bluuebunny/crossref_metadata_2025 huggingface dataset:
Ral GTPases regulate neurite branching through GAP-43 and the exocyst complex
Authors: Lalli Giovanna , Hall Alan
Published: December 2005

Neurite branching is essential for the establishment of appropriate neuronal connections during development and regeneration. We identify the small GTPase Ral as a mediator of neurite branching. Active Ral promotes neurite branching in cortical and sympathetic neurons, whereas Ral inhibition decreases laminin-induced branching. In addition, depletion of endogenous Ral by RNA interference decreases branching in cortical neurons. The two Ral isoforms, RalA and -B, promote branching through distinct pathways, involving the exocyst complex and phospholipase D, respectively. Finally, Ral-dependent branching is mediated by protein kinase C–dependent phosphorylation of 43-kD growth-associated protein, a crucial molecule involved in pathfinding, plasticity, and regeneration. These findings highlight an important role for Ral in the regulation of neuronal morphology.
The Rac activator Tiam1 is required for α3β1-mediated laminin-5 deposition, cell spreading, and cell migration
Authors: Hamelers Irene H.L. , Olivo Cristina , Mertens Alexander E.E. , Pegtel D. Michiel , van der Kammen Rob A. , Sonnenberg Arnoud , Collard John G.
Published: December 2005

The Rho-like guanosine triphosphatase Rac1 regulates various signaling pathways, including integrin-mediated adhesion and migration of cells. However, the mechanisms by which integrins signal toward Rac are poorly understood. We show that the Rac-specific guanine nucleotide exchange factor Tiam1 (T-lymphoma invasion and metastasis 1) is required for the integrin-mediated laminin (LN)-5 deposition, spreading, and migration of keratinocytes. In contrast to wild-type keratinocytes, Tiam1-deficient (Tiam1−/−) keratinocytes are unable to adhere to and spread on a glass substrate because they are unable to deposit their own LN5 substrate. Both Tiam1 and V12Rac1 can rescue the defects of Tiam1−/− keratinocytes, indicating that these deficiencies are caused by impaired Tiam1-mediated Rac activation. Tiam1−/− cells are unable to activate Rac upon α3β1-mediated adhesion to an exogenous LN5 substrate. Moreover, Tiam1 deficiency impairs keratinocyte migration in vitro and reepithelialization of excision wounds in mouse skin. Our studies indicate that Tiam1 is a key molecule in α3β1-mediated activation of Rac, which is essential for proper production and secretion of LN5, a requirement for the spreading and migration of keratinocytes.
Location, movement and survival: the role of chemokines in haematopoiesis and malignancy
Authors: Laurence Arian D. J.
Published: December 2005

Chemokines are a family of over 40 small (8 kDa) related proteins with the function of moving cells along a chemotactic gradient, either to organise cells within an organ or to facilitate the movement of leucocytes around the body. Mouse models have implicated the importance of the chemokine CXCL12 in haematopoiesis and this has lead to the use of the inhibitor AMD3100 for autologous transplantation. This review will briefly discuss the biology of chemokines and their role in haematopoiesis and haematological malignancy together with the possible benefits and hazards of therapeutic modification of the chemokine system.
Multilineage involvement of the fusion gene in patients with FIP1L1/PDGFRA‐positive hypereosinophilic syndrome
Authors: Robyn Jamie , Lemery Steven , Philip McCoy J. , Kubofcik Joseph , Kim Yae‐Jean , Pack Svetlana , Nutman Thomas B. , Dunbar Cynthia , Klion Amy D.
Published: December 2005

Myeloproliferative hypereosinophilic syndrome (MHES) is a disorder characterised by male predominance, marked eosinophilia, splenomegaly, tissue fibrosis, elevated serum tryptase and the presence of the FIP1L1/PDGFRA fusion gene in peripheral blood mononuclear cells. The characteristic hypercellular bone marrow with dysplastic eosinophils and spindle‐shaped mast cells suggest that multiple lineages may be involved in the clonal process. To determine which haematopoietic lineages are involved in MHES, we purified cells of specific lineages from patients with MHES and used nested reverse transcription polymerase chain reaction (RT‐PCR), quantitative RT‐PCR and fluorescence in situ hybridisation to analyse the purified cell populations for the presence of the fusion gene. The fusion gene was detected in eosinophils, neutrophils, mast cells, T cells, B cells and monocytes. These results suggest that the mutation arises in a pluripotential haematopoietic progenitor cell capable of giving rise to multiple lineages. The basis for the preferential expansion of eosinophils and mast cells remains unclear.
Two new phosphoglycerate kinase mutations associated with chronic haemolytic anaemia and neurological dysfunction in two patients from Spain
Authors: Noel Núria , Flanagan John , Kalko Susana G. , Bajo Maria Jose Ramirez , Mañú María del Mar , Fuster José Luis Garcia , Beutler Ernest , Corrons Joan‐Lluís Vives
Published: December 2005

