bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Hydrophobic Residues in the Central Ectodomain of gp41 in Maintaining the Association between Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Subunits gp120 and gp41
Authors: York Joanne , Nunberg Jack H. 
Published: April 2004

ABSTRACT
The interaction between the gp120 and gp41 subunits of the human immunodeficiency virus envelope glycoprotein serves to stabilize the virion form of the complex and to transmit receptor-induced conformational changes in gp120 to trigger the membrane fusion activity of gp41. In this study, we used site-directed mutagenesis to identify amino acid residues in the central ectodomain of gp41 that contribute to the stability of the gp120-gp41 association. We identified alanine mutations at six positions, including four tryptophan residues, which result in mutant envelope glycoprotein complexes that fail to retain gp120 on the cell surface. These envelope glycoproteins readily shed their gp120 and are unable to mediate cell-cell fusion. These findings suggest an important role for the conserved bulky hydrophobic residues in stabilizing the gp120-gp41 complex.
Intraepithelial γδ T Cells May Bridge a Gap between Innate Immunity and Acquired Immunity to Herpes Simplex Virus Type 2
Authors: Nishimura Hitoshi , Yajima Toshiki , Kagimoto Yoshiko , Ohata Mutsuhiro , Watase Taketo , Kishihara Kenji , Goshima Fumi , Nishiyama Yukihiro , Yoshikai Yasunobu 
Published: April 2004

ABSTRACTMice depleted of γδ T cells by in vivo administration of anti-TCRγδ monoclonal antibodies showed susceptibility against an intravaginal infection with herpes simplex virus type 2 (HSV-2). The systemic Th1 response was impaired in the γδ T-cell-depleted mice. Mice deficient in the Vδ1 T subset were susceptible to an intravaginal infection with HSV-2. Intraepithelial γδ T cells bearing Vδ1 may help protect against intravaginal infection with HSV-2 through promoting the systemic Th1 response.
Mutagenesis of Tyrosine 24 in the VPg Protein Is Lethal for Feline Calicivirus
Authors: Mitra Tanaji , Sosnovtsev Stanislav V. , Green Kim Y. 
Published: April 2004

ABSTRACT
The genome of feline calicivirus (FCV) is an ∼7.7-kb single-stranded positive-sense RNA molecule that is polyadenylated at its 3′ end and covalently linked to a VPg protein (calculated mass, 12.6 kDa) at its 5′ end. We performed a mutational analysis of the VPg protein in order to identify amino acids potentially involved in linkage to the genome and replication. The tyrosine residues at positions 12, 24, 76, and 104 were changed to alanines by mutagenesis of an infectious FCV cDNA clone. Viruses were recovered when Tyr-12, Tyr-76, or Tyr-104 of the VPg protein was changed to alanine, but virus was not recovered when Tyr-24 was changed to alanine. Growth properties of the recovered viruses were similar to those of the parental virus. We examined whether the amino acids serine, threonine, and phenylalanine could substitute for the tyrosine at position 24, but these mutations were lethal as well. A tyrosine at this relative position is conserved among all calicivirus VPg proteins examined thus far, suggesting that the VPg protein of caliciviruses, like those of picornaviruses and potyviruses, utilizes tyrosine in the formation of a covalent bond with RNA.
The Herpesvirus Saimiri Open Reading Frame (ORF) 50 (Rta) Protein Contains an AT Hook Required for Binding to the ORF 50 Response Element in Delayed-Early Promoters
Authors: Walters Matthew S. , Hall Kersten T. , Whitehouse Adrian 
Published: April 2004

