bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preorganized Bis‐Zinc Phosphodiester Cleavage Catalysts Possessing Natural Ligands: A Lesson Pertinent to Bimetallic Artificial Enzymes
Authors: Worm Karen , Chu Feiya , Matsumoto Kazunari , Best Michael D. , Lynch Vincent , Anslyn Eric V. 
Published: February 2003

AbstractTwo preorganized bis‐zinc receptors (2 and 3) were synthesized wherein the metals were ligated with ligands present in natural phosphodiesterases: imidazoles and carboxylates. The intrametallic distance is near 4.5 Å, that found in natural nucleases and other successful artificial nucleases. With only two imidazoles (2), the zinc binding affinities were not high enough to achieve cooperativity. Yet, with a third ligand, a carboxylate (3), cooperativity was found in the cleavage of HPNPP. The preorganization of 3 was achieved using a “steric gearing” strategy. The enhancement was 80‐fold for cooperation between the two metals relative to a mono‐metallic analogue (5). However, there was no observable enhancement in the hydrolysis of RNA using 3 relative to 5. Therefore, we conclude that placing two zinc atoms that are ligated with natural ligands at the appropriate distance for catalysis is not sufficient to enhance the cleavage of RNA, but is successful for activated RNA substrate mimics.
An Alternative Way of Characterising the Bonding in Compounds Featuring Main‐Group Elements and with the Potential for Multiple Bonding: On the Dissociation of Binary Main‐Group Hydrides
Authors: Himmel Hans‐Jörg , Schnöckel Hansgeorg 
Published: February 2003

AbstractHerein the bonding in compounds featuring main‐group elements and with the potential for multiple bonding is studied theoretically by examination of their fragmentation into two fragments that still exhibit the same structure as they had in the molecule prior to dissociation. The fragments were calculated both in their electronic ground state and in an excited electronic state, in which the number of unpaired electrons is equal to the maximal number of bonds in the compounds before dissociation. The energies of the fragmentation processes (ΔEfrag) can be more directly linked to the bond strengths than the dissociation energies (ΔEdiss), because of the absence of any secondary effects like relaxation of the electronic state or of the geometry of the fragments. These relaxation energies of the fragments (ΔEfrag) are also studied herein. The energies derived in this work allow for an accurate comparison of the bonding properties in main‐group‐element hydrides. The trends of the fragmentation and relaxation energies are discussed in detail. It will be shown that the relaxation energies allow for a classification of the bonds (“classical” σ and π bonds or donor–acceptor interactions), while the fragmentation energies are good quantitative measures for the total bond strength. Similar calculations are on the way to explore the bonding in systems in which the hydrogen atoms are replaced by organic groups or halogen atoms.
Highly Enantioselective Conjugate Addition of AlMe3 to Linear Aliphatic Enones by a Designed Catalyst
Authors: Fraser Paul K. , Woodward Simon 
Published: February 2003

Abstract2‐Hydroxy‐2′‐alkylthio‐1,1′‐binaphthyl compounds are catalytic promoters of the 1,4‐addition of AlMe3 to linear aliphatic enones in THF at −40 to −48 °C in the presence of [Cu(MeCN)4]BF4. At ligand loadings of 5–20 mol %, enantioselectivities of 80–93 % are realised for most substrates. To attain these values, the use of highly pure AlMe3 is mandatory. The presence of methylalumoxane (MAO), derived by hydrolysis, leads to reduced enantioselectivity and a conjugate addition product.
Recognition of Caffeine in Aqueous Solutions
Authors: Fiammengo Roberto , Crego‐Calama Mercedes , Timmerman Peter , Reinhoudt David N. 
Published: February 2003

AbstractBinding of caffeine in aqueous solutions has been achieved for the first time by using water‐soluble, tetracationic peptide–porphyrin conjugates Zn‐1 as the receptor molecules. The association constant for caffeine with receptor Zn‐1 is in some cases as high as 6000 M−1, only 5–6 times lower than the highest binding constant reported for an artificial caffeine receptor in low polarity aprotic solvents. The binding mechanism has been studied by a combination of experimental techniques such as UV‐visible and NMR spectroscopy and microcalorimetry. Recognition of caffeine involves both stacking with the porphyrin ring and metal coordination. Subtle variations of the receptor structure affect the complexation. Receptors Zn‐1 have also been investigated for the recognition of molecules structurally related to caffeine, for example, 1‐methylimidazole. Selectivity towards oxopurine derivatives (caffeine and theophylline) have been found.
Unidirectional Threading of Triphenylureidocalix[6]arene‐Based Wheels: Oriented Pseudorotaxane Synthesis
Authors: Arduini Arturo , Calzavacca Francesco , Pochini Andrea , Secchi Andrea 
Published: February 2003

