bluuebunny/crossref_metadata_2025_split huggingface dataset:
Where are we with the supra‐Descemetic KPro (Keralia)?
Authors: LAMAR PD , ALFONSO E , STOIBER J , FERNANDEZ V , KAMINSKI S , LACOMBE E , DUCHESNE B , ACOSTA C , PAREL JM 
Published: October 2007

Abstract Purpose: To assess a non‐perforating supraDescemetic synthetic cornea (Keralia) in rabbits and patients. Methods: Over 100 rabbits and 20 human cadaver eyes received a sDSC made of 4 polymers, intrastromally (~90% depth) in 59 rabbits, on denuded DM in 17 rabbits, and in a 3rd group (15 rabbits), ~45 days after the application of 1‐heptanol and limbus surgical removal. The corneal surface was covered with a conjunctiva‐Tenon flap trephined ~63 days in postop. 9 last resort cases received a Keralia over the span of 5 years. Results: sDSC implanted in deep stroma developed opacities in the DM‐KPro optic interface while it rarely occurred with a sDSC placed directly on DM. In burned eyes, 5 animals needed conjunctival flap repair. No eyes had epithelium downgrowth. The Eye Bank eye experiment confirmed implantation to be feasible even in cases of microperforation (3 eyes) but not with macroperforation (1 eye). Histological evaluation displayed a very thin layer of stroma (<2um) remaining on DM in 5 eyes and a minimally thin layer (<10μm) in the others. Of the 9 Keralia, 8 implanted in patients having had multiple PKs, other KPros or previous extensive surgery extruded between 3 months and 1 year while one Keralia implanted in a case of decompensation not amenable to PK remains in place at >2 years. Conclusions: The supraDescemetic Synthetic Corneas made of HEMA‐MMA34 showed promising results. As opening of the anterior chamber is not required, the sDSC theoretically offers less risks and complications than penetrating KPros.Support: European project BMH4‐CT97‐9507, Florida Lions Eye Bank, Research to Prevent Blindness, FWF Austrian Science Fund, NIH center grant P30‐EY014801; and the Henri and Flore Lesieur Foundation
An update on the synthetic collagenous artificial cornea
Authors: FAGERHOLM P , GRIFFITH M 
Published: October 2007

AbstractDuring embryonic development, cells secrete an extracellular matrix (ECM) around themselves that is turn provides cues to the cells to direct organ development. The same ECM componants would therefore also be likely to direct repair and regeneration of these organs. Our goal, therefore, was to develop biomimetic materials that are ECM analogs, capable of sustaining a native‐like ECM environment and interacting with host tissues and stem cells to effect regeneration.Specifically for the cornea, we have successfully completed a 12 month study on corneal substitutes fabricated from recombinant human collagen that were implanted into mini‐pigs be lamellar keratoplasty. Implants made from type I and type III recombinant collagens were compared. Both collagens could be crosslinked and moulded into the shape and size of human corneas. While we found that type III implants had a tendency to be mechanically stronger, both types of implants gave very similar results. They retained optical clarity by both slit lamp biomicroscopy and fundus imaging. They also retained their thickness indicating graft stability. Regeneration of corneal epithelial and stromal cells were also observed. In addition, corneal nerves and the tear film were regenerated. These results were comparable to those we had previously reported in shorter term studies. These recombinant collagens, as thin sheets, were also found to be suitable as scaffolds for proliferation of human corneal limbal cells.As the collagen source is recombinant, made from yeast, we have therefore shown that completely man‐made corneal substitutes can be produced as substitutes of the corneal matrix. Biomimetic materials, therefore, are likely to be successful for reproducing the natural scaffolding in tissue engineering applications, such as the development of corneal substitutes.
AER lecture: Some reflections on corneal thickness
Authors: EHLERS N 
Published: October 2007