ABSTRACT

The herpesvirus saimiri open reading frame (ORF) 50 encodes two proteins, which activate transcription directly, following interactions with delayed-early (DE) promoters containing a specific motif. In this report, we demonstrate that ORF 50 contains a DNA binding domain that has homology to an AT hook DNA binding motif. Deletion analysis of this domain reduces ORF 50-mediated transactivation of the DE ORF 6 and ORF 57 promoters by 100 and 90%, respectively. Furthermore, gel retardation experiments demonstrated that the AT hook motif is required for binding the ORF 50 response element in the promoters of DE genes. Single site-directed mutagenesis of the AT hook revealed that mutation of the glycine residue at position 408 to an alanine reduces ORF 50 transactivation of the ORF 57 promoter by 40%. Moreover, the mutation of multiple basic residues in conjunction with the glycine residue within the core element of the AT hook abolishes ORF 50-mediated transactivation. In addition, p50GFPΔAT-hook is capable of functioning as a
trans-
dominant mutant, leading to a reduction in virus production of approximately 50% compared to that for wild-type ORF 50.
Ror
γ (
Rorc
) Is a Common Integration Site in Type B Leukemogenic Virus-Induced T-Cell Lymphomas
Authors: Broussard Dana R. , Lozano Mary M. , Dudley Jaquelin P. 
Published: April 2004

ABSTRACT

The retrovirus type B leukemogenic virus (TBLV) causes T-cell lymphomas in mice. We have identified the
Ror
γ locus as an integration site in 19% of TBLV-induced tumors. Overexpression of one or more
Ror
γ isoforms in >77% of the tumors tested may complement apoptotic effects of c-
myc
overexpression.
MATERIAL PROPERTIES OF THE SUPRASPINATUS TENDON AT ITS INSERTION — A MEASUREMENT WITH THE SCANNING ACOUSTIC MICROSCOPY
Authors: Sano Hirotaka , Saijo Yoshifumi , Kokubun Shoichi 
Published: April 2004

The acoustic properties of the supraspinatus tendon insertions of three adult Japanese white rabbits (male, 3.2–3.5 kg) were measured by scanning acoustic microscopy (SAM). After cutting parallel to the supraspinatus tendon fibers, specimens were fixed with 10% neutralized formalin, embedded in paraffin and sectioned at 5 μm thickness. The sound speed and the attenuation constant along the articular surface of the tendon from the insertion site to the musculotendinous junction were measured by SAM. The two-dimensional distribution of the acoustic properties was displayed with color-coded scales and was compared to the histologic structure. Toluidine-blue staining and immunohistochemical staining against type II collagen were performed to determine the presence of fibrocartilage besides a standard Elastica–Masson staining to assess the overall histologic structure. The distribution of the sound speed and the attenuation constant showed an almost identical pattern. Both parameters were lower in the non-mineralized fibrocartilage than those in the tendon proper. The area indicating low sound speed corresponded well to the area of metachromasia and type II collagen. The non-mineralized fibrocartilage indicated softer material properties than the tendon proper, which could be interpreted as an adaptation for the various biomechanical stresses at the insertion site.
THE ASSESSMENT OF THE KINEMATICS OF THE CERVICAL SPINE USING OPEN (INTERVENTIONAL) MRI
Authors: Emohare O. , McGregor A. H. , Wragg P. , Gedroyc W. M. W. 
Published: April 2004

The scope of serial studies into the kinematics of the cervical vertebrae, have been limited by the methods available for imaging. Plain radiography has been one of the main methods by which data has been collected. The widespread use of this method has, however, been restricted by factors including exposure to ionizing radiation and magnification errors. With the advent of Interventional Magnetic Resonance (iMR) scanners, however, the authors sought to determine the utility of an iMR scanner in obtaining functional images of the cervical vertebrae, from which repeatable measurements of vertebral kinematics can be collected.20 healthy volunteers (mean age 25.4 ± 3.7 years) were recruited. They had their cervical vertebrae scanned in three positions: neutral, flexed and extended. Sagittal images were obtained for each subject from between the level of the C2 vertebra to the T1 vertebra and measurements of inter-segmental motion were made, using established clinical methodology.Clear images of the cervical vertebrae were obtained in all positions from which measures of motion were made. Greatest angular motions were found to occur in the mid-cervical level, C4/C5. Non-osseous structures, including the intervertebral discs and nerve roots were well visualized.Our results suggest that iMR scanning may have an important role in the imaging of cervical spine and its associated structures. It offers a modality that allows the determination of both normal and abnormal kinematics on a large scale.
MUSCLES WITHIN MUSCLES: ANATOMICAL AND FUNCTIONAL SEGMENTATION OF SELECTED SHOULDER JOINT MUSCULATURE
Authors: Wickham J. B. , Brown J. M. M. , McAndrew D. J. 
Published: April 2004

