bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temperature–pressure stability of green fluorescent protein: A Fourier transform infrared spectroscopy study
Authors: Scheyhing Carsten H. , Meersman Filip , Ehrmann Matthias A. , Heremans Karel , Vogel Rudi F. 
Published: October 2002

AbstractGreen fluorescent protein (GFP) is widely used as a marker in molecular and cell biology. For its use in high‐pressure microbiology experiments, its fluorescence under pressure was recently investigated. Changes in fluorescence with pressure were found. To find out whether these are related to structural changes, we investigated the pressure stability of wild‐type GFP (wtGFP) and three of its red shift mutants (AFP, GFPmut1, and GFPmut2) using Fourier transform infrared spectroscopy. For the wt GFP, GFPmut1, and GFPmut2 we found that up to 13–14 kbar the secondary structure remains intact, whereas AFP starts unfolding around 10 kbar. The 3‐D structure is held responsible for this high‐pressure stability. Previously observed changes in fluorescence at low pressure are rationalized in terms of the pressure‐induced elastic effect. Above 6 kbar, loss of fluorescence is due to aggregation. Revisiting the temperature stability of GFP, we found that an intermediate state is populated along the unfolding pathway of wtGFP. At higher temperatures, the unfolding resulted in the formation of aggregates of wtGFP and its mutants. © 2002 Wiley Periodicals, Inc. Biopolymers 65: 244–253, 2002
Axonal neurofilament‐H immunolabeling in the rabbit retina
Authors: Völgyi Béla , Bloomfield Stewart A. 
Published: October 2002

AbstractA monoclonal antibody directed at the multiphosphorylated epitope of axonal neurofilament‐H (NF‐H) was used to label axon‐like fibers in the rabbit retina. NF‐H‐immunopositive fibers were found in the outer plexiform layer (OPL), inner plexiform layer (IPL), and optic fiber layer (OFL). The morphological characteristics of the labeled processes identified those in the OPL as horizontal cell axons and axon terminals and fibers in the OFL as axons of ganglion cells. The NF‐H‐positive profiles in the OPL formed a subset of horizontal cell processes labeled for calbindin. In the IPL, NF‐H‐immunoreactive profiles lay at all levels but were detected most often in the middle strata, 2–4. Occasionally, we observed NF‐H‐immuoreactive processes emerging from the IPL and entering either the GCL or the inner nuclear layer (INL). The labeled fibers in the IPL were typically very thin, less than 1 μm in diameter, and could often be followed for over 1 mm as they ran laterally across the retina. Cell bodies were never labeled by the immunoserum. To identify the NF‐H‐immunopositive fibers in the IPL, standard immunocytochemical double‐labeling techniques were applied, using antibodies directed against several neurotransmitters or modulators thought to be expressed by axon‐bearing amacrine cells. The NF‐H‐positive processes in the IPL were found to correspond to those labeled for tyrosine hydroxylase, somatostatin, substance P, and NADPH diaphorase activity. However, the NF‐H labels did not colocalize with those against the vasoactive intestinal peptide‐associated protein PHM27. Our results indicate that putative axons in the retina possess the multiphosphorylated NF‐H protein found within classic axons in the central nervous system. These results thus support the idea that certain subtypes of amacrine and horizontal cells maintain true axons in the mammalian retina. J. Comp. Neurol. 453:269–279, 2002. © 2002 Wiley‐Liss, Inc.
Skeletal muscle transformation into electric organ in s. macrurus depends on innervation
Authors: Unguez Graciela A. , Zakon Harold H. 
Published: October 2002

AbstractThe cells of the electric organ, called electrocytes, of the weakly electric fish Sternopygus macrurus derive from the fusion of mature fast muscle fibers that subsequently disassemble and downregulate their sarcomeric components. Previously, we showed a reversal of the differentiated state of electrocytes to that of their muscle fiber precursors when neural input is eliminated. The dependence of the mature electrocyte phenotype on neural input led us to test the hypothesis that innervation is also critical during formation of electrocytes. We used immunohistochemical analyses to examine the regeneration of skeletal muscle and electric organ in the presence or absence of innervation. We found that blastema formation is a nerve‐dependent process because regeneration was minimal when tail amputation and denervation were performed at the same time. Denervation at the onset of myogenesis resulted in the differentiation of both fast and slow muscle fibers. These were fewer in number, but in a spatial distribution similar to controls. However, in the absence of innervation, fast muscle fibers did not progress beyond the formation of closely apposed clusters, suggesting that innervation is required for their fusion and subsequent transdifferentiation into electrocytes. This study contributes further to our knowledge of the influence of innervation on cell differentiation in the myogenic lineage. © 2002 Wiley Periodicals, Inc. J Neurobiol 53: 391–402, 2002
Novel
Saccharomyces cerevisiae
Screen Identifies WR99210 Analogues That Inhibit
Mycobacterium tuberculosis
Dihydrofolate Reductase
Authors: Gerum A'Lissa B. , Ulmer Jonathan E. , Jacobus David P. , Jensen Norman P. , Sherman David R. , Sibley Carol Hopkins 
Published: October 2002