AbstractTriphenylureidocalix[6]arenes 5 a,b are heteroditopic receptors having a pinched cone structure able to interact with both the cation and the anion of ion pairs. They are able to act as wheels and form complexes of the pseudorotaxane type with axles derived from dialkylviologen salts. An investigation into the possibility of exploiting the different structural and chemical information present on the two distinct rims of the calixarene wheel as control elements to pivot the direction of the axle threading processes and give access to oriented pseudorotaxanes is reported. It was verified that, in C6D6, an asymmetric dicationic axle derived from 4,4′‐bipyridil bearing two alkyl chains, one of which has a stopper, and triphenylureidocalix[6]arenes 5 a or 5 b form 1:1 supramolecular complexes belonging to the class of pseudorotaxanes. The structure of these complexes has been inferred through 1H NMR techniques. The data show that the axle accesses the calixarene cavity only through the wider rim. To further verify this issue, the new rotaxane 8, obtained by stoppering the pseudorotaxane derived from 5 b and the symmetrical axle 7 with diphenylacetyl chloride, was synthesised. In the 1H NMR spectrum of 8, the aliphatic protons of the axle portion that resides at the wide rim of the wheel show chemical shifts that are almost identical to those observed in pseudorotaxanes 6. On the other hand, those that stick out of the narrow rim of 8 experience chemical shifts that could not be found in the oriented pseudorotaxanes 6.
Molecular Switch Triggered by Solvent Polarity: Synthesis, Acid–Base Behavior, Alkali Metal Ion Complexation, and Crystal Structure
Authors: Ambrosi Gianluca , Dapporto Paolo , Formica Mauro , Fusi Vieri , Giorgi Luca , Guerri Annalisa , Micheloni Mauro , Paoli Paola , Pontellini Roberto , Rossi Patrizia 
Published: February 2003

AbstractThe synthesis and characterization of the new tetraazamacrocycle L, bearing two 1,1′‐bis(2‐phenol) groups as side‐arms, is reported. The basicity behavior and the binding properties of L toward alkali metal ions were determined by means of potentiometric measurements in ethanol/water 50:50 (v/v) solution (298.1±0.1 K,I=0.15 mol dm−3). The anionic H−1L−species can be obtained in strong alkaline solution, indicating that not all of the acidic protons of L can be removed under the experimental conditions used. This species behaves as a tetraprotic base (logK1=11.22, logK2=9.45, logK3=7.07, logK4=5.08), and binds alkali metal ions to form neutral [MH−1L] complexes with the following stability constants: logKLi=3.92, logKNa=3.54, logKK=3.29, logKCs=3.53. The arrangement of the acidic protons in the H−1L−species depends on the polarity of the solvents used, and at least one proton switches from the amine moiety to the aromatic part upon decreasing the polarity of the solvent. In this way two different binding areas, modulated by the polarity of solvents, are possible in L. One area is preferred by alkali metal ions in polar solvents, the second one is preferred in solvents with low polarity. Thus, the metal ion can switch from one location to the other in the ligand, modulated by the polarity of the environment. A strong hydrogen‐bonding network should preorganize the ligand for coordination, as confirmed by MD simulations. The crystal structure of the [Na(H−1L)]⋅CH3CN complex (space groupP21/c, a=12.805(1),b=20.205(3),c=14.170(2) Å,β=100.77(1)°,V=3601.6(8) Å3,Z=4,R=0.0430,wR2=0.1181), obtained using CH2Cl2/CH3CN as mixed solvent, supports this last aspect and shows one of the proposed binding areas.
Angiographic subsegmentectomy for the treatment of patients with small hepatocellular carcinoma
Authors: Iwamoto Shozo , Sanefuji Hayato , Okuda Kunio 
Published: February 2003

