTANAPANYASAT KOVIT , ANSARI AFTAB A.
Published: July 2005

Abstract:The goal of this communication is to summarize the following—the types of autoimmune responses that have been characterized in human HIV‐1 infection; the potential mechanisms that were initially thought to be the basis for such autoimmune responses; the prevalence and incidence of conventional autoimmune diseases with HIV‐1 infection; the spectrum of autoimmune disorders following the institution of HAART and its associated mechanisms; the role of such autoimmunity in SIV‐infected nonhuman primates; and the molecular basis for autoimmune responses, such as the role of exosomes in lentiviral disease.
Autoimmune Nature of Influenza Atherogenicity
Authors: GUREVICH VICTOR S. , PLESKOV VLADIMIR M. , LEVAYA MARGARITA V.
Published: July 2005

Abstract:It has been observed during influenza epidemics and in a number of population and clinical trials that this prevalent viral infection was associated with increased death rates from cardiovascular diseases. The clinical and experimental data that may explain accelerated coronary atherosclerosis in influenza infection with implications involving autoimmune mechanisms are analyzed in this article. Both cellular and humoral autoimmune modes could be proposed to participate in the onset or progression of atheromatous lesions due to influenza infection.
Bovine Spongiform Encephalopathy, Multiple Sclerosis, and Creutzfeldt‐Jakob Disease Are Probably Autoimmune Diseases Evoked by Acinetobacter Bacteria
Authors: EBRINGER ALAN , RASHID TAHA , WILSON CLYDE
Published: July 2005

Abstract: Bovine spongiform encephalopathy (BSE) belongs to a group of conditions named together as transmissible spongiform encephalopathies (TSE). They are fatal neurodegenerative diseases that include “scrapie” in sheep, Creutzfeldt‐Jakob disease (CJD) and kuru in humans, and chronic wasting disease in deers. BSE‐affected animals suffer from “hindquarters” paralysis, which is also one of the main features of “experimental allergic encephalomyelitis” (EAE). EAE is considered an animal model of multiple sclerosis (MS) and lower limb ataxia is often observed in MS patients. The presence of clinical and histopathological similarities in these diseases suggests a common pathology. Specific brain peptides, which produce EAE, were shown to have “molecular mimicry” with the soil and skin saprophytic microbe, Acinetobacter. BSE‐affected animals and patients suffering from MS have been found to have elevated levels of antibodies to both Acinetobacter and Pseudomonas bacteria, as well as autoantibodies to both white and gray matter brain components. The hypothesis is proposed that Acinetobacter/Pseudomonas bacteria may have evoked both BSE and MS through the mechanism of “molecular mimicry” and autoimmunity in a similar way to Streptococcus microbes producing rheumatic fever and Sydenham's chorea. The possibility that CJD patients may show similar features remains to be determined.
DNA Lesions and Repair in Immunoglobulin Class Switch Recombination and Somatic Hypermutation
Authors: XU ZHENMING , FULOP ZSOLT , ZHONG YUAN , EVINGER ALBERT J. , ZAN HONG , CASALI PAOLO
Published: July 2005

Abstract: Immunoglobulin (Ig) gene somatic hypermutation (SHM) and class switch DNA recombination (CSR) are critical for the maturation of the antibody response. These processes endow antibodies with increased antigen‐binding affinity and acquisition of new biological effector functions, thereby underlying the generation of memory B cells and plasma cells. They are dependent on the generation of specific DNA lesions and the intervention of activation‐induced cytidine deaminase as well as newly identified translesion DNA polymerases, which are expressed in germinal center B cells. DNA lesions include mismatches, abasic sites, nicks, single‐strand breaks, and double‐strand breaks (DSBs). DSBs in the switch (S) region DNA are critical for CSR, but they also occur in V(D)J regions and possibly contribute to the events that lead to SHM. The nature of the DSBs in the Ig locus, their generation, and the repair processes that they trigger and that are responsible for their regulation remain poorly understood. Aberrant regulation of these events can result in chromosomal breaks and translocations, which are significant steps in B‐cell neoplastic transformation.
Improved Hepatic Toxicity Profile of Portal Vein Adjuvant Hepatic Infusional Chemotherapy
Authors: Faynsod Moshe , Wagman Lawrence D. , Longmate Jeff , Carroll Mary , Leong Lucille A.
Published: July 2005

Purpose

To determine whether floxuridine (FUDR) can be delivered with low hepatic toxicity through the portal vein (PV) as an adjuvant to surgically treated colorectal metastases.

Patients and Methods

Fifty-one patients undergoing complete resection and/or ablation for colorectal hepatic metastases were prospectively enrolled at a National Cancer Institute–designated comprehensive cancer center. Two sequential phase II trials were performed. Each trial included complete surgical treatment followed by sequential, alternating (22 patients) or concurrent (29 patients) regional PV FUDR and systemic fluorouracil (FU) with leucovorin chemotherapy.