ABSTRACT

The ongoing selection of multidrug-resistant strains of
Mycobacterium tuberculosis
has markedly reduced the effectiveness of the standard treatment regimens. Thus, there is an urgent need for new drugs that are potent inhibitors of
M. tuberculosis
, that exhibit favorable resistance profiles, and that are well tolerated by patients. One promising drug target for treatment of mycobacterial infections is dihydrofolate reductase (DHFR; EC 1.5.1.3), a key enzyme in folate utilization. DHFR is an important drug target in many pathogens, but it has not been exploited in the search for drugs effective against
M. tuberculosis
. The triazine DHFR inhibitor WR99210 has been shown to be effective against other mycobacteria. We show here that WR99210 is also a potent inhibitor of
M. tuberculosis
and
Mycobacterium bovis
BCG growth in vitro and that resistance to WR99210 occurred less frequently than resistance to either rifampin or isoniazid. Screening of drugs with
M. tuberculosis
cultures is slow and requires biosafety level 3 facilities and procedures. We have developed an alternative strategy: initial screening in an engineered strain of the budding yeast
Saccharomyces cerevisiae
that is dependent on the
M. tuberculosis
DHFR for its growth. Using this system, we have screened 19 compounds related to WR99210 and found that 7 of these related compounds are also potent inhibitors of the
M. tuberculosis
DHFR. These studies suggest that compounds of this class are excellent potential leads for further development of drugs effective against
M. tuberculosis
.
Pharmacokinetics and Pharmacodynamics of Gatifloxacin against
Streptococcus pneumoniae
and
Staphylococcus aureus
in a Granulocyte-Rich Exudate
Authors: Trampuz Andrej , Laifer Gerd , Wenk Markus , Rajacic Zarko , Zimmerli Werner 
Published: October 2002

ABSTRACT

The pharmacokinetics of gatifloxacin were assessed in serum and in skin blister fluid (SBF), as was the pharmacodynamic activity in SBF. Five hours after a single dose of gatifloxacin, SBF killed 2.5 logs of
Streptococcus pneumoniae
and 1.5 log of
Staphylococcus aureus
during a 2-h incubation ex vivo.
In Vivo Penicillin MIC Drift to Extremely High Resistance in Serotype 14
Streptococcus pneumoniae
Persistently Colonizing the Nasopharynx of an Infant with Chronic Suppurative Lung Disease: a Case Study
Authors: Leach Amanda J. , Morris Peter S. , Smith-Vaughan Heidi , Mathews John D. 
Published: October 2002

ABSTRACT

This is the first report of in vivo pneumococcal penicillin MIC drift from 4.0 to 16.0 mg/liter, possibly associated with alterations in the
pbp1a
gene. The case presented here is of an infant with early onset recurrent pneumonia and chronic bronchitis requiring repeated antibiotics.
Sequential Emergence of Antibiotic Resistance in Enterococcal Bloodstream Isolates over 25 Years
Authors: Murdoch David R. , Mirrett Stanley , Harrell Lizzie J. , Monahan Janet S. , Reller L. Barth 
Published: October 2002

ABSTRACT

We determined the antibiotic susceptibilities of 1,785 enterococcal bloodstream isolates collected over 25 years. Antibiotic resistance emerged at a greater rate in
Enterococcus faecium
than in other enterococcal species, and
E. faecium
isolates became proportionally more common over time. Our findings confirm the pattern of emerging antibiotic resistance among enterococci and highlight the increasing importance of
E. faecium
as a cause of bloodstream infection.
Flow cytometric disease monitoring in multiple myeloma: the relationship between normal and neoplastic plasma cells predicts outcome after transplantation
Authors: Rawstron Andy C. , Davies Faith E. , DasGupta Ranjit , Ashcroft A. John , Patmore Russell , Drayson Mark T. , Owen Roger G. , Jack Andrew S. , Child J. Anthony , Morgan Gareth J. 
Published: October 2002