We report two previously undescribed mutations of the phosphoglycerate kinase gene (PGK1) leading to enzyme deficiency. In both cases, the patients were of Spanish origin and they exhibited a severe life‐long chronic haemolytic anaemia associated with progressive neurological impairment. Sequence analysis of the first patient's entire PGK1 gene found a novel missense mutation (140T > A). This mutation caused an amino acid change of Ile to Asn at 46th position from the NH2‐terminal serine residue (Ile46Asn), which has been called PGK‐Barcelona based on the place of origin of the patient. In the second patient, a G to A transversion was discovered at nucleotide 958 (958G > A). This caused a Ser319Asn amino acid substitution. Since this mutation had not been previously described, the provisional name of PGK‐Murcia was given to this deficient enzyme. The crystal structure of porcine PGK was used as a molecular model to investigate how these mutations may affect enzyme structure and function. In both cases, the mutations did not modify any of the PGK binding sites for ATP or 3PG, so their consequence is related to a loss of enzyme stability rather than a decrease of enzyme catalytic function.
Genomic and expression profiling identifies the B‐cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma
Authors: Rinaldi Andrea , Kwee Ivo , Taborelli Monica , Largo Cristina , Uccella Silvia , Martin Vittoria , Poretti Giulia , Gaidano Gianluca , Calabrese Giuseppe , Martinelli Giovanni , Baldini Luca , Pruneri Giancarlo , Capella Carlo , Zucca Emanuele , Cotter Finbarr E. , Cigudosa Juan C. , Catapano Carlo V. , Tibiletti Maria G. , Bertoni Francesco
Published: December 2005

Among B‐cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC. Among the transcripts with high correlation between DNA and RNA, we identified SYK, a tyrosine kinase involved in B‐cell receptor signalling. SYK was amplified at DNA level, as validated by fluorescence in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein levels in the JeKo‐1 cell line. Low‐level amplification, with protein overexpression of Syk was demonstrated by FISH in a small subset of clinical samples. After treatment with low doses of the Syk inhibitor piceatannol, cell proliferation arrest and apoptosis were induced in the cell line overexpressing Syk, while cells expressing low levels of Syk were much less sensitive. A combination of genomic and expression profiling suggested Syk inhibition as a new therapeutic strategy to be explored in lymphomas.
The involvement of osteopontin and its receptors in multiple myeloma cell survival, migration and invasion in the murine 5T33MM model
Authors: Caers Jo , Günthert Ursula , De Raeve Hendrik , Valckenborgh Els Van , Menu Eline , Riet Ivan Van , Camp Benjamin Van , Vanderkerken Karin
Published: December 2005

Multiple myeloma (MM) is a malignancy characterised by the accumulation of monoclonal plasma cells in the bone marrow. Different reports indicate the expression of CD44 variant isoforms (CD44v) by MM cells. Osteopontin (OPN), which is expressed by MM cells, is known to be a ligand for CD44v6. In this study, we investigated the role of OPN with emphasis on a functional correlation between OPN and CD44v in the 5T33MM model. Our group reported the expression of CD44v by 5T33MM cells. Using this model, we have demonstrated the secretion of OPN by 5T33MM cells. OPN affected 5T33MM cell survival by increasing proliferation and inhibiting apoptosis. OPN also stimulated 5T33MM cell migration, transendothelial migration and matrix metalloproteinase‐9 activity. We confirmed the proliferative and migratory effects of OPN on human MM cells. By applying inhibiting anti‐CD44v6 antibodies, we found that OPN stimulated cell proliferation by engaging this isoform. Anti‐CD44v antibodies and RGD peptides both inhibited cell migration, suggesting an involvement of both, CD44v isoforms and integrins. In conclusion, OPN may act as a mediator of MM cell survival by engaging CD44v. The protein is further involved in migration and invasion of MM cells through the activation of either αvβ3 integrin or CD44v isoforms.
The effect of low‐temperature blanching on the quality of fresh and frozen/thawed mashed potatoes
Authors: Fernández Cristina , Dolores Alvarez M. , Canet Wenceslao
Published: December 2005

The effect of low‐temperature blanching (LTB) prior to cooking on colour, textural, firmness and oscillatory parameters, sensory attributes and overall acceptability of either fresh or frozen/thawed mashed potatoes was studied using response surface methodology (RSM) to establish the optimum temperature and time for blanching in both types of mashed potatoes. A central composite rotatable design was used to study the effects of variation in levels of blanching temperature (57.93–72.07 °C) and time (15.86–44.14 min) on the quality parameters. Stationary points showing maximum thickening had critical temperatures (approximately 67–69 °C) and times (approximately 26–30 min) in the ranges of temperature and time used for each independent variable for both fresh and frozen/thawed mashed potato. Results showed a high correlation between structural reinforcement and overall acceptability under optimum experimental blanching conditions. This demonstrates the potential of this experimental approach in terms of tailoring physical properties to predetermined levels in order to meet consumer preferences in mashed potatoes, and of altering the changes that occur after freezing and thawing.
Multiple gene genealogies and AFLPs suggest cryptic speciation and long‐distance dispersal in the basidiomycete Serpula himantioides (Boletales)
Authors: KAUSERUD HÅVARD , STENSRUD ØYVIND , DECOCK CONY , SHALCHIAN‐TABRIZI KAMRAN , SCHUMACHER TROND
Published: December 2005

