bluuebunny/crossref_metadata_2025 huggingface dataset:
Localization of Nucleoside Triphosphate Diphosphohydrolase-1 (NTPDase1) and NTPDase2 in Pancreas and Salivary Gland
Authors: Kittel Agnes , Pelletier Julie , Bigonnesse François , Guckelberger Olaf , Kordás Krisztina , Braun Norbert , Robson Simon C. , Sévigny Jean
Published: June 2004

Ectonucleoside triphosphate diphosphohydrolases (NTPDases) are membrane-bound ectoenzymes that hydrolyze extracellular nucleotides. We investigated the distribution of NTPDase1 and NTPDase2 in murine salivary gland and pancreas. Histochemistry and immunostaining (by both light and electron microscopy), combined with functional assays, were used to describe the localization patterns and enzyme activities in the organs of wild-type and NTPDase1/cd39-null mice. Pancreatic acinar cells and salivary gland acinar/myoepithelial cells were positive for NTPDase1 and NTPDase2. Ecto-ATPase activity was slightly higher in salivary glands. Ductal epithelial cells expressed ecto-ATPase activity but NTPDase1 and NTPDase2 expression were weak at best. ATPase activity was found in blood vessels of both tissues and its localization pattern overlapped with NTPDase1 staining. In these structures, NTPDase2 antibodies stained the basolateral aspect of endothelial cells and the supporting cells. Biochemical assays and histochemical staining showed relatively high levels of ATPase activity in both glands of cd39−/− mice. Our data therefore support a physiological role for NTPDase2 and other ectonucleotidases in the pancreas and salivary glands. Because NTPDase1 is expressed in non-vascular cell types, this finding suggests that NTPDase1 may have functions in the gastrointestinal tract that differ from those demonstrated in the vascular system. (J Histochem Cytochem 52:861–871, 2004)
Microdissected Region-specific Gene Expression Analysis with Methacarn-fixed, Paraffin-embedded Tissues by Real-time RT-PCR
Authors: Takagi Hironori , Shibutani Makoto , Kato Natsumi , Fujita Haruka , Lee Kyoung-Youl , Takigami Shu , Mitsumori Kunitoshi , Hirose Masao
Published: June 2004

We have previously shown methacarn to be a versatile fixative for analysis of proteins, DNA, and RNA in paraffin-embedded tissues (PETs). In this study we analyzed its suitability for quantitative mRNA expression analysis of microdissected PET specimens using a real-time RT-PCR technique. Fidelity of expression in the methacarn-fixed PET sections, with reference to dose-dependent induction of cytochrome P450 2B1 in the phenobarbital-treated rat liver, was high in comparison with the unfixed frozen tissue case, even after hematoxylin staining. RNA yield from methacarn-fixed PET sections was equivalent to that in unfixed cryosections and was also not significantly affected by hematoxylin staining. Correlations between the expression levels of target genes and input amounts of extracted RNA in the range of 1–1000 pg were very high (correlation coefficients >0.98), the regression curves being similar to those with unfixed cryosections. Although cell numbers should be optimized for each target gene/tissue, ≥200 cells were necessary for accurate measurement in 10-μm-thick rat liver sections judging from the variation of measured value in small microdissected areas. These results indicate high performance with methacarn, close to that of unfixed tissues, regarding quantitative expression analysis of mRNAs in microdissected PET-specimens. (J Histochem Cytochem 52:903–913, 2004)
Neurocan–GFP Fusion Protein
Authors: Zhang Hui , Baader Stephan L. , Sixt Michael , Kappler Joachim , Rauch Uwe
Published: June 2004

Hyaluronan is an unsulfated glycosaminoglycan (GAG) that is ubiquitously expressed in the extracellular matrix (ECM) of all vertebrates, where hyaluronan rich matrices constitute a particular permissive environment for the development of complex biological structures and also for tumor progression. Because of its conserved structure and ubiquitous expression, antibodies for its histochemical detection cannot be produced. We have engineered a fusion protein, neurocan–GFP, and expressed it as a secreted molecule in mammalian cells. Neurocan–GFP fusion protein specifically binds to hyaluronan and directly visualizes hyaluronan on tissue sections, revealing a very detailed picture of hyaluronan distribution. The fluorescent fusion protein can be used in combination with antibodies and nuclear markers for double or triple staining. In addition, it is suitable to visualize hyaluronan on living cells by time-lapse video microscopy. The successful production and application of the neurocan–GFP fusion protein opens up new perspectives for using GFP fusion proteins as detection tools in histological and cytological studies complementing conventional antibody and biotin/avidin techniques. (J Histochem Cytochem 52:915–922, 2004)
Presence and Distribution of Cholinergic Nerves in Rat Mediastinal Brown Adipose Tissue
Authors: Giordano Antonio , Frontini Andrea , Castellucci Mario , Cinti Saverio
Published: June 2004

Brown adipose tissue (BAT) is richly provided with sympathetic noradrenergic nerves but is believed to lack a parasympathetic nerve supply. Acetylcholine is the predominant transmitter of postganglionic parasympathetic nerves. The vesicular acetylcholine transporter (VAChT) resides in synaptic vesicles of cholinergic nerve terminals and is used as a marker for peripheral cholinergic nerves. We sought cholinergic nerves in rat BAT using VAChT immunohistochemistry (IHC) on cryosections of interscapular, cervical, mediastinal, and perirenal depots. Mediastinal BAT was the sole depot provided with putative parasympathetic perivascular and parenchymal cholinergic nerves. The absence of vasoactive intestinal peptide-positive nerves suggested their nature as pure cholinergic fibers. By confocal microscopy, both cholinergic and noradrenergic nerves were detected in mediastinal BAT. Cold exposure and fasting led to increased density of VAChT-positive fibers and of noradrenergic sympathetic nerves at morphometry. The unexpected double innervation of mediastinal BAT may explain the inhibitory influence on thermogenesis observed after systemic injection of muscarinic antagonists in rats, and raises questions about the physiological role of its cholinergic nerve supply. (J Histochem Cytochem 52:923–930, 2004)
The Developmental Transcription Factor Slug Is Widely Expressed in Tissues of Adult Mice
Authors: Parent Allison E. , Choi Changsun , Caudy Kristin , Gridley Thomas , Kusewitt Donna F.
Published: June 2004