AbstractThe corneal thickness as an object for studies was recognized in the renaissance. A value of 1 mm, representing the maximally swollen human cornea, was reported. Optical in vivo measurements were done by Blix in 1880 reporting a thickness of about 0.5 mm, the value that we today know is correct.Blix lived in “the golden age of physiologic optics”. His interest was the contribution of the cornea to the optical refraction of the eye, and was thus the distance between the anterior and the posterior surface rather than the thickness of the cornea as such.A biomechanical interest in corneal thickness was initiated by the studies of tonometry, in particular Hans Goldmann’s development of applanation tonometry. He predicted correctly that corneal thickness would influence the estimated pressure reading.Another physiological aspect of the cornea is its transparency. Earlier explanations by equal refractive index was revolutionized by the interference theory by David Maurice. Optical transparency required a regular fiber pattern, and thus a stabilized thickness and stromal hydration. This led to extensive interest in the permeability of the limiting layers, in particular the transport of fluid across the endothelium. The physiological concepts required a regulated or stabilized thickness. The thickness as such became interesting.The human cornea is thinner in the center than more peripherally and the central, presumably regulated central thickness (CCT) became a biometric and clinical study object. The exact individual value became of interest. Several optical and later ultrasonic principles were presented.Questions addressed were: Is CCT a life‐long, age independent characteristics. Is CCT diagnostic for certain disease conditions (e.g. Macular dystrophy of Groenouw). Is CCT a useful clinical parameter to follow disease processes (e.g. progression in keratoconus or acute changes in graft rejections).Today refractive surgery has revived the interest in biomechanical and optical properties of the cornea. Modern computer technology allows for a description of the “thickness profile” of the entire cornea. This gives us access to an overwhelming amount of data, and reopen many issues of the past. We must realize, however, that what we see is the pendulum swinging back to the problems of the last century. The machinery is smarter but many of the basic questions remain to be solved.
EVER Lecture: Can uveal melanoma be conquered?
Authors: KIVELÄ T 
Published: October 2007

AbstractThe deadly natural history of uveal melanoma was fully described, unknowingly, in a well known English artist in 1792 and soon thereafter in an unknown Scottish woman around 1808. It became a well recognised entity much later, by 1868. Today, with the exception of being able to save the eye of their patient, ocular oncologists managing patients with uveal melanoma find themselves in essentially the same situation than their forebears: mortality rates have not noticeably decreased and metastatic melanoma continues to be the “hideous picture of disease” that it was 150 years ago. Metastatic melanoma is the single overwhelming cause of death in patients with uveal melanoma, and no consistently effective treatment is known for disseminated disease. One reason for this unhappy state of affairs is that patients formerly were dismissed after enucleation until they presented with advanced metastasis to an oncologist who did not recognise uveal melanoma as a disease very different from cutaneous melanoma. The advent of ocular oncology has led to rational early detection programs for subclinical metastasis, validated staging of metastatic disease, and first controlled clinical trials of managing metastases with therapies specifically aimed against this cancer. Basic research highlights uveal melanoma as a typically slowly growing, early metastasising cancer, and staging, grading and typing of primary tumours is leading to rational assignment of patients to follow‐up and adjuvant treatment trials, which hopefully will improve their survival rate. The current understanding is that, by the time the eye becomes symptomatic, uveal melanomas prone to metastasis already have seeded micrometastases, which need to be kept under control if we are to eventually conquer this disease.
Delivery of Eye Care in Developing Countries ‐ Role of Research
Authors: RAO G 
Published: October 2007

Abstract Purpose: To present the information and problems of global blindness and how research can help in addressing these problems. Methods: Blindness is a serious public health problem in developing countries. Most (almost 90 percent) of avoidable – preventable and treatable – blindness exists in the developing countries of the world. Through a variety of innovations, based on epidemiological and operations research, innovative models of eye care delivery have been developed to make eye care effective and cost‐effective. The next step is large scale replication with appropriate local modifications. A challenge before the research community is to extend the scope of translational research from the traditional “laboratory to the clinic” mode to an enhanced version of “laboratory to clinic to community” mode. Results: The eye care delivery model should encompass all levels of care from the primary to advanced tertiary with clear delineation of functions at every level, referral linkages, without compromising on quality or equity and making programmes sustainable.While prevention strategies against trachoma and onchocerciasis are successful and tackling cataract problem is getting better, the more complex issues of glaucoma and diabetic retinopathy are looming large. Significant attention has to be paid to develop appropriate public health and clinical approaches to control blindness from these problems too if VISION 2020: The Right to Sight has to realize the aspiration of controlling global blindness to a significant degree by 2020. Conclusions: Global cooperation and collaboration may be the key to arrive at solutions in an accelerated manner given the environment of increasingly limited resources and competing demands.
Antigen‐presenting cells and the eye
Authors: JAGER MJ 
Published: October 2007

