bluuebunny/crossref_metadata_2025 huggingface dataset:
Juvenile disciform macular degeneration
Authors: Gíslason Ingimundur
Published: May 2009

Abstract A retrospective study of ten Icelandic cases of juvenile disciform macular degeneration, 1981 – 1988 was undertaken in the only referral clinic of a country of 250000 people. Some of these cases were associated with punctate inner choroidopathy or recurrent multifocal choroiditis and the disciform lesions occurred primarily in young, otherwise healthy, moderately myopic women.
Pneumatic retinopexy
Authors: Gunnarson Gun , Byhr Eva , Leyon Hans
Published: May 2009

Abstract Sixtythree cases of primary retinal detachments were treated with pneumatic retinopexy and analyzed retrospectively. The method differed slightly from the original procedure in the fact that highly elevated retinal detachments were generously drained for subretinal fluid, 12 of 63 cases. The follow‐up time was 7 – 23 months. After the primary operation 49 = 78% healed anatomically. The total success rate was 92 percent with additional operations. New breaks were found in 6 percent and 8 percent developed PVR. Results in visual acuity correspond well with results from scleral buckling.
ADHESIVE MECHANISMS OF THE CORNEAL EPITHELIUM
Authors: Gipson Ilene K.
Published: May 2009

Abstract The corneal epithelium adheres to the stro‐ma through a series of linked structures termed collectively the adhesion complex. These structures include; intermediate filaments (keratin filaments) which are linked to the hemidesmosome; the hemidesmo‐some; the anchoring filaments which extend from the membrane at the hemidesmosome through the lamina lucida to the lamina densa region of the basement membrane; the anchoring fibrils which insert into the basement membrane from the stromal side; and the anchoring plaque on which anchoring fibrils terminate distal from their insertion on the basement membrane. Upon wounding, basal cells of the corneal epithelium disassemble their hemidesmosomes. During migration, the membranes along the wound bed exhibit a different kind of adhesion junction, the focal contact. This junction is present primarily in cells of the leading edge of migration and may be the provisional adhesion junction used by epithelial sheet moving to cover a wound.
INTEGRINS AS RECEPTORS FOR EXTRACELLULAR MATRIX PROTEINS IN HUMAN CORNEA
Authors: Virtanen Ismo , Tervo Kaarina , Korhonen Matti , Päällysaho Taru , Tervo Timo
Published: May 2009

Abstract Extracellular matrix (ECM) proteins form distinct proteinfamilies that play a role during tissue maturation, wound healing and maintenance of tissue architecture. Recent studies show that there are tissue type ‐specific variations in their expression. ECM proteins function by complexing with each other and also by interacting with their cellular receptors, called integrins. Integrins are heterodimeric membrane.

glycoproteins that are partly cell type ‐specifically expressed in human tissues. Like other stratified epithelia, corneal epithelium expresses α2β1, α3β1, α6β1,4, and αvβ1 integrins that mediate attachment to the basement membrane and cell‐cell interactions.
INTEGRINS IN THE NORMAL AND HEALING CORNEAL EPITHELIUM
Authors: Päällysaho Taru , Tervo Timo , Virtanen Ismo , Tervo Kaarina
Published: May 2009

Abstract Integrins are heterodimeric plasma membrane glycoproteins involved in cell‐matrix and cell‐cell interactions. The present communication reviews the distribution of several of the currently known inte‐grin subunits in the corneal epithelium. The corneal epithelium contains the following integrin hetero‐dimers: α2β1, α3β1, and α6β4. The expression of αv with an unknown β subunit is also recognized, whereas the expression of α4 and α5 subunits remains controversial. Some of the changes occurring in the distribution of integrins in response to wounding will also be discussed.
SURFACE‐ASSOCIATED ACTIVATION OF PLASMINOGEN ON GRAM‐POSITIVE BACTERIA
Authors: Kuusela Pentti , Ullberg M. , Kronvall G. , Tervo Timo , Tarkkanen Ahti , Saksela O.
Published: May 2009

Abstract In this article we review a novel type of plasminogen activation on staphylococcal and strep‐tococcal cells. The activation mechanism implies a specific binding of glu‐plasminogen to bacterial surface via the lysine‐binding sites of plasminogen. Association of plasminogen with bacterial surfaces greatly enchances the t‐PA mediated activation which takes place only poorly in solution. The end product, surface‐associated plasmin, is enzymatically active, protected against high molecular weight plasmin inhibitors and capable of converting itself from glu‐plasmin to the lys‐form. The modification is associated with an increased affinity of the bound lys‐plasmin towards the binding molecules on bacterial surface. This novel way of retaining plasmin on the surface may be important for the bacteria to invade and penetrate surrounding tissues. Our data on the effect of plasmin on staphylococcal adherence indicate that plasmin is not very effective in cleaning bacteria from surfaces coated with extracellular matrix components, fibronec‐tin and fibrinogen.
EXPERIENCE WITH PLASMIN INHIBITORS
Authors: Tervo Timo , van Setten Gysbert‐Botho , Tervo Kaarina , Tarkkanen Ahti
Published: May 2009

Abstract The involvement and role of the plasmino‐gen activator‐plasmin system in normal and pathological wound healing is reviewed. The methods currently available for demonstrating plasmin activity are briefly described. The article also reviews some other serine proteases potentially involved in pathological wound healing processes. The current ophthalmolog‐ical therapeutic measures used to regulate tissue pro‐teolysis are also described.
EFFECTS OF GROWTH FACTORS ON CORNEAL WOUND HEALING
Authors: Schultz Gregory , Chegini Nasser , Grant Maria , Khaw Peng , MacKay Sally
Published: May 2009