Results

Fifty percent of patients were male. The mean age at diagnosis was 57 years. The mean number of lesions resected was three (range, one to 11 lesions). The stage at diagnosis was II, III, and IV in 16.9%, 52.8%, and 28.3% of patients, respectively. One- and 3-year overall survival rates were 92.7% and 41.8%, respectively. The 1- and 3-year disease-free survival rates were 64.5% and 19%, respectively. The site of first recurrence was hepatic in 35.9% of patients. Treatment was terminated early in 24 patients (17 patients progressed, two refused treatment, and five had nonhepatic toxicities). Fifty-five percent of patients received 75% to 100% of the planned FUDR courses, and 72% received greater than 50% of the planned FUDR dose. Only four patients required dose reductions of FUDR because of grade 3 hepatic toxicity. No patient required biliary stenting or had discontinuation of PV infusion because of hepatic toxicity.

Conclusion

The delivery of PV FUDR and FU with leucovorin can be performed with a high percentage of expected drug delivery and a low drug-induced hepatic toxicity rate, while achieving acceptable overall and disease-free survival.
Enhanced Tumorocidal Effect of Chemotherapy With Preoperative Radiotherapy for Rectal Cancer: Preliminary Results—EORTC 22921
Authors: Bosset Jean-François , Calais Gilles , Mineur Laurent , Maingon Philippe , Radosevic-Jelic Ljiljana , Daban Alain , Bardet Etienne , Beny Alexander , Briffaux Antoine , Collette Laurence
Published: July 2005

Purpose

The European Organisation for Research and Treatment of Cancer (EORTC) trial evaluated the addition of chemotherapy (CT) to preoperative radiation (preop RT) and the value of postoperative CT for improving the survival in patients with T3-4 resectable rectal cancer. Patients were allocated to the following four arms: arm 1, preop RT 45 Gy in 5 weeks; arm 2, preop RT plus two 5-day CT courses (fluorouracil 350 mg/m2/d and leucovorin 20 mg/m2/d) in the first and fifth week of RT; arm 3, preop RT plus four postoperative CT courses; and arm 4, preop RT and CT plus postoperative CT. We investigated the effect of adding CT on the pathologic parameters.

Patients and Methods

One thousand eleven patients were entered onto the trial; 505 received preop RT (arms 1 and 3), and 506 received preop RT-CT (arms 2 and 4). We analyzed the differences in tumor size, tumor node stage, number of retrieved nodes, and histologic features such as lymphatic, venous, and perineural invasions, tumor differentiation, and tumor type.

Results

After preop RT-CT, tumors were smaller (P < .0001), had less advanced pT (P < .001) and pN stages (P < .001), had small numbers of examined nodes (P = .046), and less frequent LVN invasions (P ≤ .008). Mucinous tumors increased after preop RT-CT (P < .001).

Conclusion

In patients with rectal cancer, preliminary results of EORTC Trial 22921 indicate that the addition of CT to preop RT induces downsizing, downstaging, and significant changes in histologic characteristics. Longer follow-up is needed to assess the impact on local control and survival.
Phase I Trial of Systemic Oxaliplatin Combination Chemotherapy With Hepatic Arterial Infusion in Patients With Unresectable Liver Metastases From Colorectal Cancer
Authors: Kemeny Nancy , Jarnagin William , Paty Philip , Gönen Mithat , Schwartz Lawrence , Morse Meroë , Leonard Gregory , D’Angelica Michael , DeMatteo Ronald , Blumgart Leslie , Fong Yuman
Published: July 2005

Purpose

To determine the maximum-tolerated dose (MTD) of concurrent systemic oxaliplatin (Oxal) combinations plus hepatic arterial infusion (HAI) in patients with unresectable hepatic metastases from colorectal cancer.

Patients and Methods

Thirty-six patients (89% previously treated) with unresectable liver metastases were treated with concurrent HAI and systemic Oxal plus irinotecan (CPT-11; group A) or Oxal, fluorouracil (FU), and leucovorin (LV; group B). Systemic chemotherapy was administered every 2 weeks concurrent with 2 weeks of HAI floxuridine (FUDR) and dexamethasone (Dex) every 28 days.

Results

The MTD for patients in group A was Oxal 100 mg/m2, CPT-11 150 mg/m2, and FUDR 0.12 mg/kg × 30 mL divided by pump flow rate. The MTD for group B was Oxal 100 mg/m2, LV 400 mg/m2, and FU 1,400 mg/m2 by continuous infusion over 48 hours, with the same FUDR dose as in group A. Grade 3 or 4 toxicities in groups A and B included diarrhea (24% and 20%), neutropenia (10% and 7%), neurotoxicity (24% and 20%), and bilirubin more than 3 mg/mL (5% and 7%, respectively). The complete and partial response rate totaled 90% for group A and 87% for group B. Median survival time was 36 and 22 months for groups A and B, respectively. Seven patients in group A were ultimately able to undergo liver resection.