AbstractAntigen‐presenting cells (APC) carry many different functions such as phagocytosis, antigen processing, antigen presentation. Depending on the nature of the APC, presentation of an antigen may lead to an active immune response, or lead to inhibition of the specific immune response. Some ocular subjects where APCs are of special interest are corneal immune responses, e.g against viral infections, the development of ACAID (anterior chamber associated immune deviation), and tumor immunology. In the last case, a good response might help the patient survive, but the development of an inferior response might suppress any useful anti‐tumor responses. These controversies will be discussed.
From Helmholtz to the scanning laser ophthalmoscope. 150 years of ophthalmoscopy.
Authors: DE LAEY JJ 
Published: October 2007

Abstract Purpose: To give a brief overview on Helmholtz and the history of ophthalmoscopy. Methods: Literature survey. Results: Hermann von Helmholtz (1821‐1894), although not an ophthalmologist but a physiologist, invented the ophthalmoscope, not yet 30 years old, and is thus one of the most important scientists in European ophthalmology.Yet Charles Bobbage may have preceeded Helmholtz. Unfortunately an "expert" gave him a negative critic and his work was only published in 1854, 3 years after Helmholtz's monography: "Beschreibung einer Augenspiegels zur Untersuchung des Netzhaut im lebenden Auge". Helmholtz's discovery as well as the first international congress of Ophthalmology exactly 150 years ago, introduced the modern era of ophthalmology. Within a few years several modifications of Helmholtz's ophthalmoscope were presented by Ruete (1852), Coccius (1853 and 1855), Anagnostakis (1854), Gillet de Grandmont (1859),Galezowski (1862), Beale (1869) and others. Marc‐Antoine Giraud‐Teulon (1861) designed the first binocular ophthalmoscope. The first coloured drawing of the fundus was published in Utrecht in 1853 (Van Tricht) and Fallon (1863) published the first atlas of ophthalmoscopy. Conclusions: Despite limitations due to poor illumination the introduction of ophthalmoscopy resulted in the discovery of a completely new field in ophthalmology.
Antimicrobial Drug Resistance of
Salmonella enterica
Serovar Typhi in Asia and Molecular Mechanism of Reduced Susceptibility to the Fluoroquinolones
Authors: Chau Tran Thuy , Campbell James Ian , Galindo Claudia M. , Van Minh Hoang Nguyen , Diep To Song , Nga Tran Thu Thi , Van Vinh Chau Nguyen , Tuan Phung Quoc , Page Anne Laure , Ochiai R. Leon , Schultsz Constance , Wain John , Bhutta Zulfiqar A. , Parry Christopher M. , Bhattacharya Sujit K. , Dutta Shanta , Agtini Magdarina , Dong Baiqing , Honghui Yang , Anh Dang Duc , Canh Do Gia , Naheed Aliya , Albert M. John , Phetsouvanh Rattanaphone , Newton Paul N. , Basnyat Buddha , Arjyal Amit , La Tran Thi Phi , Rang Nguyen Ngoc , Phuong Le Thi , Van Be Bay Phan , von Seidlein Lorenz , Dougan Gordon , Clemens John D. , Vinh Ha , Hien Tran Tinh , Chinh Nguyen Tran , Acosta Camilo J. , Farrar Jeremy , Dolecek Christiane 
Published: October 2007

ABSTRACT

This study describes the pattern and extent of drug resistance in 1,774 strains of
Salmonella enterica
serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between 1993 (4%) and 2005 (97%). In a cross-sectional sample of 381 serovar Typhi strains from 8 Asian countries, Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and central Vietnam, collected in 2002 to 2004, various rates of multidrug resistance (16 to 37%) and nalidixic acid resistance (5 to 51%) were found. The eight Asian countries involved in this study are home to approximately 80% of the world's typhoid fever cases. These results document the scale of drug resistance across Asia. The Ser83→Phe substitution in GyrA was the predominant alteration in serovar Typhi strains from Vietnam (117/127 isolates; 92.1%). No mutations in
gyrB
,
parC
, or
parE
were detected in 55 of these strains. In vitro time-kill experiments showed a reduction in the efficacy of ofloxacin against strains harboring a single-amino-acid substitution at codon 83 or 87 of GyrA; this effect was more marked against a strain with a double substitution. The 8-methoxy fluoroquinolone gatifloxacin showed rapid killing of serovar Typhi harboring both the single- and double-amino-acid substitutions.
Antileishmanial Structure-Activity Relationships of Synthetic Phospholipids: In Vitro and In Vivo Activities of Selected Derivatives
Authors: Seifert Karin , Lemke Andreas , Croft Simon L. , Kayser Oliver 
Published: October 2007

