bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adolescent resilience: a concept analysis
Authors: Olsson Craig A , Bond Lyndal , Burns Jane M , Vella‐Brodrick Dianne A , Sawyer Susan M 
Published: January 2003

AbstractThere is need for greater clarity around the concept of resilience as it relates to the period of adolescence. Literature on resilience published between 1990 and 2000 and relevant to adolescents aged between 12‐ and 18‐years of age was reviewed with the aim of examining the various uses of the term, and commenting on how specific ways of conceptualizing of resilience may help develop new research agendas in the field. By bringing together ideas on resilience from a variety of research and clinical perspectives, the purpose of the review is to explicate core elements of resilience in more precise ways, in the hope that greater conceptual clarity will lead to a range of tailored interventions that benefit young people.
Prognostic value of serial cardiac assessment and familial screening in patients with dilated cardiomyopathy
Authors: Grünig Ekkehard , Benz Andreas , Mereles Derliz , Unnebrink Kristina , Kücherer Helmut , Haass Markus , Kübler Wolfgang , Katus Hugo A. 
Published: January 2003

AbstractObjectives:This prospective study was performed to analyse whether routine clinical follow‐up investigations at 12±6 months add to risk stratification and improve survival rates in patients with a first diagnosis of dilated cardiomyopathy (DCM).Methods:Four hundred and eighty consecutive patients (mean age 53.4±12.3 years, 369 males, mean NYHA class 2.4±0.8) with invasively confirmed DCM were included and followed for 3.9±3.5 years. Patients were requested to adhere to a follow up investigation within 6–18 months either at the referring physicians or at our out patient department. Two hundred and eighty‐one of the 480 patients presented for follow up which consisted of a detailed evaluation of symptoms, standardized physical examination, 12‐lead‐electrocardiogram recording and echocardiography. Seventeen patients were lost for follow up, 182 did not seek specialized medical follow up. Patients outcome was assessed by structured telephone interviews.Results:Independent predictors of death or transplantation at initial diagnosis were LV–ejection fraction <30% (P=0.0001, risk ratio 2.25), LV–end diastolic pressure ≥15 mmHg (P=0.002, risk ratio 2.0), age ≥54 years, (P=0.04, risk ratio 1.55), and presence of left bundle branch block (P=0.046, risk ratio 1.53). On follow up investigations only deterioration of clinical status by at least one NYHA‐class (P=0.001, risk ratio 2.6) and new onset or worsening of mitral regurgitation (P=0.02, risk ratio 1.8), remained independent prognostic factors for cardiac death. Patients who presented for routine follow up revealed significant better 5‐year survival rates (n=281, 70%) than those who did not (n=153, 55%, P=0.005).Conclusions:Routine clinical follow up investigations within 6–18 months after first diagnosis of DCM adds to risk stratification and improves survival rates.
Neurohormonal effects of furosemide withdrawal in elderly heart failure patients with normal systolic function
Authors: van Kraaij Dave J.W. , Jansen René W.M.M. , Sweep Fred C.G.J. , Hoefnagels Willibrord H.L. 
Published: January 2003

AbstractBackground:In heart failure patients, diuretics cause renin–angiotensin–aldosterone system (RAS) activation, which may lead to increased morbidity and mortality despite short‐term symptomatic improvement.Aim:To determine changes in RAS activation and clinical correlates following furosemide withdrawal in elderly heart failure patients without left ventricular systolic dysfunction.Methods and results:We performed clinical assessments and laboratory determinations of aldosterone, plasma renin activity (PRA), atrial natriuretic peptide (ANP), norepinephrine, and endothelin in 29 heart failure patients [aged 75.1±0.7 (mean±S.E.M.) years], before, 1 and 3 months after placebo‐controlled furosemide withdrawal. Recurrent congestion occurred in 2 of 19 patients withdrawn, and in 1 of 10 patients continuing on furosemide. Three months after withdrawal, PRA had decreased −1.61±0.71 nmol/l/h (P<0.05). Decreases in aldosterone levels did not reach significance (−0.17±0.38 nmol/l). The decreases in PRA after withdrawal correlated with decreases in systolic (rs=0.61, P=0.020) and diastolic blood pressure (rs=0.80, P=0.01). Successful withdrawal was associated with increases in norepinephrine (+0.58±0.22 nmol/l) and ANP (+3.5±1.3 pmol/l) (P<0.05) after 1 month, but these changes did not persist after 3 months. Endothelin levels did not change in both groups.Conclusion:Successful furosemide withdrawal in elderly heart failure patients causes persistent decreases in RAS activation.
The successful clone: the vector of dissemination of resistance in Streptococcus pneumoniae
Authors: Klugman K. P. 
Published: January 2003

