bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Mechanism of Antibiotic Resistance Originating in Vancomycin-Intermediate
Staphylococcus aureus
Authors: Cui Longzhu , Iwamoto Akira , Lian Jian-Qi , Neoh Hui-min , Maruyama Toshiki , Horikawa Yataro , Hiramatsu Keiichi 
Published: January 2006

ABSTRACT

As an aggressive pathogen,
Staphylococcus aureus
poses a significant public health threat and is becoming increasingly resistant to currently available antibiotics, including vancomycin, the drug of last resort for gram-positive bacterial infections.
S. aureus
with intermediate levels of resistance to vancomycin (vancomycin-intermediate
S. aureus
[VISA]) was first identified in 1996. The resistance mechanism of VISA, however, has not yet been clarified. We have previously shown that cell wall thickening is a common feature of VISA, and we have proposed that a thickened cell wall is a phenotypic determinant for vancomycin resistance in VISA (L. Cui, X. Ma, K. Sato, et al., J. Clin. Microbiol.
41:
5-14, 2003). Here we show the occurrence of an anomalous diffusion of vancomycin through the VISA cell wall, which is caused by clogging of the cell wall with vancomycin itself. A series of experiments demonstrates that the thickened cell wall of VISA could protect ongoing peptidoglycan biosynthesis in the cytoplasmic membrane from vancomycin inhibition, allowing the cells to continue producing nascent cell wall peptidoglycan and thus making the cells resistant to vancomycin. We conclude that the cooperative effect of the clogging and cell wall thickening enables VISA to prevent vancomycin from reaching its true target in the cytoplasmic membrane, exhibiting a new class of antibiotic resistance in gram-positive pathogens.
The Two-Component Regulatory System
mtrAB
Is Required for Morphotypic Multidrug Resistance in
Mycobacterium avium
Authors: Cangelosi Gerard A. , Do Julie S. , Freeman Robert , Bennett John G. , Semret Makeda , Behr Marcel A. 
Published: January 2006

ABSTRACT

Clinical isolates of the opportunistic pathogen
Mycobacterium avium
complex (MAC) undergo a reversible switch between red and white colony morphotypes on agar plates containing the lipoprotein stain Congo red. Compared to their isogenic red counterparts, white morphotypic variants are more virulent and more resistant to multiple antibiotics. This report shows that the two-component regulatory system
mtrAB
is required for the red-to-white switch as well as for other morphotypic switches of MAC. A mutant with a transposon insertion in the histidine protein kinase gene
mtrB
was isolated from a morphotypically white parent clone. The mutant resembled a naturally occurring red morphotypic variant in that it stained with Congo red, was sensitive to multiple antibiotics, and was permeable by a fluorescent DNA stain. However, it differed from a red variant in that it could not switch to the white or transparent morphotype, and it could not survive intracellularly within macrophage-like cells. Transcomplementation with a cloned wild-type
mtrB
gene restored to the mutant the ability to form impermeable, drug-resistant white and transparent variants. Quantitative reverse transcriptase PCR showed that
mtrB
was required for the normal expression of cell surface Mce proteins, some of which are up-regulated in the red-to-white switch. The results indicate that
mtrAB
functions in regulating the composition and permeability of mycobacterial cell walls and plays a role in the reversible colony type switches of MAC.
Fluconazole Treatment Is Effective against a
Candida albicans erg3/erg3
Mutant In Vivo Despite In Vitro Resistance
Authors: Miyazaki Taiga , Miyazaki Yoshitsugu , Izumikawa Koichi , Kakeya Hiroshi , Miyakoshi Shunichi , Bennett John E. , Kohno Shigeru 
Published: January 2006