The Slug transcription factor plays an important role in epithelial-mesenchymal transformation during embryogenesis and is expressed in adult tissues during carcinogenesis. By detecting expression of a Slug–β-galactosidase fusion protein, we have now demonstrated that Slug is also re-expressed in a variety of normal tissues in the adult mouse. Slug is expressed at relatively high levels in patchy stretches of basal cells in stratified and pseudostratified epithelium, including skin, oral mucosa, esophagus, stomach, rectum, cervix, and trachea. Slug is also found at variable levels in fibroblasts and stromal smooth muscle cells in many tissues. Sites of more intense Slug expression in mesenchymal tissues include cartilage, kidney glomeruli, lung, ovary, and uterus. Therefore, Slug expression is not restricted to the period of embryonic development or to pathological processes. The pattern of localization to basal cells in various epithelia suggests that Slug may play a role in the cell migration that occurs during continual renewal of these tissues. (J Histochem Cytochem 52:959–965, 2004)
Triple Immunofluorescent Labeling of FtsZ, Dynamin, and EF-Tu Reveals a Loose Association Between the Inner and Outer Membrane Mitochondrial Division Machinery in the Red Alga Cyanidioschyzon merolae
Authors: Nishida Keiji , Misumi Osami , Yagisawa Fumi , Kuroiwa Haruko , Nagata Toshiyuki , Kuroiwa Tsuneyoshi
Published: June 2004

In the mitochondria of primitive eukaryotes, FtsZ and dynamin are part of the machinery involved in division of the inner and outer membranes, respectively. These genes also commonly function in the same manner during chloroplast division. In this study, a relationship between the localization of the inner and outer division machinery was directly shown for the first time. Triple immunofluorescent labeling was performed in the red alga Cyanidioschyzon merolae by a device using narrow bandpass filter sets and bright photostable dyes. FtsZ (CmFtsZ1) and dynamin (CmDnm1) localizations were examined simultaneously throughout the mitochondrial division cycle with an alternative mitochondrial marker protein, the mitochondrial translation elongation factor EF-Tu, whose localization was also shown to be identical to the mitochondrial matrix. FtsZ and dynamin did not necessarily co-localize when both were recruited to the mitochondrial constriction site, indicating that inner and outer dividing machineries are not in tight association during the late stage of division. (J Histochem Cytochem 52:843–849, 2004)
Detection of Genetic Variants of Transthyretin by Liquid Chromatography–Dual Electrospray Ionization Fourier-Transform Ion-Cyclotron-Resonance Mass Spectrometry
Authors: Nepomuceno Angelito I , Mason Christopher J , Muddiman David C , Bergen H Robert , Zeldenrust Steven R
Published: June 2004

Background: One of the numerous proteins causing amyloidosis is transthyretin (TTR), a protein usually responsible for the transport of thyroxine and retinol-binding protein. Variants within TTR cause it to aggregate and form insoluble fibers that accumulate in tissue, leading to organ dysfunction.

Methods: TTR was immunoprecipitated from serum by use of a polyclonal antibody and subsequently reduced with tris(2-carboxyethyl)phosphine. The purified TTR was then analyzed by fast-gradient liquid chromatography–dual-electrospray ionization Fourier-transform ion-cyclotron-resonance (FT-ICR) mass spectrometry. DNA sequencing was performed on all samples used in this study.

Results: Because of the inherent limitations in achieving high mass measurement accuracy based on the most abundant isotopic mass, we applied a fitting procedure that allowed determination of monoisotopic mass. Wild-type TTR (mean molecular mass, 13 761 Da) and its associated variant forms could be distinguished because of the high molecular mass accuracy afforded by FT-ICR (≤3 ppm) except for instances involving isobaric species or when isotopic distributions overlapped significantly. The [M + 11 H+]11+ charge state for all samples was used to determine the mass accuracies for both wild-type and variant forms of the protein. We correctly assigned seven of seven TTR variants. Moreover, using a combination of proteomic and genomic technologies, we discovered and characterized a previously unreported cis double mutation with a mass only 2 Da different from wild-type TTR. Furthermore, DNA sequencing of the TTR gene for all individuals in this study completely agreed with the intact protein measurements.

Conclusions: FT-ICR mass spectrometry has sufficient mass accuracy to identify genetic variants of immunoaffinity-purified TTR. We believe that 91% of known TTR variants could be detected by this technique.
Assessment of the Drug Interaction Between Alteplase and Nitroglycerin: An In Vitro Study
Authors: White C. Michael , Fan Chengde , Chen Bonnie P. , Kluger Jeffrey , Chow Moses S. S.
Published: June 2004

Alteplase is the most commonly administered thrombolytic agent in the United States. However, concurrent therapy with nitroglycerin reduces plasma alteplase concentrations and its clinical efficacy. We sought to determine if this interaction is concentration and pH dependent. Seventy plasma samples were prepared and divided into three groups: alteplase 500 IU/ml alone (group 1), alteplase 500 IU/ml plus nitroglycerin 5 ng/ml (group 2), and alteplase 500 IU/ml plus nitroglycerin 200 ng/ml (group 3). The samples were analyzed at time zero and 3 hours (incubated at 37°C). Group 1 had significantly higher plasma alteplase concentrations than group 3 (p<0.001). When alteplase and nitroglycerin are combined, the degradation of alteplase in plasma is enhanced.
Relationship between Benign Prostatic Hyperplasia and History of Coronary Artery Disease in Elderly Men
Authors: Weisman Kenneth M. , Larijani Ghassem E. , Goldstein Mark R. , Goldberg Michael E.
Published: June 2004

Study Objective. To assess the relationship between the occurrence of benign prostatic hyperplasia (BPH), an androgen‐dependent disease, and coronary artery disease (defined as history of coronary artery bypass grafting, coronary angioplasty, myocardial infarction) in elderly men.

