bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient leukopenia and anaphylatoxin production during granulocyte apheresis as treatment for ulcerative colitis
Authors: Yonemura Katsuhiko , Ohashi Naro , Kajimura Masayoshi , Hishida Akira 
Published: October 2002

AbstractIt is well known that transient leukopenia due to activation of the alternative pathway of the complement system accompanies hemodialysis when cellulose acetate dialyzers are used. However, it has not been evaluated whether leukopenia also occurs during granulocyte apheresis (GCAP) as treatment for ulcerative colitis, in which an extracorporeal column is filled with cellulose acetate beads in order to remove circulating leukocytes. The aim of the present study was to evaluate whether transient leukopenia and activation of the alternative pathway of the complement system were observed during GCAP. In 8 patients undergoing GCAP weekly for 10 weeks, circulating leukocyte counts and plasma concentrations of C3a, a product of the activated alternative pathway of the complement system, were determined. GCAP elicited a rapid decline in the number of circulating leukocytes to 61.8 ± 13.8% of the baseline value after 15 minutes of GCAP (P < 0.02). Thereafter, the number of circulating leukocytes returned to approximately baseline after 60 minutes. The baseline plasma C3a concentration was 123 ± 61 ng/mL, and a significant increase to 425 ± 123 ng/mL was observed after 15 minutes of GCAP (P < 0.02). The plasma C3a concentration reached 417 ± 96 ng/mL after 60 minutes (P < 0.02). It thus follows that GCAP activates the alternative pathway of the complement system, resulting in anaphylatoxin production. J. Clin. Apheresis 17:107–110, 2002. © 2002 Wiley‐Liss, Inc.
Depression in Alzheimer’s disease: is there a temporal relationship between the onset of depression and the onset of dementia?
Authors: Heun Reinhard , Kockler Martin , Ptok Ursula 
Published: October 2002

SummaryAlzheimer’s disease (AD) patients often present with concurrent major depression (MD). To investigate the reasons for this comorbidity, e.g. MD being a risk factor for AD, or both diagnoses having a common neurobiology, the temporal relationship between the first onset of AD and of MD during lifetime was investigated—57 out of 146 AD patients had a lifetime diagnosis of MD. The correlation between the ages at onset of MD and dementia was calculated. The incidence of MD in AD patients in several 5-year-intervals before and after the onset of AD was compared with the average incidence of MD in the present AD sample and with the expected incidence of MD in the general population. No significant correlation between the onset of AD and of MD could be found after controlling for age, gender and the Mini-Mental-State. However, the incidence of MD 5 years before and after the onset of AD significantly exceeded the expected incidences—MD is only partially related to AD. However, the increased incidence of MD within 5 years before and after the onset of dementia may indicate that a common neurobiological process causes cognitive decline and depression in a subsample of AD patients.
Antivaccinia Activities of Acyclic Nucleoside Phosphonate Derivatives in Epithelial Cells and Organotypic Cultures
Authors: Snoeck R. , Holý A. , Dewolf-Peeters C. , Van Den Oord J. , De Clercq E. , Andrei G. 
Published: October 2002

ABSTRACT
Organotypic “raft” cultures of epithelial cells allow the reconstitution of a skin equivalent that is easily infectible with different viruses with cutaneous tropism. Among these, poxvirus and particularly vaccinia virus (VV) are good candidates for use in antiviral tests, giving histological pictures comparable to those observed in humans infected with smallpox. Therefore, we decided to evaluate a series of phosphonate derivatives for their ability to inhibit VV growth in epithelial cell monolayers, and the most powerful derivatives were tested in the organotypic cultures. The most active compound was 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine [(S)-HPMPA], followed by 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-2,6-diaminopurine, cyclic (S)-HPMPA, 9-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine [(S)-HPMPC; cidofovir, Vistide], and cyclic (S)-HPMPC. Cidofovir, which is on the market for the treatment of human cytomegalovirus retinitis in immunocompromised patients, is potentially a good candidate for the treatment of a poxvirus outbreak, in the absence of any vaccination.
Dual Targeting of DNA Gyrase and Topoisomerase IV: Target Interactions of Garenoxacin (BMS-284756, T-3811ME), a New Desfluoroquinolone
Authors: Ince Dilek , Zhang Xiamei , Silver L. Christine , Hooper David C. 
Published: October 2002