ABSTRACT

Candida albicans ERG3
encodes a sterol C5,6-desaturase which is essential for synthesis of ergosterol. Defective sterol C5,6 desaturation has been considered to be one of the azole resistance mechanisms in this species. However, the clinical relevance of this resistance mechanism is still unclear. In this study, we created a
C. albicans erg3/erg3
mutant by the “Ura-blaster” method and confirmed the expected azole resistance using standard in vitro testing and the presence of ergosta-7,22-dien-3β-ol instead of ergosterol. For in vivo studies, a wild-type
URA3
was placed back into its native locus in the
erg3
homozygote to avoid positional effects on
URA3
expression. Defective hyphal formation of the
erg3
homozygote was observed not only in vitro but in kidney tissues. A marked attenuation of virulence was shown by the longer survival and the lower kidney burdens of mice inoculated with the reconstituted Ura
+
erg3
homozygote relative to the control. To assess fluconazole efficacy in a murine model of disseminated candidiasis, inoculum sizes of the control and the
erg3
homozygote were chosen which provided a similar organ burden. Under these conditions, fluconazole was highly effective in reducing the organ burden in both groups. This study demonstrates that an
ERG3
mutation causing inactivation of sterol C5,6-desaturase cannot confer fluconazole resistance in vivo by itself regardless of resistance measured by standard in vitro testing. The finding questions the clinical significance of this resistance mechanism.
Pharmacokinetics, Safety, and Efficacy of Posaconazole in Patients with Persistent Febrile Neutropenia or Refractory Invasive Fungal Infection
Authors: Ullmann A. J. , Cornely O. A. , Burchardt A. , Hachem R. , Kontoyiannis D. P. , Töpelt K. , Courtney R. , Wexler D. , Krishna G. , Martinho M. , Corcoran G. , Raad I. 
Published: January 2006

ABSTRACT

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (
P
= 0.0004) and 182% (
P
< 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (
n
= 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure.
Prediction of the Evolution of Ceftazidime Resistance in Extended-Spectrum β-Lactamase CTX-M-9
Authors: Delmas J. , Robin F. , Carvalho F. , Mongaret C. , Bonnet R. 
Published: January 2006

ABSTRACT

A random mutagenesis technique was used to predict the evolutionary potential of β-lactamase CTX-M-9 toward the acquisition of improved catalytic activity against ceftazidime. Thirty CTX-M mutants were obtained during three rounds of mutagenesis. These mutants conferred 1- to 128-fold-higher MICs of ceftazidime than the parental enzyme CTX-M-9. The CTX-M mutants contained one to six amino acid substitutions. Mutants harbored the substitutions Asp240Gly and Pro167Ser, which were previously observed in clinical CTX-M enzymes. Additional substitutions, notably Arg164His, Asp179Gly, and Arg276Ser, were observed near the active site. The kinetic constants of the three most active mutants revealed two distinct ways of improving catalytic efficiency against ceftazidime. One enzyme had a 17-fold-higher
k
cat
value than CTX-M-9 against ceftazidime. The other two had 75- to 300-fold-lower

K
m

values than CTX-M-9 against ceftazidime. The current emergence of CTX-M β-lactamases with improved activity against ceftazidime may therefore be the beginning of an evolutionary process which might subsequently generate a great diversity of CTX-M-type ceftazidimases.
Medicaid reimbursement for prenatal smoking intervention influences quitting and cessation
Authors: Petersen R , Garrett J M , Melvin C L , Hartmann K E 
Published: January 2006

Background:40% of births in the USA are covered by Medicaid and smoking is prevalent among recipients. The objective of this study was to evaluate the association between levels of Medicaid coverage for prenatal smoking cessation interventions on quitting during pregnancy and maintaining cessation after delivery.Methods:Population based survey study of 7513 post-partum women from 15 states who: participated in Pregnancy Risk Assessment Monitoring System (PRAMS) during 1998–2000; smoked at the beginning of their pregnancy; and had Medicaid coverage. Participating states were categorised into three levels of Medicaid coverage for smoking cessation interventions during prenatal care: extensive (pharmacotherapiesandcounselling); some (pharmacotherapiesorcounselling); or none. Quit rates among women who smoked before pregnancy and rates of maintaining cessation were examined.Results:Higher levels of coverage during prenatal care for smoking cessation interventions were associated with higher quit rates; 51%, 43%, and 39% of women quit in states with extensive, some, and no coverage, respectively. Compared to women in states with no coverage, women in states with extensive coverage had 1.6 times the odds of quitting smoking (odds ratio (OR) 1.58, 95% confidence interval (CI) 1.00 to 2.49). Maintenance of cessation after delivery was associated with extensive levels of Medicaid coverage; 48% of women maintained cessation in states with extensive coverage compared to 37% of women in states with no coverage. Compared to women in states with no coverage, women with extensive coverage had 1.6 times the odds of maintaining cessation (OR 1.63, 95% CI 1.04 to 2.56).Conclusions:Prenatal Medicaid coverage for both pharmacotherapiesandcounselling is associated with higher rates of quitting and continued cessation. This suggests policymakers can promote cessation by broadening smoking cessation services in Medicaid prenatal coverage.
Tobacco industry litigation strategies to oppose tobacco control media campaigns
Authors: Ibrahim J K , Glantz Stanton A 
Published: January 2006