Design. Retrospective chart review.

Setting. Urology practice.

Patients. Seven hundred two elderly men aged 65–80 years.

Intervention. The men's charts were reviewed for data pertaining to coronary artery disease, risk factors for coronary artery disease, and serum prostate‐specific antigen (PSA) levels. Men who had medical conditions, pharmacologic interventions, or surgical procedures that could alter PSA, and those taking lipid‐lowering agents were not included.

Measurements and Main Results. PSA levels correlate positively with prostatic volume of BPH. In men with levels under 1.0 μg/L (no BPH) and over 1.0 μg/L (BPH present), the frequency of coronary artery disease was 9% and 29%, respectively (p<0.03). No significant differences were noted between groups in other accepted risk factors for coronary artery disease including age, smoking, diabetes mellitus, or hypertension.

Conclusion. Smooth muscle proliferation is an important and possibly androgen‐dependent step in the development of atherosclerosis and BPH. Prospective studies are required to assess the effect of antiandrogens on atherosclerosis.
Underuse of Inhaled Corticosteroids in Adults with Asthma
Authors: Yuksel Nesé , Ginther Scott , Man Paul , Tsuyuki Ross T.
Published: June 2004

Despite strong evidence that inhaled corticosteroids are beneficial in treating asthma, a number of small studies suggest a use rate of only 34–56%. The primary objective of this study was to determine patterns of prescribing inhaled corticosteroids for high‐risk patients with asthma. Secondary objectives were to assess patterns of practice with respect to other agents prescribed before and at hospital discharge, and to determine if an emergency room asthma care map at one of the study hospitals was being followed. We retrospectively reviewed charts of 1022 patients with an acute attack of asthma treated in the emergency rooms of the Royal Alexandra Hospital and University of Alberta Hospital from January 1, 1996, to March 31, 1997. A forward stepwise logistic regression analysis was performed with the dependent variable defined as whether or not the patient was using an inhaled or oral corticosteroid during the index visit, and the independent variable being all major demographic variables. Inhaled corticosteroids were prescribed for 460 patients (52.0%) at the index visit. Overall, anti‐inflammatory drugs were prescribed for 548 patients (62.1%). An asthma care map was followed for 107 (16.8%) patients treated at the Royal Alexandra Hospital at the index visit. Logistic regression analysis showed that women and patients with more than one emergency room visit most likely were to be using inhaled or inhaled plus oral corticosteroids at the index visit. Documentation of drug therapy at discharge was poor for 42% of patients; therefore, analysis of practice patterns in this group was not attempted. This study shows that inhaled corticosteroids were prescribed for only about one‐half of patients with an acute asthma attack. Given this low use by high‐risk patients, the need for programs designed to improve asthma therapy is evident.
Antibiotic‐Heparin Lock: In Vitro Antibiotic Stability Combined with Heparin in a Central Venous Catheter
Authors: Vercaigne Lavern M. , Sitar Daniel S. , Penner S. Brian , Bernstein Keevin , Wang Gu Qui , Burczynski Frank J.
Published: June 2004

Long‐term hemodialysis frequently requires vascular access through central venous catheters (CVCs). Infection related to these catheters is a significant complication. The use of an antibiotic‐heparin lock could decrease the risks associated with infected permanent catheters. As an initial step in developing an antibiotic‐heparin lock, we investigated the in vitro stability of antibiotic‐heparin combinations in CVCs. Initially, cefazolin, vancomycin, ceftazidime, ciprofloxacin 10 mg/ml each, and gentamicin 5 mg/ml were incubated separately in glass test tubes in the dark at 37°C for 72 hours. Samples were analyzed spectrophotometrically for stability at 24‐hour intervals. The procedure was repeated with the addition of heparin (final concentration 5000 U/ml in glass test tubes), and the combination was also examined in CVCs. High‐performance liquid chromatography analysis was conducted on the antibiotic‐heparin combinations at 72 hours to confirm the spectrophotometric results. Ciprofloxacin produced an immediate precipitate with the addition of heparin and was not analyzed further. Absorbance values decreased for all antibiotics, with the greatest decreases at 72 hours for cefazolin (27.4%), vancomycin (29.7%), ceftazidime (40.2%), and gentamicin (8%) when combined with heparin. These decreases were postulated to be secondary to adsorption of the antibiotics to the luminal surface of the catheters because submitting the catheters to ultrasound with 1% sodium bicarbonate and analyzing the resulting solution for absorbance revealed that some of the drug was recovered. Although free antibiotic in CVC solution was reduced, the concentration should be sufficient (approximately 5 mg/ml) to decrease the frequency of infections associated with CVCs. We conclude that the concentrations of vancomycin, ceftazidime, cefazolin, or gentamicin used in our study should be sufficient for an antibiotic‐heparin lock.
Impact of Pharmacy Counseling on Compliance and Effectiveness of Combination Lipid‐Lowering Therapy in Patients Undergoing Coronary Artery Revascularization: A Randomized, Controlled Trial
Authors: Faulkner Michele A. , Wadibia E. Chuma , Lucas B. Daniel , Hilleman Daniel E.
Published: June 2004