ABSTRACT

We determined the target enzyme interactions of garenoxacin (BMS-284756, T-3811ME), a novel desfluoroquinolone, in
Staphylococcus aureus
by genetic and biochemical studies. We found garenoxacin to be four- to eightfold more active than ciprofloxacin against wild-type
S. aureus.
A single topoisomerase IV or gyrase mutation caused only a 2- to 4-fold increase in the MIC of garenoxacin, whereas a combination of mutations in both loci caused a substantial increase (128-fold). Overexpression of the NorA efflux pump had minimal effect on resistance to garenoxacin. With garenoxacin at twice the MIC, selection of resistant mutants (<7.4 × 10
−12
to 4.0 × 10
−11
) was 5 to 6 log units less than that with ciprofloxacin. Mutations inside or outside the quinolone resistance-determining regions (QRDR) of either topoisomerase IV, or gyrase, or both were selected in single-step mutants, suggesting dual targeting of topoisomerase IV and gyrase. Three of the novel mutations were shown by genetic experiments to be responsible for resistance. Studies with purified topoisomerase IV and gyrase from
S. aureus
also showed that garenoxacin had similar activity against topoisomerase IV and gyrase (50% inhibitory concentration, 1.25 to 2.5 and 1.25 μg/ml, respectively), and although its activity against topoisomerase IV was 2-fold greater than that of ciprofloxacin, its activity against gyrase was 10-fold greater. This study provides the first genetic and biochemical data supporting the dual targeting of topoisomerase IV and gyrase in
S. aureus
by a quinolone as well as providing genetic proof for the expansion of the QRDRs to include the 5′ terminus of
grlB
and the 3′ terminus of
gyrA.
Identification of a Chromosome-Borne Expanded-Spectrum Class A β-Lactamase from
Erwinia persicina
Authors: Vimont Sophie , Poirel Laurent , Naas Thierry , Nordmann Patrice 
Published: October 2002

ABSTRACT

From whole-cell DNA of an enterobacterial
Erwinia persicina
reference strain that displayed a penicillinase-related antibiotic-resistant phenotype, a β-lactamase gene was cloned and expressed in
Escherichia coli.
It encoded a clavulanic-acid-inhibited Ambler class A β-lactamase, ERP-1, with a pI value of 8.1 and a relative molecular mass of ca. 28 kDa. ERP-1 shared 45 to 50% amino acid identity with the most closely related enzymes, the chromosomally encoded enzymes from
Citrobacter koseri
,
Kluyvera ascorbata
,
Kluyvera cryocrescens
,
Klebsiella oxytoca
,
Proteus vulgaris
,
Proteus penneri
,
Rahnella aquatilis
,
Serratia fonticola
,
Yersinia enterocolitica
, and the plasmid-mediated enzymes CTX-M-8 and CTX-M-9. The substrate profile of the noninducible ERP-1 was similar to that of these β-lactamases. ERP-1 is the first extended-spectrum β-lactamase from an enterobacterial species that is plant associated and plant pathogenic.
Complete Nucleotide Sequence of
Klebsiella pneumoniae
Multiresistance Plasmid pJHCMW1
Authors: Sarno Renee , McGillivary Glen , Sherratt David J. , Actis Luis A. , Tolmasky Marcelo E. 
Published: October 2002