Serpula himantioides (Boletales, Basidiomycota) produces thin resupinate basidiocarps on dead coniferous wood worldwide and causes damage in buildings as well. In this study, we present evidence for the existence of at least three phylogenetically defined cryptic species (referred to as Sib I–III) within the morphospecies S. himantioides, a conclusion based on analyses of sequence data from four DNA regions and amplified fragment length polymorphisms (AFLPS). A low degree of shared sequence polymorphisms was observed among the three lineages indicating a long‐lasting separation. The AFLPs revealed two additional subgroups within Sib III. Results from mating studies were consistent with the molecular data. In Sib III, no correspondence between genetic and geographical distance was observed among isolates worldwide, presumably reflecting recent dispersal events. Our results indicate that at least two of the lineages (Sib II and Sib III) have wide sympatric distributions. A population genetic analysis of Sib III isolates, scoring sequence polymorphisms as codominant SNP markers, indicates that panmictic conditions exist in the Sib III group. This study supports the view that cryptic speciation is a common phenomenon in basidiomycete fungi and that phylogenetic species recognition can be a powerful inference to detect cryptic species. Furthermore, this study shows that AFLP data are a valuable supplement to DNA sequence data in that they may detect a finer level of genetic variation.
Inefficient photosynthesis in the Mediterranean orchid Limodorum abortivum is mirrored by specific association to ectomycorrhizal Russulaceae
Authors: GIRLANDA M. , SELOSSE M. A. , CAFASSO D. , BRILLI F. , DELFINE S. , FABBIAN R. , GHIGNONE S. , PINELLI P. , SEGRETO R. , LORETO F. , COZZOLINO S. , PEROTTO S.
Published: December 2005

Among European Neottieae, Limodorum abortivum is a common Mediterranean orchid. It forms small populations with a patchy distribution in woodlands, and is characterized by much reduced leaves, suggesting a partial mycoheterotrophy. We have investigated both the photosynthetic abilities of L. abortivum adult plants and the diversity of mycorrhizal fungi in Limodorum plants growing in different environments and plant communities (coniferous and broadleaf forests) over a wide geographical and altitudinal range. Despite the presence of photosynthetic pigments, CO2 fixation was found to be insufficient to compensate for respiration in adult plants. Fungal diversity was assessed by morphological and molecular methods in L. abortivum as well as in the related rare species Limodorum trabutianum and Limodorum brulloi. Phylogenetic analyses of the fungal internal transcribed spacer (ITS) sequences, obtained from root samples of about 80 plants, revealed a tendency to associate predominantly with fungal symbionts of the genus Russula. Based on sequence similarities with known species, most root endophytes could be ascribed to the species complex encompassing Russula delica, Russula chloroides, and Russula brevipes. Few sequences clustered in separate groups nested within Russula, a genus of ectomycorrhizal fungi. The morphotypes of ectomycorrhizal root tips of surrounding trees yielded sequences similar or identical to those obtained from L. abortivum. These results demonstrate that Limodorum species with inefficient photosynthesis specifically associate with ectomycorrhizal fungi, and appear to have adopted a nutrition strategy similar to that known from achlorophyllous orchids.
Antigenic variation in Babesia bovis occurs through segmental gene conversion of the ves multigene family, within a bidirectional locus of active transcription
Authors: Al‐Khedery Basima , Allred David R.
Published: December 2005

Antigenic variation in Babesia bovis is one aspect of a multifunctional virulence/survival mechanism mediated by the heterodimeric variant erythrocyte surface antigen 1 (VESA1) protein that also involves endothelial cytoadhesion with sequestration of mature parasitized erythrocytes. The ves1α gene encoding the VESA1a subunit was previously identified. In this study, we present the unique organization of the genomic locus from which ves1α is transcribed, and identify a novel branch of the ves multigene family, ves1β. These genes are found together, closely juxtaposed and divergently oriented, at the locus of active transcription. We provide compelling evidence that variation of both transcriptionally active genes occurs through a mechanism of segmental gene conversion involving sequence donor genes of similar organization. These results also suggest the possibility of epigenetic regulation through in situ switching among gene loci, further expanding the potential repertoire of variant proteins.
Growth inhibition mediated by excess negative supercoiling: the interplay between transcription elongation, R‐loop formation and DNA topology
Authors: Drolet Marc
Published: December 2005

It has been known for a long time that supercoiling can affect gene expression at the level of promoter activity. Moreover, the results of a genome‐wide analysis have recently led to the proposal that supercoiling could play a role in the regulation of gene expression at this level by acting as a second messenger, relaying environmental signals to regulatory networks. Although evidence is lacking for a regulatory role of supercoiling following transcription initiation, recent results from both yeast and bacteria suggest that the effect of supercoiling on gene expression can be considerably more dramatic after this initiation step. Transcription‐induced supercoiling and its associated R‐loops seem to be involved in this effect. In this context, one major function of topoisomerases would be to prevent the generation of excess negative supercoiling by transcription elongation, to inhibit R‐loop formation and allow gene expression. This function would be especially evident when substantial and rapid gene expression is required for stress resistance, and it may explain, at least in part, why topoisomerase I synthesis is directed from stress‐induced promoters in Escherichia coli. Growth inhibition mediated by excess negative supercoiling might be related to this interplay between transcription elongation and supercoiling.
Antigenic variation by protozoan parasites: insights from Babesia bovis
Authors: Dzikowski Ron , Deitsch Kirk
Published: December 2005

Antigenic variation of surface membrane proteins by protozoan parasites enables these pathogenic organisms to avoid host immune responses and thus perpetuate long‐term infections. Babesia bovis, the causative agent of severe babesiosis in cattle, was previously shown to undergo antigenic variation through modifications to its primary surface antigen, a protein called VESA1. In this issue, Al‐Khedery and Allred provide a detailed description of the genes that encode VESA1 and present convincing evidence for progressive, segmental gene conversion in the generation of variant forms of this surface antigen.
HvMCB1, a R1MYB transcription factor from barley with antagonistic regulatory functions during seed development and germination
Authors: Rubio‐Somoza Ignacio , Martinez Manuel , Diaz Isabel , Carbonero Pilar
Published: December 2005