Abstract Healing of ocular surface wounds is a complex process involving migration, mitosis, and differentiation of epithelial and stromal cells. Endogenously produced peptide growth factors such as epidermal growth factor (EGF), transforming growth factor alpha (TGF‐α), or transforming growth factor beta (TGF‐β) may play key roles in the natural wound healing process. Lacrimal gland cells were reported to synthesize and secrete EGF into tear fluid where it may enhance healing of corneal epithelial and stromal injuries by an exocrine pathway. EGF stimulated DNA synthesis of epithelial cells and stromal fibroblasts in culture, stimulated synthesis of fibronectin by epithelial cells and was chemotactic for human epithelial and stromal cells. Human corneal epithelial cells also synthesized TGF‐α which may influence epithelial cells by an autocrine pathway. TGF‐β, which is a potent in‐ducer of lysyl oxidase mRNA levels in cultures of human scleral fibroblasts, may be the factor most responsible for inducing synthesis of corneal extracellular matrix components after an injury. Treatment of epithelial injuries ocular surface wounds with exogenous peptide growth factors also accelerated healing in rabbits and primates. Treatment of severe ocular surface injuries caused by alkali with a combination of EGF, fibronectin, a synthetic collagenase inhibitor, and Aprotinin significantly blocked ulceration and enhanced epithelial regeneration. Clinical trials of topical treatment of EGF for ocular surface wounds suggest that peptide growth factors may be a valuable adjuvant for treatment of ocular surface wounds.
The pathology of after‐cataract
Authors: Kappelhof Johan P. , Vrensen Gijs F. J. M.
Published: May 2009

Abstract After‐cataract can be defined as the retropupillary, non‐vitreal opacification of the lens remnants occurring after extracapsular cataract extraction (ECCE) leading to disturbance of transparency and impairment of vision. The synonymous secondary cataract is confusing, since it is also and more frequently used as cataract secondary to ocular diseases (Duke‐Elder 1969). The synonymous opacification of the posterior capsule is, in fact, a misnomer, since histological observations revealed that after‐cataract is not proven to be the result of changes in the remaining posterior capsule itself, but is caused by proliferation of lenticular epithelial cells, fibroblasts, macrophages and even iris‐derived pigment cells on the posterior capsule (Fig. 1).
Anterior capsule opacification: A cell culture model
Authors: Ohara Kunitoshi , Itakura Kenzo , Ibaraki Nobuhiro
Published: May 2009

Abstract We cultured the human lens epithelial cells with attaching anterior lens capsule using surgically removed capsular flaps obtained in intraocular lens implantation. The capsular flap was placed with cell side down in a small culture well. In phase contrast microscopy, an anti‐meniscus plate was placed on the bathing medium to avoid optical aberration. The human lens epithelial cells showed outgrowth which ceased after 3 to 4 weeks of incubation. The cells under the capsule lost distinctive cell margin. The cells outgrew from the capsular edge both onto the anterior capsular surface and the well bottom. The outgrowth length and Bromodeoxyuridine uptake indicated a low proliferative potency of the human lens epithelial cells.
Lens cytoskeleton and after‐cataract
Authors: Rafferty N. S. , Rafferty K. A.
Published: May 2009

Abstract Lens epithelial and other ocular cells contain complex arrays of actin filaments which might be expected to allow them to migrate following injury: specifically into the capsular sac in cases of extracapsular cataract extraction or traumatic cataract. To test the possibility, a culture system was developed using a melanotic strain of mice, in which migrating cells are often ‘marked’ by melanosomes. Injured lenses were cultured on permeable membranes in contact with nutrient medium, and surrounded by iridial tract fragments. After study by light and electron microscopy, it was established that both pigmented and unpigmented cells migrated from the surrounding explants, apparently along the substrate meniscus, to the outside of the lens capsule and then through the wound to the capsule interior. This study suggests a source of cells in development of after‐cataract syndrome.
Echographic differentation of intraocular melanomas by computer analysis
Authors: Thijssen J. M. , Verbeek A.M. , Romijn R.L. , de Wolf‐Rouendaal D. , Oosterhuis J A
Published: May 2009

Abstract The aim of this study was to assess the differentiation of histologically different types of choroidal melanomas by means of clinical and quantitative acoustic/texture parameters of echograms. Clinical parameters were graded by morphological, kinetic and quantitative statements about the A‐ and B‐mode echograms by a skilled diagnostician. Acoustic/texture parameters were obtained by processing and analysing radio frequency, AM‐demodulated and FM‐demodulated echograms. The latter data were preprocessed to remove influence induced by beam diffraction and focusing. The best set of four clinical echographic parameters enabled a retrospective classification of spindle type melanomas vs. mixed + epithelioid type melanomas with an accuracy of 77% (area under the ROC‐curve of 86%). The discriminant analysis performed with the best four acoustic/texture parameters (n = 30) yielded a sensitivity of 89%, a specificity of 92%, and an area under the ROC‐curve which corresponds to a probability of correct classification of 96.6%. When using these data prospectively to classify tumours of unknown cell type (n = 21), this classification could be performed in 86% of cases.
An application of ultrasonic tissue characterization to the diagnosis of cataract
Authors: Sugata Yasuo , Murakami Kimio , Ito Masayasu , Shiina Tsuyoshi , Yamamoto Yukio
Published: May 2009

Abstract From a therapeutic and pathological point of view, it is important to classify types of cataract and to identify their stages. However, accepted criteria for quantitative diagnosis have not been established. On the other hand, based on the experience from tissue characterization applied to other clinical fields, the attenuation characteristics of the lens are expected to change according to the stage of disease and the type of cataract.

