bluuebunny/crossref_metadata_2025_split huggingface dataset:
A MULTICENTRE STUDY OF THE EFFECT AND TOLERANCE OF OCUSERT‐P‐40
Authors: ÅKERBLOM T. , AURELL E. , CRISTIANSSON J. , KRIISA‐KUNNOS V. , WIEBERT O. 
Published: May 2009

The suitability of treatment with Ocusert®‐P‐40, a lamellar system inserted in the eye and allowing the constant release of pilocarpine, was studied in a group of patients (age range 43–83 years) with wide‐angle glaucoma. Those patients completing a 3‐week trial were included in an 8 month follow‐up study in which the long‐term efficacy and tolerance of Ocusert® were studied.Treatment was discontinued in 13 of the 42 patients in the 3‐week trial owing to initial irritation and retention problems (n= 11) or unsatisfactory control of the intraocular pressure (I.O.P.) (n=2). Of the 29 patients entering the long‐term study, two were withdrawn because of tolerance problems and two as a result of unsatisfactory control of I.O.P. The 25 patients completing the study considered the Ocusert® system more convenient and less liable to produce troublesome side‐effects than their previous therapy. Ocusert® was best tolerated by the younger patients.
TIMOLOL VERSUS PILOCARPINE SEPARATELY OR COMBINED WITH ACETAZOLAMIDE‐EFFECTS ON INTRAOCULAR PRESSURE
Authors: CALISSENDORFF B. , MARÉN N. , WETTRELL K. , ÖSTBERG A. 
Published: May 2009

Fifty‐eight patients with intraocular hypertension or primary open angle glaucoma participated in a double masked randomized study. Timolol in concentrations 0.25% and 0.5% was compared with 1, 2, or 4% pilocarpine. Acetazolamide (250 mg × 3) was added if intraocular pressure (IOP) was uncontrolled with the highest concentrations tested.No statistical difference was found in hypotensive effect between pilocarpine and timolol neither on ocular hypertensions nor glaucomas. The additive hypotensive effect of acetazolamide was the same for both substances. Once a day administration of timolol was sufficient in 17 of 20 cases controlled merely by topical administration.
SEMIQUANTITATIVE CYTOLOGIC ANALYSIS OF FLUID WASHED THROUGH THE LACRIMAL PASSAGE
Authors: NORN M. S. 
Published: May 2009

A quantitative cytologic analysis of the sediment of 5 ml of saline (0.9%) washed through the lacrimal drainage system of 25 normal and 84 diseased eyes revealed that the cytological picture reflects the conditions in the lacrimal passages and not in the conjunctiva.Neutrophilia was seen to become increasingly frequent with slowing down of the flow through the lacrimal passage, estimated on the basis of dye dilution in the lacrimal river and dye dilution in the fluid washed through the lacrimal drainage system, and also by the spontaneous passing of the dye to the nasopharynx.Neutrophilia was present in no more than 8% of normal eyes, as against 69% of eyes with epiphora, 83% with infectious conjunctivitis, 40% with conjunctivitis sicca, and 50% with chronic simple conjunctivitis.Neither lymphocytosis nor eosinophilia was seen in any normal eyes.Erythrocytes were admixed artificially by washing through and probing.Granules were absent in normal eyes, but present in 5% of the diseased eyes, while hairs were found in 4 and 14%, respectively, and the fungus Alternaria in 4 and 1%.
THE COLOUR OF THE OPTIC DISC VARIATION WITH LOCATION OF ILLUMINATION
Authors: SØRENSEN PER NELLEMANN 
Published: May 2009

Read in part before the 482 meeting at the Danish Ophthalmological Society, January 19th., 1980.The variation of the colour of the optic disc was examined with a slit lamp and contact lens in 200 normal subjects simply by moving the image of the slit acress the optic disc. This event was photographed in 15 subjects and colour densitometry was performed. The temporal part of the pale central excavation changes colour to red, when illuminated nasally and vice versa.The colour change could not be provoked in subjects with normal discs with flattening of the temporal disc sector. The whole neurorim reddens the whole way round when the slit hits the optic disc border, and dependent on fundus pigmentation slight redness was produced even when the slit was placed outside the disc in the neighbourhood of the border.
Characteristics of corneal endothelial cells in Fuchs' heterochromic cyclitis
Authors: Alanko Hannu I. , Vuorre Ilkka , Saari K. Matti 
Published: May 2009