The functional analysis of hydrolase gene promoters induced by gibberellin (GA) in barley aleurone cells upon germination has identified a tripartite GA‐response complex (GARC) containing a 5′‐TATCCAC‐3′ box as well as the GA‐responsive element (GARE) recognized by GAMYB and the pyrimidine box interacting with the DOF transcription factors BPBF and SAD. We show here that the MCB1 gene encoding a R1MYB protein binds to the 5′‐TATCCAC‐3′ (GATA core) box in vitro and is a transcriptional repressor of a GA‐induced amylase (Amy6.4) promoter in bombarded aleurone layers. Northern blot and mRNA in situ hybridization analyses showed that the MCB1 transcripts accumulate in the aleurone cells upon germination, as well as in endosperm tissues during seed development. The HvMCB1 protein expressed in bacteria binds in a specific manner to a 27‐mer oligonucleotide containing the 5′‐TATCCAC‐3′ sequence, derived from the promoter region of the Amy6.4 gene. Accumulation of the MCB1 transcript diminished in response to external GA incubation in aleurone cells, and in transient expression experiments HvMCB1 repressed transcription of the Amy6.4 promoter in GA‐treated aleurone layers and reversed the GAMYB‐mediated activation of this amylase promoter. In contrast, during endosperm maturation HvMCB1 acted as a transcription activator of the seed‐specific Itr1 gene promoter through binding to a 5′‐GATAAGATA‐3′ box.
An active DNA transposon nDart causing leaf variegation and mutable dwarfism and its related elements in rice
Authors: Tsugane Kazuo , Maekawa Masahiko , Takagi Kyoko , Takahara Hiroyuki , Qian Qian , Eun Chang‐Ho , Iida Shigeru
Published: December 2005

While characterized mutable alleles caused by DNA transposons have been abundant in maize since the discovery of Dissociation conferring variegation by Barbara McClintock, only a few mutable alleles have been described in rice even though the rice genome contains various transposons. Here, we show that a spontaneous mutable virescent allele, pyl‐v, is caused by the disruption of the nuclear‐coded essential chloroplast protease gene, OsClpP5, due to insertion of a 607‐bp non‐autonomous DNA transposon, non‐autonomous DNA‐based active rice transposon one (nDart1), belonging to the hAT superfamily. The transposition of nDart1 can be induced by crossing with a line containing an autonomous element, aDart, and stabilized by segregating out of aDart. We also identified a novel mutable dwarf allele thl‐m caused by an insertion of nDart1. The japonica cultivar Nipponbare carries no aDart, although it contains epigenetically silenced Dart element(s), which can be activated by 5‐azacytidine. Nipponbare bears four subgroups of about 3.6‐kb Dart‐like sequences, three of which contain potential transposase genes, and around 3.6‐kb elements without an apparent transposase gene, as well as three subgroups of about 0.6‐kb nDart1‐related elements that are all internal deletions of the Dart‐like sequences. Both nDart1 and 3.6‐kb Dart‐like elements were also present in indica varieties 93‐11 and Kasalath. nDart1 appears to be the most active mutagen among nDart1‐related elements contributing to generating natural variations. A candidate for an autonomous element, aDart, and a possible application of nDart1 for transposon tagging are discussed.
The Gross Anatomy of the Male Reproductive System of a Neotropical Rodent: the Agouti (Dasyprota leporina)
Authors: Mollineau W. , Adogwa A. , Jasper N. , Young K. , Garcia G.
Published: December 2005

The literature available on the agouti (Dasyprocta leporina) is very limited. The agouti is a Neotropical rodent found in Trinidad and Tobago, Central and South America. This study focuses on one of the many unexplored areas relating to the species, the male reproductive system. The results showed that the mean testicular length, diameter and weight was 3.67 ± 0.12 cm, 1.67 ± 0.04 cm and 5.03 ± 0.52 g respectively. The paired testes and epididymis were found in contact with the abdominal muscles within scrotal pouches, which are evaginations of the caudoventral abdominal wall. The caput epididymis is enclosed by a fat body. The ductus deferens has a mean length and diameter of 10.98 ± 0.40 cm and 0.14 ± 0.01 cm respectively. At the urethral end of the ductus deferens the diameter of each duct expends to form the ampulla. The mean diameter of each of the ampulla was 0.25 cm. The accessory sex organs of the male agouti (D. leporina) include the vesicular glands, the coagulating glands, the prostate glands and the bulbourethral glands. The penis of the agouti is U‐shaped with a mean length of 9.90 ± 0.43 cm. The glans penis contains an os penis, a pair of lateral penile cartilages and paired ventral keratinaceous styles.
Influences on the early training of nurses in Denmark
Authors: Nielsen Michael
Published: December 2005

This paper attempts to uncover some of the factors that may have influenced the choice of model for the systematic training of nurses in Denmark. From a historical analysis of selected historical literature, nursing magazines, and archival documents, three themes emerge: the interest from (and of) the medical profession, the strategy on nurse training of the Danish Nurses’ Organization, and the societal context of the time. Despite there being a Deaconess Institution in Copenhagen from 1863, it was ultimately the Nightingale model that formed the basis for the training programme. Findings suggest that the Nightingale influence within the medical establishment and among leaders in Danish nursing played a vital role in this choice. As well, the Danish Nurses’ Organization actively promoted their preferred 3‐year training model, which had strong similarities to the Nightingale model. Changes in family and social life after the 1864 defeat in the Prussian war fostered a growing demand for the liberalization of women's rights and a need for increased professionalization in the nursing and caring function.
Nursing and care for the aged in Victoria: 1950s to 1970s
Authors: Hunter Cecily
Published: December 2005