Abstract
A small number of pneumococcal clones dominate the population of antibiotic-resistant pneumococci. The emergence of fluoroquinolone resistance in these clones predicts the dissemination of fluoroquinolone resistance in countries where the clones are present and community use of fluoroquinolones for respiratory infections is common. The molecular basis of resistance to a number of classes of antimicrobials can be used to predict the likelihood of dissemination of the resistance genes.
Antimicrobial resistance: a class effect?
Authors: Prieto J. , Calvo A. , Gómez-Lus M. L. 
Published: January 2003

Abstract
Antibiotic use has led to increased resistance to certain group markers: penicillin, erythromycin and ciprofloxacin for β-lactams, macrolides and quinolones, respectively. The influence of resistance to markers in decreasing susceptibility to the drugs included (on the basis of chemical structure) in the corresponding antibiotic group can be defined as ‘resistance class effect’. In the case of macrolides, this effect is dependent on the prevalent resistant phenotype among the isolates of the target bacteria: the class effect exists completely if the mechanism of resistance is constitutive MLS B (all macrolides are affected by resistance to erythromycin), and only partially if the mechanism is the efflux M phenotype (all but 16-membered macrolides are affected). In Spain, the first case is exemplified by Streptococcus pneumoniae and the second by Streptococcus pyogenes . For β-lactams and quinolones, resistance to the group markers results in large decreases in the antimicrobial activity of the less potent members of the group, penicillin being a better driver of resistance for oral cephalosporins than for aminopenicillins, and ciprofloxacin being a better driver for older rather than for the newer quinolones, which have enhanced anti-pneumococcal activity. Empirical prescription guidelines based on the pharmacoepidemiology of resistance, recommending the use of potent drugs that are less influenced by resistance to the marker, may help to counter the spread of resistance in the community.
A Glutamate Mutase Is Involved in the Biosynthesis of the Lipopeptide Antibiotic Friulimicin in
Actinoplanes friuliensis
Authors: Heinzelmann E. , Berger S. , Puk O. , Reichenstein B. , Wohlleben W. , Schwartz D. 
Published: January 2003

ABSTRACT

Actinoplanes friuliensis
produces the lipopeptide antibiotic friulimicin. This antibiotic is active against gram-positive bacteria such as multiresistant
Enterococcus
and
Staphylococcus
strains. It consists of 10 amino acids that form a ring structure and 1 exocyclic amino acid to which an acyl residue is attached. By a reverse genetic approach, biosynthetic genes were identified that are required for the nonribosomal synthesis of the antibiotic. In close proximity two genes (
glmA
and
glmB
) were found which are involved in the production of methylaspartate, one of the amino acids of the peptide core. Methylaspartate is synthesized by a glutamate mutase mechanism, which was up to now only described for glutamate fermentation in
Clostridium
sp. or members of the family
Enterobacteriaceae
. The active enzyme consists of two subunits, and the corresponding genes overlap each other. To demonstrate enzyme activity in a heterologous host, it was necessary to genetically fuse
glmA
and
glmB
. The resulting gene was overexpressed in
Streptomyces lividans
, and the fusion protein was purified in an active form. For gene disruption mutagenesis, a host-vector system was established which enables genetic manipulation of
Actinoplanes
spp. for the first time. Thus, targeted inactivation of biosynthetic genes was possible, and their involvement in friulimicin biosynthesis was demonstrated.
Biological Properties of Novel Antistaphylococcal Quinoline-Indole Agents
Authors: Oliva Brunello , Miller Keith , Caggiano Nico , O'Neill Alexander J. , Cuny Gregory D. , Hoemann Michael Z. , Hauske James R. , Chopra Ian 
Published: January 2003