Conclusion

Combination therapy with HAI FUDR and Dex plus systemic Oxal combinations may be safely administered to patients with colorectal cancer. The high response rate (88%) and the possibility of conversion to resectability, despite disease progression on prior systemic regimens, suggest that these combinations should be evaluated in larger studies as first- or second-line therapy in patients with hepatic metastases from colorectal cancer.
Phase II Multicenter Study of the Antiepidermal Growth Factor Receptor Monoclonal Antibody Cetuximab in Combination With Platinum-Based Chemotherapy in Patients With Platinum-Refractory Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck
Authors: Baselga José , Trigo José M. , Bourhis Jean , Tortochaux Jacques , Cortés-Funes Hernán , Hitt Ricardo , Gascón Pere , Amellal Nadia , Harstrick Andreas , Eckardt André
Published: July 2005

Purpose

To evaluate the efficacy and safety of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

Patients and Methods

Ninety-six eligible patients received cetuximab (initial dose of 400 mg/m2 followed by subsequent weekly doses of 250 mg/m2) followed by platinum chemotherapy at the same dose and schedule at which progressive disease was documented before entry onto the study.

Results

The response rate, based on an independently read assessment, in the intent-to-treat population was 10%, with a disease control rate (complete response, partial response [PR], and stable disease) of 53%. The median time to progression and overall survival were 85 and 183 days, respectively; both were longest in patients achieving a PR (median, 203.5 and 294 days, respectively). Treatment was well tolerated. The most common cetuximab-related adverse events were skin reactions, particularly an acne-like rash.

Conclusion

The combination of cetuximab and platinum chemotherapy is an active and well-tolerated approach to the treatment of this poor-prognosis patient population with platinum-refractory recurrent or metastatic SCCHN for whom there are no recommended standard therapeutic options.
Phase II Multicenter Study of the Epidermal Growth Factor Receptor Antibody Cetuximab and Cisplatin for Recurrent and Refractory Squamous Cell Carcinoma of the Head and Neck
Authors: Herbst Roy S. , Arquette Matthew , Shin Dong M. , Dicke Karel , Vokes Everett E. , Azarnia Nozar , Hong Waun Ki , Kies Merrill S.
Published: July 2005

Purpose

This multicenter phase II study was undertaken to define the efficacy and safety of cetuximab, an antiepidermal growth factor receptor chimeric human and murine monoclonal antibody, administered with cisplatin to patients with refractory metastatic or recurrent squamous cell carcinoma of the head and neck (SCCHN).

Patients and Methods

One hundred thirty-two patients were to receive two 3-week cycles with cisplatin/paclitaxel or cisplatin/fluorouracil. Patients (n = 30) with a complete or partial response continued standard therapy. Seventy-six patients with stable disease (SD; n = 51) or progressive disease (PD/1; n = 25) received combination therapy with cetuximab (400 mg/m2 intravenously on day 1, then 250 mg/m2/wk) and cisplatin (75 or 100 mg/m2 intravenously on day 1 every 3 weeks). The protocol was subsequently amended to enroll patients who had developed PD within 90 days after platinum-based therapy (PD/2; n = 54).

Results

Five patients (20%) in PD/1, three patients (6%) in PD/2, and nine patients (18%) with SD achieved an objective response. Median duration of response was 4.2, 4.1, and 7.4 months for the PD/1, PD/2, and SD groups, respectively, with median overall survival times of 6.1, 4.3, and 11.7 months. The most common toxicities were anemia, acne-like skin rash, leukopenia, fatigue and malaise, and nausea and vomiting. Seven patients (5%) developed a grade 3 or 4 hypersensitivity reaction to cetuximab.

Conclusion

Cetuximab and cisplatin is an active regimen in refractory SCCHN. The relative contribution of cetuximab is better defined in a single-agent trial. Cetuximab did not exacerbate cisplatin toxicity but was associated with skin rash in a majority of patients and occasional serious allergic reactions. Further study of this compound is warranted.
Phase I and Pharmacodynamic Study of the Oral MEK Inhibitor CI-1040 in Patients With Advanced Malignancies
Authors: LoRusso Patricia M. , Adjei Alex A. , Varterasian Mary , Gadgeel Shirish , Reid Joel , Mitchell David Y. , Hanson Lorelei , DeLuca Pamela , Bruzek Laura , Piens Jill , Asbury Peggy , Van Becelaere Keri , Herrera Roman , Sebolt-Leopold Judith , Meyer Mark B.
Published: July 2005

Purpose

This phase I study was undertaken to define the toxicity, pharmacokinetics, pharmacodynamics, maximum tolerated dose (MTD), and clinical activity of CI-1040, a small-molecule inhibitor of the dual-specificity kinases MEK(mitogen-activated protein kinase kinase) -1 and MEK2 , in patients with advanced malignancy.