In the state of Victoria, Australia in the late 1950s and early 1960s, restorative treatment was introduced into the state‐subsidised benevolent homes, and they were reclassified as geriatric hospitals. In the process, the nursing care of incapacitated old people was identified in terms of particular skills and knowledge, and specific forms of training were established for nurses at two levels of training: nurses’ aides and supervisory nurses with a postbasic qualification. These institutional changes were complemented by the introduction of a nursing role into the body responsible for overseeing care for the aged in Victoria. Little was made of this opportunity to establish a leading role for nurses in the field of care for the aged. However, this episode raises fertile questions for further research into the development of nursing in Australia, as a set of practices divided along the lines of acute and chronic illness.
Why is the moon white?
Authors: Sivaprasad Sobha , Saleh George M
Published: December 2005

Abstract

Land's Retinex theory is used to explain why we perceive the colour of the moon as white. The lightness values of coloured areas are computed and the energy at the particular area (moon) is compared with the surrounding area (space‐vacuum).
Visual experience during phacoemulsification under topical anaesthesia: a nationwide survey of Singapore ophthalmologists
Authors: Leo Seo‐Wei , Lee Llewellyn Kuan‐Ming , Au Eong Kah‐Guan
Published: December 2005

Abstract

Background:  All patients undergoing phacoemulsification under topical anaesthesia experience a variety of visual sensations that may be frightening in a small proportion of patients. This study evaluates Singapore ophthalmologists’ knowledge and practices regarding patients’ visual experience during phacoemulsification under topical anaesthesia.

Methods:  A nationwide survey of all ophthalmologists in Singapore who had performed at least one cataract surgery within the last year was carried out. Questions regarding patients’ experience were asked. Surgeons were also asked about patients’ fear during surgery, usefulness of preoperative counselling and feedback from patients postoperatively.

Results:  Of 105 ophthalmologists 89 responded, of which 44 performed phacoemulsification under topical anaesthesia. The percentage of respondents who thought that the patients experienced the various visual sensations were: no light perception (4.6%), light perception (97.7%), one or more colours (95.5%), flashes of light (77.3%), movements (90.9%), instruments (61.4%), surgeon's hands/fingers (56.8%), surgeon (47.7%) and change in brightness of light (90.9%). Although 52.3% of surgeons believed that patients may be frightened by their visual experience and 50.0% felt that preoperative counselling would be useful in reducing such fear, only 11.4% routinely offered preoperative counselling and 18.2% counselled their patients occasionally. In total, 50.0% ophthalmologists had patients who reported to them that they could see during surgery, whereas 20.5% had been told by patients that they were frightened by the visual experience.

Conclusion:  Despite the awareness of patients’ visual experience and the belief that preoperative counselling may be useful, most ophthalmologists do not counsel their patients preoperatively.
Cicatricial entropion and trichiasis in an urban Australian population
Authors: Shiu Michael , McNab Alan A
Published: December 2005

Abstract

Background:  Cicatricial entropion and trichiasis may be caused by a variety of diseases, of which trachomatous entropion is the commonest worldwide. The spectrum of disease in the authors’ community is quite different. The purpose of this study was to establish the aetiology of entropion and trichiasis in patients referred to a Melbourne‐based subspecialty oculoplastics practice, excluding epiblepharon, congenital entropion and involutional entropion, and to compare the final diagnosis with the referring diagnosis.

Methods:  All records of patients with cicatricial entropion and trichiasis presenting to the practice of one of the authors over the period 1990–2000 were analysed. Demographic data, referring diagnosis and final diagnosis were tabulated.

Results:  The commonest final diagnosis was ocular cicatricial pemphigoid. In only a small proportion of cases was this diagnosis considered by the referring practitioners. In addition, two cases of undiagnosed conjunctival neoplasia presented with entropion and trichiasis.

Conclusion:  In all patients with entropion and trichiasis, a careful history and examination should be obtained and appropriate investigations performed to try and establish a firm diagnosis.
Extensive submacular haemorrhage in polypoidal choroidal vasculopathy managed by sequential gas displacement and photodynamic therapy: a pilot study of one‐year follow up
Authors: Chan Wai‐Man , Liu David TL , Lai Timothy YY , Li Haitao , Tong Jian‐Ping , Lam Dennis SC
Published: December 2005

Abstract

Background:  Polypoidal choroidal vasculopathy (PCV) with peculiar vascular lesions presents frequently as recurrent submacular haemorrhage. The best treatment is still not certain. It is the authors’ objective to evaluate the 1‐year safety and efficacy of photodynamic therapy (PDT) using verteporfin for persistent macular PCV after pneumatic displacement of the massive submacular haemorrhage with intravitreal perfluoropropane (C3F8).

Methods:  A prospective, non‐comparative, interventional case series on patients with extensive and thick submacular haemorrhage secondary to PCV, which was displaced pneumatically with intravitreal pure 0.4 ml C3F8. Fluorescein angiography and indocyanine green angiography were repeated 1–2 weeks later to delineate any persistent active leaking polypoidal lesions, which were then treated with PDT. Retreatment might be considered in each follow up at every 3 months.