This randomized, controlled trial evaluated the impact of personalized follow‐up on compliance rates in high‐risk patients receiving combination lipid‐lowering therapy over 2 years. A random sample of 30 patients 7–30 days after cardiac surgery had baseline fasting low‐density lipoprotein levels higher than 130 mg/dl. All patients received lovastatin 20 mg/day and colestipol 5 g twice/day. Weekly telephone contact was made with each patient for 12 weeks. Short‐ and long‐term compliance was assessed by pill and packet counts and refill records. Compliance and lipid profile results were significantly better in the intervention group (p<0.05) up to 2 years after the start of therapy than in the control group for all parameters except high‐density lipoprotein. However this effect was not apparent during the first 12 weeks of therapy. Short‐term telephone follow‐up favorably affected compliance and lipid profile results up to 2 years after start of therapy.
Increased circulating levels of thrombin‐activatable fibrinolysis inhibitor in lung cancer patients
Authors: Hataji Osamu , Taguchi Osamu , Gabazza Esteban Cesar , Yuda Hisamichi , D'Alessandro‐Gabazza C.N. , Fujimoto Hajime , Nishii Yoichi , Hayashi Tatsuya , Suzuki Koji , Adachi Yukihiko
Published: June 2004

Impairment of fibrinolytic function plays an important role in the mechanism of thrombotic disorders in cancer patients. This study assessed the circulating level of thrombin‐activatable fibrinolysis inhibitor in patients with lung cancer and its expression by several lung cancer cell lines. The plasma concentrations of thrombin‐activatable fibrinolysis inhibitor were significantly increased in lung cancer patients compared to healthy subjects. The concentration of thrombin‐activatable fibrinolysis inhibitor was particularly higher in patients with small cell carcinoma compared to those with adenocarcinoma or squamous cell carcinoma, and in cancer patients that responded to chemotherapy compared to non‐responders. In vitro studies showed more expression of thrombin‐activatable fibrinolysis inhibitor in small cell carcinoma than in adenocarcinoma cell lines and more expression in lung cancer cell lines sensitive to anti‐cancer agents than in resistant cell lines. This study suggests that thrombin‐activatable fibrinolysis inhibitor, in part secreted from lung cancer cells, may play a role in the pathogenesis of thrombotic disorders in lung cancer patients. Am. J. Hematol. 76:214–219, 2004. © 2004 Wiley‐Liss, Inc.
Hydrops fetalis associated with homozygosity for hemoglobin Taybe (α 38/39 THR deletion) in newborn triplets
Authors: Arnon Shmuel , Tamary Hannah , Dgany Orly , Litmanovitz Ita , Regev Rivka , Bauer Sofia , Dolfin Tzipora , Yacobovich Joanne , Wolach Baruch , Jaber Lutfi
Published: June 2004

Hemoglobin Taybe is an unstable α‐chain hemoglobin variant caused by a deletion of a threonine residue at codon 38 or 39 of the α‐1 globin chain. We describe preterm infant triplets born with hydrops fetalis and anemia who were found by DNA analysis to be homozygous for hemoglobin Taybe. All three infants developed intrauterine hemolytic anemia, which subsequently led to hydrops fetalis. To the best of our knowledge, this is the first description of hydrops fetalis associated with this hemoglobinopathy. We suggest that hemoglobin Taybe be considered in the differential diagnosis of hydrops fetalis and that known affected fetuses be carefully followed both antenatally and postnatally. Am. J. Hematol. 76:263–266, 2004. © 2004 Wiley‐Liss, Inc.
Imatinib mesylate‐sensitive blast crisis immediately after discontinuation of imatinib mesylate therapy in chronic myelogenous leukemia: Report of two cases
Authors: Higashi Takehiro , Tsukada Junichi , Kato Chiaki , Iwashige Atsushi , Mizobe Takamitsu , Machida Shinichiro , Morimoto Hiroaki , Ogawa Ryosuke , Toda Yoko , Tanaka Yoshiya
Published: June 2004

Although imatinib mesylate has shown encouraging activity in chronic myelogenous leukemia (CML), disease progression during therapy has been observed, manifested by clonal expansion of imatinib mesylate‐resistant leukemia cells. On the other hand, myelosuppression related to treatment of imatinib mesylate is often managed with temporary interruption of treatment or dose reduction. We here report two CML patients who had imatinib mesylate‐sensitive blast crisis (BC) immediately after discontinuation of imatinib mesylate therapy. The patients discontinued therapy because of neutropenia. Although there was no evidence of blastic phase during therapy, BC occurred 2 weeks after the withdrawal of treatment in both cases. Interestingly, additional chromosomal abnormalities were detected following the withdrawal of imatinib mesylate and disappeared by re‐introduction of this agent. The same doses of imatinib mesylate was still effective and remission was sustained with imatinib mesylate alone again. Our report suggests the possibility that withdrawal of imatinib mesylate may lead to proliferation of blast clones even in patients showing good responses to imatinib mesylate without signs of disease progression. Am. J. Hematol. 76:275–278, 2004. © 2004 Wiley‐Liss, Inc.
Genomic instability in bone marrow failure syndromes
Authors: Kearns William G. , Sutton Joanne F. , Maciejewski Jaroslaw P. , Young Neal S. , Liu Johnson M.
Published: June 2004