ABSTRACT

The antibacterial properties of novel quinoline-indole (QI) agents were examined. QI agents demonstrated potent bactericidal activities against
Staphylococcus aureus
, killing by lytic and nonlytic mechanisms.
S. aureus
mutants resistant to a lytic QI agent (SEP 155342) and a nonlytic QI agent (SEP 118843) arose at frequencies of 1.4 × 10
−9
and 1.2 × 10
−8
, respectively, by selection at four times the MICs. Mutants resistant to QI agent SEP 155342 were unstable, but mutants resistant to QI agent SEP 118843 displayed stable resistance. Mutants resistant to QI agent SEP 118843 were not cross resistant to other inhibitors, including QI agent SEP 155342. Addition of QI agents SEP 118843 and SEP 155342 at four times the MIC caused nonspecific inhibition of several macromolecular biosynthetic pathways in
S. aureus
. Within 10 min, QI agents SEP 118843 and SEP 155342 both interfered with bacterial membrane integrity, as measured by uptake of propidium iodide. Agents from the two classes of the QI agents probably kill staphylococci by separate mechanisms which, nevertheless, both involve interference with cytoplasmic membrane function. Precise structure-activity relationships for the division of QI agents into two classes could not be determined. However, lytic activity was often associated with substitution of a basic amine at position 4 of the quinoline nucleus, whereas compounds with nonlytic activity usually contained an aromatic ring with or without a methoxy substituent at position 4. Nonlytic QI agents such as SEP 118843 may possess selective activity against the prokaryotic membrane since this compound failed to lyse mouse erythrocytes when it was added at a concentration equivalent to four times the MIC for
S. aureus.
In Vitro Parasiticidal Effect of Nitazoxanide against
Echinococcus multilocularis
Metacestodes
Authors: Stettler Marianne , Fink Renate , Walker Mirjam , Gottstein Bruno , Geary Timothy G. , Rossignol Jean François , Hemphill Andrew 
Published: January 2003

ABSTRACT

When humans serve as inadvertent intermediate hosts for
Echinococcus multilocularis
, disease (alveolar echinococcosis [AE]) may result from the expanding parasite metacestode in visceral organs, mostly in the liver. Benzimidazole carbamate derivatives such as mebendazole and albendazole are used for chemotherapeutic treatment of AE. However, these treatments are, in most cases, parasitistatic rather than parasiticidal. As treatment is discontinued, a recurrence of parasite growth has been observed in many AE patients with nonradical resections. The only curative treatment for AE is radical surgical resection of the parasite tissue and support by chemotherapy. As there is a need for new treatment options for AE, the in vitro efficacy of nitazoxanide (NTZ), a broad-spectrum drug used against intestinal parasites and bacteria, was investigated. We showed that in vitro treatment of
E. multilocularis
metacestodes with NTZ induced high levels of alkaline phosphatase activity in the medium. Concurrently, distinct morphological and ultrastructural alterations were detected. Most significantly, two distinct types of alterations were observed as soon as after 3 h of NTZ treatment. At first, the drug induced a peripheral output of membranous vesicles from the tegumental membrane into the laminated layer. Simultaneously, germinal layer-associated undifferentiated cells produced large vacuoles filled with lipid-like and often electron-dense membranous segments. Other alterations were observed at later time points, including vacuolization of the germinal layer, accumulation of lipid droplets, and lastly, loss of microtriches and separation of the laminated and germinal layers. The pattern of damage induced by NTZ was different from the alterations earlier observed in albendazole sulfoxide-treated vesicles. The nonviability of NTZ-treated metacestodes was confirmed through bioassay, i.e., inoculation of treated and untreated parasites into mice. These experiments demonstrate the in vitro parasiticidal effect of NTZ on
E. multilocularis
metacestodes.
Trypanosoma cruziInactivation in Human Platelet Concentrates and Plasma by a Psoralen (Amotosalen HCl) and Long-Wavelength UV
Authors: Van Voorhis Wesley C. , Barrett Lynn K. , Eastman Richard T. , Alfonso Ryan , Dupuis Kent 
Published: January 2003

ABSTRACTTrypanosoma cruzi,the protozoan pathogen that causes Chagas' disease, can be found in the blood of infected individuals for their entire life span. This presents a serious challenge in safeguarding blood products. Transmission ofT. cruzifrom blood products is a frequent occurrence in Latin America, where Chagas' disease is endemic. This study was designed to determine whetherT. cruzicould be inactivated in human platelet concentrates and plasma by a photochemical treatment process with long-wavelength UV A light (UVA, 320 to 400 nm) plus the psoralen amotosalen HCl (Cerus Corporation). Units of platelet concentrates (300 ml) and plasma (300 ml) were intentionally contaminated with approximately 106T. cruzitrypomastigotes, theT. cruziform found in the bloodstream, per ml. The viability ofT. cruziafter photochemical inactivation was determined by their ability to replicate in 3T3 fibroblasts. Controls, including treatment with 150 μM amotosalen or 3 J/cm2UVA alone, did not lead to reduction of the viability ofT. cruziin plasma or platelet concentrates. However, treatment with 150 μM amotosalen plus 3 J/cm2UVA inactivatedT. cruzito undetectable levels in plasma and platelet concentrates. This represented a >5.4-log reduction ofT. cruziin platelet concentrates and >5.0-log reduction ofT. cruziin plasma. We conclude that the amotosalen plus UVA photochemical inactivation technology is effective in inactivating high levels of protozoan pathogens, such asT. cruzi,in platelet concentrates and plasma, as has been previously shown for numerous viruses and bacteria.
MC21-A, a Bactericidal Antibiotic Produced by a New Marine Bacterium,
Pseudoalteromonas phenolica
sp. nov. O-BC30
T
, against Methicillin-Resistant
Staphylococcus aureus
Authors: Isnansetyo Alim , Kamei Yuto 
Published: January 2003

