bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel AntibacterialClass
Authors: Dandliker Peter J. , Pratt Steve D. , Nilius Angela M. , Black-Schaefer Candace , Ruan Xiaoan , Towne Danli L. , Clark Richard F. , Englund Erika E. , Wagner Rolf , Weitzberg Moshe , Chovan Linda E. , Hickman Robert K. , Daly Melissa M. , Kakavas Stephan , Zhong Ping , Cao Zhensheng , David Caroline A. , Xuei Xiaoling , Lerner Claude G. , Soni Niru B. , Bui Mai , Shen Linus L. , Cai Yingna , Merta Philip J. , Saiki Anne Y. C. , Beutel Bruce A. 
Published: November 2003

ABSTRACT

We
report the discovery and characterization of a novel ribosome inhibitor
(NRI) class that exhibits selective and broad-spectrum antibacterial
activity. Compounds in this class inhibit growth of many gram-positive
and gram-negative bacteria, including the common respiratory pathogens
Streptococcus pneumoniae
,
Haemophilus influenzae
,
Staphylococcus aureus
, and
Moraxella catarrhalis
, and
are nontoxic to human cell lines. The first NRI was discovered in a
high-throughput screen designed to identify inhibitors of cell-free
translation in extracts from
S. pneumoniae.
The chemical
structure of the NRI class is related to antibacterial quinolones, but,
interestingly, the differences in structure are sufficient to
completely alter the biochemical and intracellular mechanisms of
action. Expression array studies and analysis of NRI-resistant mutants
confirm this difference in intracellular mechanism and provide evidence
that the NRIs inhibit bacterial protein synthesis by inhibiting
ribosomes. Furthermore, compounds in the NRI series appear to inhibit
bacterial ribosomes by a new mechanism, because NRI-resistant strains
are not cross-resistant to other ribosome inhibitors, such as
macrolides, chloramphenicol, tetracycline, aminoglycosides, or
oxazolidinones. The NRIs are a promising new antibacterial class with
activity against all major drug-resistant respiratory
pathogens.
Randomized, Single-Blind, Placebo-Controlled Studyof Topical Application of the Immune Response ModulatorResiquimod in HealthyAdults
Authors: Sauder Daniel N. , Smith Michael H. , Senta-McMillian Therese , Soria Inmaculada , Meng Tze-Chiang 
Published: November 2003

ABSTRACT

Resiquimod
is a Toll-like receptor 7 (TLR7) and TLR8 agonist that is a potent
inducer of alpha interferon (IFN-α) and other cytokines. The
effects of multiple applications of resiquimod gel were assessed in a
randomized, single-blind, dose-ranging, placebo-controlled study with
41 healthy subjects. Over a 3-week period, 1-g doses of resiquimod or
vehicle gel (3:1 randomization) were applied to a 50-cm
2
area of the upper arm according to the following regimens: 0.25%
applied for 8 h two times per week, 0.05% applied for
8 h two times per week, 0.05% applied for 8
h three times per week, and 0.01% applied for 24 h
three times per week. Skin biopsy specimens were obtained prior to the
application of the first dose and after the completion of application
of the last dose. Dosing with 0.01 and 0.05% resiquimod was well
tolerated, but that with 0.25% was not; a dose-response
relationship for local adverse effects was observed. The
level of systemic exposure during multiple topical dosings was<1% of the applied dose. A significant increase in
responders after completion of application of the last dose was
observed for serum IFN and the interleukin-1 (IL-1) receptor antagonist
(
P
< 0.01, Fisher's exact test). Increased levels
of mRNA for IL-6, IL-8, IFN-α, and Mx (an
IFN-α-inducible protein) were seen in posttreatment biopsy
specimens from the group receiving 0.25% resiquimod compared to
the levels seen in specimens from the group receiving vehicle only
(
P
< 0.01, Wilcoxon rank sum test). A
dose-response-related increase in CD3-positive cells consistent with
T-lymphocyte infiltration and a decrease in CD1a-positive
cells, consistent with emigration of Langerhans' cells, were
observed in treated skin. This study suggests that resiquimod is a
potent topically active immune response modifier that significantly
enhances the cutaneous immune
response.
Activity of9-(S)-[3-Hydroxy-2-(Phosphonomethoxy)Propyl]AdenineagainstSchistosomiasis mansoniinMice
Authors: Botros Sanaa , William Samia , Hammam Olfat , Zídek Zden˘ek , Holý Antonín 
Published: November 2003