ABSTRACT

Antileishmanial activities of 91 synthetic phospholipids against
Leishmania donovani
were evaluated in vitro and cytotoxicity assessed against two mammalian cell lines. Promising compounds were tested further in vivo. In vitro structure-activity relationships showed a positive contribution of head groups bearing ring systems (
N
-methylpiperidino and
N
-methylmorpholino) to antileishmanial activity.
In Vitro Susceptibility of Methicillin-Resistant
Staphylococcus aureus
and Methicillin-Susceptible
Staphylococcus aureus
to a New Antimicrobial, Copper Silicate
Authors: Carson Kerry C. , Bartlett Jessica G. , Tan Trina-Jean , Riley Thomas V. 
Published: October 2007

ABSTRACT

The soluble copper silicate (CS) MIC of 100 strains of methicillin-resistant
Staphylococcus aureus
and 100 strains of methicillin-susceptible
S. aureus
(MSSA) was 175 mg Cu/liter. Bactericidal and postantibiotic effects (≥1 h) were seen at 2× MIC and 4× MIC. The frequency of mutation was <10
−9
, and serial passage could not extend growth beyond 1.6× MIC.
A MurF Inhibitor That Disrupts Cell Wall Biosynthesis in
Escherichia coli
Authors: Baum Ellen Z. , Crespo-Carbone Steven M. , Klinger Alexandra , Foleno Barbara D. , Turchi Ignatius , Macielag Mark , Bush Karen 
Published: October 2007

ABSTRACT

MurF is an essential enzyme of bacterial cell wall biosynthesis. Few MurF inhibitors have been reported, and none have displayed measurable antibacterial activity. Through the use of a MurF binding assay, a series of 8-hydroxyquinolines that bound to the
Escherichia coli
enzyme and inhibited its activity was identified. To derive additional chemotypes lacking 8-hydroxyquinoline, a known chelating moiety, a pharmacophore model was constructed from the series and used to select compounds for testing in the MurF binding and enzymatic inhibition assays. Whereas the original diverse library yielded 0.01% positive compounds in the binding assay, of which 6% inhibited MurF enzymatic activity, the pharmacophore-selected set yielded 14% positive compounds, of which 37% inhibited the enzyme, suggesting that the model enriched for compounds with affinity to MurF. A 4-phenylpiperidine (4-PP) derivative identified by this process displayed antibacterial activity (MIC of 8 μg/ml against permeable
E. coli
) including cell lysis and a 5-log
10
-unit decrease in CFU. Importantly, treatment of
E. coli
with 4-PP resulted in a 15-fold increase in the amount of the MurF UDP-MurNAc-tripeptide substrate, and a 50% reduction in the amount of the MurF UDP-MurNAc-pentapeptide product, consistent with inhibition of the MurF enzyme within bacterial cells. Thus, 4-PP is the first reported inhibitor of the MurF enzyme that may contribute to antibacterial activity by interfering with cell wall biosynthesis.
In Vitro Resistance Study of Rupintrivir, a Novel Inhibitor of Human Rhinovirus 3C Protease
Authors: Binford S. L. , Weady P. T. , Maldonado F. , Brothers M. A. , Matthews D. A. , Patick A. K. 
Published: October 2007