Abstract
Conventional monitoring strategies for myeloma are not sufficiently sensitive to identify patients likely to benefit from further therapy immediately after transplantation. We have used a sensitive flow cytometry assay that quantitates normal and neoplastic plasma cells to monitor the bone marrow of 45 patients undergoing high-dose chemotherapy. Neoplastic plasma cells were detectable at 3 months after transplantation in 42% of patients. Once detected, neoplastic cell levels increased steadily until clinical progression: these patients had a significantly shorter progression-free survival (PFS) (median, 20 months) than those with no detectable disease (median, longer than 35 months; P = .003). Neoplastic plasma cells were detectable in 27% (9 of 33) of immunofixation-negative complete-remission patients. These patients had a significantly shorter PFS than immunofixation-negative patients with no detectable neoplastic plasma cells (P = .04). Normal plasma cells were present in 89% of patients immediately after transplantation, but were not sustained in most cases. Patients with only normal phenotype plasma cells present at 3 months after transplantation and also at second assessment had a low risk of disease progression. Patients with neoplastic plasma cells present at 3 months after transplantation, or with only normal plasma cells present at first assessment and only neoplastic plasma cells at second assessment, had a significantly higher risk of early disease progression (P < .0001) with a 5-year survival of 54% for the high-risk group, compared with 100% in the low-risk group (P = .036). Analysis of normal and neoplastic plasma cell levels is more sensitive than immunofixation and can identify which patients may benefit from additional treatment strategies at an early stage after transplantation.
Emergence of muscle and neural hematopoiesis in humans
Authors: Jay Karen E. , Gallacher Lisa , Bhatia Mickie 
Published: October 2002

AbstractDuring human development, hematopoiesis is thought to be compartmentalized to the fetal circulation, liver, and bone marrow. Here, we show that combinations of cytokines together with bone morphogenetic protein-4 and erythropoietin could induce multiple blood lineages from human skeletal muscle or neural tissue. Under defined serum-free conditions, the growth factors requirements, proliferation, and differentiation capacity of muscle and neural hematopoiesis were distinct to that derived from committed hematopoietic sites and were uniquely restricted to CD45−CD34− cells expressing the prominin AC133. Our study defines epigenetic factors required for the emergence of hematopoiesis from unexpected tissue origins and illustrates that embyronically specified microenvironments do not limit cell fate in humans.
The histone deacetylase inhibitor AN-9 has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines
Authors: Batova Ayse , Shao Li-en , Diccianni Mitchell B. , Tanaka Alice L.Yu, Tetsuya , Rephaeli Ada , Nudelman Abraham , Yu John 
Published: October 2002

Abstract
The novel prodrug of butyric acid, pivaloyloxymethyl butyrate (AN-9), a histone deacetylase inhibitor, shows great promise as an effective and relatively nontoxic anticancer agent for solid malignancies. However, little is known about its effects on hematopoietic malignancies. In this study, we show that 21 primary samples of acute leukemia were sensitive to the antiproliferative effects of AN-9, with a 50% inhibitory concentration (IC50) of 45.8 ± 4.1 μM. In colony-forming assays, primary T-cell acute lymphoblastic leukemia (T-ALL) cells were 3-fold more sensitive to AN-9 than the normal hematopoietic progenitors, erythroid burst-forming units and granulocyte/monocyte colony-forming units. AN-9 induced apoptosis in the T-ALL cell line CEM. A common problem with cancer is chemoresistance, which is often typical of relapsed cancers. Remarkably, a T-ALL sample at diagnosis and an acute myeloid leukemia sample at relapse that were resistant to doxorubicin in vitro were sensitive to AN-9, with an IC50 of 50 μM for both samples. More strikingly, samples from 2 infants with t(4;11) ALL obtained at diagnosis and relapse each were the most sensitive to AN-9, with IC50values of 25 μM and 17 μM, respectively. Furthermore, a doxorubicin-resistant clone of HL60, HL60/ADR, obtained by the transfection of the MDR-1 gene, was equally sensitive to AN-9 cytotoxicity as the parental cells. AN-9 induced the expression of p21 in an infant leukemia sample with 11q23 rearrangement, but not in T- or B-precursor ALL. Collectively, our results suggest that AN-9 is a selective agent for hematopoietic malignancies that can circumvent the mechanisms of chemoresistance limiting most conventional chemotherapy.
Homozygosity mapping of a second gene locus for hereditary combined deficiency of vitamin K–dependent clotting factors to the centromeric region of chromosome 16
Authors: Fregin Andreas , Rost Simone , Wolz Werner , Krebsova Alice , Muller Clemens R. , Oldenburg Johannes 
Published: October 2002

