bluuebunny/crossref_metadata_2025 huggingface dataset:
Auditory Responses in Cochlear Implant Users With and Without GJB2 Deafness
Authors: Propst Evan Jon , Papsin Blake C. , Stockley Tracy L. , Harrison Robert V. , Gordon Karen A.
Published: February 2006

Objective/Hypothesis: It is reasonable to suppose that the pattern of sensorineural damage along the length of the cochlea depends on the etiology of a hearing loss (HL). In GJB2‐related deafness, we hypothesize that gap junction deficits are uniformly distributed and will result in similar damage along the length of the cochlea as compared with non‐GJB2 subjects. We assessed this by measuring patterns of neural activity and hearing from apical versus basal cochlear implant electrode regions.

Study Design: This was a prospective, blind, controlled study.

Methods: Blood from 301 pediatric cochlear implant users was analyzed for mutations in GJB2 by direct sequencing. After exclusion of patients with monoallelic GJB2 mutations, associated syndromes, or risk factors for HL that were not congenital, 39 children with biallelic GJB2 mutations and 58 without GJB2 mutations were evaluated. Hearing was measured before implantation at frequencies ranging from 250 Hz to 8 kHz. After implantation, neural activity at the apical and basal ends of the implanted array was measured using electrically evoked compound action potentials of the auditory nerve (ECAPs) and evoked stapedius reflexes (ESRs).

Results: GJB2 and non‐GJB2 groups were not significantly different with respect to sex, age at implantation, duration of auditory deprivation, hearing aid use, duration of aided hearing, ear implanted, implant model, or depth of insertion (P > .05). Children with GJB2‐related HL had greater similarities between low‐ and high‐frequency residual hearing and between neural activity electrically evoked at apical and basal regions of the cochlea as compared with children with non‐GJB2‐related HL who demonstrated larger deficits in basal regions.

Conclusion: Results suggest more consistent spiral ganglion survival along the length of the cochlea in GJB2‐related HL as compared with non‐GJB2‐related HL, which appears to involve a decreasing gradient of spiral ganglion survival from the apex to the base of the cochlea. Our findings support our premise that in GJB2‐related HL, dysfunction of gap junctions likely occurs to a similar degree in the apical and basal regions of the cochlea. This knowledge might be used to customize implantable devices for patients with HL in the future.
Scanning Electron Microscopic Study of the Nasolabial Cyst: Its Clinical and Embryological Implications
Authors: Su Chih‐Ying , Huang Hung‐Tu , Liu Ho‐Yih , Huang Chao‐Cheng , Chien Chih‐Yen
Published: February 2006

Objective: Nasolabial cyst is an uncommon midfacial cyst. It is considered to be a developmental anomaly arising from the rest of nasal respiratory epithelium. Although the cyst is a well‐recognized entity, there remains some confusion of its origin, cell types, and ultrastructures. Based on the routine light microscopic study, some authors reported the epithelial cells of the inner lining of the nasolabial cyst were ciliated; some others reported they were nonciliated. To clarify this, a scanning electron microscopic study is needed.

Study Design: This was a prospective clinical series.

Methods: A transnasal marsupialization method was used to treat 10 patients with nasolabial cyst. With patients under local anesthesia, the roof of the cyst wall and a disk of nearby nasal mucosa were excised together with a sickle knife and scissors. Surgical specimens were dissected and processed for scanning electron microscopy and histochemistry. Patients were followed up for 8 to 65 months.

Results: Marsupialization of cysts was successfully performed on all patients. Electron microscopically, the inner surface of the nasolabial cysts in all the cases was lined with nonciliated columnar epithelium consisting chiefly of goblet cells and basal cells. It is suggested that goblet cells contributed to clear, thin, and yellow mucus present in the cyst lumen. Instead of cilia, these epithelial cell surfaces were equipped with numerous short, globular, or irregular microvilli. Apical cytoplasm of adjacent cells did not tightly adhere to each other. Instead, microsulci of 1 to 3 μm in width formed between cells. Cytoplasmic processes from the lateral border spanned the microsulcus and contacted with those from neighboring cells.

Conclusion: The novel study has proved that the lining epithelium on the inner surface of the nasolabial cyst is columnar epithelium that chiefly consisted of two types of cells: goblet cells and basal cells. Not present were ciliated cells that were essential in the other portion of the respiratory tract. Numerous microvilli, instead of cilia, covered the inner lining of the nasolabial cyst, probably as a result of lacking the stimulation of air in ventilation as that on the other portion of the respiratory tract. The cilia of the epithelium were ill developed.
Prediction of Auditory Brainstem Reflex Screening Referrals in High‐Risk Infants
Authors: Lieu Judith E. Cho , Champion Gretchen
Published: February 2006

Objectives/Hypothesis: The objectives of this study were to 1) quantify the relative importance of established risk factors for congenital hearing loss (HL), 2) identify other risk factors for congenital HL, and 3) create a prognostic system that can predict the chance of an infant having HL.

Methods: The authors conducted a retrospective cohort study with validation of a prognostic system. The authors used a medical record review on 1,863 infants admitted to level II and level III nurseries who underwent auditory brainstem reflex (ABR) hearing screening from 1998 to 1999 (derivation cohort). The primary outcome was hearing screening referral (i.e., hearing screening failure) classified as mild to moderate, moderate to severe, and severe to profound loss. To validate the prognostic system, a medical record review of a separate cohort of 437 infants admitted to a level III nursery who underwent ABR hearing screening in 2002 (validation cohort) was performed.