In this study from echo signals we tried to measure the attenuation coefficient of the lens with the purpose of quantiatively diagnosing the cataract, and at an early stage. It is shown that the attenuation of the cataractous lens is larger than that of the normal lens and its value depends on the type of the cataract, an indication of the possibility of using tissue characterization in the evaluation of cataract.
Real‐time sonography of orbital tumours Colour Doppler characterization: Initial experience
Authors: Jain Rajeev , Sawhney Sukhpal , Berry Manorama
Published: May 2009

Abstract Fifty‐seven patients with orbital tumours were examined with 3.5 MHz and 5 MHz real‐time sector sonography. The lesions were evaluated for their echomorphology, relationship to anatomical structures of the orbit, and extra‐orbital extension. Twenty‐two patients were further evaluated by Colour Doppler Flow Imaging (CDFI).

The lesions were located to four compartments, namely intraocular, intraconal, extraconal and extraorbital. An attempt was made to provide a histological diagnosis on the basis of clinical features and sonographic morphology. Colour Doppler flow patterns in 22 patients were correlated with the presumed or proven histological diagnosis in an attempt to detect and classify any specific patterns.

Real‐time US is an excellent screening procedure in the evaluation of orbital mass lesions. CT/MRI should be added in selected cases where extra‐orbital extension requires evaluation. CDFI of tumours still being in its infancy it seems promising and may help in providing a more precise pre‐operative histological diagnosis non‐invasively.
Color Doppler imaging of the eye and orbit A synopsis of a 400 case experience
Authors: Lieb Wolfgang E. , Flaharty Patrick M. , Ho Allen , Sergott Robert C.
Published: May 2009

Abstract Color Doppler imaging (CDI) is a recent advance in ultrasonography that allows simultaneous two‐dimensional imaging of structure and blood flow. Doppler information is superimposed in color over a conventional gray‐scale ultrasound image. Using this technique we have examined 400 eyes. The central retinal artery, posterior ciliary arteries, ophthalmic artery, the central retinal vein and the vortex veins could be located in all normal eyes. Using the color image as a guide, Doppler spectral analysis is used for quantitative assessment of blood flow velocity in these vessels. We also studied patients with intraocular tumors, arterial and venous retinal occlusions, orbital vascular anomalies and tumors. Color Doppler imaging is a new and promising modality for the study of ocular and orbital hemodynamics.
High resolution B mode echography and colour Doppler (CDFI) of the macula
Authors: Berges O. , Nau E.
Published: May 2009

Abstract Based on experience from 30 patients the usefulness of high resolution B‐scan echography and colour Doppler flow imaging for evaluating lesions of the macula is discussed. With B‐scan there is a high detectability of even very flat lesions (< 1 mm) but fluorescein angiography still gives more detail regarding specific diagnosis. In lesions thicker than 2 mm the Doppler imaging technique adds valuable information about vascularity, to make the assessment of differential diagnosis more exact. The results are considered preliminary; obviously focused ultrasound transducers of high frequency (20 mHz and above) will increase the possibilities of the method.
Choroidal metastases. Echographic experience from 42 patients
Authors: Perri P. , Chiarelli M. , Monari P. , Ravalli L. , Mazzeo V.
Published: May 2009

Abstract Over an 18 year period 42 patients with ocular metastases, age 30–75 years, 27 female and 15 male, were evaluated echographically. The right eye was affected in 18, the left in 17, and both eyes in 7. The most frequent primary tumours were carcinomas from breast (n = 25), lung (n = 6), and urinary bladder (n = 2). The choroidal metastases appeared mainly flat‐infiltrating or dome‐shaped, on B‐scan. A‐scan generally revealed high or medium reflectivity, however with important exceptions. Atypical cases are discussed. Usually eyes with metastases should not be enucleated. Accordingly, ultrasonic evaluation and follow‐up is of obvious importance.
Comparison between echographic and histological findings in choroidal malignant melanomas
Authors: Rosa N. , Cennamo G. , Tranfa F.
Published: May 2009

Abstract Echography is crucial in making a diagnosis of malignant melanoma when ocular media are opaque. Even with clear ocular media, standardized echography is important to confirm or to rule out a malignant melanoma in the eye. In this study the reflectivity in 27 cases of malignant melanomas has been evaluated and compared to cell type, pigmentation and number and size of blood vessels. No significant correlations have been found.
Capillary and cavernous hemanigoma of the optic disc Echographic and histological findings
Authors: Pierro L. , Guarisco L. , Zaganelli E. , Freschi M. , Brancato R.
Published: May 2009

Abstract The ultrasonography features of optic disc hemangioma have been described in various reports but the extreme rarity of this ocular tumour makes any univocal interpretation of echographic findings difficult. The two cases of hemangioma of the optic disc described here, one of capillary hemangioma and the other of cavernous hemangioma, presented different echographic patterns. In the capillary hemangioma B‐scan showed a mass lesion with smooth anterior border, acoustic solidity and no choroidal excavation. With A‐scan there was an initial high spike with low/medium internal reflectivity. In the cavernous hemangioma, B‐scan showed an elevated dome‐shaped mass, with an anechoic area inside, and no choroidal excavation. With A‐scan there was a high initial spike and irregular reflectivity. The eyes were enucleated for intractable neovascular glaucoma. Histological examination of the lesion explained the different echographic patterns. Ultrasonography is useful in the differential diagnosis of capillary and cavernous hemangioma.
Unusual echographic form of retinoblastoma
Authors: Németh János , Szabó Ágnes , Végh Mihály
Published: May 2009