Aneuploidy is frequently seen in leukemia and myelodysplasia (MDS) but was thought to be uncommon in aplastic anemia (AA). We examined marrow cells from 96 unselected patients with bone marrow failure syndromes to assess the frequency of undetected aneuploidy for chromosomes 7 and 8 by fluorescence in situ hybridization (FISH) as compared to routine cytogenetic analysis. Twenty‐eight percent (27/96) of patients had an abnormal karyotype. FISH identified an additional 27 patients with undetected monosomy 7 or trisomy 8. Those patients with undetected monosomy 7 generally had a poor clinical outcome, suffering from lack of response to medical therapy or early death. In one AA/MDS patient with normal cytogenetics, FISH identified a large population of monosomy 7 cells, which clearly heralded a clinical relapse. In another patient, FISH studies were used to delineate instability of chromosome 8, with apparent disease progression from AA to MDS. We conclude that undetected aneuploidy exists in marrow cells of a significant percentage of patients with bone marrow failure syndromes. Am. J. Hematol. 76:220–224, 2004. Published 2004 Wiley‐Liss, Inc.
A novel MSX1 mutation in hypodontia
Authors: De Muynck S. , Schollen E. , Matthijs G. , Verdonck A. , Devriendt K. , Carels C.
Published: June 2004

MSX1 mutations have been reported in four unrelated families with autosomal dominant tooth agenesis. In one family, some individuals also had cleft lip and/or palate. We have identified a novel MSX1 mutation (559 C → T, resulting in Gln187Stop) in three individuals of one family. © 2004 Wiley‐Liss, Inc.
Impact of excluding cases with known chromosomal abnormalities on the prevalence of structural birth defects, Hawaii, 1986–1999
Authors: Forrester Mathias B. , Merz Ruth D.
Published: June 2004

Chromosomal abnormalities are more common in the presence of structural birth defects. However, much of the literature have only provided chromosomal abnormality rates for one or a few structural birth defects at a time. This study calculated the chromosomal abnormality rates for a number of structural birth defects using data from the Hawaii Birth Defects Program (HBDP) for deliveries during 1986–1999 and evaluated the impact of exclusion of cases with chromosomal abnormalities when calculating birth prevalence. The chromosomal abnormality rates were highest for endocardial cushion defect (40%) and omphalocele (27%), while no chromosomal abnormalities were reported for pyloric stenosis, persistent cloaca, and deficiency of lower limbs. The majority of chromosomal abnormality rates fell within a certain range, with 32 (63%) of the birth defect categories having chromosomal abnormality rates of 5–15%. The chromosomal abnormality rates also tended to be higher for multiple than for isolated cases. For three of the structural birth defects (ventricular septal defect, atrial septal defect, endocardial cushion defect), the birth prevalence of the defect, when cases with a chromosomal abnormality were excluded, was significantly lower than the birth prevalence that included those cases. Chromosomal abnormality rates varied by type of structural birth defect and presence of other major structural birth defects. For at least several structural birth defects, exclusion of cases with chromosomal abnormalities significantly underestimated the birth prevalence. This underestimation may be important, depending on the purpose of the analysis. © 2004 Wiley‐Liss, Inc.
Palladiumoxidasekatalyse: selektive Oxidation durch direkte disauerstoffgekoppelte Umsetzung
Authors: Stahl Shannon S.
Published: June 2004

Die selektive aerobe Oxidation organischer Verbindungen ist eines der fundamentalsten Probleme der modernen organischen Chemie. Effektive Lösungen müssen die spezifische Reaktivität und Selektivität von molekularem Sauerstoff berücksichtigen und unterschiedliche Klassen von Oxidationsreaktionen abdecken. Die Palladiumoxidasekatalyse kombiniert die Vielseitigkeit Palladium(II)‐vermittelter Oxidationen organischer Substrate mit der Oxidation des reduzierten Palladium‐Katalysators durch Disauerstoff und ermöglicht so einen Zugang zu einer breiten Auswahl an selektiven aeroben Oxidationsreaktionen. Neuere Ergebnisse zeigen, dass Cokatalysatoren wie Kupfer(II), Polyoxometallate und Benzochinone in der Oxidation von Palladium(0) durch molekularen Sauerstoff verzichtbar sind. Eine große Bedeutung für diese Reaktionen haben oxidativ stabile Liganden, die die Katalysatorzersetzung minimieren, die direkte Reaktion von Palladium mit Disauerstoff fördern, die Reaktivität des organischen Substrats regulieren und asymmetrische Katalysen ermöglichen.
Titelbild: Palladiumoxidasekatalyse: selektive Oxidation durch direkte disauerstoffgekoppelte Umsetzung (Angew. Chem. 26/2004)
Authors: Stahl Shannon S.
Published: June 2004

Von der Natur selbst holt sich eine umweltschonende Chemie ihre Anregungen. Das Titelbild illustriert jüngste Fortschritte bei der palladiumkatalysierten selektiven Oxidation von organischen Verbindungen mit molekularem Sauerstoff. Im Aufsatz auf S. 3480 ff. schildert S. S. Stahl die mechanistischen Prinzipien der “Palladiumoxidasekatalyse”. Diese katalytischen Reaktionen erinnern an enzymatische Oxidasereaktionen, bei denen die Disauerstoffreduktion und die Substratoxidation zu einem sequenziellen, zweistufigen Mechanismus gekoppelt sind.
Optimization of polyhydroxybutyrate production by mixed cultures submitted to aerobic dynamic feeding conditions
Authors: Serafim Luísa S. , Lemos Paulo C. , Oliveira Rui , Reis Maria A.M.
Published: June 2004

Activated sludge submitted to aerobic dynamic feeding conditions showed a good and stable capacity to store polyhydroxybutyrate (PHB). The system, working for 2 years, selected a microbial population with a high PHB storage capacity. The influence of carbon and nitrogen concentrations on the PHB accumulation yield was studied in a range of 15–180 Cmmol/l for acetate and 0–2.8 Nmmol/l for ammonia. Low ammonia concentrations favored PHB accumulation. The maximum PHB content, 67.5%, was obtained for 180 Cmmol/l of acetate supplied in one pulse. However, such high substrate concentration proved to be inhibitory for the storage mechanism, causing a slowdown of the specific PHB storage rate. In order to avoid substrate inhibition, 180 Cmmol/l of acetate was supplied in different ways: continuously fed and in three pulses of 60 Cmmol/l each. In both cases the specific PHB storage rate increased and the PHB content obtained were 56.2% and 78.5%, respectively. The latter value of PHB content is similar to that obtained by pure cultures and was never reported for mixed cultures. Addition of acetate by pulses controlled by the oxygen concentration was kept for 16 days, the PHB content being always above 70% of cell dry weight. © 2004 Wiley Periodicals, Inc.
Induction of adhesion molecule expression in liver ischaemia–reperfusion injury is associated with impaired hepatic parenchymal microcirculation
Authors: El-Wahsh M , Seifalian A M , Fuller B J , Rolles K , Davidson B R
Published: June 2004