Objective:To document the tobacco industry’s litigation strategy to impede tobacco control media campaigns.Methods:Data were collected from news and reports, tobacco industry documents, and interviews with health advocates and media campaign staff.Results:RJ Reynolds and Lorillard attempted to halt California’s Media Campaign alleging that the campaign polluted jury pools and violated First Amendment rights because they were compelled to pay for anti-industry ads. The American Legacy Foundation was accused of violating the Master Settlement Agreement’s vilification clause because its ads attacked the tobacco industry. The tobacco companies lost these legal challenges.Conclusion:The tobacco industry has expanded its efforts to oppose tobacco control media campaigns through litigation strategies. While litigation is a part of tobacco industry business, it imposes a financial burden and impediment to media campaigns’ productivity. Tobacco control professionals need to anticipate these challenges and be prepared to defend against them.
CCL5-enhanced human immature dendritic cell migration through the basement membrane in vitro depends on matrix metalloproteinase-9
Authors: Chabot Valérie , Reverdiau Pascale , Iochmann Sophie , Rico Angélique , Sénécal Delphine , Goupille Caroline , Sizaret Pierre-Yves , Sensebé Luc 
Published: January 2006

AbstractThe proinflammatory chemokine CC chemokine ligand 5 (CCL5) is a potent chemoattractant of immature dendritic cells (iDCs). It remains to be elucidated whether CCL5 may also enhance iDC migration through the basement membrane by affecting matrix metalloproteinase (MMP)-9 secretion. In this study, iDCs were differentiated in vitro from human monocytes of healthy donors. Zymographic analysis of cellular membranes of nontreated iDCs revealed a basal secretion of the pro- and active MMP-9, whereas only pro-MMP-9 was detected in conditioned media. Increasing concentrations of CCL5 significantly enhanced MMP-9 secretion by iDCs, peaking at 100 ng/ml, which optimally increased iDC migration through a reconstituted basement membrane (Matrigel™) in vitro. The CCL5-enhanced secretion of MMP-9 occurred early (2 h) and was maintained at least for 10 h. A significant increase in MMP-9 mRNA synthesis was detected by reverse transcriptase-polymerase chain reaction, only at 6 h of CCL5 treatment, which suggests that the early effect of CCL5 (0–4 h) on MMP-9 secretion was independent of mRNA synthesis, whereas the more delayed effect (6–10 h) could be mediated through an increase in MMP-9 gene expression. In a Matrigel migration assay, the CCL5-enhanced iDC migration was reduced significantly by specific inhibitors of MMP-9, such as tissue inhibitor of metalloproteinase-1 or an anti-MMP-9 antibody, which indicates that iDC migration through the basement membrane depends on MMP-9. These results suggest that under inflammatory conditions, the chemokine CCL5 may enhance iDC migration through the basement membrane by rapidly increasing their MMP-9 secretion.
The macrophage scavenger receptor CD163: endocytic properties of cytoplasmic tail variants
Authors: Nielsen Marianne Jensby , Madsen Mette , Møller Holger J , Moestrup Søren K 
Published: January 2006