Abstract We studied the corneal endothelial cells in 14 patients (6 men and 8 women, ranging in age from 15 to 70 years) with unilateral Fuchs' heterochromic cyclitis (FHC) by means of specular microscopy. The healthy fellow eyes of the patients served as control material. Two affected eyes had undergone an intracapsular cataract extraction before specular microscopy. In one patient, the cyclitic eye also had glaucoma. Changes of the endothelium characterized by intra‐and intercellular dark bodies, larger dark defects spanning several endothelial cells and bright irregular patchy areas crossing cell borders on the specular reflex were found in all eyes with FHC.Individual cell analysis did not reveal any significant differences in the endothelial cell density, cell area, coefficient of variation for cell area, cell perimeter, cell shape and in the number of endothelial cell apices between unoperated cyclitic and healthy fellow eyes. The mean cell density was 4.9% lower in the unoperated eyes with FHC than in the control eyes. A significant negative correlation was observed between the patients' age and the cell density both in the healthy and the cyclitic eyes. On the other hand, the correlation between follow‐up period and cell density was not statistically significant in the cyclitic eyes. Although FHC does not seem to accelerate significantly the age‐related cell density reduction, the magnitude of the cell loss found in the two operated eyes (45.5% and 49.8%) and in the eye with glaucoma (45.2%) may indicate altered tolerance against endothelial traumas in this disease.
The Zoonotic Flaviviruses of Southern, South‐Eastern and Eastern Asia, and Australasia: The Potential for Emergent Viruses
Authors: Mackenzie J. S. , Williams D. T. 
Published: May 2009

SummaryThe genus Flaviviridae comprises about 70 members, of which about 30 are found in southern, south‐eastern and eastern Asia and Australasia. These include major pathogens such as Japanese encephalitis (JE), West Nile (WN), Murray Valley encephalitis (MVE), tick‐borne encephalitis, Kyasanur Forest disease virus, and the dengue viruses. Other members are known to be associated with mild febrile disease in humans, or with no known disease. In addition, novel flaviviruses continue to be discovered, as demonstrated recently by New Mapoon virus in Australia, Sitiawan virus in Malaysia, and ThCAr virus in Thailand. About 19 of these viruses are mosquito‐borne, six are tick‐borne, and four have no known vector and represent isolates from rodents or bats. Evidence from phylogenetic studies suggest that JE, MVE and Alfuy viruses probably emerged in the Malaya‐Indonesian region from an African progenitor virus, possibly a virus related to Usutu virus. WN virus, however, is believed to have emerged in Africa, and then dispersed through avian migration. Evidence suggests that there are at least seven genetic lineages of WN virus, of which lineage 1b spread to Australasia as Kunjin virus, lineages 1a and 5 spread to India, and lineage 6 spread to Malaysia. Indeed, flaviviruses have a propensity to spread and emerge in new geographic areas, and they represent a potential source for new disease emergence. Many of the factors associated with disease emergence are present in the region, such as changes in land use and deforestation, increasing population movement, urbanization, and increasing trade. Furthermore, because of their ecology and dependence on climate, there is a strong likelihood that global warming may significantly increase the potential for disease emergence and/or spread.
Emerging Infections: A Tribute to the One Medicine, One Health Concept
Authors: Kahn R. E. , Clouser D. F. , Richt J. A. 
Published: May 2009

SummaryEvents in the last decade have taught us that we are now, more than ever, vulnerable to fatal zoonotic diseases such as those caused by haemorrhagic fever viruses, influenza, rabies and BSE/vCJD. Future research activities should focus on solutions to these problems arising at the interface between animals and humans. A 4‐fold classification of emerging zoonoses was proposed: Type 1: from wild animals to humans (Hanta); Type 1 plus: from wild animals to humans with further human‐to‐human transmission (AIDS); Type 2: from wild animals to domestic animals to humans (Avian flu) and Type 2 plus: from wild animals to domestic animals to humans, with further human‐to‐human transmission (Severe Acute Respiratory Syndrome, SARS). The resulting holistic approach to emerging infections links microbiology, veterinary medicine, human medicine, ecology, public health and epidemiology. As emerging ‘new’ respiratory viruses are identified in many wild and domestic animals, issues of interspecies transmission have become of increasing concern. The development of safe and effective human and veterinary vaccines is a priority. For example, the spread of different influenza viruses has stimulated influenza vaccine development, just as the spread of Ebola and Marburg viruses has led to new approaches to filovirus vaccines. Interdisciplinary collaboration has become essential because of the convergence of human disease, animal disease and a common approach to biosecurity. High containment pathogens pose a significant threat to public health systems, as well as a major research challenge, because of limited experience in case management, lack of appropriate resources in affected areas and a limited number of animal research facilities in developed countries. Animal models that mimic certain diseases are key elements for understanding the underlying mechanisms of disease pathogenesis, as well as for the development and efficacy testing of therapeutics and vaccines. An updated veterinary curriculum is essential to empower future graduates to work in an international environment, applying international standards for disease surveillance, veterinary public health, food safety and animal welfare.
Sequence Analyses of Just Four Genes To Detect Extensively Drug-Resistant
Mycobacterium tuberculosis
Strains in Multidrug-Resistant Tuberculosis Patients Undergoing Treatment
Authors: Feuerriegel Silke , Cox Helen S. , Zarkua Nana , Karimovich Hamraev A. , Braker Kai , Rüsch-Gerdes Sabine , Niemann Stefan 
Published: May 2009