Background

Activated neutrophils may be important mediators in liver ischaemia–reperfusion injury (I/R). Adhesion of leucocytes to the endothelial cell surface is a result of activation of cell adhesion molecules. The aim of this study was to investigate the effect of I/R on the hepatic microcirculation (HM) and intercellular adhesion molecule (ICAM) 1 expression.

Methods

Four groups of six Sprague–Dawley rats underwent laparotomy for liver exposure. Group 1 acted as controls, and groups 2–4 underwent partial liver ischaemia for 30, 45 and 60 min respectively followed by reperfusion for 60 min. Flow in the HM was measured by laser Doppler flowmetry. Liver biopsies were taken at the end of the reperfusion period. ICAM-1 expression was assessed by immunohistochemistry (graded 0–3).

Results

Mean flow in the HM was significantly reduced with I/R (mean(s.e.m.) red cell flux 140(21), 52(3) and 43(2) with 30, 45 and 60 min ischaemia compared with control 230(17); all P < 0·001). ICAM-1 expression was significantly induced (mean(s.e.m.) 1·30(0·21), 2·50(0·22) and 2·80(0·17) with 30, 45 and 60 min ischaemia versus control 0·50(0·22); all P < 0·001).

Conclusion

I/R produced a significant upregulation of ICAM-1 expression which correlated with impaired flow in the HM.
Stereoselectivity in formation of oxacephams from 1,3‐alkylidene‐threitols
Authors: Borsuk Katarzyna , Grzeszczyk Barbara , Szczukiewicz Patrycja , Przykorska Beata , Frelek Jadwiga , Chmielewski Marek
Published: June 2004

The [2+2]cycloaddition of CSI to the (Z)‐propenyl ethers derived from respective 1,3‐methylidene‐ and 1,3‐ethylidene‐threitols, contrary to the corresponding erythritol derivatives, is characterized by a low stereoselectivity and a lack of stereospecificity. On the other hand, the alternative method of the oxacepham formation, based on the 4‐vinyloxy‐azetidinone, proceeds with an excellent stereoselectivity. The CD‐spectroscopy offers an attractive tool for determination of the absolute configuration of the bridgehead carbon atom at the 5‐oxacepham skeleton. Chirality 16:414–421, 2004. © 2004 Wiley‐Liss, Inc.
Biochemical outcome after radical prostatectomy among men with normal preoperative serum prostate‐specific antigen levels
Authors: Freedland Stephen J. , Aronson William J. , Kane Christopher J. , Terris Martha K. , Presti Joseph C. , Trock Bruce , Amling Christopher L.
Published: June 2004

BACKGROUND

Recent studies have shown that a significant number of men with normal prostate‐specific antigen (PSA) levels have prostate carcinoma. Whether malignancies in such men are associated with better outcomes is unclear. The authors compared the risk of biochemical failure after radical prostatectomy (RP) between men with normal PSA levels and men with elevated PSA levels.

METHODS

Data were examined from 1582 men who underwent RP between 1988 and 2002 at 1 of 5 equal‐access medical centers. Patients were segregated into groups based on serum PSA levels (with stratification according to age‐specific reference ranges). Clinical and pathologic characteristics and biochemical outcome data were compared across groups using analyses of variance, log‐rank tests, and Cox proportional hazards analysis.

RESULTS

Men who had normal PSA levels had significantly fewer high‐grade tumors compared with men who had higher PSA levels (P < 0.001). The former group had a significantly decreased incidence of positive surgical margins, extracapsular disease, seminal vesicle invasion, and lymph node involvement (P < 0.001). On multivariate analysis, only serum PSA level (P < 0.001) and biopsy Gleason score (P < 0.001) predicted the time to disease recurrence. When only men with serum PSA levels < 10 ng/mL were examined, PSA level treated as a continuous variable remained a significant predictor of time to biochemical failure (P = 0.02).

CONCLUSIONS

Men who had normal PSA levels had significantly fewer high‐grade tumors and significantly better biochemical outcomes after undergoing RP compared with men who had elevated PSA levels. Overall, men with normal PSA levels who undergo RP represent a favorable risk group. Cancer 2004. © 2004 American Cancer Society.
Pilot study of high‐dose, concurrent biochemotherapy for advanced melanoma
Authors: Kim Kevin B. , Eton Omar , East Mary Jo , Hodges Cynthia , Papadopoulos Nicholas E. , Grimm Elizabeth A. , Bedikian Agop Y.
Published: June 2004

BACKGROUND

Durable complete response rates ranging from 5% to 20% have been reported in association with biochemotherapy for patients with metastatic melanoma, with response rates on the low end of this range being observed in trials that used lower doses and less intense treatment schedules. In the current study, the authors addressed the feasibility of increasing the doses of agents used in concurrent biochemotherapy.

METHODS

Three patients with metastatic melanoma were enrolled at each of six concurrent biochemotherapy dose levels. The doses were as follows: dacarbazine 800 mg/m2 or 1000 mg/m2 (Day 1); cisplatin 25 mg/m2 or 30 mg/m2 (Days 1–4); vinblastine 1.6 mg/m2 or 1.8 mg/m2 (Days 1–5); interleukin‐2 9 million units (MU) per m2 or 12 MU/m2 as a 24‐hour continuous infusion (Days 1–4); and interferon‐alpha‐2b 5 MU/m2, 10 MU/m2, or 15 MU/m2 (Days 1–5) and 5 MU/m2 (Days 7, 9, and 11) administered subcutaneously.