Abstract A case of an 8‐year‐old girl with unilateral retinoblastoma is presented. The clinical picture was dominated by inflammatory signs and retinal detachment. Ultrasonographic A/B‐scan showed a funnel‐shaped total retinal detachment and a thick solid mass with similar shape just behind it. The main characteristics of the mass were: irregular inside echo pattern, medium high internal reflectivity, no sign of vascularity, no aftermovements following a sudden ocular movement, and no shadowing of the scleral or orbital tissues behind it. The vitreous cavity in front of the retina and behind the mass was ultrasonographically clear. The described funnel‐shaped echographic pattern might be typical of the diffuse infiltrating retinoblastoma.
Morbidity and mortality in 262 infants with birth weight below 1500 g born in Stockholm county 1988–1992
Authors: Broberger U. , Forssberg H. , Lagercrantz H. , Katz‐Salamon M.
Published: May 2009

Abstract. The aim of this study was to examine the relationship between neonatal clinical conditions and the development of senso‐motoric handicaps. Two hundred and sixty‐two infants with a birth weight < 1500 g, born in or referred to the Karolinska/S:t Göran's Children Hospital from September 1988 to april 1992 were studied prospectively. The total survival was 83%. Preliminary results of the Griffiths' test of these infants showed an average cognitive ability of the same level as for fullterms except for those pre‐term infants who had suffered from the combination of chronic lung disease and leucomalacia. The incidence of moderate to severe senso‐motoric disability is up to the present time 5%.
Epidemiology of ROP in the Stockholm area of Sweden
Authors: Holmström G. , el Azazi M. , Jacobson L. , Sachs D. , Sule J. , Lennerstrand G.
Published: May 2009

Abstract. A prospective, population‐based study of the epidemiology of ROP in a well‐defined geographical area of Sweden was performed. Two hundred and sixty children with a birth weight of 1500 g or less, and surviving for at least eight weeks, were included in the study. ROP was seen in 40.4% of the children. We suggest that prematurely born children with a gestational age of 32 weeks or less ought to be screened for ROP.
Retinopathy of prematurity in the southern part of Sweden
Authors: Barnekow Britt Beding , Stigmar Göran
Published: May 2009

Abstract. The incidence of retinopathy of prematurity (ROP) was studied in prematures in the southern part of Sweden during one year. Nine hospitals participated in the prospective study. During the period 23 745 children were born in the region. One hundred and ninety‐three of 214 prematures of gestational age ≤32 weeks and/or birth weight ≤ 1500 g, were subjected to ophthalmic investigation. The incidence of ROP among the prematures under study was calculated to 9% (17 children). Six of them had severe ROP (3%). Some risk factors associated to ROP are discussed.
Cryotherapy for retinopathy of prematurity
Authors: Flage Tor
Published: May 2009

Abstract. Retinopathy of prematurity (ROP) is a leading cause of severe visual impairment and blindness in infancy. Transscleral cryotherapy has been shown to be effective in arresting the progression of ROP into the sightthreatening fibrovascular stages of the disease. It is currently recommended that all eyes reaching ‘threshold’ ROP should be treated. If both eyes of an infant reach ‘threshold’, both eyes should be treated. For centers that handle a limited number of infants with ROP it is suggested that the cryotherapy should be done under general anesthesia.
Follow‐up of 15 children with severe ROP 1987–1989
Authors: Crafoord Sven , Stenström Ingeborg , Schollin Jens
Published: May 2009

Abstract. Between 1987–89 fifteen premature infants with severe retinopathy of prematurity (ROP), at the age of ten months or less, were admitted as outpatients to the Department of Ophthalmology at the Örebro Medical Center Hospital. Initial examination of the infants showed that 6 eyes had stage 3+, 3 eyes had stage 4 B and 21 eyes had stage 5 ROP. All 15 infants were born at gestational week 24–28 (mean value 26) and had a birth weight between 600 and 1310 g (mean 907 g). For stage 3+ cryotherapy was performed. For stage 4 B and 5 buckling procedure and vitreous surgery was performed in an attempt to re‐attach the retina. The children were followed 2–5.5 years. Postoperatively, the retinas of all eyes in stage 3+ and 4B were attached. Four retinas out of seventeen stage 5 eyes were later found to be centrally re‐attached. One eye with stage 3+ and four eyes with stage 5 were not treated at all. At follow‐up of stage 3+ and 4B, visual acuity was measurable in all eyes; in stage 5 only two out of four eyes with anatomically reattached retinas had perception of light.
Study on reaction mechanism of Si and pure CeO2 for chemical-mechanical-grinding process
Authors: Kamiya Sumio , Iwase Hisao , Kishita Keisuke , Zhou Libo , Eda Hiroshi , Yoshida Yuji
Published: May 2009

The thinning process of silicon wafer for power device in automotive applications requires stress relief and relatively high Si removal rate. The innovative process of chemical mechanical grinding (CMG) has been developed for the surface finishing of Si wafer by means of solid state chemical reaction with CeO2 abrasives under dry condition. However, the reaction mechanisms of Si and pure CeO2 in the dry CMG process are yet fully understood. The chips of Si wafer produced during CMG process were analyzed using x-ray diffraction (XRD), transmission electron microscopy (TEM), and TEM/energy dispersive x-ray fluorescence spectrometer. Those analyses clearly indicated that the chips were thin, elongated, and acicular, as well as partially curved. The large amount of Si in amorphous phase and CeO2 were detected in the CMG chips by XRD, except Si crystalline. The reaction experiments between Si and CeO2 were also performed where the pellets composed of mixed Si∕CeO2 powders were heat treated at 400–1200°C in both air and vacuum (10−4torr), then quenched. The specimens heated in air and vacuum above 900°C contained Si, CeO2, a trace of amorphous phase, CeSi1.9 (cerium-silicon alloy), and Ce4.667(Si4)3O (cerium silicate), respectively. This means that the reaction mechanism in heat treatment of the Si∕CeO2 powders is not exactly the same as CMG process. The findings from analyses of CMG chip products proved that the reaction of 2CeO2+Si→Ce2O3+SiO (amorphous) took place during CMG process of Si wafer using CeO2 fixed abrasive. The produced Ce2O3 can be easily transformed to CeO2 by the reaction Ce2O3+1∕2O2→2CeO2.
Modeling and fabrication of thin film thermopile sensor
Authors: Kim Jung-Kyun , Kim Tae-Hwa , Cho Sung-Cheon , Shin Sang-Mo , Lee Sun-Kyu
Published: May 2009