Results:  Six eyes of six patients with the mean age of 53.6 years had been recruited and completed 1‐year follow up. The mean baseline Snellen equivalent best‐corrected visual acuity (BCVA) was 6/92 and the mean final BCVA at 1 year was 6/17. The mean improvement in logMAR BCVA after the sequential treatments was seven lines (range +3 to +19 lines) (Wilcoxon signed‐ranks test, P = 0.03). All patients had at least moderate visual gains. No patient suffered serious complications from PDT.

Conclusions:  This first report on combined treatment with intravitreal gas injection and sequential PDT on PCV seems to be a well‐tolerated option. Further comparative studies with larger sample size and longer follow up are warranted.
D‐TAT transporter as an ocular peptide delivery system
Authors: Schorderet Daniel F , Manzi Violaine d’Allèves , Canola Kriss , Bonny Christophe , Arsenijevic Yvan , Munier Francis L , Maurer Fabienne
Published: December 2005

Abstract

Background:  Future treatment for genetic diseases may involve the replacement of malfunctioning genes through virus‐mediated gene therapy. However, this approach is plagued with many problems, both ethical and scientific. Therefore, alternative treatments based on new molecules may represent a safer option. Molecular treatment of many eye diseases will need to bring active molecules into the photoreceptors. Recently, the trans‐activator protein (TAT) human immunodeficiency virus type 1 (HIV‐1) transcriptional factor has proven to be effective in transporting molecules across cellular membranes. The half‐life of these molecules does not exceed 48 hours. The potential use of the retro‐inverso form of the TAT (D‐TAT) peptide, the protein transducing domain of the HIV‐1 transcriptional factor, as a molecular transporter was investigated.

Methods:  FITC‐labelled D‐TAT (D‐TAT FITC) was applied to the 661W murine photoreceptor cell line in culture. The labelled peptide was also injected into the vitreous body or the subretinal space of adult mice. Cells and cryosections of eyes were analysed under fluorescence microscopy at various time points after peptide treatment. Coimmunostaining with various antibodies was performed in order to characterize the transduces cells.

Results:  D‐TAT was effective in transducing photoreceptor cells in culture. Transduction of D‐TAT FITC was also effective when injected into the vitreous or subretinal space and was observed for a longer period of time than L‐TAT FITC.

Conclusions:  The retro‐inverso form of the TAT sequence is effective in transducing cells from various compartments of the eye. After 14 days, the D‐TAT FITC was clearly visible in the retina whereas L‐TAT FITC had almost disappeared. The D‐TAT peptide represents an interesting molecular transporter that, when coupled to a specific effector, may have potential therapeutic future, especially when a long‐lasting action is needed.
Herpes zoster ophthalmicus: presenting as giant‐cell arteritis
Authors: De Castro Luis E Fernández , Petersen Aaron M , Givre Syndee J , Solomon Kerry D , Vroman David T
Published: December 2005

Abstract

A 74‐year‐old woman was referred to the authors’ clinic with a 1‐week suspicion of giant‐cell arteritis. Uncomplicated, bilateral temporal artery biopsies were performed 3 days after admission for therapy. Four hours after the procedure she developed vesicular lesions of the face compatible with herpes zoster ophthalmicus. The temporal artery biopsy revealed perineural lymphocytic aggregation. Both giant‐cell arteritis and herpes zoster ophthalmicus form part of the differential diagnosis in elderly patients with headache. In such cases, clues from a temporal artery biopsy may aid in diagnosis of herpes zoster. In addition, the patient in this case developed the rash 10 days after onset of symptoms, which is rare as the average time from onset of symptoms to rash in zoster is 3–5 days.
Pleomorphic adenoma of the lacrimal gland in a nine‐year‐old child
Authors: Chen Ching‐Long , Chen Chiao‐Hong , Tai Ming‐Cheng , Lu Da‐Wen , Cheng Mieng‐Fang , Li Wei‐Hua
Published: December 2005

Abstract

A case of a 9‐year‐old child with pleomorphic adenoma of the lacrimal gland is described. This tumour is usually found in adults; cases younger than 10 years of age have proved to be extremely rare. Because of its age distribution, pleomorphic adenoma of the lacrimal gland is usually overlooked as a possible cause of unilateral proptosis in children. Also, the history of disease provided by the family may be incorrect, possibly leading to misdiagnosis by the ophthalmologist.
Traumatic cataract and intralenticular foreign body
Authors: Kumar Anupma , Kumar Vinod , Dapling Robert B
Published: December 2005

Abstract

Traumatic cataracts resulting from penetrating injuries occur most frequently from projectile metallic foreign bodies. The majority of intraocular foreign bodies cause sight‐threatening damage including traumatic cataract in up to 25% of the cases. A case of traumatic cataract and retained intralenticular foreign body that was removed successfully with phacoemulsification and foldable intraocular lens implantation in the capsular bag is described. This case report highlights the benefit in planning surgical management as a two‐staged procedure after appropriate investigations.
Orbital foreign body masquerading as conjunctival melanoma 60 years after injury
Authors: Gelston Christopher D , Mandava Naresh , Durairaj Vikram D
Published: December 2005