The objectives of this study were two-fold. Firstly we wished to investigate the segmental anatomy, geometry and gross innervation patterns of selected shoulder joint musculature (pectoralis major, latissimus dorsi and deltoid) to establish if these muscles could be anatomically subdivided according to predetermined criteria. We then wished to use this information to help determine if a segments activation pattern was reliant on an efficient line of action and a large moment arm for the intended movement. Surface electromyography was used for this purpose whilst manipulating the independent variable of contraction intensity (% MVC) during two shoulder joint flexion tasks. For the anatomical portion of the study the dissection of ten cadaveric shoulders revealed the deltoid to consist of seven segments whilst the pectoralis major and the latissimus dorsi were both ascribed six segments according to predetermined anatomical/functional criteria. Primary nerve branching was evident in each muscle but no apparent relationship existed between the designated anatomical segments and the primary nerve branches. Differences were evident in the geometry of each segment in regard to moment arms and orientations of each segments line of action. The functional portion of this study, which utilized miniature bipolar surface electrodes during the performance of a static shoulder joint flexion task at 75% and 25% MVC, showed significant differences (p<0.05) in the activation patterns of active segments between the two tasks. Specifically, a "drop out" of segments with smaller flexion moment arms and more diverging lines of action in comparison to the movement plane was evident for all subjects in the 25% MVC task in comparison to the 75% MVC task.
Complete remission of alopecia universalis after allogeneic hematopoietic stem cell transplantation
Authors: Seifert Bettina , Passweg Jakob R. , Heim Dominik , Rovó Alicia , Meyer-Monard Sandrine , Buechner Stanislaus , Tichelli Andre , Gratwohl Alois 
Published: April 2004

Abstract
This case report is on a 40-year-old male patient with chronic myeloid leukemia (CML) receiving an allogeneic hematopoietic stem cell transplantation (HSCT) in first chronic phase from an HLA-identical sibling brother. He suffered from alopecia universalis occurring 11 years previously. The alopecia involved all body hair, including eyebrows and eyelashes. Between day 40 and day 55 after transplantation, hair started to grow on the chin, eyelashes, and on the top of his head. Immunosuppression was stopped at 6 months because of cytogenetic relapse and incomplete donor chimerism with some renewed hair loss. He returned to full donor chimerism with mild chronic graft-versus-host disease and continued hair growth. With 2 years of follow-up he has remained in continuous remission. Chimerism analyses of hair follicles did not show any donor alleles. Alopecia universalis is probably a chronic autoimmune disorder, curable with replacement of the immune system with an allogeneic HSCT. (Blood. 2005;105:426-427)
Phase I Trial of Tirapazamine and Cyclophosphamide in Children With Refractory Solid Tumors: A Pediatric Oncology Group Study
Authors: Aquino Victor M. , Weitman Steve D. , Winick Naomi J. , Blaney Susan , Furman Wayne L. , Kepner James L. , Bonate Peter , Krailo Mark , Qu Wenchun , Bernstein Mark 
Published: April 2004