A thin film micro heat-flux sensor using thermopile, which can measure the heat flow, was fabricated by a complementary-metal-oxide-semiconductor-compatible process. The combination of a ten-junction polysilicon and aluminum thermoelectric sensor with an ultralow noise preamplifier and low pass Butterworth filter has enabled the resolution of 3.4μW power and shows the sensitivity of 2.43mV∕μW. In order to estimate the heat generation of samples from the output measurement of a micro heat-flux sensor, a methodology for modeling and simulating electro-thermal behavior in a micro heat-flux sensor with integrated electronic circuit is presented and validated. The electro-thermal model was constructed by using system dynamics, particularly the bond graph methodology. The electro-thermal system model, where the thermal domain and the electrical domain are coupled, expresses the behavior that the heat generation of samples converts thermal input to electrical output through the system model. The proposed electro-thermal system model shows good agreement with measured voltage responses.
Comparative study on structural and optical properties of ZnO films grown by metalorganic molecular beam deposition and metalorganic chemical vapor deposition
Authors: Terasako Tomoaki , Yura Shinichiro , Azuma Suguru , Shimomura Satoshi , Shirakata Sho , Yagi Masakazu
Published: May 2009

Polycrystalline zinc oxide films were grown on glass substrates by low pressure metal organic chemical vapor deposition (LP-MOCVD) and metal organic molecular beam deposition (MOMBD) using diethlyzinc and water as precursors. With increasing substrate temperature (TS), preferential growth direction of the LP-MOCVD films changed from c-axis direction to a-axis direction, while that of the MOMBD films changed from random direction to c-axis direction. Photoluminescence (PL) spectra of the LP-MOCVD films exhibited an orange band emission related to interstitial oxygen atoms, while those of the MOMBD films exhibited a green band emission related to oxygen vacancies. This PL result suggests that the LP-MOCVD films are in oxygen excess condition, but the MOMBD films are in oxygen deficient condition. Photoacoustic measurements revealed that the energy level of the nonradiative center formed in the LP-MOCVD films is deeper than that in the MOMBD films.
Debating Reality and Relevance

Revisiting Race in a Genomic Age
Barbara A. Koenig, Sandra Soo-Jin Lee, and Sarah S. Richardson, Eds.

Rutgers University Press, New Brunswick, NJ, 2008. 394 pp. $80. ISBN 9780813543231. Paper, $32.95. ISBN 9780813543246. Studies in Medical Anthropology.
Authors: Duster Troy
Published: May 2009

Anthropologists, historians, geneticists, philosophers, and bioethicists explore what recent and current research on human genetics implies about the concepts of race and racial difference.
It's the DNA That Counts
Authors: Smolke Christina D.
Published: May 2009

A simple genetic circuit that counts molecular events may be further developed to program complex cell behaviors.
New Rules for Biosecurity
Authors: Berger Kavita M. , Leshner Alan I.
Published: May 2009

Biosecurity regulations are back on the table again, and revised policies could have broad implications for the entire scientific enterprise. In response to an Executive Order by President Bush on 9 January 2009, an interagency working group is reviewing all U.S. laws and regulations governing the conduct of research with biological materials that are potential security threats—so-called select agents. The issue at hand concerns how to balance the risks associated with select agents against ensuring that the public can reap the full potential benefits of research on them. The report of the working group is expected in July, and it will propose an array of policies for improving laboratory biosafety and security, from defining what select agents are and who has access to them, to specifying the oversight of laboratories that handle them. Done well, the review could greatly improve biosecurity and the climate for biological research in the United States and abroad. Done poorly, there could be a variety of unintended negative consequences, including over-restricted access to vital resources and a constrained ability to collaborate internationally on a broad range of topics.
Arsenic and Old Mummies: Poison May Have Spurred First Mummies
Authors: Pringle Heather
Published: May 2009

Arsenic-laced drinking water and resulting child mortality may help explain the puzzle of the world's first mummies.
A Cloudy Crystal Ball for the Coming Season's Hurricanes
Authors: Kerr Richard A.
Published: May 2009

A group of meteorologists that each year for 25 years has tried to decipher what the coming summer and fall have in store for hurricane country has graded itself for the first time.
Biologists Struggle to Solve Bat Deaths
Authors: Zimmerman Robert
Published: May 2009

An epidemic has stricken the northeastern United States for 3 years. As it spreads, researchers wonder whether a white fungus is the real killer.
Obama Moves to Revitalize Chesapeake Bay Restoration
Authors: Stokstad Erik
Published: May 2009

With progress stalled for years, the U.S. Environmental Protection Agency is taking the reins on cleaning up the largest estuary in the United States. It's not going to be easy.
Investigation of Different Group A Immunoassays following One Dose of Meningococcal Group A Conjugate Vaccine or A/C Polysaccharide Vaccine in Adults
Authors: Findlow H. , Plikaytis B. D. , Aase A. , Bash M. C. , Chadha H. , Elie C. , Laher G. , Martinez J. , Herstad T. , Newton E. , Viviani S. , Papaspyridis C. , Kulkarni P. , Wilding M. , Preziosi M. P. , Marchetti E. , Hassan-King M. , La Force F. M. , Carlone G. , Borrow R.
Published: May 2009