ABSTRACT

The multiresistance plasmid pJHCMW1, harbored by a clinical
Klebsiella pneumoniae
strain isolated from a neonate with meningitis, was sequenced. A circular sequence of 11,354 bp was generated, of which 7,993 bp make up Tn
1331
, a transposon including the antibiotic resistance genes
aac
(
6
′)
-Ib
,
aadA1
,
bla
OXA-9
, and
bla
TEM-1
. The gene
aac
(
6
′)
-Ib
is included in a gene cassette, and both
aadA1
and
bla
OXA-9
are included in a single-gene cassette that may have arisen as a consequence of a recombination event involving two integrons. The pJHCMW1 plasmid replicates through a ColE1-like RNA-regulated mechanism, includes a functional
oriT
, and two loci with similarity to XerCD site-specific recombination target sites involved in plasmid stabilization by the resolution of multimers. One of these two loci,
mwr
, is active and has been the subject of previous studies, and the other,
dxs
, is not functional but binds the recombinase XerD with low affinity. Two additional open reading frames were identified, one with low similarity to two hypothetical membrane proteins from
Mycobacterium tuberculosis
and
Mycobacterium leprae
and the other with low similarity to
psiB
, a gene encoding a function that facilitates the establishment of the transferring plasmid in the recipient bacterial cell during the process of conjugation.
In Vivo Pharmacodynamics of a New Oxazolidinone (Linezolid)
Authors: Andes D. , van Ogtrop M. L. , Peng J. , Craig W. A. 
Published: October 2002

ABSTRACT

Linezolid is a new oxazolidinone with activity against gram-positive cocci. We determined the in vivo activity of linezolid against four strains of
Staphylococcus aureus
(two methicillin-susceptible
S. aureus
[MSSA] strains and two methicillin-resistant
S. aureus
strains) and one penicillin-susceptible
Streptococcus pneumoniae
(PSSP) strain, two penicillin-intermediate
S. pneumoniae
strains, and five penicillin-resistant
S. pneumoniae
strains. The mice had 10
6.3
to 10
7.7
CFU/thigh before therapy and were then treated for 24 h with 5 to 1,280 mg of linezolid/kg divided into 1, 2, 4, 8, or 16 doses. The killing activities after 4 h of therapy ranged from 2.4 to 5.0 log
10
CFU/thigh against
S. pneumoniae
and 1.35 to 2.2 log
10
CFU/thigh against
S. aureus
. Increasing doses produced minimal concentration-dependent killing; doses of 20 and 80 mg/kg produced no in vivo postantibiotic effects (PAEs) with PSSP and modest PAEs (3.4 and 3.2 h) with MSSA. Pharmacokinetic studies at doses of 20 and 80 mg/kg by high-pressure liquid chromatography analysis exhibited peak dose values of 0.68 and 0.71 and elimination half-lives of 1.02 and 1.00 h. Linezolid MICs ranged from 0.5 to 1.0 μg/ml for
S. pneumoniae
and from 1.0 to 4.0 μg/ml for
S. aureus
. A sigmoid dose-response model was used to estimate the dose required to achieve a net bacteriostatic effect over 24 h. Static doses against
S. pneumoniae
ranged from 22.2 to 97.1 mg/kg/24 h and from 133 to 167 mg/kg/24 h for
S. aureus
. The 24-h area under the concentration-time curve (AUC)/MIC ratio was the major parameter determining the efficacy of linezolid against PSSP (
R
2
= 82% for AUC/MIC versus 57% for T>MIC and 59% for the peak level in serum/MIC [peak/MIC]). It was difficult to determine the most relevant pharmacokinetic/pharmacodynamic parameter with
S. aureus
, although the outcomes correlated slightly better with the 24-h AUC/MIC ratio (
R
2
= 75%) than with the other parameters (T>MIC
R
2
= 75% and peak/MIC
R
2
= 65%). The 24-h AUC/MIC ratio required for a bacteriostatic effect with linezolid varied from 22 to 97 (mean = 48) for pneumococci and from 39 to 167 (mean = 83) for staphylococci. Based upon a pharmacokinetic goal of a 24-h AUC/MIC of 50 to 100, a dosage regimen of 600 mg given either intravenously or orally twice daily would achieve success against organisms with MICs as high as 2 to 4 μg/ml.
Antifungal Activity of Amphotericin B, Fluconazole, and Voriconazole in an In Vitro Model of
Candida
Catheter-Related Bloodstream Infection
Authors: Lewis Russell E. , Kontoyiannis Dimitrios P. , Darouiche Rabih O. , Raad Issam I. , Prince Randall A. 
Published: October 2002