AbstractFamilial multiple coagulation factor deficiency (FMFD) of factors II, VII, IX, X, protein C, and protein S is a very rare bleeding disorder with autosomal recessive inheritance. The phenotypic presentation is variable with respect to the residual activities of the affected proteins, its response to oral administration of vitamin K, and to the involvement of skeletal abnormalities. The disease may result either from a defective resorption/transport of vitamin K to the liver, or from a mutation in one of the genes encoding γ-carboxylase or other proteins of the vitamin K cycle. We have recently presented clinical details of a Lebanese family and a German family with 10 and 4 individuals, respectively, where we proposed autosomal recessive inheritance of the FMFD phenotype. Biochemical investigations of vitamin K components in patients' serum showed a significantly increased level of vitamin K epoxide, thus suggesting a defect in one of the subunits of the vitamin K 2,3-epoxide reductase (VKOR) complex. We now have performed a genome-wide linkage analysis and found significant linkage of FMFD to chromosome 16. A total maximum 2-point LOD score of 3.4 at θ = 0 was obtained in the interval between markers D16S3131 on 16p12 and D16S419 on 16q21. In both families, patients were autozygous for 26 and 28 markers, respectively, in an interval of 3 centimorgans (cM). Assuming that FMFD and warfarin resistance are allelic, conserved synteny between human and mouse linkage groups would restrict the candidate gene interval to the centromeric region of the short arm of chromosome 16.
Characterization of a surface modified dry powder inhalation carrier prepared by “particle smoothing”
Authors: Young P M , Cocconi D , Colombo P , Bettini R , Price R , Steele D F , Tobyn M J 
Published: October 2002

Abstract
Atomic force microscopy (AFM) was used to investigate drug-carrier interactions between beclometasone dipropionate (BDP) and a series of untreated and modified lactose surfaces. This quantitative information was correlated with bulk characterization methods and an in-vitro study. Modified lactose surfaces were prepared using a proprietary process referred to as “particle smoothing” to obtain smooth carrier surfaces with or without the presence of magnesium stearate. The engineering of lactose carrier surfaces using the particle smoothing process resulted in significant differences in surface morphology when compared with the “as supplied” starting material. The energy of separation, between BDP and lactose samples, determined by AFM suggested similar lognormal distributions with a rank decrease in median separation energy (e0.5) (26.7, 20.6 and 7.7 μJ for untreated, particle-smoothed and particle-smoothed with magnesium stearate, respectively). A series of in-vitro twin stage impinger studies showed good correlation with the AFM separation energy measurements. The mean fine particle dose increased for the two processed lactose samples, with a significant increase for the lactose processed with magnesium stearate, 102.0 ± 16 μg compared with 24.2 ± 10.7 μg for the untreated lactose. Thus, the AFM presents as a possible pre-formulation tool for rapid characterization of particle interactions.
Effect of oxyethylene moiety in polyoxyethylene sorbitan esters on the pharmacokinetics of menatetrenone incorporated in O/W lipid emulsions prepared with polyoxyethylene sorbitan esters and soybean oil in rats
Authors: Ueda Kumiko , Fujimoto Masanori , Noto Hiromi , Kawaguchi Yuriko , Sakaeda Toshiyuki , Iwakawa Seigo 
Published: October 2002

Abstract
Oil-in-water (O/W) lipid emulsions are suitable drug carriers for lipophilic drugs; however, the effects of numbers or chains of oxyethylene units within a surfactant molecule such as polyoxyethylene sorbitan esters (PSs) on the biological fate of these lipid emulsions have not yet been clarified. In this study, a series of PSs and soybean oil (SO) were utilized to prepare menatetrenone-incorporated lipid emulsions (SO/PSs), and the biological fate of menatetrenone administered as SO/PSs was studied at a clinical injection volume (0.1 mL kg−1) in rats. The plasma concentration and organ uptake of menatetrenone administered as SO/20OE-PSs (PSs with 20 oxyethylene units) was similar to that of SO/egg-yolk phosphatides (SO/EYP). The plasma concentration of menatetrenone was extensively lower for SO/6OE-PSs (PSs with 6 oxyethylene units) and SO/20OE-3FA-PSs (PSs with 20 oxyethylene units and 3 fatty acid chains) than that for SO/EYP, and menatetrenone uptake by the liver and spleen was higher for SO/6OE-PSs and SO/20OE-3FA-PSs, respectively, than those for SO/EYP. Furthermore, menatetrenone uptake by the lungs was also increased for SO/6OE-PS and SO/20OE-3FA-PS with double bonds in the fatty acid moieties of the PSs. These findings suggested that shortening the oxyethylene units or decreasing the oxyethylene chain numbers of emulsifiers resulted in a rapid clearance of the lipid emulsions from the circulation by extensive uptake via the liver, spleen or lungs.
Recent Progress of Functional Glycoconjugated Metal Complexes
Authors: Yano Shigenobu , Mikata Yuji 
Published: October 2002