A double-blind, randomized, controlled phase I study to assess the safety, immunogenicity, and antibody persistence of a new group A conjugate vaccine (PsA-TT) in volunteers aged 18 to 35 years was previously performed. Subjects received one dose of either the PsA-TT conjugate vaccine, meningococcal A/C polysaccharide vaccine (PsA/C), or tetanus toxoid vaccine. The conjugate vaccine was shown to be safe and immunogenic as demonstrated by a standardized group A-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and by a serum bactericidal antibody (SBA) assay using rabbit complement (rSBA). This report details further analysis of the sera using four additional immunologic assays to investigate the relationship between the different immunoassays. The immunoassays used were an SBA assay that used human complement (hSBA), a group A-specific IgG multiplexed bead assay, and two opsonophagocytic antibody (OPA) assays which used two different methodologies. For each vaccine group, geometric mean concentrations or geometric mean titers were determined for all assays before and 4, 24, and 48 weeks after vaccination. Pearson's correlation coefficients were used to assess the relationship between the six assays using data from all available visits. An excellent correlation was observed between the group A-specific IgG concentrations obtained by ELISA and those obtained by the multiplexed bead assay. hSBA and rSBA titers correlated moderately, although proportions of subjects with putatively protective titers and those demonstrating a ≥4-fold rise were similar. The two OPA methods correlated weakly and achieved only a low correlation with the other immunoassays. The correlation between hSBA and group A-specific IgG was higher for the PsA-TT group than for the PsA/C group.
Antibodies Specific for the Hia Adhesion Proteins of NontypeableHaemophilus influenzaeMediate Opsonophagocytic Activity
Authors: Winter Linda E. , Barenkamp Stephen J.
Published: May 2009

The Hia autotransporter proteins are highly immunogenic surface adhesins expressed by nontypeableHaemophilus influenzae(NTHI). The objective of our study was to assess the opsonophagocytic activity of anti-Hia antibodies against homologous and heterologous NTHI. A segment of thehiagene that encodes a surface-exposed portion of theH. influenzaestrain 11 Hia protein was cloned into a pGEMEX-2 expression vector.Escherichia coliJM101 was transformed with the resulting pGEMEX-Hia BstEII del recombinant plasmid, and recombinant fusion protein was recovered. An immune serum against recombinant GEMEX-Hia (rGEMEX-Hia)-mediated killing of the homologous NTHI strain 11 at a 1:160 titer and five heterologous Hia-expressing strains at titers of ≥1:40. Immune serum did not mediate killing of two Hia-knockout strains whosehiagenes were inactivated but did mediate killing of one knockout strain at a high titer after the strain was transformed with a plasmid containing thehiagene. Immune serum did not mediate killing of HMW1/HMW2-expressing NTHI strains, which do not express the Hia adhesin. However, when two representative HMW1/HMW2-expressing strains were transformed with the plasmid containing thehiagene, they expressed abundant Hia and were susceptible to killing by the immune serum. Immune serum did not mediate killing of HMW1/HMW2-expressing strains transformed with the plasmid without thehiagene. Our results demonstrate that the Hia proteins of NTHI are targets of opsonophagocytic antibodies and that shared epitopes recognized by such antibodies are present on the Hia proteins of unrelated NTHI strains. These data argue for the continued investigation of the Hia proteins as vaccine candidates for the prevention of NTHI disease.
Early Detection of Human Immunodeficiency Virus Type 1-Specific B-Lymphocyte-Derived Antibodies in a High-Risk Population
Authors: Odinsen Odd , Parker David , Radebe Frans , Guness Mikey , Lewis David A
Published: May 2009

Diagnosis of acute human immunodeficiency virus (HIV) infection, a key driver of the HIV epidemic, remains a public health challenge. The PlasmAcute technology offers an opportunity to detect early anti-HIV antibody responses. B lymphocytes (B cells) were isolated from the blood of seronegative miners in South Africa by using the PlasmAcute method. B-cell lysates and paired sera were tested for anti-HIV-1 antibodies by two different enzyme-linked immunosorbent assays; immunoreactivity was confirmed by Western blotting. All volunteers were tested for HIV type 1 (HIV-1) viral load, p24 antigen, and CD4 count. Sera from HIV-seronegative men who had positive viral loads and were positive for p24 antigen were retested for anti-HIV antibodies after immune complex dissociation. Anti-HIV antibodies were detected in lysates from 16/259 subjects without immunoreactivity in paired sera. Four subjects, one of whom had a positive viral load initially, subsequently seroconverted. Six subjects showed transient anti-HIV-1 antibodies in the lysates and tested negative for all markers at the follow-up. Five subjects without follow-up data initially had lysate-positive/serum-negative samples, and these cases were classified as inconclusive. One subject had lysate antibodies and a detectable viral load but was seronegative at follow-up. In conclusion, lysate-derived anti-HIV-1 B-cell antibodies can be detected prior to seroconversion and earlier than or contemporary with HIV-1 RNA detection.
Ultra-High-Throughput, Automated Nucleic Acid Detection of Human Immunodeficiency Virus (HIV) for Infant Infection Diagnosis Using the Gen-Probe Aptima HIV-1 Screening Assay
Authors: Stevens Wendy S. , Noble Lara , Berrie Leigh , Sarang Somaya , Scott Lesley E.
Published: May 2009