ABSTRACT

The activity of five simulated antifungal regimens for eradication of catheter-related bloodstream
Candida
infection was evaluated with an in vitro pharmacodynamic model. Single-lumen central venous catheters were colonized with
Candida
species by sequentially incubating central venous catheters in plasma and then in growth medium (RPMI plus morpholinepropanesulfonic acid) containing a standardized suspension (10
5
CFU/ml) of
Candida albicans
,
Candida glabrata
, or slime-producing
Candida parapsilosis
. Colonized central venous catheters were then placed in a one-compartment pharmacodynamic model where five antifungal regimens (plus control) were simulated: amphotericin B, 1.0 mg/kg every 24 h; amphotericin B, 0.5 mg/kg every 24 h; fluconazole, 400 mg every 24 h; fluconazole, 800 mg every 24 h; and voriconazole, 4 mg/kg every 12 h. During exposure to the simulated clinical regimens, samples were serially removed from the model over 48 h for quantitation of viable organisms. All antifungal regimens suppressed fungal counts by both peripheral and catheter sampling versus control (
P
= 0.001). Overall, antifungal activity ranked amphotericin B (1 mg/kg) > amphotericin B (0.5 mg/kg) ≥ voriconazole > fluconazole (800 mg) ≥ fluconazole (400 mg). No regimen, however, completely eradicated (by culture and electron microscopy) central venous catheter colonization. Regrowth was noted in the model during therapy against
C. glabrata
and
C. parapsilosis
but was not associated with an increase in the MICs for the isolates. Lack of in vitro antifungal activity against biofilm-encased organisms appeared to be the primary reason for mycological failure of antifungal regimens in the model.
Pharmacokinetics of Ertapenem in Healthy Young Volunteers
Authors: Majumdar A. K. , Musson D. G. , Birk K. L. , Kitchen C. J. , Holland S. , McCrea J. , Mistry G. , Hesney M. , Xi L. , Li S. X. , Haesen R. , Blum R. A. , Lins R. L. , Greenberg H. , Waldman S. , Deutsch P. , Rogers J. D. 
Published: October 2002

ABSTRACT

Ertapenem (INVANZ) is a new once-a-day parenteral β-lactam antimicrobial shown to be effective as a single agent for treatment of various community-acquired and mixed infections. The single- and multiple-dose pharmacokinetics of ertapenem at doses up to 3 g were examined in healthy young men and women volunteers. Plasma and urine samples collected were analyzed using reversed-phase high-performance liquid chromatography with UV detection. Ertapenem is highly bound to plasma protein. The protein binding changes from ∼95% bound at concentrations of <50 μg/ml to ∼92% bound at concentrations of 150 μg/ml (concentration at the end of a 30-min infusion following the 1-g dose). The nonlinear protein binding of ertapenem resulted in a slightly less than dose proportional increase in the area under the curve from 0 h to infinity (AUC
0-∞
) of total ertapenem. The single-dose AUC
0-∞
of unbound ertapenem was nearly dose proportional over the dose range of 0.5 to 2 g. The mean concentration of ertapenem in plasma ranged from ∼145 to 175 μg/ml at the end of a 30-min infusion, from ∼30 to 34 μg/ml at 6 h, and from ∼9 to 11 μg/ml at 12 h. The mean plasma
t
1/2
ranged from 3.8 to 4.4 h. About 45% of the plasma clearance (CL
P
) was via renal clearance. The remainder of the CL
P
was primarily via the formation of the β-lactam ring-opened metabolite that was excreted in urine. There were no clinically significant differences between the pharmacokinetics of ertapenem in men and women. Ertapenem does not accumulate after multiple once-daily dosing.
Emergence in Vietnam of
Streptococcus pneumoniae
Resistant to Multiple Antimicrobial Agents as a Result of Dissemination of the Multiresistant Spain
23F
-1 Clone
Authors: Parry Christopher M. , Duong Nguyen Minh , Zhou Jiaji , Mai Nguyen Thi Hoang , Diep To Song , Thinh Le Quoc , Wain John , Van Vinh Chau Nguyen , Griffiths David , Day Nicholas P. J. , White Nicholas J. , Hien Tran Tinh , Spratt Brian G. , Farrar Jeremy J. 
Published: October 2002