Purpose To determine the dose limiting toxicity (DLT), maximum-tolerated dose (MTD), and pharmacokinetic profile of tirapazamine (Sanofi Synthelabo Research, Malvern, PA) combined with cyclophosphamide in children with recurrent solid tumors. Patients and Methods Patients received a 2-hour infusion of tirapazamine, followed by 1,500 mg/m2 cyclophosphamide, and mesna once every 3 weeks. Dose escalation of tirapazamine began at 250 mg/m2 and was increased by 30% in subsequent cohorts. If DLT was hematologic, less-heavily pretreated patients were to be enrolled until their DLTs were encountered, and MTDs defined. Pharmacokinetic profiles were also characterized. Results Twenty-three patients were enrolled onto the study. Pharmacokinetic data were calculated for 22 patients. Prolonged neutropenia was the DLT at 420 mg/m2 in heavily pretreated patients. Grade 3, reversible ototoxicity was the DLT in less-heavily pretreated patients at 420 mg/m2. Two (one with neuroblastoma and one with rhabdomyosarcoma) had partial responses. One child with neuroblastoma had prolonged stable disease (10 cycles) at a dose of 250 mg/m2. This patient had disease detectable in the bone marrow only and all evidence of bone marrow involvement resolved for 17 cycles of therapy. Four other patients had stable disease. An apparent dose-proportional increase in tirapazamine maximal concentration and area under the curvelast was observed. Tirapazamine clearance, volume of distribution at steady-state, and terminal half-life did not appear to be dose-dependent. Conclusion The recommended dose of tirapazamine given with 1,500 mg/m2 of cyclophosphamide once every 3 weeks is 325 mg/m2. Neutropenia and ototoxicity were dose-limiting. Based on early evidence of antitumor activity, additional studies appear warranted.
Phase II Trial of Infusional Cyclophosphamide, Doxorubicin, and Etoposide in Patients With HIV-Associated Non-Hodgkin’s Lymphoma: An Eastern Cooperative Oncology Group Trial (E1494)
Authors: Sparano Joseph A. , Lee Sandra , Chen Michael G. , Nazeer Tipu , Einzig Avi , Ambinder Richard F. , Henry David H. , Manalo Jane , Li Tianhong , Von Roenn Jamie H. 
Published: April 2004

Purpose To determine the effectiveness of an infusional chemotherapy regimen in patients with HIV-associated lymphoma treated before and after the use of highly active antiretroviral therapy (HAART) in routine clinical practice. Patients and Methods Ninety-eight assessable patients with HIV-associated intermediate- or high-grade non-Hodgkin’s lymphoma received cyclophosphamide 200 mg/m2/d, doxorubicin 12.5 mg/m2/d, and etoposide 60 mg/m2/d (CDE) given by continuous intravenous infusion for 4 days (96 hours) every 4 weeks plus filgrastim. Concurrent antiretroviral treatment consisted of the nucleoside analog didanosine in the first 43 patients enrolled before December 1996 (pre-HAART group), or HAART in the remaining 55 patients enrolled after that time (HAART group). Results Complete response occurred in 44 patients (45%; 95% CI, 35% to 55%). Failure-free survival and overall survival (OS) at 2 years was 36% (95% CI, 26% to 46%) and 43% (95% CI, 33% to 53%), respectively. At the time of the analysis, 30% in the pre-HAART group were alive compared with 47% in the HAART group; when adjusted for varying length of follow-up, patients in the HAART group had improved OS (P = .039). Patients in the HAART group experienced less grade 4 nonhematologic toxicity (22% v 42%; P = .037), thrombocytopenia (31% v 52%; P = .033), and anemia (9% v 27%; P = .021), and had fewer treatment-associated deaths (0% v 10%; P = .013). Conclusion Infusional CDE is an effective and potentially curative regimen for patients with HIV-associated lymphoma. Patients treated in the HAART era have less chemotherapy-associated toxicity and improved survival.
Relationship of Baseline Serum Bilirubin to Efficacy and Toxicity of Single-Agent Irinotecan in Patients With Metastatic Colorectal Cancer
Authors: Meyerhardt Jeffrey A. , Kwok Ambrose , Ratain Mark J. , McGovren J. Patrick , Fuchs Charles S. 
Published: April 2004