ABSTRACT

We previously reported a new marine bacterium,
Pseudoalteromonas phenolica
sp. nov. O-BC30
T
, which produced a bactericidal antibiotic against methicillin-resistant
Staphylococcus aureus
(MRSA). In the present study, we purified an anti-MRSA substance (MC21-A) from the methanol extract of the cells of
P. phenolica
O-BC30
T
and analyzed its chemical structure. MC21-A was determined to be 3,3′,5,5′-tetrabromo-2,2′-biphenyldiol by spectrometric analyses. Its anti-MRSA activity against 10 clinical isolates of MRSA was comparable to that of vancomycin (MC21-A MICs, 1 to 2 μg/ml; vancomycin MICs, <0.25 to 2 μg/ml). This substance was also high active against
Enterococcus serolicida
,
Enterococcus faecium
, and
Enterococcus faecalis
but was less active against
Streptococcus
spp. A time-kill study also demonstrated that MC21-A was bactericidal and that its killing rate was much higher than that of vancomycin. The postantibiotic effect (PAE) of MC21-A against a clinical MRSA isolate, strain E 31243, was also comparable to that of vancomycin (MC21-A PAEs, 1.46 to 1.65 h; vancomycin PAEs, 0.84 to 1.43 h). However, a lysis experiment demonstrated that this substance failed to lyse MRSA cells. This substance also did not lyse human erythrocytes. A SYTOX Green staining experiment implied that this substance permeabilized the cell membrane of MRSA as its mode of action. When its activities against a hypersensitive
Escherichia coli
mutant (KO 1489) and wild-type strains were tested, MC21-A exhibited higher levels of activity against the former. Furthermore, MC21-A was not cytotoxic to human normal fibroblast, rat pheochromocytoma, and Vero cells at concentrations up to 50 μg/ml. These results suggest that MC21-A might be useful as a lead compound in the development of new types of anti-MRSA substances with modes of action different from those of vancomycin and teicoplanin.
Macrolide-Resistant
Streptococcus pneumoniae
and
Streptococcus pyogenes
in the Pediatric Population in Germany during 2000-2001
Authors: Reinert Ralf René , Lütticken Rudolf , Bryskier André , Al-Lahham Adnan 
Published: January 2003

ABSTRACT

In a nationwide study in Germany covering 13 clinical microbiology laboratories, a total of 307
Streptococcus pyogenes
(mainly pharyngitis) and 333
Streptococcus pneumoniae
(respiratory tract infections) strains were collected from outpatients less than 16 years of age. The MICs of penicillin G, amoxicillin, cefotaxime, erythromycin A, clindamycin, levofloxacin, and telithromycin were determined by the microdilution method. In
S. pyogenes
isolates, resistance rates were as follows: penicillin, 0%; erythromycin A, 13.7%; and levofloxacin, 0%. Telithromycin showed good activity against
S. pyogenes
isolates (MIC
90
= 0.25 μg/ml; MIC range, 0.016 to 16 μg/ml). Three strains were found to be telithromycin-resistant (MIC ≥ 4 μg/ml). Erythromycin-resistant strains were characterized for the underlying resistance genotype, with 40.5% having the efflux type
mef
(A), 38.1% having the
erm
(A), and 9.5% having the
erm
(B) genotypes.
emm
typing of macrolide-resistant
S. pyogenes
isolates showed
emm
types 4 (45.2%), 77 (26.2%), and 12 (11.9%) to be predominant. In
S. pneumoniae
, resistance rates were as follows: penicillin intermediate, 7.5%; penicillin resistant, 0%; erythromycin A, 17.4%; and levofloxacin, 0%. Telithromycin was highly active against pneumococcal isolates (MIC
90
≤ 0.016 μg/ml; range, 0.016 to 0.5 μg/ml). The overall resistance profile of streptococcal respiratory tract isolates is still favorable, but macrolide resistance is of growing concern in Germany.
NP-1, a Rabbit α-Defensin, Prevents the Entry and Intercellular Spread of Herpes Simplex Virus Type 2
Authors: Sinha Sara , Cheshenko Natalia , Lehrer Robert I. , Herold Betsy C. 
Published: January 2003