ABSTRACT

Surveillance for
Streptococcus pneumoniae
resistant to penicillin and other antimicrobial agents is necessary to define the optimal empirical antibiotic therapy for meningitis in resource-poor countries such as Vietnam. The clinical and microbiological features of 100 patients admitted to the Centre for Tropical Diseases in Ho Chi Minh City, Vietnam, between 1993 and 2002 with invasive pneumococcal disease were studied. A penicillin-nonsusceptible pneumococcus (MIC, ≥0.1 μg/ml) was isolated from the blood or cerebrospinal fluid of 8% of patients (2 of 24) between 1993 and 1995 but 56% (20 of 36) during 1999 to 2002 (
P
< 0.0001). Pneumococcal isolates resistant to penicillin (MIC, ≥2.0 μg/ml) increased from 0% (0 of 24) to 28% (10 of 36) (
P
= 0.002). Only one isolate was ceftriaxone resistant (MIC, 2.0 μg/ml). Penicillin-nonsusceptible pneumococci were isolated from 78% of children younger than 15 years (28 of 36) compared with 25% of adults (16 of 64) (
P
= 0.0001). Isolation of a penicillin-nonsusceptible pneumococcus in adults with meningitis was independently associated with referral from another hospital (
P
= 0.005) and previous antibiotic therapy (
P
= 0.025). Multilocus sequence typing showed that 86% of the invasive penicillin-resistant pneumococcus isolates tested (12 of 14) were of the Spain
23F
-1 clone. The serotypes of >95% of the penicillin-nonsusceptible pneumococci were included in the currently available pneumococcal vaccines. Our findings point to the recent introduction and spread of the Spain
23F
-1 clone of penicillin-resistant pneumococci in Vietnam. Simple clinical predictors can be used to guide empirical antibiotic therapy of meningitis. Pneumococcal vaccination may help to control this problem.
In Vitro and In Vivo Activities of Newer Fluoroquinolones against
Vibrio vulnificus
Authors: Tang Hung-Jen , Chang Ming-Chung , Ko Wen-Chien , Huang Kun-Yen , Lee Chih-Lung , Chuang Yin-Ching 
Published: October 2002

ABSTRACT

The MICs of six fluoroquinolones as well as minocycline and cefotaxime for 46 clinical isolates of
Vibrio vulnificus
were determined by the agar dilution method. All the drugs tested had good activities against all isolates, with the MICs at which 90% of the isolates tested were inhibited (MIC
90
s) by five of the fluoroquinolones ranging between 0.03 and 0.06 μg/ml. The MIC
90
of lomefloxacin, on the other hand, was 0.12 μg/ml. Time-kill studies were conducted with these agents and a clinical strain of
V. vulnificus
, VV5823. When approximately 5 × 10
5
CFU of
V. vulnificus
/ml was incubated with any one of the above-mentioned six fluoroquinolones at concentrations of two times the MIC, there was an inhibitory effect on
V. vulnificus
that persisted for more than 48 h with no noted regrowth. The efficacies of the fluoroquinolones were further evaluated in vivo in the mouse model of experimental
V. vulnificus
infection and compared to the efficacy of a combination therapy using cefotaxime plus minocycline. With an inoculum of 1.5 × 10
7
CFU, 28 (87.5%) of 32 mice in the cefotaxime-minocycline-treated group survived and 29 (91%) of the 32 mice in the moxifloxacin-treated group survived while none of the 32 mice in the control group did. With an inoculum of 3.5 × 10
7
CFU, the difference in survival rates among groups of 15 mice treated with levofloxacin (13 of 15), moxifloxacin (10 of 15), gatifloxacin (10 of 15), sparfloxacin (11 of 15), ciprofloxacin (12 of 15), or lomefloxacin (10 of 15) was not statistically significant while none of the 15 mice treated with saline survived. We concluded that the newer fluoroquinolones as single agents are as effective as the cefotaxime-minocycline combination in inhibiting
V. vulnificus
both in vitro and in vivo.
In Vitro Antibacterial Activities of Phloxine B and Other Halogenated Fluoresceins against Methicillin-Resistant
Staphylococcus aureus
Authors: Rasooly Avraham , Weisz Adrian 
Published: October 2002