Patients and Methods

CI-1040 was tested in multiple daily dosing frequencies administered for 21 days repeated every 28 days leading ultimately to continuous administration, and effect of food on absorption was tested. Single dose and steady-state pharmacokinetics were assessed during cycle 1 and phosphorylated extracellular receptor kinase (pERK) levels were assessed in WBCs and also in tumor tissue from selected patients.

Results

Seventy-seven patients received CI-1040 at dose levels ranging from 100 mg QD to 800 mg tid. Grade 3 asthenia was dose limiting at the highest dose level tested, 800 mg tid administered with food. Ninety-eight percent of all drug-related adverse events were grade 1 or 2 in severity; most common toxicities included diarrhea, asthenia, rash, nausea, and vomiting. Plasma concentrations of CI-1040 and its active metabolite, PD 0184264, increased in a less than dose proportional manner from 100 to 800 mg QD. Administration with a high-fat meal resulted in an increase in drug exposure. The MTD and recommended phase II dose was 800 mg BID administered with food. Sixty-six patients were assessable for response. One partial response was achieved in a patient with pancreatic cancer and 19 patients (28%) achieved stable disease lasting a median of 5.5 months (range, 4 to 17 months). Inhibition of tumor pERK (median, 73%; range, 46% to 100%) was demonstrated in 10 patients.

Conclusion

CI-1040 was well tolerated at 800 mg BID administered with food. Both target suppression and antitumor activity were demonstrated in this phase I study.
Clinicopathologic and Genetic Profile of Intracranial Marginal Zone Lymphoma: A Primary Low-Grade CNS Lymphoma That Mimics Meningioma
Authors: Tu Pang-hsien , Giannini Caterina , Judkins Alexander R. , Schwalb Jason M. , Burack Richard , O'Neill Brian P. , Yachnis Anthony T. , Burger Peter C. , Scheithauer Bernd W. , Perry Arie
Published: July 2005

Purpose

Although rare overall, marginal zone B-cell lymphoma (MZBCL) is the most common primary low-grade CNS lymphoma reported in the literature. The aim of this study is to elucidate the biology and genetic features of this unusual tumor.

Patients and Methods

Fifteen CNS MZBCLs were studied clinically, pathologically, and genetically, including fluorescent in situ hybridization analyses with commercially available MALT1 and IgH break-apart and centromere 3, 7, 12, and 18 probes.

Results

CNS MZBCLs preferentially affect middle-aged women (female-to-male ratio, 4:1), with 93% presenting as dural-based masses mimicking meningioma. Ten patients with 1 to 7.6 years of follow-up after diagnosis showed no evidence of disease after radiation and/or chemotherapy. Like MZBCLs outside of the CNS, they consisted of CD20+, CD3−small B lymphocytes with varying degrees of plasmacytic differentiation and predominantly κ light-chain restriction (78%). Lymphoid follicles with follicular colonization were seen in three patients and deposition of amyloid was noted in samples from two patients, one of which was tumefactive. Neither Bcl-6 protein nor Epstein-Barr virus–encoded RNA was expressed. Trisomy 3 was detected in six of 12 patients, with no rearrangements of MALT1 or IgH and no trisomies of 7, 12, or 18 detected.

Conclusion

Our data suggest that intracranial MZBCL is an indolent primary CNS lymphoma that typically presents as a meningioma-like dural-based mass. Trisomy 3, but not MALT1 or IgH translocation, is a common genetic abnormality that may contribute to the pathogenesis of this CNS lymphoma.
Lymphocyte-Rich Classical Hodgkin's Lymphoma: Clinical Presentation and Treatment Outcome in 100 Patients Treated Within German Hodgkin's Study Group Trials
Authors: Shimabukuro-Vornhagen Alexander , Haverkamp Heinz , Engert Andreas , Balleisen Leopold , Majunke Peter , Heil Günther , Eich Hans Theodor , Stein Harald , Diehl Volker , Josting Andreas
Published: July 2005

Purpose

To investigate the clinical characteristics and treatment outcome of patients with lymphocyte-rich classical Hodgkin's lymphoma (LRCHL) compared with other histologic subtypes of Hodgkin's lymphoma (HL).