AbstractBACKGROUNDThe therapeutic results of nonsurgical treatment for patients with hepatocellular carcinoma (HCC) have been poor, and improved treatments are needed. The authors recently developed a new technique called angiographic subsegmentectomy for the treatment of patients with small HCC.METHODSThe technique includes confirming the diagnosis of small HCC using a helical computed tomography (CT) scan combined with an angiography system for identifying the tumor‐feeding subsegmental hepatic artery, injecting lipiodol containing farmorubicin until it enters the portal vein in sufficient amounts, and injecting sponge particles into the hepatic artery for embolization. Occlusion of the hepatic artery with gel particles and occlusion of the portal vein by lipiodol induce infarction necrosis, which encompasses the entire tumor and the surrounding liver parenchyma.RESULTSThe treatment was given to 23 patients with 30 HCC tumors that measured < 20 mm in greatest dimension. It was successful in all 23 patients. Serum alanine aminotransferase levels were elevated to a significant level in the majority of patients after treatment, mild ascites developed in three patients, and the patients complained of pain and fever posttreatment that were controlled readily. No patients developed hepatic failure. Only one patient developed recurrent disease posttreatment at 1.5 years, for a recurrence rate of 5% at 1 year and 6.6% at 1.5 years, a rate that has never been achieved with other treatment modalities.CONCLUSIONSAngiographic subsegmentectomy is a novel treatment for patients with small HCC. The results indicated that it is equivalent to undergoing small resection and is superior to conventional arterial chemoembolization. Cancer 2003;97:1051–6. © 2003 American Cancer Society.DOI 10.1002/cncr.11106
Can older cancer patients tolerate chemotherapy?
Authors: Chen Hongbin , Cantor Alan , Meyer Julie , Beth Corcoran Mary , Grendys Edward , Cavanaugh Denise , Antonek Shirley , Camarata Angela , Haley William , Balducci Lodovico , Extermann Martine 
Published: February 2003

AbstractBACKGROUNDTo the authors' knowledge, few data currently are available regarding the tolerance to chemotherapy in older cancer patients. This prospective pilot study evaluated the changes in functional, mental, nutritional, and comorbid status, as well as the quality of life (QOL), in geriatric oncology patients receiving chemotherapy.METHODSSixty patients age ≥ 70 years who were undergoing cancer chemotherapy were recruited in a university‐based comprehensive cancer center. Changes in physical function were measured by the Eastern Cooperative Oncology Group performance status (ECOG PS) and Instrumental Activities of Daily Living (IADLs), mental health changes were measured by the Mini‐Mental State Examination and the Geriatric Depression Scale (GDS), comorbidity was measured by Charlson's index and the Cumulative Illness Rating Scale‐Geriatric, nutrition was measured by the Mini‐Nutritional Assessment, and QOL was measured by the Functional Assessment of Cancer Therapy‐General (FACT‐G). Changes were assessed at baseline and at the end of treatment (EOT). Grade 4 hematologic and Grade 3–4 nonhematologic toxicities were recorded.RESULTSThirty‐seven patients (63%) completed both assessments. Older cancer patients demonstrated a significant decline in measurements of physical function after receiving chemotherapy, as indicated by changes in scores on the IADL (P = 0.04) and on the physical (P = 0.01) and functional (P = 0.03) subscales of the FACT‐G. They also displayed worse scores on the GDS administered postchemotherapy (P < 0.01). Patients who experienced severe chemotoxicity had more significant declines in ECOG PS (P = 0.03), IADL (P = 0.03), and GDS (P = 0.04), and more gain in the social well‐being subscale (P = 0.02) of the FACT‐G, than those who did not experience severe chemotoxicity. However, changes in most scores were small in magnitude clinically. No significant change was found between baseline and EOT in nutrition, comorbidity, and other aspects of the FACT‐G.CONCLUSIONSOlder cancer patients undergoing chemotherapy may experience toxicity but generally can tolerate it with limited impact on independence, comorbidity, and QOL levels. It is important to recognize and monitor these changes during geriatric oncology treatment. Cancer 2003;97:1107–14. © 2003 American Cancer Society.DOI 10.1002/cncr.11110
Refractory Aspergillus pneumonia in patients with acute leukemia
Authors: Aliff Timothy B. , Maslak Peter G. , Jurcic Joseph G. , Heaney Mark L. , Cathcart Kathleen N. , Sepkowitz Kent A. , Weiss Mark A. 
Published: February 2003