ABSTRACT

The rapid detection of
Mycobacterium tuberculosis
isolates resistant to second-line drugs is crucial for the institution of appropriate treatment regimens as early as possible. Although molecular methods have successfully been used for the rapid detection of resistance to first-line drugs, there are limited data on mutations that confer resistance to second-line drugs. To address this question, we analyzed
Mycobacterium tuberculosis
strains resistant to ofloxacin (
n
= 26) and to capreomycin and/or amikacin (
n
= 48) from Uzbekistan for variations in target genes (
gyrA
,
gyrB
,
rrs
, and
tlyA
). Strains susceptible to ofloxacin (
n
= 49) and capreomycin and/or amikacin (
n
= 39) were included as controls. Mutations in
gyrA
or
gyrB
were found in 96% (25/26 strains) of the ofloxacin-resistant strains, while none of the susceptible strains displayed mutations in those two genes. The most common mutation occurred in
gyrA
at codon 94 (17/26 strains [65.4%]), followed by mutations at codons 90 and 91. Two strains showed a mutation in
gyrB
, at codons 485 and 543, respectively; both mutations have not been reported previously. The most frequent mutation in strains resistant to both amikacin and capreomycin was A1401G in
rrs
(34/40 strains [85.0%]). Three strains had mutations in
tlyA
, of which two (at codons 18 and 118) were associated with resistance to capreomycin alone. Overall, none of the 10 resistant strains (5 amikacin-resistant and capreomycin-susceptible strains) and none of the 39 susceptible control strains had mutations in the genes investigated. Our results clearly demonstrate the potential of sequence analyses of short regions of relatively few target genes for the rapid detection of resistance to second-line drugs among strains isolated from patients undergoing treatment for multidrug-resistant tuberculosis. The mechanisms that confer amikacin resistance in this setting remain unclear.
Outer Membrane Protein STM3031 (Ail/OmpX-Like Protein) Plays a Key Role in the Ceftriaxone Resistance of
Salmonella enterica
Serovar Typhimurium
Authors: Hu Wensi S. , Lin Jing-Fang , Lin Ying-Hsiu , Chang Hsin-Yu 
Published: May 2009

ABSTRACT

Previously, the putative outer membrane protein STM3031 has been correlated with ceftriaxone resistance in
Salmonella enterica
serovar Typhimurium. In this study, this protein was almost undetectable in the ceftriaxone-susceptible strain 01-4, but its levels were increased in 01-4 isogenic strains for which MICs were higher. The
stm3031
gene deletion mutant, R200(Δ
stm3031
), was generated and showed >64-fold lower ceftriaxone resistance than R200, supporting a key role for STM3031 in ceftriaxone resistance. To investigate which outer membrane protein(s) was associated with resistance, the outer membrane protein profiles of 01-4, R200, and R200(Δ
stm3031
) were compared proteomically. Nine proteins were identified as altered. The expression levels of AcrA, TolC, STM3031, STM1530, VacJ, and Psd in R200 were increased; those of OmpC, OmpD, and OmpW were decreased. The expression levels of OmpD, OmpW, STM1530, VacJ, and Psd, but not those of OmpC, AcrA, and TolC, in R200(Δ
stm3031
) were returned to the levels in strain 01-4. Furthermore, the genes' mRNA levels correlated with their protein levels when the three strains were compared. The detection of higher AcrB levels, linked to higher
acrB
,
acrD
, and
acrF
mRNA levels, in strain R200 than in strains 01-4 and R200(Δ
stm3031
) suggests that AcrB, AcrD, and AcrF participate in ceftriaxone resistance. Taken together with the location of STM3031 in the outer membrane, these results suggest that STM3031 plays a key role in ceftriaxone resistance, probably by reducing permeability via a decreased porin OmpD level and enhancing export via increased AcrD efflux pump activity.
Peptide-Lipid Huge Toroidal Pore, a New Antimicrobial Mechanism Mediated by a Lactococcal Bacteriocin, Lacticin Q
Authors: Yoneyama Fuminori , Imura Yuichi , Ohno Kanako , Zendo Takeshi , Nakayama Jiro , Matsuzaki Katsumi , Sonomoto Kenji 
Published: May 2009