Patients and Methods

From a total of 2,715 patients with biopsy-proven HL treated within the trials HD7 to HD12 of the German Hodgkin's Study Group, 100 patients (4%) with LRCHL, 145 patients (5%) with lymphocyte-predominant HL (LPHL), 1,688 patients (62%) with nodular sclerosis, 731 patients (27%) with mixed cellularity, and 23 patients (1%) with lymphocyte depletion were identified. Patients with LRCHL had a median age of 38 years (range, 16 to 74 years).

Results

Compared with other histologic subtypes, patients with LRCHL are, on average, older and usually present with early stages of disease (stage I, 34%; stage II, 46%). The median time of follow-up was 32.2 months (95% CI, 28.2 to 37.0 months). Complete and partial remission was achieved in 96 patients (96%) and four patients (4%), respectively, with LRCHL. The event-free and overall survival rates were 97% (95% CI, 96.7% to 96.9%) and 97% (95% CI, 96.8% to 97.0%), respectively, at 30 months. Only three patients died; all of the deaths were caused by treatment-related toxicities.

Conclusion

LRCHL is a distinct subtype of CHL, with features of CHL and LPHL, and is a rare entity accounting for only 4% of HLs. LRCHL has a different pattern of clinical presentation and age and sex distribution than other CHLs. It is associated with an excellent prognosis if treated with current treatment regimens. When treating patients with LRCHL, great attention should be paid to avoid acute toxicities.
Function of the ETS transcription factor Yan in border cell migration
Authors: Schober Markus , Rebay Ilaria , Perrimon Norbert
Published: July 2005

Invasive cell migration in both normal development and metastatic cancer is regulated by various signaling pathways, transcription factors and cell-adhesion molecules. The coordination between these activities in the context of cell migration is poorly understood. During Drosophilaoogenesis, a small group of cells called border cells exit the follicular epithelium to perform a stereotypic, invasive migration. We find that the ETS transcription factor Yan is required for border cell migration and that Yan expression is spatiotemporally regulated as border cells migrate from the anterior pole of the egg chamber towards the nurse cell-oocyte boundary. Yan expression is dependent on inputs from the JAK/STAT, Notch and Receptor Tyrosine Kinase pathways in border cells. Mechanistically, Yan functions to modulate the turnover of DE-Cadherin-dependent adhesive complexes to facilitate border cell migration. Our results suggest that Yan acts as a pivotal link between signal transduction, cell adhesion and invasive cell migration in Drosophila border cells.
Depletion of TSG101 forms a mammalian `Class E' compartment: a multicisternal early endosome with multiple sorting defects
Authors: Doyotte Aurelie , Russell Matthew R. G. , Hopkins Colin R. , Woodman Philip G.
Published: July 2005

The early endosome comprises morphologically distinct regions specialised in sorting cargo receptors. A central question is whether receptors move through a predetermined structural pathway, or whether cargo selection contributes to the generation of endosome morphology and membrane flux. Here, we show that depletion of tumour susceptibility gene 101 impairs the selection of epidermal growth factor receptor away from recycling receptors within the limiting membrane of the early endosome. Consequently, epidermal growth factor receptor sorting to internal vesicles of the multivesicular body and cargo recycling to the cell surface or Golgi complex are inhibited. These defects are accompanied by disruption of bulk flow transport to the lysosome and profound structural rearrangement of the early endosome. The pattern of tubular and vacuolar domains is replaced by enlarged vacuoles, many of which are folded into multicisternal structures resembling the `Class E' compartments that define several Saccharomyces cerevisiae vacuolar protein sorting mutants. The cisternae are interleaved by a fine matrix but lack other surface elaborations, most notably clathrin.
Early growth response proteins EGR-4 and EGR-3 interact with immune inflammatory mediators NF-κB p50 and p65
Authors: Wieland Gerhard D. , Nehmann Nina , Müller Doreen , Eibel Hermann , Siebenlist Ulrich , Sühnel Jürgen , Zipfel Peter F. , Skerka Christine
Published: July 2005

Here, we characterize the basis for the T-cell-specific activity of the human zinc-finger protein early growth response factor 4 (EGR-4). A yeast two-hybrid screen showed interaction of EGR-4 with NF-κB p50. Using recombinant proteins, stable physical complex formation was confirmed for EGR-4 and EGR-3 with p50 and with p65 using glutathione-S-transferase pull-down assays and surface-plasmon-resonance and peptide-spot analyses. In vivo interaction of EGR-4 and EGR-3 with NF-κB p65 was demonstrated by immunoprecipitation experiments and fluorescence-resonance-energy transfer (FRET) analysis showing interaction in the nucleus of transfected Jurkat T cells. In transfection assays, EGR-p50 complexes were transcriptionally inactive and EGR-p65 complexes strongly activated transcription of the promoters of the human genes encoding the cytokines interleukin 2, tissue necrosis factor α and ICAM-1. The EGR-p65 complexes increased reporter-gene activity about 100-fold and thus exceeded the transcriptional activities of the p65 homodimer and the p65/p50 heterodimers. The major interaction domain for p65 was localized within the third zinc finger of EGR-4 using deletion mutants for pull-down assays and peptide-spot assays. By computer modeling, this interaction domain was localized to an α-helical region and shown to have the central amino acids surface exposed and thus accessible for interaction. In summary, in T cells, the two zinc-finger proteins EGR-4 and EGR-3 interact with the specific nuclear mediator NF-κB and control transcription of genes encoding inflammatory cytokines.
HOPS: a novel cAMP-dependent shuttling protein involved in protein synthesis regulation
Authors: Fazia Maria Agnese Della , Castelli Marilena , Bartoli Daniela , Pieroni Stefania , Pettirossi Valentina , Piobbico Danilo , Viola-Magni Mariapia , Servillo Giuseppe
Published: July 2005