AbstractBACKGROUNDPulmonary aspergillosis and other invasive fungal infections (IFIs) commonly complicate the management of patients with acute leukemia. Standard amphotericin‐based therapies may be ineffective for many patients and the available salvage agents (itraconazole and caspofungin) are reported to possess only moderate activity against resistant infections. Laboratory evidence suggests a synergistic interaction between amphotericin and caspofungin. The authors treated a group of patients with amphotericin‐refractory IFIs with the combination of caspofungin and amphotericin (or liposomal amphotericin).METHODSA retrospective evaluation of patients with amphotericin‐resistant IFIs was conducted. Diagnosis was based on clinical, radiographic, and when available, microbiologic data. Response to combination antifungal therapy was graded as either favorable or unfavorable. Favorable responses included improvement of both clinical and radiographic signs of fungal pneumonia. All other responses were graded as unfavorable.RESULTSThirty patients were included in this analysis. Twenty‐six patients had acute leukemia. Based on recently published criteria, the IFIs were classified as proven in 6 patients, probable in 4 patients, and possible in 20 patients. The median duration and dose of amphotericin monotherapy were 12 days (range, 4–65 days) and 7.8 mg/kg (range, 4.2–66.1 mg/kg), respectively. The median duration of combination therapy was 24 days (range, 3–74 days). Eighteen patients (60%) experienced a favorable antifungal response. Twenty patients with acute leukemia received combination therapy for fungal pneumonias arising during intensive chemotherapy treatments. Favorable responses were observed in 15 of these patients (75%), and antifungal response did not depend on the response of the underlying leukemia. Survival to hospital discharge was significantly better (P < 0.001) in patients having a favorable response. Mild to moderate nephrotoxicity was noted in 50% of patients, necessitating the substitution of liposomal amphotericin. Mild elevation of alkaline phosphatase levels occurred in 30% of patients. Caspofungin was temporarily withheld from one patient who developed moderate but reversible biochemical hepatotoxicity.CONCLUSIONSThe antifungal combination of caspofungin and amphotericin can be administered safely to high‐risk patients with hematologic malignancies. Although an absolute assessment of efficacy is limited by the design of this study, encouraging outcomes were noted for many patients. The authors plan to evaluate this regimen further in a randomized clinical trial. Cancer 2003;97:1025–32. © 2003 American Cancer Society.DOI 10.1002/cncr.11115
Utilization of special education services and educational attainment among long‐term survivors of childhood cancer
Authors: Mitby Pauline A. , Robison Leslie L. , Whitton John A. , Zevon Michael A. , Gibbs Iris C. , Tersak Jean M. , Meadows Anna T. , Stovall Marilyn , Zeltzer Lonnie K. , Mertens Ann C. 
Published: February 2003

AbstractBACKGROUNDThe objective of the current report was to compare the self‐reported rates of special education (SE) and educational attainment among specific groups of childhood cancer survivors and a random sample of sibling controls.METHODSThe Childhood Cancer Survivor Study is a retrospective cohort of individuals who were diagnosed with a cancer in childhood and survived at least 5 years postdiagnosis. This analysis includes 12,430 survivors and 3410 full siblings. Reported use of SE services and educational attainment were analyzed within subgroups defined by type of cancer, age at diagnosis, and type of treatment.RESULTSThe use of SE services was reported in 23% of survivors and 8% of siblings, with the greatest differences observed among survivors who were diagnosed before age 6 years, most notably survivors of central nervous system (CNS) tumors (odds ratio [OR], 18.8; 95% confidence interval [95%CI], 15.01–23.49), leukemia (OR, 4.4; 95%CI, 3.75–5.16), and Hodgkin disease (OR, 4.4; 95%CI, 2.64–7.24). It was found that intrathecal methotrexate (IT MTX) and cranial radiation (CRT), administered alone or in combination, significantly increased the likelihood that a survivor would use SE (IT MTX only: OR, 1.3; 95%CI, 1.09–1.78; CRT only: OR, 7.2; 95%CI, 6.14–8.39; IT MTX and CRT combined: OR, 2.6; 95%CI, 2.30–2.95). A positive dose response was identified between higher doses of CRT and use of SE. It was determined that survivors of leukemia (OR, 1.6; 95%CI, 1.23–2.16), CNS tumors (OR, 2.7; 95%CI, 1.92–3.81), non‐Hodgkin lymphoma (OR, 1.8; 95%CI, 1.15–2.78), and neuroblastoma (OR, 1.7; 95%CI, 1.14–2.61) were significantly less likely to finish high school compared with siblings; however, when survivors received SE services, risk estimates approximated those of the sibling SE population.CONCLUSIONSChildren who are diagnosed with cancer should be followed closely during and after treatment to identify early signs of learning disabilities and to maximize intervention strategies for the successful completion of scholastic goals. Cancer 2003;97:1115–26. © 2003 American Cancer Society.DOI 10.1002/cncr.11117
Breast boost: Are we missing the target?
Authors: Benda Rashmi K. , Yasuda Gopika , Sethi Anil , Gabram Sheryl G.A. , Hinerman Russell W. , Mendenhall Nancy Price 
Published: February 2003