ABSTRACTThe activity of the acyclic nucleotide analogue 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine [(S)-HPMPA] againstSchistosoma mansoniwas investigated in mice. The compound was injected intraperitoneally, usually on two or five consecutive days, at 10 to 20 mg/kg of body weight/day. The treatment started before, at the time of, and after the onset of egg laying (oviposition) byS. mansoni. The animals were killed from 7 to 40 days after the cessation of treatment. Significant reductions in the total numbers of female and coupled worms were found. Female fecundity and both hepatic and intestinal egg loads were suppressed. These effects were more pronounced with dosing regimens launched before the time of oviposition. The complete disappearance of immature eggs and a significant reduction to the complete absence of mature eggs, with 99 to 100% of the eggs being dead, were produced. No hepatic egg-induced granulomas were present in mice treated at the time of oviposition, and the granulomas were smaller in mice treated beforeS. mansonioviposition. These preliminary findings extend the knowledge of the antiparasitic properties of (S)-HPMPA.
Acquired Macrolide Resistance Genes in Pathogenic
Neisseria
spp. Isolated between 1940 and1987
Authors: Cousin Sydney , Whittington William L. H. , Roberts Marilyn C. 
Published: November 2003

ABSTRACT

Seventy-six
Neisseria gonorrhoeae
isolates, isolated between 1940 and
1987, and seven
Neisseria meningitidis
isolates, isolated
between 1963 and 1987, were screened for the presence of acquired
mef
(A),
erm
(B),
erm
(C), and
erm
(F)
genes by using DNA-DNA hybridization, PCR analysis, and sequencing. The
mef
(A),
erm
(B), and
erm
(F) genes were all
identified in a 1955
N. gonorrhoeae
isolate, while the
erm
(C) gene was identified in a 1963
N. gonorrhoeae
isolate. Similarly, both the
mef
(A) and
erm
(F) genes
were identified in a 1963
N. meningitidis
isolate. All four
acquired genes were found in later isolates of both species. The
mef
(A) gene from a 1975
N. gonorrhoeae
isolate was
sequenced and had 100% DNA and amino acid identity with the
mef
(A) gene from a 1990s
Streptococcus pneumoniae
isolate. Selected early isolates were able to transfer their acquired
genes to an
Enterococcus faecalis
recipient, suggesting that
these genes are associated with conjugative transposons. These isolates
are the oldest of any species to carry the
mef
(A) gene and
among the oldest to carry these
erm
genes.
Singleand Double Mutations in
gyrA
but Not in
gyrB
AreAssociated with Low- and High-Level Fluoroquinolone Resistance in
Helicobacterpylori
Authors: Tankovic Jacques , Lascols Christine , Sculo Quentin , Petit Jean-Claude , Soussy Claude-James 
Published: November 2003

ABSTRACT

In
one French hospital the rate of resistance to ciprofloxacin in
Helicobacter pylori
was 3.3% (2 of 60 strains) in 1999.
The six resistant clinical strains (four from 1996 and two from 1999)
and three ciprofloxacin-selected single-step mutants studied carried
one
gyrA
mutation but none in
gyrB
. Clinafloxacin and
garenoxacin were the most active fluoroquinolones against these
mutants. Occurrence of a second
gyrA
mutation was associated
with high MICs of all fluoroquinolones
tested.
MolecularEpidemiology of orf513-Bearing Class 1 Integrons in MultiresistantClinical Isolates from ArgentineanHospitals
Authors: Arduino Sonia M. , Catalano Mariana , Orman Betina E. , Roy Paul H. , Centrón Daniela 
Published: November 2003

ABSTRACT

The
spread of orf513-bearing class 1 integrons is associated with
bla
CTX-M-2
in gram-negative clinical isolates in
Argentina, with In35 being the most frequently found integron
(74%). Among 65 isolates without
bla
CTX-M-2
,
only one harbored a novel orf513-bearing class 1 integron with the
dfrA3b
gene. The finding of orf513 not associated with class 1
integrons in two gram-positive strains indicates the widespread
occurrence of this putative site-specific
recombinase.
Structures,Locations, and Transfer Frequencies of Genetic Elements ConferringHigh-Level Gentamicin Resistance in
Enterococcusfaecalis
Isolates inGreece
Authors: Daikos George L. , Bamias George , Kattamis Christos , Zervos Marcus J. , Chow Joseph W. , Christakis George , Petrikkos George , Triantafyllopoulou Penelope , Alexandrou Helen , Syriopoulou Vassiliki 
Published: November 2003