ABSTRACT
Rupintrivir (formerly AG7088) is an irreversible inhibitor of the human rhinovirus (HRV) 3C protease that has been demonstrated to have in vitro activity against all HRVs tested, consistent with its interaction with a strictly conserved subset of amino acids in the 3C protease. The potential for resistance was studied following in vitro serial passage of HRV serotypes 14, 2, 39, and Hanks in the presence of increasing rupintrivir concentrations. HRV variants with reduced susceptibilities to rupintrivir (sevenfold for HRV 14) or with no significant reductions in susceptibility but genotypic changes (HRV 2, 39, and Hanks) were initially isolated following 14 to 40 cumulative days in culture (three to six passages). Sequence analysis of the 3C protease identified one to three substitutions in diverse patterns but with common features (T129T/A, T131T/A, and T143P/S in HRV 14; N165T in HRV 2; N130N/K and L136L/F in HRV 39; T130A in HRV Hanks). Notably, three of the four HRV variants contained a substitution at residue 130 (residue 129 in HRV 14). Continued selection in the presence of escalating concentrations of rupintrivir (40 to 72 days) resulted in the accumulation of additional mutations (A121A/V and Y139Y/H in HRV 14, E3E/G and A103A/V in HRV 2, S105T in HRV 39), with only minimal further reductions in susceptibility (up to fivefold). The ability of specific substitutions to confer resistance was examined by susceptibility testing of HRV 14 variants constructed to contain 3C protease mutations. In summary, the slow accumulation of multiple amino acid substitutions with only minimal to moderate reductions in susceptibility highlight the advantages of 3C protease as an antiviral target.
The p38 Mitogen-Activated Protein Kinase Signaling Pathway Is Coupled to Toll-Like Receptor 5 To Mediate Gene Regulation in Response toPseudomonas aeruginosaInfection in Human Airway Epithelial Cells
Authors: Zhang Zhe , Reenstra William , Weiner Daniel J. , Louboutin Jean-Pierre , Wilson James M. 
Published: October 2007

ABSTRACTIn this study, we show that stimulation of human airway epithelial cells (HAECs) byPseudomonas aeruginosastrain PAO1 induces time- and dose-dependent activation of p38 mitogen-activated protein kinase (MAPK). Activated p38 MAPK stayed in the cytoplasm instead of translocating to the nucleus, as shown by cellular fractionation. p38 MAPK was activated when HAECs were incubated withP. aeruginosastrain PAK andBurkholderia cepacia, while little activation was observed with the isogenic flagellin-free strains PAK/fliCandB. cepaciaBC/fliC. The presence of Toll-like receptor 5 (TLR5) in 293 cells mediated PAO1-dependent activation of p38 MAPK, and in HAECs p38 MAPK activation was blocked by the overexpression of a dominant negative TLR5. Two inhibitors of p38 MAPK, SB202190 and SB203580, significantly attenuated PAO1-dependent expression of an NF-κB-dependent luciferase reporter gene, suggesting that p38 MAPK activation is required for full activation of NF-κB-dependent signaling. Microarray analysis of NF-κB target genes revealed up-regulation of multiple genes by PAO1 in HAECs. Reverse transcription-PCR and protein expression analysis were used to show that up-regulation of NF-κB-dependent genes induced by PAO1, such as the genes encoding Cox-2 and interleukin-8, was attenuated by SB203580. These results demonstrate a role for p38 MAPK signaling in gene regulation in response toP. aeruginosavia TLR5.
Combination of Protein and Viral Vaccines Induces Potent Cellular and Humoral Immune Responses and Enhanced Protection from Murine Malaria Challenge
Authors: Hutchings Claire L. , Birkett Ashley J. , Moore Anne C. , Hill Adrian V. S. 
Published: October 2007

ABSTRACTThe search for an efficacious vaccine against malaria is ongoing, and it is now widely believed that to confer protection a vaccine must induce very strong cellular and humoral immunity concurrently. We studied the immune response in mice immunized with the recombinant viral vaccines fowlpox strain FP9 and modified virus Ankara (MVA), a protein vaccine (CV-1866), or a combination of the two; all vaccines express parts of the same preerythrocytic malaria antigen, thePlasmodium bergheicircumsporozoite protein (CSP). Mice were then challenged withP. bergheisporozoites to determine the protective efficacies of different vaccine regimens. Two immunizations with the protein vaccine CV-1866, based on the hepatitis B core antigen particle, induced strong humoral immunity to the repeat region of CSP that was weakly protective against sporozoite challenge. Prime-boost with the viral vector vaccines, FP9 followed by MVA, induced strong T-cell immunity to the CD8+epitope Pb9 and partially protected animals from challenge. Physically mixing CV-1866 with FP9 or MVA and then immunizing with the resultant combinations in a prime-boost regimen induced both cellular and humoral immunity and afforded substantially higher levels of protection (combination, 90%) than either vaccine alone (CV-1866, 12%; FP9/MVA, 37%). For diseases such as malaria in which different potent immune responses are required to protect against different stages, using combinations of partially effective vaccines may offer a more rapid route to achieving deployable levels of efficacy than individual vaccine strategies.