The liver has the ability to autonomously regulate growth and mass. Following partial hepatectomy, hormones, growth factors, cytokines and their coupled signal transduction pathways have been implicated in hepatocyte proliferation. To understand the mechanisms responsible for the proliferative response, we studied liver regeneration by characterization of novel genes that are activated in residual hepatocytes. A regenerating liver cDNA library screening was performed with cDNA-subtracted probes derived from regenerating and normal liver. Here, we describe the biology of Hops (for hepatocyte odd protein shuttling). HOPS is a novel shuttling protein that contains an ubiquitin-like domain, a putative NES and a proline-rich region. HOPS is rapidly exported from the nucleus and is overexpressed during liver regeneration. Evidence shows that cAMP governs HOPS export in hepatocytes of normal and regenerating liver and is mediated via CRM-1. We demonstrate that HOPS binds to elongation factor eEF-1A and interferes in protein synthesis. HOPS overexpression in H-35-hepatoma and 3T3-NIH cells strongly reduces proliferation.
The duration, magnitude and compartmentalization of ERK MAP kinase activity: mechanisms for providing signaling specificity
Authors: Ebisuya Miki , Kondoh Kunio , Nishida Eisuke
Published: July 2005

ERK MAP kinase signaling plays a pivotal role in diverse cellular functions, including cell proliferation, differentiation, migration and survival. One of the central questions concerning this signaling is how activation of the same protein kinase, ERK, elicits distinct cellular outcomes. Recent progress has demonstrated that differences in the duration, magnitude and subcellular compartmentalization of ERK activity generate variations in signaling output that regulate cell fate decisions. Furthermore, several molecules have been identified as spatial, temporal or strength-controlling regulators of ERK activity. Signaling by various extracellular stimuli thus could be modulated by these regulators to give qualitative and quantitative differences in ERK activity, which are then interpreted by the cells as determinants for appropriate responses.
Infrared Study of Phenyl Acetate in Dilute Solutions
Authors: Nyquist R. A. , Settineri S. E.
Published: July 2005

Two bands of significant intensity are observed for phenyl acetate in CHCl3 and/or CCl4 solution. The experimental data indicate that the two bands result from carbonyl stretching in Fermi resonance (FR) with a combination tone, and the amount of FR interaction changes with change in the mole % CHCl3/CCl4 or from change in the reaction field of the CHCl3/CCl4 solution. In general the vC=O frequencies decrease as the acceptor number (AN) of the solvent increases. The correlation is not linear, and it is suggested that steric factors hindering the intermolecular association between solute and solvent are involved in these cases. However, in alcohol solutions intermolecular hydrogen bonding between the alcoholic OH proton and the carbonyl group of phenyl acetate (ROH: O=C) is a contributing factor to this nonlinear correlation.
Parametric Effects on Plasma Emission Produced during Excimer Laser Ablation of YBa2Cu3O7-x
Authors: Geyer T. J. , Weimer W. A.
Published: July 2005

The effects of changes in experimental parameters on the plasma emission spectra produced during excimer laser ablation of YBa2Cu3O7 were investigated. Emission from YO is observed for low-incident laser fluences, but is absent for fluences at or above those used for thin film deposition by laser ablation. Excitation within the plasma appears to be primarily due to electron impact. The effects of incident laser fluence and ambient gas pressure on the plasma emission are distinct enough to allow adjustment of either parameter based on the observed change in the emission spectrum. Therefore, optical emission spectroscopy is well suited as a technique for in situ monitoring of the deposition of thin films by laser ablation.
Raman Microprobe Spectroscopy of Uranium Dioxide Single Crystals and Ion Implanted Polycrystals
Authors: Graves P. R.
Published: July 2005