RESULTS

Of the 19 patients who were enrolled, 18 were evaluable for toxicity and response. Sixty‐nine treatment courses were administered in total (median, 4 courses per patient; range, 1–6 courses per patient), with reduction of the dose of at least 1 agent being required in 7 courses (10%). Twenty‐six courses were delayed by a median of 7 days (range, 3–29 days), with interferon‐alpha‐2b administration frequently omitted because of thrombocytopenia, most often after Day 5. Blood product support was required in 40 courses. Dose‐limiting toxic effects included global encephalopathy, renal and hepatic dysfunction, pancreatitis, and ileus. There was 1 complete response, and there were 10 partial responses. The median time to disease progression was 6.9 months, and the median survival duration was 12.2 months.

CONCLUSIONS

Although dose intensification can be achieved safely in patients with advanced melanoma, other strategies should be pursued to enhance the clinical activity of biochemotherapy as a response induction regimen. Cancer 2004. © 2004 American Cancer Society.
Brain metastases of malignant germ cell tumors in children and adolescents
Authors: Spunt Sheri L. , Walsh Michael F. , Krasin Matthew J. , Helton Kathleen J. , Billups Catherine A. , Cain Alvida M. , Pappo Alberto S.
Published: June 2004

BACKGROUND

Brain metastases of pediatric germ cell tumors are uncommon, and there is limited information regarding their incidence, clinical presentation, response to treatment, and influence on survival.

METHODS

The authors reviewed the experience with brain metastases from pediatric germ cell tumors at St. Jude Children's Research Hospital (Memphis, TN) over a 40‐year period.

RESULTS

Between March 1962 and February 2002, 16 of 206 patients with germ cell tumors (7.8%) had brain metastases at the time of initial presentation (n = 2), later in the course of the illness (n = 12), or at autopsy (n = 2). Twelve of 16 patients (75%) had symptoms referable to the brain (nausea/emesis, headaches, or seizures), and 14 (88%) had pulmonary metastases at the time brain metastases were identified. Patients with brain metastases were more likely to have an extragonadal primary tumor (P = 0.013), advanced‐stage disease at initial presentation (P = 0.016), and choriocarcinoma within the primary tumor (P < 0.001). The incidence of brain metastases was significantly lower in the second 2 decades of the study period (5 of 135 patients [3.7%]) than in the first 2 decades (11 of 71 patients [15.5%]; P = 0.005). Two of the 16 patients in the current study are long‐term survivors.

CONCLUSIONS

Brain metastases are uncommon in childhood germ cell tumors, and their incidence appears to be decreasing. In the current study, most patients with such metastases were symptomatic and had pulmonary metastases at the time brain metastases were identified. Patients with the highest risk of developing brain metastases include those with extragonadal tumors, those with high disease stage at initial presentation, and those with choriocarcinoma as a component of the primary tumor. The probability of survival is poor, although a small proportion of patients may become long‐term survivors. Cancer 2004. © 2004 American Cancer Society.
The incidence of testicular recurrence in boys with acute leukemia treated with total body and testicular irradiation and stem cell transplantation
Authors: Quaranta Brian P. , Halperin Edward C. , Kurtzberg Joanne , Clough Robert , Martin Paul L.
Published: June 2004

BACKGROUND

The incidence of testicular recurrence of childhood acute leukemia after total body irradiation (TBI) in conjunction with stem cell transplantation (SCT) has been reported to be as high as 24%. The authors studied the incidence of testicular failure in a large series of male patients who underwent SCT using either TBI and a testicular irradiation boost or chemotherapy alone.

METHODS

One hundred thirty‐one boys with either acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) were treated with SCT with either TBI with testicular boost (n= 94 patients), TBI without testicular boost (n= 1 patient), or chemotherapy alone (n= 36 patients) between 1991 and 1999.

RESULTS

The median follow‐up was 26.5 months (range, 0.6–99.5 months) from the date of bone marrow infusion. Two patients in the study had a primary testicular failure after TBI with testicular boost followed by an umbilical cord blood transplantation. The first patient had ALL, did not engraft, and was rescued with autologous cells. He developed disease in the testicle 15 months afterward and subsequently died. The second patient had Philadelphia chromosome‐positive ALL and developed a testicular recurrence 26 months after SCT. He was treated with orchiectomy, further testicular irradiation, and chemotherapy and remained in complete remission > 3 year after his failure. The incidence of testicular failure in boys who received TBI and testicular irradiation who survived ≥ 1 year was 4.2%. There were no primary testicular failures reported in boys who received chemotherapy alone.

CONCLUSIONS

Boys with AML or ALL had a low incidence of primary testicular failure when they were treated with TBI plus a testicular boost or with chemotherapy alone. Cancer 2004. © 2004 American Cancer Society.
Prostate needle biopsies
Authors: Poulos Chistopher K. , Daggy Joanne K. , Cheng Liang
Published: June 2004

BACKGROUND

Tumor volume is one of the most powerful predictors of patient outcome in prostatic adenocarcinoma. It is uncertain as to which preoperative variables are most predictive of final tumor volume at radical prostatectomy, especially among patients who have had positive biopsies at multiple biopsy sites. The current study attempted to identify the biopsy variables that are most predictive of final tumor volume.