AbstractBACKGROUNDRandomized trials have shown improved local control with the use of a breast boost for patients given breast‐conserving treatment for breast carcinoma. Although the use of a breast boost is routine practice, no standard technique has been established. The authors compared the commonly used clinical technique with a technique based on computed tomography (CT) imaging of surgical clips in the tumor bed.METHODSThirty patients underwent CT simulation for postoperative radiation treatment planning as part of breast conservation therapy. During simulation, a CT‐compatible wire was placed on the patient's skin, outlining the intended electron boost field; an electron boost volume (EBV) was generated by contouring the tissue underlying the wire. Also contoured was a CT‐based clinical target volume (CTV) using surgical clips and postsurgical changes in the tumor bed as a guide. A planning target volume (PTV) was generated using a 1 cm margin around the CTV. An electron beam treatment plan was generated for each technique using the FOCUS three‐dimensional treatment planning system. Dose–volume histograms (DVH) were generated to determine the fraction of the PTV receiving 90% of the prescribed dose if treatment was delivered using the EBV. In addition, DVH analysis was done to determine the volume of normal tissue unnecessarily irradiated when using the EBV.RESULTSAlthough the electron cone size remained unchanged in most patients for both EBV and PTV, the isocenter differed more than 1 cm in the medial‐lateral direction in 5 patients and in the cephalocaudal direction in 12 patients. The en face gantry angle differed for most patients. On average, only 51% (range, 27–79%) of the PTV received 90% or more of the prescribed dose when the electron plan was generated using the EBV (P < 0.0001). Ten patients received the prescription dose to less than 50% of the PTV. Mean volume of normal tissue receiving more than 50% of prescribed dose was 64.5 cm3 (range, 24–119 cm3).CONCLUSIONSClinical delineation of the tumor bed not only carries a significant risk of missing the target, but unnecessarily treats breast tissue that may otherwise be spared. Better delineation of the tumor bed, which optimizes coverage of the target volume and spares normal breast tissue, has the potential to improve both local control and cosmetic outcome. The authors recommend the use of surgical clips to delineate the target volume, followed by CT‐based treatment planning, accounting for not only microscopic disease, but also organ motion and daily setup error. Cancer 2003;97:905–9. © 2003 American Cancer Society.DOI 10.1002/cncr.11142
Long‐term outcomes after treatment with external beam radiation therapy and palladium 103 for patients with higher risk prostate carcinoma
Authors: Dattoli Michael , Wallner Kent , True Lawrence , Cash Jennifer , Sorace Richard 
Published: February 2003

AbstractBACKGROUNDThe objective of this study was to define the long‐term prognostic significance of prostatic acid phosphatase (PAP) levels in patients with higher risk, early‐stage prostate carcinoma.METHODSOne hundred sixty‐one consecutive patients with Stage T1–T3 prostate carcinoma (according to the 1992 criteria of the American Joint Committee on Cancer) were treated from 1992 through 1996. Each patient had a Gleason score ≥ 7 and/or a prostate specific antigen (PSA) level > 10 ng/mL. The original biopsy slides for 130 of 161 patients were retrieved and rereviewed by a single pathologist (L.T.). Enzymatic PAP measurements were determined using a standard method. Values up to 2.5 Units were considered normal. Patients received 41 grays (Gy) of external beam radiation therapy to a limited pelvic field followed 4 weeks later by a palladium 103 (Pd‐103) boost using transrectal ultrasound and fluoroscopic guidance as described previously. The prescribed minimum Pd‐103 dose to the prostate was 80 Gy (pre‐National Institute of Standards and Technology [NIST]‐99). Freedom from biochemical failure was defined as a serum PSA level ≤0.2 ng/mL at last follow‐up.RESULTSThere was little correlation between pretreatment PSA levels, Gleason scores, and PAP measurements. Thirty‐eight patients developed biochemical failure. The overall actuarial freedom from biochemical progression at 10 years is 79%, with 118 patients followed for > 5 years. In a multivariate Cox proportional hazards analysis that considered each factor as a continuous variable, the strongest predictor of failure was PAP (P = 0.0001), followed by Gleason score (P = 0.13), and PSA (P = 0.04). PAP was especially helpful in stratifying patients with pretreatment PSA levels between 4 ng/mL and 20 ng/mL, for whom the prognosis does not different when they are subdivided into PSA categories. When the PAP subgroup analysis was limited to this relatively favorable group, there was a wide range of prognoses.CONCLUSIONSThe biochemical cure rate was remarkably high among the 161 patients evaluated. The fact that the PAP was the strongest predictor of long‐term biochemical failure in patients with otherwise higher risk features reported here suggests that it may be a more accurate indicator of micrometastatic disease compared with the Gleason score and the PSA level. This report adds to the rationale for reintroducing PAP measurement into general practice. Cancer 2003;97:979–83. © 2003 American Cancer Society.DOI 10.1002/cncr.11154