The early diagnosis of human immunodeficiency virus (HIV) infection in infants is critical to ensure the initiation of treatment before significant immunological compromise. Each year an estimated 300,000 HIV-exposed infants in South Africa require access to tests for the diagnosis of HIV infection. Currently, testing is performed at several facilities by using PCR amplification of HIV DNA at 6 weeks of age by the use of dried blood spots (DBSs) and whole blood (WB). The Gen-Probe Aptima HIV type 1 (HIV-1) screening assay (the Aptima assay) is a qualitative nucleic acid test based on transcription-mediated amplification (TMA), a technology routinely used in blood banks in South Africa. The performance characteristics of Gen-Probe's TMA technology compared well to those of the Roche Amplicor HIV-1 DNA (version 1.5) assay. The sensitivity of the assay with WB and DBS samples was 100%, and the specificities were 99.4% and 99.5% for DBSs and WB, respectively. The detection of HIV by the Aptima assay at greater levels of dilution in samples negative by the comparator assay indicates an improvement in sensitivity by the use of the TMA technology. The ability to process 1,900 samples in a 24-h period on the Tigris instrument makes the Aptima assay an attractive option for high-volume, centralized laboratories.
Mupirocin Resistance among Methicillin-ResistantStaphylococcus aureus-Colonized Patients at Admission to a Tertiary Care Medical Center
Authors: Babu Tara , Rekasius Violeta , Parada Jorge P. , Schreckenberger Paul , Challapalli Malliswari
Published: May 2009

All patients admitted to our tertiary care hospital from 1 December 2007 to 10 June 2008 were screened for methicillin (meticillin)-resistantStaphylococcus aureus(MRSA) nasal colonization, and the isolates were tested for mupirocin susceptibility by using Etest. Mupirocin resistance (MR) was noted to occur in 3.4% of MRSA carriers, and high-level MR was noted to occur in 0.62% of carriers.
Lack of Adaptation of Chimeric GB Virus B/Hepatitis C Virus in the Marmoset Model: Possible Effects of Bottleneck
Authors: Weatherford Trudie , Chavez Deborah , Brasky Kathleen M. , Lemon Stanley M. , Martin Annette , Lanford Robert E.
Published: May 2009

Approximately 3% of the world population is chronically infected with hepatitis C virus (HCV). GB virus B (GBV-B), a surrogate model for HCV, causes hepatitis in tamarins and is the virus phylogenetically most closely related to HCV. Previously we described a chimeric GBV-B containing an HCV insert from the 5′ noncoding region (NCR) that was adapted for efficient replication in tamarins (
Saguinus
species). We have also demonstrated that wild-type (WT) GBV-B rapidly adapts for efficient replication in a closely related species, the common marmoset (
Callithrix jacchus
). Here, we demonstrate that the chimeric virus failed to adapt during serial passage in marmosets. The chimeric virus was passaged four times through 24 marmosets. During passage, two marmoset phenotypes were observed: susceptible and partially resistant. Although appearing to adapt in a resistant animal during a prolonged and gradual increase in viremia, the chimeric GBV-B failed to replicate efficiently upon passage to a naïve marmoset. The resistance was specific to the chimeric virus, as the chimeric virus-resistant animals were susceptible to marmoset-adapted WT virus during rechallenge studies. Three isolates of the chimeric virus were sequenced, and 20 nucleotide changes were observed, including eight amino acid changes. Three unique changes were observed in the 5′ NCR chimeric insert, an area that is highly conserved in HCV. We speculate that the failure of the chimeric virus to adapt in marmosets might be due to a bottleneck that occurs at the time of infection of resistant animals, which may lead to a loss of fitness upon serial passage.
Mutations That Increase DNA Binding by the Processivity Factor of Herpes Simplex Virus Affect Virus Production and DNA Replication Fidelity
Authors: Jiang Changying , Komazin-Meredith Gloria , Tian Wang , Coen Donald M. , Hwang Charles B. C.
Published: May 2009

The interactions of the herpes simplex virus processivity factor UL42 with the catalytic subunit of the viral polymerase (Pol) and DNA are critical for viral DNA replication. Previous studies, including one showing that substitution of glutamine residue 282 with arginine (Q282R) results in an increase of DNA binding in vitro, have indicated that the positively charged back surface of UL42 interacts with DNA. To investigate the biological consequences of increased DNA binding by
UL42
mutations, we constructed two additional UL42 mutants, including one with a double substitution of alanine for aspartic acid residues (D270A/D271A) and a triple mutant with the D270A/D271A and Q282R substitutions. These UL42 mutants exhibited increased and prolonged DNA binding without an effect on binding to a peptide corresponding to the C terminus of Pol. Plasmids expressing any of the three UL42 mutants with an increased positive charge on the back surface of UL42 were qualitatively competent for complementation of growth and DNA replication of a
UL42
null mutant on Vero cells. We then engineered viruses expressing these mutant proteins. The UL42 mutants were more resistant to detergent extraction than wild-type UL42, suggesting that they are more tightly associated with DNA in infected cells. All three UL42 mutants formed smaller plaques on Vero cells and replicated to reduced yields compared with results for a control virus expressing wild-type UL42. Moreover, mutants with double and triple mutations, which contain D270A/D271A mutations, exhibited increased mutation frequencies, and mutants containing the Q282R mutation exhibited elevated ratios of virion DNA copies per PFU. These results suggest that herpes simplex virus has evolved so that UL42 neither binds DNA too tightly nor too weakly to optimize virus production and replication fidelity.
Deficiency of Niemann-Pick Type C-1 Protein Impairs Release of Human Immunodeficiency Virus Type 1 and Results in Gag Accumulation in Late Endosomal/Lysosomal Compartments
Authors: Tang Yuyang , Leao Ihid Carneiro , Coleman Ebony M. , Broughton Robin Shepard , Hildreth James E. K.
Published: May 2009