Abstract
CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants are substantially expressed in blood, liver, and spleen, and the short tail variant is the predominant mRNA species. Using cell transfectants in which cDNA encoding the CD163 variants was inserted at the same site in the genome, we evaluated the expression and endocytic properties of the tail variants. Ligand uptake analysis showed that cells expressing the CD163 short tail variant exhibited a higher capacity for ligand endocytosis than cells expressing the CD163 long tail variants. The difference in endocytic activity was explained by confocal microscopic analysis, showing marked deviations in subcellular distribution. Surface expression was far most pronounced for the CD163 short tail variant, whereas the long tail variants were most abundant in the Golgi region/endosomes. Mutational change of a putative signal for endocytosis (Tyr-Arg-Glu-Met), present in a common part of the cytoplasmic tail of the variants, almost completely inactivated the endocytic activity of the short tail variant. In conclusion, the three physiological tail variants of CD163 may contribute to Hp-Hb endocytosis by means of the common ligand-binding region and endocytic signal. However, the high mRNA expression level and relatively high endocytic capacity of the short tail variant suggest that it accounts for the majority of Hp-Hb uptake from the circulation, whereas the long tail variants may have yet-unknown intracellular roles.
Transient Goiter Enlargement after Administration of 0.3 mg of Recombinant Human Thyrotropin in Patients with Benign Nontoxic Nodular Goiter: A Randomized, Double-Blind, Crossover Trial
Authors: Nielsen Viveque Egsgaard , Bonnema Steen J. , Hegedüs Laszlo 
Published: January 2006

Background: Recombinant human (rh) TSH, in doses from 0.01 to 0.9 mg, has been used to augment the effect of radioiodine (131I) therapy in patients with a benign nontoxic nodular goiter. Transient thyroid enlargement and thyrotoxicosis may be seen following 131I therapy.
Aim: The aim of the study was to investigate whether rhTSH per se causes goiter enlargement, until now an issue evaluated only in healthy nongoitrous subjects.
Methods: In random order, 10 patients with nontoxic nodular goiter [mean 39.8 ± 20.5 (sd) ml] received either 0.3 mg rhTSH or isotonic saline in a double-blinded crossover design. Thyroid volume (by ultrasound) and function were closely monitored during the following 28 d.
Results: Saline injection did not affect thyroid function or size. After rhTSH, median serum TSH increased from baseline 0.97 mU/liter (range 0.39–1.56) to 37.0 mU/liter (range 18.5–55.0) at 24 h (P &lt; 0.01), with a subsequent decline to subnormal levels at d 7. Mean free T4 and free T3 increased significantly from baseline to a maximum at 48 h. Twenty-four hours after rhTSH, the mean goiter volume was significantly increased by 9.8 ± 2.3% (sem) (P = 0.01) and after 48 h by 24.0 ± 5.1% (P = 0.002). The goiter enlargement had reverted at d 7. Nine patients had symptoms of hyperthyroidism and/or cervical compression after rhTSH, as opposed to one during placebo treatment (P &lt; 0.02).
Conclusions: A transient average goiter enlargement of up to 24% is seen after 0.3 mg rhTSH. This may lead to a significant cervical compression when used for augmentation of 131I therapy in patients with goiter. The use of lower doses of rhTSH needs to be explored.
Loss ofp53Induces Changes in the Behavior of Subventricular Zone Cells: Implication for the Genesis of Glial Tumors
Authors: Gil-Perotin Sara , Marin-Husstege Mireya , Li Jiadong , Soriano-Navarro Mario , Zindy Frederique , Roussel Martine F. , Garcia-Verdugo Jose-Manuel , Casaccia-Bonnefil Patricia 
Published: January 2006

The role of multipotential progenitors and neural stem cells in the adult subventricular zone (SVZ) as cell-of-origin of glioblastoma has been suggested by studies on human tumors and transgenic mice. However, it is still unknown whether glial tumors are generated by all of the heterogeneous SVZ cell types or only by specific subpopulations of cells. It has been proposed that transformation could result from lack of apoptosis and increased self-renewal, but the definition of the properties leading to neoplastic transformation of SVZ cells are still elusive. This study addresses these questions in mice carrying the deletion ofp53, a tumor-suppressor gene expressed in the SVZ. We show here that, although loss ofp53by itself is not sufficient for tumor formation, it provides a proliferative advantage to the slow- and fast-proliferating subventricular zone (SVZ) populations associated with their rapid differentiation. This results in areas of increased cell density that are distributed along the walls of the lateral ventricles and often associated with increasedp53-independent apoptosis. Transformation occurs when loss ofp53is associated with a mutagenic stimulus and is characterized by dramatic changes in the properties of the quiescent adult SVZ cells, including enhanced self-renewal, recruitment to the fast-proliferating compartment, and impaired differentiation.Together, these findings provide a cellular mechanism for how the slow-proliferating SVZ cells can give rise to glial tumors in the adult brain.
Cost of Care for Newborns With Neonatal Abstinence Syndrome in a State Medicaid Program
Authors: Jenkins Caroline , Hudnall Matthew , Hanson Courtney , Lewis Dwight , Parton Jason M. 
Published: February 2024