METHODS

The authors examined prostate biopsy specimens from 151 consecutive patients with at least 2 positive biopsy sites. The following data were collected: highest percentage of adenocarcinoma at any biopsy site, percentage of adenocarcinoma at the biopsy site with the highest Gleason score, highest percentage of cores positive for adenocarcinoma at any biopsy site, percentage of positive cores with carcinoma at the site with the highest Gleason score, number of positive sites, tumor bilaterality, and percentage of biopsy sites positive for disease. All patients underwent radical prostatectomy. The prostatectomy specimens were entirely embedded and whole mounted. Tumor volume was measured using the grid method. Logarithmic transformation was applied to tumor volumes for the purposes of the analysis.

RESULTS

Highest percentage of adenocarcinoma at any biopsy site (P = 0.012), percentage of adenocarcinoma at the biopsy site with the highest Gleason score (P = 0.021), number of positive biopsy sites (P = 0.026), tumor bilaterality (P = 0.008), and percentage of biopsy sites positive for disease (P = 0.0001) all were significant predictors of tumor volume on linear regression analysis. Highest percentage of cores positive for adenocarcinoma (P = 0.081) and percentage of positive cores with carcinoma at the site with the highest Gleason score (P = 0.240) were not significant predictors of tumor volume. Based on the model F statistic, percentage of biopsy sites positive for tumor, tumor bilaterality, and highest percentage of adenocarcinoma at any biopsy site were the variables that were most predictive of tumor volume.

CONCLUSIONS

Highest percentage of adenocarcinoma at any biopsy site, percentage of adenocarcinoma at the biopsy site with the highest Gleason score, number of positive biopsy sites, tumor bilaterality, and percentage of biopsy sites positive for disease all are useful preoperative predictors of tumor volume in radical prostatectomy specimens. Although these preoperative biopsy parameters were significant in linear regression models, none was sufficient as a single predictor of tumor volume. Cancer 2004. © 2004 American Cancer Society.
Ruthenium‐Mediated C−C Coupling Reactions of Alkynes − The Key Role of Ruthenacyclopentatriene Complexes
Authors: Schmid Roland , Kirchner Karl
Published: June 2004

This review describes the highlights of the reactions of the substitutionally labile neutral pseudo 14VE complexes RuCp′(COD)Cl (Cp′ = Cp, Cp*; COD = 1,5‐cyclooctadiene) and the cationic complexes [CpRu(CH3CN)2L]+ and [Ru(η5‐C5H4CH2CH2‐κ1P‐PPh2)]+ with alkynes. The ligand L is a co‐ligand, whose nature turns out to be critical to the outcome of the reaction, and varies from halides to tertiary phosphanes, tertiary stibines, CO, and acetonitrile. Along these lines vast and diversified varieties of rearrangements within and between molecules ligated to the transition‐metal center has been discovered. A crucial role in all reactions reported is the intermediacy of electrophilic ruthenacyclopentatriene complexes, an entity featuring a biscarbene functionality. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
A Structural Study of Bisphosphonate Metal Complexes − Three New Polymeric Structures of the Calcium Complex of Clodronic Acid
Authors: Kontturi Mervi , Peräniemi Sirpa , Vepsäläinen Jouko J. , Ahlgrén Markku
Published: June 2004

Three novel calcium complexes of clodronic acid were prepared and their structures determined by single‐crystal X‐ray diffractometry. Previously, a monomeric structure, [Ca{Cl2C(PO3H)2}(H2O)5] (1), has been determined, but the new structures are polymeric: [{Ca2[Cl2C(PO3)2](H2O)6}·4.5H2O]n (2), [{Ca2Na0.5[Cl2C(PO3)2](H2O)8}Cl0.5·4H2O]n (3) and [{Ca5[Cl2C(PO3)2]2(H2O)15}(NO3)2·1.5H2O]n (4); and they provide new, important information about the binding abilities of clodronic acid. Compounds 2−4 crystallise in the triclinic crystal system, the space group being P$\bar 1$
with Z = 2. Compound 2 consists of Ca atoms and Cl2MBP ligands connected to one‐dimensional chains. The chains are held together by hydrogen bonds formed by aqua ligands and lattice water molecules. The structure of 3 consists of similar calcium clodronate chains forming two‐dimensional layers through additional, six‐coordinate Na atoms. Compound 4 consists of two‐dimensional calcium clodronate layers, the calcium atoms are connected by Cl2MBP− and aqua ligands. The nitrate groups and lattice water molecules lie between the layers and hold them together. The layered compounds 3 and 4 reveal substantial porosity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Selection of sampling units under a correlated population based on the eigensystem of the population covariance matrix
Authors: Chao Chang‐Tai
Published: June 2004

For the prediction problem in survey sampling under a finite population,nsampling units are selected out ofNpopulation units and observed to predict the population quantity of interest. For a correlated spatial population, one can obtain lower prediction mean‐square error with careful sampling arrangement of the sampling sites. For example, a systematic design can be used to select samples for better prediction results. However, it is only effective under certain population covariance structures. For more general cases, the optimal sampling strategies proposed by different authors in the past can be used to select the optimal sample with which the mean‐square error can be minimized. Nevertheless, the computational load can be very intensive, and also the optimization algorithm used is not easy to implement. In addition, the exact population distribution has to be assumed. Two sampling methods, that are based on the eigensystem of the population covariance matrix, are proposed in this article. These sampling methods require fewer population assumptions and the sampling procedures are straightforward. No computationally intensive algorithm is required. Simulation study shows that they can be more efficient than simple random sampling. An example on the utilization of the proposed sampling methods in practice is also presented. Copyright © 2004 John Wiley & Sons, Ltd.
Creating an Excel‐based executive support system
Authors: Friedman Mark , Munter Paul
Published: June 2004

Executive support systems (ESS) are designed to give top executives vital information for their work as high‐level managers. The author gives step‐by‐step instructions for creating a spreadsheet‐based ESS for financial officers and accountants. © 2004 Wiley Periodicals, Inc.