Abstract
Synthesis, characterizations and stereochemistry of the transition metal complexes containing glycosylamines derived from sugar molecules and polyamines have been investigated. During this study, the intelligent sugar complexes having ion recognition ability, novel sugar transformation reactions promoted by a cooperative effect of calcium ion and monoamines have been discovered. The biological activity of these metal complexes was also investigated. Antifungal nickel(II) complexes derived from amino sugars, and unprecedented sugar-dependent in vivo antitumor activity of carbohydrate-pendant cis-platinum(II) complexes are described in this article. These results suggested that the stereostructure and bioactivity of the sugar-metal complexes can be modified by varying amines and metal ions, and sugar molecules used.
Why Does a Color-Developing Phenomenon Occur on Thermal Paper Comprising of a Fluoran Dye and a Color Developer Molecule?
Authors: Takahashi Yoshiyuki , Shirai Ayako , Segawa Takako , Takahashi Tatsuya , Sakakibara Kazuhisa 
Published: October 2002

Abstract
The mechanism of the color development on thermal paper, comprising a fluoran dye (S-205) and a color developer molecule, such as bisphenol A, was elucidated based on spectroscopic analyses (IR, and NMR) on an isolated black-colored compound prepared by a reaction of S-205 and bisphenol A. We propose that this black-colored compound is, indeed, a color-developing complex (CDC) with a definite molar ratio (S-205 : bisphenol A = 1 : 4 ) which has been formed between the open-form S-205 (generated by the cleavage of the lactone ring of S-205: zwitterion) and bisphenol A through hydrogen-bonding. The enthalpy gain associated with the formation of CDC plays an important role for black-color formation on thermal paper.
Asymmetric Baeyer–Villiger Oxidation of Cyclic Ketones Using Chiral Organoselenium Catalysts
Authors: Miyake Yoshihiro , Nishibayashi Yoshiaki , Uemura Sakae 
Published: October 2002

Abstract
Novel optically active diselenides having a chiral oxazoline have been prepared and the structure of one of them is unambiguously determined by X-ray structural analysis. Treatment of a variety of cyclobutanones with 30% H2O2 in the presence of a catalytic amount of the optically active diselenides in tetrahydrofuran or 1,4-dioxane at 0 °C–rt affords the corresponding γ-lactones in up to 92% yield with up to 19% ee. The enantioselectivity of the product is not yet satisfactory, but this is the first example of asymmetric Baeyer–Villiger oxidation catalyzed by chiral organoselenium compounds.
Spectroscopic Characterization and Catalytic Application of Copper(I), Silver(I) and Gold(I) Carbonyl Cations in Strong Acids
Authors: Tsumori Nobuko , Xu Qiang , Hirahara Mai , Tanihata Souichi , Souma Yoshie , Nishimura Yasuo , Kuriyama Nobuhiro , Tsubota Susumu 
Published: October 2002

Abstract
Detailed IR, Raman, and NMR spectroscopic characterization has been carried out on the group 11 metal carbonyl cations, Cu(CO)n+ (n = 1, 2, 3, 4), Ag(CO)n+ (n = 1, 2, 3), and Au(CO)n+ (n = 1, 2), over a wide range of temperature and in a variety of strong acids. Based on these results their molecular structures were determined and their stabilities are compared and discussed. The active species have been determined to be Cu(CO)2+ (and Cu(CO)3+ as a minor species) instead of the previously assigned Cu(CO)3+, Ag(CO)+ instead of the previously assigned Ag(CO)2+, and Au(CO)2+, respectively, for the copper(I), silver(I) and gold(I) carbonyl cation-catalyzed carbonylation of olefins and alcohols in concentrated sulfuric acid. The reaction mechanism previously proposed for the metal carbonyl cation-catalyzed carbonylation has been modified to involve an olefin-metal-monocarbonyl (e.g., for Ag) or an olefin-metal-polycarbonyl (e.g., for Cu or Au) intermediate.