Purpose To examine the predictive value of baseline serum bilirubin measurement for chemotherapy-related toxicity or efficacy among patients receiving irinotecan for metastatic colorectal cancer. Methods We performed a secondary analysis of a cohort of 287 patients treated in a multicenter, phase III study with single-agent irinotecan administered either weekly or once every 3 weeks. Patients were grouped into three categories of baseline bilirubin measurements (0 to 0.4, 0.5 to 0.9, and 1.0 to 1.5 mg/dL). We performed analyses of overall survival, time to progression, and treatment-related toxicity based on bilirubin category, as well as using bilirubin as a continuous variable. Results With a median follow-up of 15.8 months, baseline serum bilirubin was not predictive of 1-year survival (42.4%, bilirubin 0 to 0.4; 42.3%, bilirubin 0.5 to 0.9; 48.1%, bilirubin 1.0 to 1.5 mg/dL), median overall survival (10.1, 9.7, and 15.6 months, respectively; P = .5), or median time to progression (2.8, 3.0, and 4.1 months, respectively; P = .5). Patients with elevated bilirubin had a significantly greater risk grade 3 to 4 neutropenia; however, this was limited to patients treated on a weekly schedule (P trend = .03) and not once every 3 weeks (P trend = .8). Other toxicities were not significantly different by initial bilirubin measurement. Conclusion Although modest elevations of bilirubin (1.0 to 1.5 mg/dL) are associated with increased grade 3 to 4 neutropenia in patients treated with weekly irinotecan, baseline serum bilirubin does not reliably predict overall irinotecan-related toxicity or efficacy. Additional methods, including potential application of pharmacogenetic information, are needed to optimize irinotecan dosing and tailor therapy to individual patients.
Phase III Trial of Gemcitabine Plus Tipifarnib Compared With Gemcitabine Plus Placebo in Advanced Pancreatic Cancer
Authors: Van Cutsem E. , van de Velde H. , Karasek P. , Oettle H. , Vervenne W.L. , Szawlowski A. , Schoffski P. , Post S. , Verslype C. , Neumann H. , Safran H. , Humblet Y. , Perez Ruixo J. , Ma Y. , Von Hoff D. 
Published: April 2004

Purpose To determine whether addition of the farnesyltransferase inhibitor tipifarnib (Zarnestra, R115777; Johnson and Johnson Pharmaceutical Research and Development, Beerse, Belgium) to standard gemcitabine therapy improves overall survival in advanced pancreatic cancer. Patients and Methods This randomized, double-blind, placebo-controlled study compared gemcitabine + tipifarnib versus gemcitabine + placebo in patients with advanced pancreatic adenocarcinoma previously untreated with systemic therapy. Tipifarnib was given at 200 mg bid orally continuously; gemcitabine was given at 1,000 mg/m2 intravenously weekly × 7 for 8 weeks, then weekly × 3 every 4 weeks. The primary end point was overall survival; secondary end points included 6-month and 1-year survival rates, progression-free survival, response rate, safety, and quality of life. Results Six hundred eighty-eight patients were enrolled. Baseline characteristics were well balanced between the two treatment arms. No statistically significant differences in survival parameters were observed. The median overall survival for the experimental arm was 193 v 182 days for the control arm (P = .75); 6-month and 1-year survival rates were 53% and 27% v 49% and 24% for the control arm, respectively; median progression-free survival was 112 v 109 days for the control arm. Ten drug-related deaths were reported for the experimental arm and seven for the control arm. Neutropenia and thrombocytopenia grade ≥ 3 were observed in 40% and 15% in the experimental arm versus 30% and 12% in the control arm. Incidences of nonhematologic adverse events were similar in two groups. Conclusion The combination of gemcitabine and tipifarnib has an acceptable toxicity profile but does not prolong overall survival in advanced pancreatic cancer compared with single-agent gemcitabine.
Tumor Recurrence and Survival in Patients Treated for Thymomas and Thymic Squamous Cell Carcinomas: A Retrospective Analysis
Authors: Ströbel Philipp , Bauer Andrea , Puppe Bernhard , Kraushaar Til , Krein Axel , Toyka Klaus , Gold Ralf , Semik Michael , Kiefer Reinhard , Nix Wilfred , Schalke Berthold , Müller-Hermelink Hans Konrad , Marx Alexander 
Published: April 2004