ABSTRACT

Lacticin Q is a pore-forming bacteriocin produced by
Lactococcus lactis
QU 5, and its antimicrobial activity is in the nanomolar range. Lacticin Q induced calcein leakage from negatively charged liposomes. However, no morphological changes in the liposomes were observed by light scattering. Concomitantly with the calcein leakage, lacticin Q was found to translocate from the outer to the inner leaflet of the liposomes, after it initially bound to the membrane within 2 s. Lacticin Q also induced lipid flip-flop. These results reveal that the antimicrobial mechanism of lacticin Q can be described by the toroidal pore model. This is the first report of a bacteriocin of gram-positive bacteria that forms a toroidal pore. From liposomes, lacticin Q leaked fluorescence-labeled dextran with a diameter of 4.6 nm. In addition, lacticin Q caused the leakage of small proteins, such as the green fluorescent protein, from live bacterial cells. There are no other reports of antimicrobial peptides that exhibit protein leakage properties. The proposed pore formation model of lacticin Q is as follows: (i) quick binding to outer membrane leaflets; (ii) the formation of at least 4.6-nm pores, causing protein leakage with lipid flip-flop; and (iii) the migration of lacticin Q molecules from the outer to the inner membrane leaflets. Consequently, we termed the novel pore model in the antimicrobial mechanism of lacticin Q a “huge toroidal pore.”
Telavancin Disrupts the Functional Integrity of the Bacterial Membrane through Targeted Interaction with the Cell Wall Precursor Lipid II
Authors: Lunde Christopher S. , Hartouni Stephanie R. , Janc James W. , Mammen Mathai , Humphrey Patrick P. , Benton Bret M. 
Published: May 2009

ABSTRACT

Telavancin is an investigational lipoglycopeptide antibiotic currently being developed for the treatment of serious infections caused by gram-positive bacteria. The bactericidal action of telavancin results from a mechanism that combines the inhibition of cell wall synthesis and the disruption of membrane barrier function. The purpose of the present study was to further elucidate the mechanism by which telavancin interacts with the bacterial membrane. A flow cytometry assay with the diethyloxacarbocyanine dye DiOC
2
(3) was used to probe the membrane potential of actively growing
Staphylococcus aureus
cultures. Telavancin caused pronounced membrane depolarization that was both time and concentration dependent. Membrane depolarization was demonstrated against a reference
S. aureus
strain as well as phenotypically diverse isolates expressing clinically important methicillin-resistant (MRSA), vancomycin-intermediate (VISA), and heterogeneous VISA (hVISA) phenotypes. The cell wall precursor lipid II was shown to play an essential role in telavancin-induced depolarization. This was demonstrated both in competition binding experiments with exogenous
d
-Ala-
d
-Ala-containing ligand and in experiments with cells expressing altered levels of lipid II. Finally, monitoring of the optical density of
S. aureus
cultures exposed to telavancin showed that cell lysis does not occur during the time course in which membrane depolarization and bactericidal activity are observed. Taken together, these data indicate that telavancin's membrane mechanism requires interaction with lipid II, a high-affinity target that mediates binding to the bacterial membrane. The targeted interaction with lipid II and the consequent disruption of both peptidoglycan synthesis and membrane barrier function provide a mechanistic basis for the improved antibacterial properties of telavancin relative to those of vancomycin.
The
Acinetobacter baumannii
19606 OmpA Protein Plays a Role in Biofilm Formation on Abiotic Surfaces and in the Interaction of This Pathogen with Eukaryotic Cells
Authors: Gaddy Jennifer A. , Tomaras Andrew P. , Actis Luis A. 
Published: May 2009