Abstract

A 74‐year‐old man presented with a 6‐month history of a pigmented conjunctival lesion on his left eye. The lesion was initially suspicious for conjunctival melanoma. The patient admitted to a remote history of trauma from a airgun pellet over 60 years ago. Anterior examination revealed a 6 × 6 mm pigmented left conjunctival lesion and B‐scan of the lesion was suggestive of a retained orbital foreign body. The lesion was removed through a transcaruncular medial orbitomy and pathology showed a retained orbital foreign body. A newly pigmented conjunctival lesion although initially concerning for melanoma represented a retained orbital body that surfaced many years after the initial orbital trauma.
Asymptomatic choroidal granulomas in common variable immunodeficiency
Authors: Kashani Shaharm , Gazzard Gus , Jolles Stephen , Larkin Genevieve
Published: December 2005

Abstract

Common variable immunodeficiency disease represents the most common cause of significant antibody deficiency in adults. It is a heterogeneous group of disorders that can be sporadic or familial with various modes of inheritance with defects in B‐cell function, regulatory T‐cells and macrophage function all being reported. Herein a case of asymptomatic bilateral choroidal granulomatous disease in a 27‐year‐old man with common variable immunodeficiency disease is described.
Compartmentalization of calcium entry pathways in mouse rods
Authors: Krizaj David
Published: December 2005

Photoreceptor metabolism, gene expression and synaptic transmission take place in a highly polarized structure consisting of the ellipsoid, subellipsoid, cell body and synaptic terminal regions. Although calcium, a key second messenger, regulates cellular functions throughout the photoreceptor, the molecular mechanisms underlying local region‐specific action of Ca2+ in photoreceptors are poorly understood. I have investigated the compartmentalization of voltage‐dependent and independent Ca2+ channels in mouse photoreceptors. Transient receptor potential channels isoform 6 (TRPC6), a putative store‐operated Ca2+ channel, was selectively localized to the cell body of rods. By contrast, voltage‐operated Ca2+ channels were expressed in the synaptic terminal and in the ellipsoid/subellipsoid regions. Likewise, Ca2+ store transporters and channels were strongly associated with the subellipsoid region. A moderate TRPC6 signal was observed in cell bodies of bipolar, amacrine and ganglion cells, but was absent from both plexiform layers. These results suggest that Ca2+ entry mechanisms in mammalian photoreceptors and bipolar cells are highly compartmentalized, consistent with local, region‐specific activation of Ca2+‐dependent processes.
Effects of extracellular δ‐aminolaevulinic acid on sodium currents in acutely isolated rat hippocampal CA1 neurons
Authors: Wang Lang , Yan Dan , Gu Yan , Sun Li‐Guang , Ruan Di‐Yun
Published: December 2005

The effects of δ‐aminolaevulinic acid (ALA) on voltage‐gated sodium channel (VGSC) currents (INa) in acutely isolated hippocampal CA1 neurons from 10‐ to 12‐day‐old Wistar rats were examined by using the whole‐cell patch‐clamp technique under voltage‐clamp conditions. ALA from 0.01 µm to 20 µm was applied to the recorded neurons. Low concentrations of ALA (0.01–1.0 µm) increased INa amplitude, whereas high concentrations of ALA (5.0–20.0 µm) decreased it. The average INa amplitude reached a maximum of 117.4 ± 3.9% (n = 9, P < 0.05) with 0.1 µm ALA, and decreased to 78.1 ± 3.8% (n = 13, P < 0.05) with 10 µm ALA. ALA shifted the steady‐state activation and inactivation curves of INa in the hyperpolarizing direction with different V0.5, suggesting that ALA could depress the opening threshold of the voltage‐gated sodium channel (VGSC) and thus increase the excitability of neurons through facilitating the opening of VGSC. The time course of recovery from inactivation was significantly prolonged at both low and high concentrations of ALA, whereas either low or high concentrations of ALA had no significant effect on the attenuation of INa during stimulation at 5 Hz, indicating that the effect of ALA on VGSC is state‐independent. Furthermore, we found that application of ascorbic acid, which blocks pro‐oxidative effects in neurons, could prevent the increase of INa amplitude at low concentrations of ALA. Baclofen, an agonist of GABAb receptors, induced some similar effects to ALA on VGSC, whereas bicuculline, an antagonist of GABAa receptors, could not prevent ALA‐induced effects on VGSC. These results suggested that ALA regulated VGSC mainly through its pro‐oxidative effects and GABAb receptor‐mediated effects.
Nestin‐expressing cells and their relationship to mitotically active cells in the subventricular zones of the adult rat
Authors: Ernst Carl , Christie Brian R.
Published: December 2005

Nestin is a protein that is thought to be expressed in neural stem cells; however, there is a paucity of data on nestin expression in vivo, and little is known of the relationship between nestin and mitotically active cell populations in the subventricular zones (SVZ). In this study, the subventricular zone of the third ventricle contained a high proportion of cells that expressed nestin, while there were significantly fewer cells that expressed nestin in the SVZ of the lateral ventricles. In contrast, bromodeoxyuridine (BrdU) immunoreactivity was the diametric opposite, being higher in the SVZ of the lateral ventricle than in the SVZ of the third ventricle. Morphological and anatomical evidence suggests that nestin‐expressing cells in these two areas may be different cell types. In a separate set of experiments, an acute localized lesion was induced adjacent to one of the ventricles. While the number of BrdU cells and Ki‐67 cells in the SVZs increased with this manipulation, the number of nestin‐expressing cells did not change significantly. These data indicate that the expression of nestin does not correlate with mitotic activity in cells of the SVZs under either normal or inflammatory conditions. It is hypothesized that nestin‐expressing cells in the SVZs may give way to transit amplifying cells that in turn give way to immature neurons or glia. These transit‐amplifying cells may have a much higher rate of mitosis than nestin‐positive cells and may react to neural damage by increasing their rate of proliferation.
Calcium concentration changes during sensory transduction in spider mechanoreceptor neurons
Authors: Höger Ulli , Torkkeli Päivi H. , French Andrew S.
Published: December 2005