ABSTRACT

Fluorescein dyes in which the benzoic acid moiety has been tetrachlorinated (50 to 100 μg/ml) inhibit in vitro
Staphylococcus aureus
growth (MIC, 25 μg/ml). Specifically, under standard room illumination, phloxine B at a concentration of 100 μg/ml killed 99% of the cultures (mid-log phase). It also reduced
S. aureus
CFU by 10
4
. Structure-activity analysis revealed that the activity against
S. aureus
increases with the increase in the number of the substituting halogens in the hydroxyxanthene moiety.
Kallistatin is a new inhibitor of angiogenesis and tumor growth
Authors: Miao Robert Q. , Agata Jun , Chao Lee , Chao Julie 
Published: October 2002

AbstractKallistatin is a unique serine proteinase inhibitor (serpin) and a heparin-binding protein. It has been localized in vascular smooth muscle cells and endothelial cells of human blood vessels, suggesting that kallistatin may be involved in the regulation of vascular function. Our previous study showed that kallistatin plays a role in neointima hyperplasia. In this study, we investigated the potential role of kallistatin in angiogenesis in vitro and in vivo. Purified human kallistatin significantly inhibited vascular endothelial growth factor (VEGF)– or basic fibroblast growth factor (bFGF)–induced proliferation, migration, and adhesion of cultured endothelial cells. Kallistatin attenuated VEGF- or bFGF-induced capillary density and hemoglobin content in subcutaneously implanted Matrigel plugs in mice. To further investigate the role of kallistatin in angiogenesis, we prepared adenovirus carrying the human kallistatin cDNA (Ad.HKBP) and evaluated the effect of kallistatin gene delivery on spontaneous angiogenesis in a rat model of hind-limb ischemia. Local kallistatin gene delivery significantly reduced capillary formation and regional blood perfusion recovery in the ischemic hind limb after removal of the femoral artery. Furthermore, a single intratumoral injection of Ad.HKBP into pre-established human breast tumor xenografts grown in athymic mice resulted in significant inhibition of tumor growth. CD31 immunostaining of tumor sections showed a decreased number of blood vessels in the kallistatin-treated group as compared to the control. These results demonstrate a novel role of kallistatin in the inhibition of angiogenesis and tumor growth.
Subtractive hybridization reveals the expression of immunoglobulinlike transcript 7, Eph-B1, granzyme B, and 3 novel transcripts in human plasmacytoid dendritic cells
Authors: Rissoan Marie-Clotilde , Duhen Thomas , Bridon Jean-Michel , Bendriss-Vermare Nathalie , Péronne Catherine , Vis Blandine de Saint , Brière Francine , Bates Elizabeth E. M. 
Published: October 2002

AbstractRecent studies in humans have highlighted the importance of a distinct cellular entity, the plasmacytoid dendritic cell (PDC). To identify genes for which expression is restricted to human PDCs, a cDNA subtraction technique was applied using cDNA from activated monocyte-derived DCs (MDDCs) as competitor. In the 650 sequences analyzed, 25% were for B-cell transcripts. We also found lymphoid-related genes, immunoglobulinlike transcript 7 (ILT7), granzyme B (GrB), Spi-B, and the receptor tyrosine kinase Eph-B1. Granzyme B was up-regulated on activation, and protein was detected only in PDCs. Eph-B1 protein was expressed in the cytoplasm and the nuclei of PDCs and MDDCs, respectively. Interestingly, several novel molecules have been identified that were predicted to encode for a type 2 transmembrane protein (BRI3), a putative cytokine (C-15, a cysteine-rich–secreted protein), and a type 1 leucine-rich repeat protein (MAPA). The identification of genes expressed in PDCs provides new insights into their function and origin.