Human immunodeficiency virus type 1 (HIV-1) relies on cholesterol-laden lipid raft membrane microdomains for entry into and egress out of susceptible cells. In the present study, we examine the need for intracellular cholesterol trafficking pathways with respect to HIV-1 biogenesis using Niemann-Pick type C-1 (NPC1)-deficient (NPCD) cells, wherein these pathways are severely compromised, causing massive accumulation of cholesterol in late endosomal/lysosomal (LE/L) compartments. We have found that induction of an NPC disease-like phenotype through treatment of various cell types with the commonly used hydrophobic amine drug U18666A resulted in profound suppression of HIV-1 release. Further, NPCD Epstein-Barr virus-transformed B lymphocytes and fibroblasts from patients with NPC disease infected with a CD4-independent strain of HIV-1 or transfected with an HIV-1 proviral clone, respectively, replicated HIV-1 poorly compared to normal cells. Infection of the NPCD fibroblasts with a vesicular stomatitis virus G-pseudotyped strain of HIV-1 produced similar results, suggesting a postentry block to HIV-1 replication in these cells. Examination of these cells using confocal microscopy showed an accumulation and stabilization of Gag in LE/L compartments. Additionally, normal HIV-1 production could be restored in NPCD cells upon expression of a functional NPC1 protein, and overexpression of NPC1 increased HIV-1 release. Taken together, our findings demonstrate that intact intracellular cholesterol trafficking pathways mediated by NPC1 are needed for efficient HIV-1 production.
Mutagenesis of Varicella-Zoster Virus Glycoprotein B: Putative Fusion Loop Residues Are Essential for Viral Replication, and the Furin Cleavage Motif Contributes to Pathogenesis in Skin Tissue In Vivo
Authors: Oliver Stefan L. , Sommer Marvin , Zerboni Leigh , Rajamani Jaya , Grose Charles , Arvin Ann M.
Published: May 2009

Glycoprotein B (gB), the most conserved protein in the family
Herpesviridae
, is essential for the fusion of viral and cellular membranes. Information about varicella-zoster virus (VZV) gB is limited, but homology modeling showed that the structure of VZV gB was similar to that of herpes simplex virus (HSV) gB, including the putative fusion loops. In contrast to HSV gB, VZV gB had a furin recognition motif ([R]-X-[KR]-R-|-X, where | indicates the position at which the polypeptide is cleaved) at residues 491 to 494, thought to be required for gB cleavage into two polypeptides. To investigate their contribution, the putative primary fusion loop or the furin recognition motif was mutated in expression constructs and in the context of the VZV genome. Substitutions in the primary loop, W180G and Y185G, plus the deletion mutation Δ
491
RSRR
494
and point mutation
491
GSGG
494
in the furin recognition motif did not affect gB expression or cellular localization in transfected cells. Infectious VZV was recovered from parental Oka (pOka)-bacterial artificial chromosomes that had either the Δ
491
RSRR
494
or
491
GSGG
494
mutation but not the point mutations W180G and Y185G, demonstrating that residues in the primary loop of gB were essential but gB cleavage was not required for VZV replication in vitro. Virion morphology, protein localization, plaque size, and replication were unaffected for the pOka-gBΔ
491
RSRR
494
or pOka-gB
491
GSGG
494
virus compared to pOka in vitro. However, deletion of the furin recognition motif caused attenuation of VZV replication in human skin xenografts in vivo. This is the first evidence that cleavage of a herpesvirus fusion protein contributes to viral pathogenesis in vivo, as seen for fusion proteins in other virus families.
Mitochondrial Antiviral Signaling Protein Plays a Major Role in Induction of the Fish Innate Immune Response against RNA and DNA Viruses
Authors: Biacchesi Stéphane , LeBerre Monique , Lamoureux Annie , Louise Yoann , Lauret Emilie , Boudinot Pierre , Brémont Michel
Published: May 2009

Viral infection triggers host innate immune responses through cellular sensor molecules which activate multiple signaling cascades that induce the production of interferons (IFN) and other cytokines. The recent identification of mammalian cytoplasmic viral RNA sensors, such as retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and their mitochondrial adaptor, the mitochondrial antiviral signaling protein (MAVS), also called IPS-1, VISA, and Cardif, highlights the significance of these molecules in the induction of IFN. Teleost fish also possess a strong IFN system, but nothing is known concerning the RLRs and their downstream adaptor. In this study, we cloned MAVS cDNAs from several fish species (including salmon and zebrafish) and showed that they were orthologs of mammalian MAVS. We demonstrated that overexpression of these mitochondrial proteins in fish cells led to a constitutive induction of IFN and IFN-stimulated genes (ISGs). MAVS-overexpressing cells were almost fully protected against RNA virus infection, with a strong inhibition of both DNA and RNA virus replication (1,000- and 10,000-fold decreases, respectively). Analyses of MAVS deletion mutants showed that both the N-terminal CARD-like and C-terminal transmembrane domains, but not the central proline-rich region, were indispensable for MAVS signaling function. In addition, we cloned the cDNAs encoding a RIG-I-like molecule from salmonid and cyprinid cell lines. Like the case with MAVS, overexpression of RIG-I CARDs in fish cells led to a strong induction of both IFN and ISGs, conferring on fish cells full protection against RNA virus infection. This report provides the first demonstration that teleost fish possess a functional RLR pathway in which MAVS may play a central role in the induction of the innate immune response.