Most mechanoreceptor neurons encode mechanical signals into action potential trains within the same cell. Evidence suggests that intracellular calcium ion concentration, [Ca2+], increases during mechanotransduction, either by direct entry through mechanically activated channels or indirectly through voltage‐activated calcium channels. However, little is known about the amounts of calcium involved or its roles in mechanotransduction. We estimated [Ca2+] in mechanoreceptor neurons of the spider, Cupiennius salei, during mechanical stimulation using Oregon Green BAPTA‐1, and a single‐compartment model of [Ca2+] as a function of action potential firing rate. Resting [Ca2+] was approximately 400 nm and increased to up to 2 µm at 30 action potentials/s. Similar levels of resting and stimulated [Ca2+] were obtained in the cell soma, axon and two parts of the sensory dendrite, including the region immediately adjacent to the site of sensory transduction. The time constant of rise and fall of [Ca2+] was 1–5 s in the dendrite and axon, but up to 15 s in the soma. Calcium elevation was dependent on action potentials and could not be induced by the receptor potential alone. Blockade of voltage‐activated calcium channels by nickel ions prevented calcium increase, but thapsigargin, which empties intracellular calcium stores, had no effect. Estimates of calcium entry per action potential from fluorescence changes agreed approximately with estimates based on action potential voltage–time profile and previous reports of calcium channel properties. This first report of calcium levels during transduction in spiking mechanoreceptors suggests that calcium signaling plays important roles in primary somatosensory neurons.
Direct pyrogenic input from prostaglandin EP3 receptor‐expressing preoptic neurons to the dorsomedial hypothalamus
Authors: Nakamura Yoshiko , Nakamura Kazuhiro , Matsumura Kiyoshi , Kobayashi Shigeo , Kaneko Takeshi , Morrison Shaun F.
Published: December 2005

Fever is induced by a neuronal mechanism in the brain. Prostaglandin (PG) E2 acts as a pyrogenic mediator in the preoptic area (POA) probably through the EP3 subtype of PGE receptor expressed on GABAergic neurons, and this PGE2 action triggers neuronal pathways for sympathetic thermogenesis in peripheral effector organs including brown adipose tissue (BAT). To explore pyrogenic efferent pathways from the POA, we determined projection targets of EP3 receptor‐expressing POA neurons with a special focus on rat hypothalamic regions including the dorsomedial hypothalamic nucleus (DMH), which is known as a center for autonomic responses to stress. Among injections of cholera toxin b‐subunit (CTb), a retrograde tracer, into hypothalamic regions at the rostrocaudal level of the DMH, injections into the DMH, lateral hypothalamic area (LH) and dorsal hypothalamic area (DH) resulted in EP3 receptor immunolabelling in substantial populations of CTb‐labeled neurons in the POA. Bilateral microinjections of muscimol, a GABAA receptor agonist, into the DMH and a ventral region of the DH, but not those into the LH, inhibited thermogenic (BAT sympathetic nerve activity, BAT temperature, core body temperature and expired CO2) and cardiovascular (arterial pressure and heart rate) responses to an intra‐POA PGE2 microinjection. Further immunohistochemical observations revealed a close association of POA‐derived GABAergic axon swellings with DMH neurons projecting to the medullary raphe regions where sympathetic premotor neurons for febrile and thermoregulatory responses are localized. These results suggest that a direct projection of EP3 receptor‐expressing POA neurons to the DMH/DH region mediates febrile responses via a GABAergic mechanism.
Effector‐independent voluntary timing: behavioural and neuroimaging evidence
Authors: Bengtsson Sara L. , Ehrsson H. Henrik , Forssberg Hans , Ullén Fredrik
Published: December 2005

We investigated effector‐independent aspects of voluntary motor timing, using behavioural measurements and functional magnetic resonance imaging. Two types of temporal pattern were investigated; one isochronous, the other a metric, rhythmic sequence of six temporal intervals. Each pattern was performed using tapping movements with the left or right index fingers, or rhythmic speech on one syllable. Deviations from the ideal temporal pattern in the rhythmic sequence tasks were consistent between the three different effectors, within subjects. This suggests that the same representation of the rhythm was used to time the movements with all effectors. To reveal brain regions involved in such effector‐independent timing, we localized the overlap in brain activity when the rhythmic sequence was performed with the different effectors. Activity was found in the mesial and lateral premotor cortices, posterior and anterior regions of the superior temporal gyrus and the inferior frontal cortex. Subcortical activations were in the left globus pallidus, the vermis and bilaterally in the cerebellar hemispheres (lobule VI) and the thalamus. The overlap in activity between the isochronous tasks included the same set of brain regions, except for the basal ganglia and the thalamus. Rhythmic sequences had significantly higher activity in mesial premotor cortex, the left superior temporal gyrus and the cerebellum, than had isochronous movements. These findings reveal a set of brain regions likely to be involved in effector‐independent representations of temporal patterns in voluntary motor timing. A subset of these regions plays important roles for the organization of rhythmic sequences of several intervals.