ABSTRACTRabbit neutrophil peptide-1 (NP-1), a prototypic α-defensin, protects cells in vitro from infection by clinical and laboratory isolates of herpes simplex virus type 2 (HSV-2). Incubation of concentrated virus stocks for 1 h with noncytotoxic concentrations of NP-1 reduces subsequent infection by >98%. Pretreating cells with NP-1 for 1 h prior to inoculation with untreated virus also prevents infection. NP-1, a cationic peptide, does not compete with viral envelope glycoproteins for binding to cellular heparan sulfate receptors, but it prevents viral entry. No VP16, a major viral tegument protein, is transported to the cell nucleus in the presence of NP-1. Infectious center assays demonstrate that NP-1 also inhibits cell-to-cell viral spread. Thus, NP-1 prevents virally mediated fusion events, entry, and cell-to-cell spread. This unique mechanism of anti-HSV activity, coupled with established antibacterial and possible anti-human immunodeficiency virus type 1 activities of defensins, render this family of compounds excellent candidates for further development as topical microbicides.
Toward the Development of a Virus-Cell-Based Assay for the Discovery of Novel Compounds against Human Immunodeficiency Virus Type 1
Authors: Adelson Martin E. , Pacchia Annmarie L. , Kaul Malvika , Rando Robert F. , Ron Yacov , Peltz Stuart W. , Dougherty Joseph P. 
Published: January 2003

ABSTRACT
The emergence of human immunodeficiency virus type 1 (HIV-1) strains resistant to highly active antiretroviral therapy necessitates continued drug discovery for the treatment of HIV-1 infection. Most current drug discovery strategies focus upon a single aspect of HIV-1 replication. A virus-cell-based assay, which can be adapted to high-throughput screening, would allow the screening of multiple targets simultaneously. HIV-1-based vector systems mimic the HIV-1 life cycle without yielding replication-competent virus, making them potentially important tools for the development of safe, wide-ranging, rapid, and cost-effective assays amenable to high-throughput screening. Since replication of vector virus is typically restricted to a single cycle, a crucial question is whether such an assay provides the needed sensitivity to detect potential HIV-1 inhibitors. With a stable, inducible vector virus-producing cell line, the inhibitory effects of four reverse transcriptase inhibitors (zidovudine, stavudine, lamivudine, and didanosine) and one protease inhibitor (indinavir) were assessed. It was found that HIV-1 vector virus titer was inhibited in a single cycle of replication up to 300-fold without affecting cell viability, indicating that the assay provides the necessary sensitivity for identifying antiviral molecules. Thus, it seems likely that HIV-1-derived vector systems can be utilized in a novel fashion to facilitate the development of a safe, efficient method for screening compound libraries for anti-HIV-1 activity.
Two Mechanisms for Human Immunodeficiency Virus Type 1 Inhibition by N-Terminal Modifications of RANTES
Authors: Pastore Cristina , Picchio Gastón R. , Galimi Francesco , Fish Richard , Hartley Oliver , Offord Robin E. , Mosier Donald E. 
Published: January 2003

ABSTRACTC-C chemokine receptor 5 (CCR5) is the primary coreceptor for human immunodeficiency virus type 1 (HIV-1) infection. Native chemokines that bind to CCR5 inhibit HIV-1 infection, albeit weakly, but chemically modified chemokines inhibit infection more efficiently. We have investigated the inhibitory mechanism of three N-terminally modified RANTES variants (AOP-, NNY-, and PSC-RANTES) with the MT-2 human T-cell line stably expressing either native or mutated CCR5. The RANTES analogues showed the same rank order (PSC > NNY > AOP) in their capacity to induce prolonged CCR5 internalization, inhibit surface reexpression, and prevent HIV-1 infection on MT-2 cells expressing wild-type CCR5 or CCR5 with four C-terminal serine phosphorylation sites mutated to alanine. None of the RANTES analogues caused internalization of a C-terminal cytoplasmic domain deletion mutant of CCR5, and each derivative had equal potency in inhibiting HIV-1 infection of MT-2 cells expressing this mutant. We conclude that the C-terminal cytoplasmic residues of CCR5 are necessary for receptor sequestration by RANTES analogues but that the process and the relative activity of each derivative are not dependent upon phosphorylation of the C-terminal serine residues. Two mechanisms of antiviral activity are demonstrated: receptor blockade and receptor sequestration. Potency correlates with the ability to induce CCR5 sequestration but not with receptor binding, suggesting that sequestration may make the greater contribution to antiviral activity.