Polarized Raman spectra of uranium dioxide single crystals were recorded with the use of a Raman microprobe. Results showed a peak at 448 cm−1, having only off-diagonal tensor elements, which was assigned to the T2 g zone center phonon. There was also a broad peak at 1156 cm−1, which was ascribed to electronic Raman scattering. Kr ion implantation of urania polycrystalline pellets produced changes in the Raman spectrum of the implanted specimens. In addition to the two bands observed for the single-crystal material, there was a peak at 576 cm−1. This frequency corresponds to a peak in the calculated phonon density of states and indicates that the scattering is due to a breakdown in the selection rules caused by lattice damage resulting from implantation.
Evaluation of a New Array Detector Atomic Emission Spectrometer for Inductively Coupled Plasma Atomic Emission Spectroscopy
Authors: Pilon Michael J. , Denton M. Bonner , Schleicher Robert G. , Moran Paul M. , Smith Stanley B.
Published: July 2005

A unique echelle spectrometer system employing charge injection device (CID) array detector technology for use in inductively coupled plasma atomic emission spectroscopy (ICP-AES) is described. Due to improvements in optical design, this system offers increased wavelength coverage and improved light throughput over those of previous systems. Low sensitivity in the far-ultraviolet has been considered a major draw-back when silicon-based detectors are used, due to absorbance in the insulating SiO2 layer. The problem has been overcome through the use of a wavelength conversion phosphor. Therefore, detection limits comparable to those available with most commercial instruments have been obtained even in the far-UV. Operating parameters including precision, resolution, and background correction are also discussed. An analysis of the National Institute of Standards and Technology (NIST) Standard Reference Material (SRM) 1643b demonstrates that the system is capable of simultaneously determining at least 15 elements using 31 emission wavelengths with a high degree of accuracy.
Characterization and Optimization of a Direct Injection Nebulizer for Introduction of Organic Solvents and Volatile Analyte Species into an Inductively Coupled Plasma
Authors: Avery Thomas W. , Chakrabarty Chitra , Thompson Joseph J.
Published: July 2005

A direct injection nebulizer (DIN) is evaluated as a means of introducing organic solvents and volatile analyte species into an inductively coupled plasma atomic emission spectrometer (ICP-AES). The DIN used in this work differs in several important aspects from a commercially available DIN, after which it is patterned. When used for flow injection analysis, the DIN exhibits a long-term precision of about 4% RSD while nebulizing pure organic solvents. Under normal operating conditions, detection limits are generally an order of magnitude worse in organic solvents than in water, but they can usually be improved by using higher forward powers and viewing higher in the plasma. Measurements of the atom/ion line intensity ratios of copper under various conditions indicate that a large but nearly constant degree of plasma cooling exists when organic solvents are nebulized. When compared to a Meinhard nebulizer-ICP system, the DIN-ICP system gives more uniform response towards different chemical species of the same element, even when great differences in volatility exist between the species.
Continuous-Flow Determination of Trace Iodine by Atmospheric-Pressure Helium Microwave-Induced Plasma Atomic Emission Spectrometry Using Generation of Volatile Iodine from Iodide
Authors: Nakahara Taketoshi , Yamada Syugo , Wasa Tamotsu
Published: July 2005

A simple continuous-flow generation of volatile iodine by oxidation of aqueous iodide is described for the determination of low concentrations of iodine by atmospheric-pressure helium microwave-induced plasma atomic emission spectrometry (MIP-AES) in the normal ultraviolet (UV) and vacuum ultraviolet (VUV) regions of the spectrum. For measuring spectral lines in the VUV region, the monochromator and the enclosed external optical path between the MIP source and the entrance slit of the monochromator have both been purged with nitrogen to minimize oxygen absorption below 190 nm. Iodine atomic emission lines at 206.16 and 183.04 nm have been selected as the analytical lines. Of various oxidation reactions examined, an oxidizing solution of 1.0 mM sodium nitrite in 5.0 M sulfuric acid is the most favorable for the generation of elemental iodine. The gaseous iodine is separated from the solution in a simple gas/liquid separator and swept into the helium stream of a microwave-induced plasma for analysis. The best attainable detection limits (3 σ criterion) for iodine at 183.04 and 206.16 nm were 2.3 and 3.2 ng/mL, respectively, with the corresponding background equivalent concentrations of 60 and 118 ng/mL in iodine concentration. The typical analytical working graphs obtained under the optimized experimental conditions were rectilinear over approximately 4 and 3 orders of magnitude in concentration for the 206.16- and 183.04-nm iodine lines, respectively.
Raman Spectroscopy Using an Echelle Spectrograph with CCD Detection
Authors: Pelletier M. J.
Published: July 2005