ABSTRACT

The
elements conferring high-level gentamicin resistance in 64 clinical
isolates of
Enterococcus faecalis
were characterized by PCR
and by restriction enzyme hybridization analysis of genomic and plasmid
DNA. There was a strong association between gentamicin resistance and
the
aac(6′)-aph(2"
) gene carried on
IS
256
-based elements with different structures, locations, and
transfer
characteristics.
LinezolidPenetration into Bone and Joint Tissues Infected withMethicillin-ResistantStaphylococci
Authors: Kutscha-Lissberg Friedrich , Hebler Ute , Muhr Gert , Köller Manfred 
Published: November 2003

ABSTRACT
Penetration
of linezolid into bone and joint tissues was studied by
high-performance liquid chromatography in 13 patients suffering from
implant-associated infections with methicillin-resistant staphylococci.
Mean concentrations of linezolid in infected tissues were greater than
10 mg/liter in a sampling time range of 35 to 124 min after
administration of the preoperative dose, except in bone specimens,
where they reached 3.9 ± 2.0
mg/liter.
Efficacyof Voriconazole in Treatment of Systemic Scedosporiosis inNeutropenicMice
Authors: Capilla Javier , Serena Carolina , Pastor F. Javier , Ortoneda Montserrat , Guarro Josep 
Published: November 2003

ABSTRACT

We
have evaluated the efficacy of voriconazole (VRC) in a murine model of
systemic infection by
Scedosporium apiospermum
. The survival
of mice treated with VRC at 5, 20, or 40 mg/kg/day was greater than
that of the control group (
P
≤ 0.0009). VRC reduced
the tissue burden in the spleen and brain (
P
< 0.001
in both organs) in comparison with that of the control
group.
Efficacyof Sulforaphane in EradicatingHelicobacter pyloriin HumanGastric Xenografts Implanted in NudeMice
Authors: Haristoy Xavier , Angioi-Duprez Karine , Duprez Adrien , Lozniewski Alain 
Published: November 2003

ABSTRACTSulforaphane, an isothiocyanate abundant in the form of its glucosinolate precursor in broccoli sprouts, has shown in vitro activity againstHelicobacter pylori. We evaluated the effect of sulforaphane in vivo against this bacterium by using human gastric xenografts in nude mice.H. pyloriwas completely eradicated in 8 of the 11 sulforaphane-treated grafts. This result suggests that sulforaphane might be beneficial in the treatment ofH. pylori-infected individuals.
InVitro Susceptibility Testing of
Geotrichum capitatum
:Comparison of the E-Test, Disk Diffusion, and Sensititre ColorimetricMethods with the NCCLS M27-A2 Broth Microdilution ReferenceMethod
Authors: Girmenia C. , Pizzarelli G. , D'Antonio D. , Cristini F. , Martino P. 
Published: November 2003

ABSTRACT

The
in vitro activities of amphotericin B, flucytosine, fluconazole,
itraconazole, and voriconazole against 23 isolates of
Geotrichum
capitatum
were determined by the National Committee for Clinical
Laboratory Standards (NCCLS) M27-A2 microdilution method and the
Sensititre and agar diffusion methods. Amphotericin B and voriconazole
appeared to be the more active drugs. Sensititre showed the highest
rates of agreement with the NCCLS M27-A2
method.
Orally Administered CpG Oligodeoxynucleotide Induces Production of CXC and CC Chemokines in the Gastric Mucosa and Suppresses Bacterial Colonization in a Mouse Model ofHelicobacter pyloriInfection
Authors: Raghavan S. , Nyström J. , Fredriksson M. , Holmgren J. , Harandi A. M. 
Published: November 2003

ABSTRACTBacterial DNA and unmethylated CpG oligodeoxynucleotides (CpG ODN) are known to be potent stimulators of the innate immune system in vitro and in vivo. We therefore investigated if oral administration of CpG ODN could enhance innate immunity in the gastric mucosa and control the extent ofHelicobacter pyloriinfection in mice. Intragastric administration of a single dose of CpG ODN significantly increased local production of the CC chemokines macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES and the CXC chemokine gamma interferon-inducible protein 10 in the stomach and/or the small intestine. Importantly, intragastric administration of CpG ODN to mice with an already establishedH. pyloriinfection, in the absence of any coadministered antigen, was found to reduce the bacterial load in the stomach compared to the load inH. pylori-infected control mice, while similar administration of non-CpG ODN had no effect on the bacterial load. The reduction in the bacterial numbers in the stomachs of mice treated with CpG ODN was associated with enhanced infiltration of immune cells and increased RANTES production in the gastric mucosa compared to the infiltration of immune cells and RANTES production inH. pylori-infected control animals. These findings suggest that intragastric administration of CpG ODN without antigen codelivery may represent a valuable strategy for induction of innate immunity againstH. pyloriinfection.
GOLOMB RULERS AND DIFFERENCE SETS FOR SUCCINCT QUANTUM AUTOMATA
Authors: BERTONI ALBERTO , MEREGHETTI CARLO , PALANO BEATRICE 
Published: November 2003