ImportanceNeonatal abstinence syndrome (NAS) is a medical condition among neonates experiencing substance withdrawal due to the mother’s substance use during pregnancy. While previous studies suggest that the overall incidence and annual costs of NAS are increasing, to date, the long-term costs have yet to be demonstrated in Medicaid populations.ObjectiveTo examine the demographic differences and long-term costs of care for neonates diagnosed with vs not diagnosed with NAS.Design, Setting, and ParticipantsThis cohort study used claims data from the Alabama Medicaid Agency for neonates born to Medicaid-eligible mothers between January 1, 2010, and December 31, 2020. Data were analyzed in June 2022.ExposureA diagnosis of NAS within 30 days of birth.Main Outcomes and MeasuresRate of NAS by demographic and birth characteristics, long-term costs attributable to NAS status and demographic and birth characteristics, and distribution of this expenditure over the enrollment period.ResultsA total of 346 259 neonates with Medicaid eligibility were born during the study period (mean [SD] gestational age, 38.4 [2.2] weeks; 50.5%, male), 4027 (1.2%) of whom had an NAS diagnosis within 30 days of birth. A larger percentage of neonates with an NAS diagnosis were male (52.7%) than in the group without NAS (50.5%). Neonates with NAS also weighed less at birth (mean difference, −212.0 g; 95% CI, −231.1 to −192.8 g) and had older mothers (mean difference, 3.4 years; 95% CI, 2.6-4.2 years). An NAS diagnosis had an estimated additional cost of $17 921 (95% CI, $14 830-$21 012) over the enrollment period, and this cost was not evenly distributed over that period.Conclusions and RelevanceIn this cohort study of neonates born into the Alabama Medicaid population, those with an NAS diagnosis had a different demographic profile and a higher cost to state Medicaid agencies than those without NAS. These findings warrant further effort to reduce the occurrence of NAS.
Effect of a Billing Code to Reimburse Nurse‐Supported Rheumatology Care on Health Care Costs and Access: An Interrupted Time Series Analysis
Authors: Trenaman Logan , Guh Daphne , Law Michael R. , Cheng Lucy , Harrison Mark 
Published: February 2024

ObjectiveThis study was undertaken to evaluate the impact of a Multidisciplinary Care Assessment (MCA) billing code on health system costs and access to care in British Columbia (BC).MethodsData on all people treated by rheumatologists in BC were obtained from five linked health administrative databases held by Population Data BC from April 1, 2006, to March 31, 2020. Rheumatologists were allocated to either the intervention (ever‐billers) or control groups (never‐billers). For the intervention group, the index date was the month of the first MCA code billing. For the control group the index dates were imputed from intervention index dates. Our analysis focused on a 48‐month period (24 months before and after the index date). We evaluated the impact on two cost (costs related to rheumatoid arthritis [RA]; total health care costs) and access outcomes (rheumatology‐related visits per rheumatologist; days between rheumatology visits for patients with RA) using an interrupted time series analysis.ResultsA total of 46 rheumatologists (31 intervention and 15 control) met our inclusion criteria. Introduction of the MCA was associated with a small but significant increase in RA‐related costs that, at 2 years, translates to a net absolute change of $9.66 per patient per month, but no statistically significant changes in total health care costs. There was no statistically significant change in the number of rheumatology‐related visits, but at 2 years there was a net absolute reduction in the median days between rheumatologist visits for patients with RA (6.3 days).ConclusionThe introduction of the MCA code was associated with a negligible increase in the RA‐related costs and an improvement in access to ongoing care for patients.