This report describes the design and performance of an f/1.9, 0.1-m-focal-length echelle spectrograph custom-designed for Raman spectroscopy using charge-coupled device (CCD) detection. This device simultaneously acquires data over a range of nearly 5000 cm−1 at 2 cm−1 resolution (resolution limited by detector granularity). Twenty-five of these spectra, corresponding to different locations on the entrance slit, are simultaneously collected in a single CCD image. With the use of 200 mW of laser power and 1 second of data acquisition time, individual cyclohexane spectra from the set of 25 had signal-to-noise ratios of 85 in the CH-stretching region.
Laser-Induced Optoacoustic Spectroscopy (LIOAS) of Proteins: Spectrum of Bovine Serum Albumin in the 532–670 nm Region
Authors: Roveri Oscar A. , Bilmes Gabriel M. , Heihoff Klaus , Braslavsky Silvia E.
Published: July 2005

Bovine serum albumin, as well as other proteins, produces optoacoustic signals when excited with a laser pulse at wavelengths from 532 to 670 nm, a region where these proteins have no reported absorption. Signals from filtered solutions (obtained at low fluences) exhibited a linear dependence on laser energy and on protein concentration. Hence, they are attributed to radiationless deactivation following weak absorption in the visible region. Molar absorption coefficients calculated for different proteins showed a similar wavelength dependence, albeit with different absolute values—differences that could not be simply correlated to the content of known protein chromophores, such as tryptophan, tyrosine, and peptide bond. Moreover, at 532 nm, such chromophores produced optoacoustic signals only slightly higher than those from the buffer. On the other hand, a synthetic copolymer of tryptophan and lysine produced signals of a magnitude comparable to those from the proteins. Therefore, the weak absorption detected by laser-induced optoacoustics should be attributed to a not-yet-well-established feature of the structure of the protein, probably related to charge transfer interactions between different amino acids. Regardless of their origin, these signals must be taken into account when chromophoric prosthetic groups are studied with the use of laser-induced optoacoustic spectroscopy.
Doppler-Free Laser Polarization Spectroscopy Using a Demountable DC Cathode Discharge Cell as a Trace Concentration Atomizer
Authors: Luena Glen A. , Tong William G.
Published: July 2005

The use of a demountable hollow cathode discharge atomizer in Doppler-free polarization spectroscopy is described for hyperfine structure analysis at trace analyte concentrations/sizes using a continuous-wave ring dye laser. Using a low-pressure demountable plasma cell in laser polarization spectroscopy yields several advantages. In addition to cancellation of Doppler broadening, Lorentzian-broadening is minimized due to low-pressure atomization in the cathode discharge cell. This in turn increases spectral resolution enough to allow isotope ratio and hyperfine structure analysis. In addition, a demountable hollow cathode cell as atomizer offers convenient and efficient small-sample (10 ng) introduction in both liquid or solid form.
Laser Vibrational Spectroscopy of Transient, Weakly Bound, and Reactive Molecules
Authors: Dai Hai-Lung
Published: July 2005

Using laser spectroscopic techniques, namely Stimulated Emission Spectroscopy (SES) and Stark Level Crossing Spectroscopy, in combination with molecular beam techniques, we can now study vibrational levels with energies from zero to tens-of-thousands wavenumbers with sub-Doppler resolution and single rotational level selectivity. Molecular species with concentrations as low as 10−4 Torr can be studied. Low-frequency intermolecular van der Waals vibrational levels in a weakly bound complex can be directly observed for the elucidation of intermolecular forces. Short-lived radicals can be studied at high vibrational excitation. The dissociation behavior of a molecule with vibrational energy higher than the dissociation barrier can be examined with single vibrational quantum state resolution.
Real Sample Analysis by ETA-LEAFS with Background Correction: Application to Gold Determination in River Water
Authors: Remy B. , Verhaeghe I. , Mauchien P.
Published: July 2005

Laser-induced fluorescence has been demonstrated to be a very powerful technique for ultratrace analysis in liquid samples. This paper presents results obtained for gold analysis in river water. Single-step excited direct line fluorescence is performed in a commercial graphite furnace tube atomizer. A specially designed dual monochromator setup is used to correct background fluorescence resulting from a high concentration of molecular species in the matrix. Sensitivity is illustrated by detection limits obtained in pure water (4 fg for cobalt and 10 fg for gold), and the background correction efficiency is demonstrated by the analysis of gold in river water at 300 fg level with a 15% precision.
Detection of Propane by IR-ATR in a Teflon®-Clad Fluoride Glass Optical Fiber
Authors: Ruddy V. , McCabe S.
Published: July 2005

The detection of propane with the use of ATR spectroscopy at 3.3 µm, as the gas diffuses through the Teflon® cladding of a fluoride optical fiber, is reported. A theoretical expression for the time-dependent absorbance of the fiber sensor as a function of diffusion coefficient and cladding dimensions is developed. The experimental data fitted to the model give a diffusion coefficient of 8.85 × 10−14 m2 s−1 for propane in Teflon®. The potential of the technique for remote or distributed sensing of hydrocarbons is discussed.