Given a function p : N → [0,1] of period n, we study the minimal size (number of states) of a one-way quantum finite automaton (Iqfa) inducing the stochastic event ap + b, for real constants a>0, b≥0, a+b≤1. First of all, we relate the estimation of the minimal size to the problem of finding a minimal difference cover for a suitable subset of Zn. Then, by observing that the cardinality of a difference cover Δ for a set A ⊆ Zn, must satisfy [Formula: see text], we investigate the class of sets A admitting difference covers of cardinality exactly [Formula: see text]. We relate this problem with the efficient construction of Golomb rulers and difference sets. We design an algorithm which outputs each of the Golomb rulers (if any) of a given set in pseudo-polynomial time. As a consequence, we obtain an efficient algorithm that construct minimal difference covers for a non-trivial class of sets. Moreover, by using projective geometry arguments, we give an algorithm that, for any n=q2+q+1 with q prime power, constructs difference sets for Zn in quadratic time.
OSCILLATION INVESTIGATIONS IN SOUDAN 2: ATMOSPHERIC νμ → ντ AND ${\rm n} \to \bar{n}$ IN IRON
Authors: MANN ANTHONY , SANCHEZ MAYLY , KAFKA TOMAS 
Published: November 2003

The 5.90 fiducial kiloton-year exposure of the Soudan-2 iron tracking calorimeter is analyzed for effects of neutrino oscillations. Using fully contained single track, single shower and multiprong events, we determine the atmospheric νμ/νe ratio-of-ratios in the sub-GeV Eν regime to be R=0.68±0.12±0.06. Assuming this anomalously low R-value to be the result of νμ flavor disappearance via νμ → ντ oscillation, we distribute fully contained and partially contained events into bins of log (L/Eν) and fit to oscillation hypotheses using extended maximum likelihood. The region in the ( sin 22θ, Δm2) plane allowed at 90% CL is obtained using the Feldman-Cousins procedure: 0.52< sin 2 2θ≤1.0 and 3×10-4<Δm2<2×10-2 eV 2. A different oscillation process which could occur in our contained event samples is baryon instability in the form of neutron-antineutron oscillations. Our search requires candidate [Formula: see text] occurrences to have ≥ 4 prongs (tracks and showers) and to have kinematics compatible with [Formula: see text] annihilation within a nucleus. We observe five candidate events, with estimated atmospheric neutrino plus cosmic ray backgrounds totalling 4.5 ± 1.2 events. Previous experiments with smaller exposures observed no candidates, with estimated background rates similar to this experiment. We set a lifetime lower limit at 90% CL for the [Formula: see text] oscillation time in iron: TA(Fe)>7.2×1031 years. The corresponding lower limit for oscillation of free neutrons is [Formula: see text] seconds.
Myelodysplastic Syndrome
Authors: Mufti Ghulam , List Alan F. , Gore Steven D. , Ho Aloysius Y.L. 
Published: November 2003

AbstractThe last decade has witnessed a multistep evolution in the understanding of the natural history, clinical manifestations, and some of the molecular mechanisms that underlie the ineffective hematopoiesis and leukemic transformation in the myelodysplastic syndrome (MDS). The international prognostic scoring system, FAB, and WHO classifications have helped define specific subgroups with their characteristic cytogenetic, molecular and immunological abnormalities. Until recently the mainstay of the treatment has been entirely supportive with blood and platelet transfusions. What is increasingly manifest now is the considerable excitement generated by the emergence of novel therapeutic strategies based on painstaking research findings from the laboratories.In Section I, Dr. Alan List reviews the therapeutic strategies with the specific emphasis on the relevance of molecular mechanism of apoptosis and targeted therapies using small molecules. Of particular interest is the excitement surrounding the clinical benefit obtained from potent immunomodulatory derivative (IMiD) of thalidomide CC5013. The review provides an update of the role of small molecule inhibitors of VEGF receptor tyrosine kinase, arsenic trioxide, oral matrix metalloprotease inhibitors, farnesyl transferase inhibitors, and imatinib mesylate in the treatment of MDS subgroups.In Section II, Dr. Steven Gore describes the results of clinical trials of inhibitors of DNA methylation such as 5 azacytidine (5 AC) and 5-aza 2-deoxycytidine (Decitabine). The review also provides an update on the rationale and results obtained from the combination therapy using histone deacetylases (HDAC) and DNA methyltransferase inhibitors in the treatment of MDS.In Section III, Professor Ghulam Mufti and Dr. Aloysius Ho describe the role of bone marrow transplantation with particular emphasis on recent results from reduced-intensity conditioned transplants, exploiting the graft versus leukemia effect without significant early treatment-related mortality. The section provides an update on the results obtained from the manipulation of the host’s immune system with immunosuppressive agents such as ALG and/or cyclosporine A.
Immunodeficiency Disorders
Authors: Cooper Max D. , Lanier Lewis L. , Conley Mary Ellen , Puck Jennifer M. 
Published: November 2003