ABSTRACT

The ability of
Acinetobacter baumannii
to adhere to and persist on surfaces as biofilms could be central to its pathogenicity. The production of pili and a biofilm-associated protein and the expression of antibiotic resistance are needed for robust biofilm formation on abiotic and biotic surfaces. This multistep process also depends on the expression of transcriptional regulatory functions, some of which could sense nutrients available to cells. This report extends previous observations by showing that although outer membrane protein A (OmpA) of
A. baumannii
19606 plays a partial role in the development of robust biofilms on plastic, it is essential for bacterial attachment to
Candida albicans
filaments and A549 human alveolar epithelial cells. In contrast to abiotic surfaces, the interaction with biotic surfaces is independent of the CsuA/BABCDE-mediated pili. The interaction of
A. baumannii
19606 with fungal and epithelial cells also results in their apoptotic death, a response that depends on the direct contact of bacteria with these two types of eukaryotic cells. Furthermore, the bacterial adhesion phenotype correlates with the ability of bacteria to invade A549 epithelial cells. Interestingly, the killing activity of cell-free culture supernatants proved to be protease and temperature sensitive, suggesting that its cytotoxic activity is due to secreted proteins, some of which are different from OmpA.
The Multiplicity of Infection of a Plant Virus Varies during Colonization of Its Eukaryotic Host
Authors: González-Jara Pablo , Fraile Aurora , Canto Tomás , García-Arenal Fernando 
Published: May 2009

ABSTRACT

The multiplicity of infection (MOI), i.e., the number of virus genomes that infect a cell, is a key parameter in virus evolution, as it determines processes such as genetic exchange among genomes, selection intensity on viral genes, epistatic interactions, and the evolution of multipartite viruses. In fact, the MOI level is equivalent to the virus ploidy during genome expression. Nevertheless, there are few experimental estimates of MOI, particularly for viruses with eukaryotic hosts. Here we estimate the MOI of
Tobacco mosaic virus
(TMV) in its systemic host,
Nicotiana benthamiana
. The progress of infection of two TMV genotypes, differently tagged with the green or red fluorescent proteins GFP and RFP, was monitored by determining the number of leaf cell protoplasts that showed GFP, RFP, or GFP and RFP fluorescence at different times postinoculation. This approach allowed the quantitative analysis of the kinetics of infection and estimation of the generation time and the number of infection cycles required for leaf colonization. MOI levels were estimated from the frequency of cells infected by only TMV-GFP or TMV-RFP. The MOI was high, but it changed during the infection process, decreasing from an initial level of about 6 to a final one of 1 to 2, with most infection cycles occurring at the higher MOI levels. The decreasing MOI can be explained by mechanisms limiting superinfection and/or by genotype competition within double-infected cells, which was shown to occur in coinfected tobacco protoplasts. To our knowledge, this is the first estimate of MOI during virus colonization of a eukaryotic host.
Call for a European programme in external quality assurance for bone marrow immunohistochemistry; report of a European Bone Marrow Working Group pilot study
Authors: Torlakovic E E , Naresh K , Kremer M , van der Walt J , Hyjek E , Porwit A 
Published: May 2009

Background and Aims:In diagnostic immunohistochemistry (IHC), daily quality control/quality assurance measures (QC/QA) and participation in external quality assurance programmes (EQA) are important in ensuring good laboratory practice and patient care. Bone marrow trephine biopsies (BMTB) have been generally excluded from EQA programmes for diagnostic IHC due to a lack of standards for tissue processing. The European Bone Marrow Working Group (EBMWG) has set up an EBMWG IHC Committee with the task of exploring the plausibility of an EQA programme for BMTB IHC in Europe.Methods:28 laboratories participated in a web-based anonymous survey; 19 laboratories submitted a total of 109 slides stained for CD34, CD117, CD20, CD3, Ki-67 and a megakaryocyte marker of choice.Results:Eight different fixatives and nine different decalcification methods were used. While 93% of participants believed that they produced excellent results in BMTB IHC, only 4/19 (21%) laboratories did not have any poor results. CD117 and Ki-67, with 53% and 50% poor results, respectively, were the most problematic immunostains, while CD20 was the least problematic, with only 11% poor results.Conclusions:The EBMWG IHC Committee calls for a reduction in the tissue processing methods for BMTB and establishment of an EQA programme for BMTB IHC to help diagnostic IHC laboratories calibrate their tests according to expert recommendations. This is especially necessary in the light of recent introduction of predictive IHC tests in BMTB.