Purpose Thymic epithelial tumors (TET) are rare epithelial neoplasms of the thymus with considerable histologic heterogeneity. This retrospective study focused on the correlation of WHO-defined TET histotypes with survival and tumor recurrence in a large cohort of patients receiving different modes of treatment. Patients and Methods Two hundred twenty-eight patients were followed for up to 21 years (median, 60 months; range, 1 to 252 months) after primary surgery. Forty-two patients received adjuvant radiotherapy (mean dose, 53 Gy), and 33 patients recieved adjuvant chemotherapy. Results Seventy-six (88%) of 86 patients with WHO type A, AB, and B1 thymomas were treated by surgery alone, with three tumor relapses after 3 to 10 years (median, 3.4 years). Twelve of 67 patients with WHO type B2 and B3 thymomas in Masaoka stages I and II were treated by adjuvant radiotherapy without evidence of tumor recurrence after 1 to 12 years (median, 4 years). Among 75 patients with B2 and B3 thymomas with incomplete resection or a tumor stage III or higher, the recurrence rate was 34% (n = 23) after 0.5 to 17 years (median, 5 years) in patients receiving adjuvant radiochemotherapy, compared to 78% (seven of nine patients) in patients without adjuvant radiochemotherapy. Incomplete tumor resection was associated with a high recurrence rate (65%) and a poor prognosis (P < .01). Conclusion The long-term outcome of TET patients is related to tumor stage, WHO histotype, completeness of surgical removal, and type of treatment. Prospective trials are warranted to formally address the efficacy of adjuvant therapy in the treatment of localized and advanced malignant TETs.
Cadmium induces both pyruvate kinase and Na+/H+exchanger activity through protein kinase C mediated signal transduction, in isolated digestive gland cells ofMytilus galloprovincialis(L.)
Authors: Dailianis Stefanos , Kaloyianni Martha 
Published: April 2004

SUMMARYThe present study investigates the transduction pathway mediated by cadmium in isolated digestive gland cells of mussel Mytilus galloprovincialis. The effects of cadmium treatment on a key glycolytic enzyme, pyruvate kinase (PK), and on Na+/H+ exchanger activity were examined. Cadmium (50 μmol l–1) caused a significant elevation of intracellular pH (pHi) and a rise (176%) of Na influx relative to control values. The amiloride analogue, EIPA (20 nmol l–1), a Na+/H+ exchanger blocker,together with cadmium, significantly reduced the effect of treatment by cadmium alone on both Na+ influx and pHi. In addition, PK activity was significantly increased after treatment with cadmium. PK activity was inhibited after treatment of cells with amiloride or EIPA together with cadmium. Moreover, phorbol-ester (PMA), a potent activator of protein kinase C(PKC), caused a significant rise in both pHi and PK activity, while staurosporine or calphostin C reversed both events. Adrenaline, isoprenaline and phenylephrine alone or together with cadmium also significantly increased the pHi and PK activity of isolated digestive gland cells. The latter effectors in combination with cadmium showed a synergistic effect on pHi and PK. These responses seem to be blocked by propranolol, metoprolol and prazosin. Our findings suggest a hormone-like effect of cadmium on digestive gland cells. The signal transduction pathway induced by cadmium involves the stimulation of PK, PKC and Na+/H+ exchanger in isolated digestive gland cells of Mytilus galloprovincialis.