AbstractHematological complications occur frequently in patients with both primary and secondary immunodeficiency disorders. Anemia, thrombocytopenia or leukopenias may bring these individuals to the attention of hematologists. Conversely, evidence suggesting a lymphoproliferative disorder may be the cause for referral. This session will provide an update on the diagnosis and treatment of immunodeficiency diseases ranging from isolated defects in antibody production to the severe combined immunodeficiencies (SCID).Immunodeficiency diseases have traditionally been defined as defects in the development and function of T and B cells, the primary effector cells of specific cellular and humoral immunity. However, it has become increasingly evident that innate immune mechanisms contribute greatly to host defense, either through acting alone or by enhancing specific T and B cell responses.In Section I, Dr. Lewis Lanier reviews the burgeoning information on the extensive families of activating and inhibitory immunoreceptors that are expressed on NK cells, dendritic cells, T and B cells, and phagocytic cells. He provides an overview on the biological functions of these receptors in host defense.In Section II, Dr. Mary Ellen Conley defines the spectrum of antibody deficiency disorders, the most frequently occurring types of primary immunodeficiencies. She covers the different defects in B-cell development and function that lead to antibody deficiencies, and includes diagnosis and therapy of these disorders.In Section III, Dr. Jennifer Puck discusses the diagnosis and treatment of the different types of SCID. She describes the genetic basis for SCID, and the benefits, pitfalls, and complications of gene therapy and bone marrow transplantation in SCID patients.
Hematopoietic Cell Transplantation for Benign Hematological Disorders and Solid Tumors
Authors: Storb Rainer F. , Lucarelli Guido , McSweeney Peter A. , Childs Richard W. 
Published: November 2003

AbstractAllogeneic hematopoietic cell transplantation (HCT) has been successfully used as replacement therapy for patients with aplastic anemia and hemoglobinopathies. Both autologous and allogeneic HCT following high-dose chemotherapy can correct manifestations of autoimmune diseases. The impressive allogeneic graft-versus-tumor effects seen in patients given HCT for hematological malignancies have stimulated trials of allogeneic immunotherapy in patients with otherwise refractory metastatic solid tumors. This session will update the status of HCT in the treatment of benign hematological diseases and solid tumors.In Section I, Dr. Rainer Storb reviews the development of nonmyeloablative conditioning for patients with severe aplastic anemia who have HLA-matched family members. He also describes the results in patients with aplastic anemia given HCT from unrelated donors after failure of responding to immunosuppressive therapy. The importance of leuko-poor and in vitro irradiated blood product transfusions for avoiding graft rejection will be discussed.In Section II, Dr. Guido Lucarelli reviews the status of marrow transplantation for thalassemia major and updates results obtained in children with class I and class II severity of thalassemia. He also describes results of new protocols for class III patients and efforts to extend HCT to thalassemic patients without HLA-matched family members.In Section III, Dr. Peter McSweeney reviews the current status of HCT for severe autoimmune diseases. He summarizes the results of autologous HCT for systemic sclerosis, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus, and reviews the status of planned Phase III studies for autologous HCT for these diseases in North America and Europe. He also discusses a possible role of allogeneic HCT in the treatment of these diseases.In Section IV, Dr. Richard Childs discusses the development and application of nonmyeloablative HCT as allogeneic immunotherapy for treatment-refractory solid tumors. He reviews the results of pilot clinical trials demonstrating graft-versus-solid tumor effects in a variety of metastatic cancers and describes efforts to characterize the immune cell populations mediating these effects, as well as newer methods to target the donor immune system to the tumor.