Results: In the derivation cohort, 1,513 infants (81%) passed the ABR screen at 30 dB, 77 (4%) had a unilateral referral, 243 (13%) had a bilateral referral, and 30 (1.6%) did not have a complete screening. In multivariable analysis, the following risk factors were clinically and statistically significant: craniofacial abnormalities, cytomegalovirus infection, bronchopulmonary dysplasia (BPD), maternal ethanol use, syndromes, hydrocephalus, and hyperbilirubinemia.

Conclusions: Our results reaffirm the importance of several established risk factors for congenital HL, but suggest that BPD is an important predictor in high‐risk populations. Whether these risk factors are causal or merely associated in congenital HL remains to be determined.
Ambiguous Figures and the Content of Experience
Authors: Macpherson Fiona
Published: February 2006

Representationalism is the position that the phenomenal character of an experience is either identical with, or supervenes on, the content of that experience. Many representationalists hold that the relevant content of experience is nonconceptual. I propose a counter‐example to this form of representationalism that arises from the phenomenon of Gestalt switching, which occurs when viewing ambiguous figures. First, I argue that one does not need to appeal to the conceptual content of experience or to judgements to account for Gestalt switching. I then argue that experiences of certain ambiguous figures are problematic because they have different phenomenal characters but that no difference in the nonconceptual content of these experiences can be identified. I consider three solutions to this problem that have been proposed by both philosophers and psychologists and conclude that none can account for all the ambiguous figures that pose the problem. I conclude that the onus is on representationalists to specify the relevant difference in content or to abandon their position.
Co‐inheritance of α+‐thalassaemia and sickle trait results in specific effects on haematological parameters
Authors: Wambua Sammy , Mwacharo Jedidah , Uyoga Sophie , Macharia Alexander , Williams Thomas N.
Published: February 2006

Both the sickle cell trait (HbAS) and α+‐thalassaemia are common in many tropical areas. While their individual haematological effects are well described, few studies describe their effects when inherited together. We present data from the Kenyan coast, which suggest that HbAS and α+‐thalassaemia may interact to produce specific effects on haematological parameters. Overall, the difference in Hb concentrations between non‐thalassaemics (αα/αα) and α+‐thalassaemia homozygotes (−α/−α) was greater in non‐HbAS (HbAA) (0·63 g/dl) than in HbAS children (0·25 g/dl). HbAS also ameliorated both the reduced mean cell volume and mean cell haemoglobin normally associated with the −α/−α genotype. Potential mechanisms and implications are discussed.
DNA bending in the Sin recombination synapse: functional replacement of HU by IHF
Authors: Rowland Sally‐J. , Boocock Martin R. , Stark W. Marshall
Published: February 2006

The serine recombinase Sin requires a non‐specific DNA‐bending protein such as Hbsu for activity at its recombination siteresH. Hbsu, and Sin subunits bound at site II ofresH, together regulate recombination, ensuring selectivity for directly repeatedresHsites by specifying assembly of an intertwined synapse. To investigate the role of the DNA‐bending protein in defining the architecture of the synapse, we constructed a chimaeric recombination site (resF) which allows Hbsu to be substituted by IHF, binding specifically between site I (the crossover site) and site II. Two Sin dimers and one IHF dimer can bind together to the closely adjoining sites inresF, forming folded complexes. The precise position of the IHF site within the site I–site II spacer determines the conformation of these complexes, and also the reactivity of theresFsites in recombination assays. The data suggest that a sharp bend with a specific geometry is required in the spacer DNA, to bring the Sin dimers at sites I and II together in the correct relative orientation for synapse assembly and regulation, consistent with our model for a highly condensed synapse in which Hbsu/IHF has a purely architectural function.
Sigma factor selectivity in Borrelia burgdorferi: RpoS recognition of the ospE/ospF/elp promoters is dependent on the sequence of the −10 region
Authors: Eggers Christian H. , Caimano Melissa J. , Radolf Justin D.
Published: February 2006

Members of the ospE/ospF/elp lipoprotein gene families of Borrelia burgdorferi, the Lyme disease agent, are transcriptionally upregulated in response to the influx of blood into the midgut of an infected tick. We recently have demonstrated that despite the high degree of similarity between the promoters of the ospF (PospF) and ospE (PospE) genes of B. burgdorferi strain 297, the differential expression of ospF is RpoS‐dependent, while ospE is controlled by σ70. Herein we used wild‐type and RpoS‐deficient strains of B. burgdorferi and Escherichia coli to analyse transcriptional reporters consisting of a green fluorescent protein (gfp) gene fused to PospF, PospE, or two hybrid promoters in which the −10 regions of PospF and PospE were switched [PospF (E − 10) and PospE (F − 10) respectively]. We found that the PospF−10 region is both necessary and sufficient for RpoS‐dependent recognition in B. burgdorferi, while σ70 specificity for PospE is dependent on elements outside of the −10 region. In E. coli, sigma factor selectivity for these promoters was much more permissive, with expression of each being primarily due to σ70. Alignment of the sequences upstream of each of the ospE/ospF/elp genes from B. burgdorferi strains 297 and B31 revealed that two B31 ospF paralogues [erpK (BBM38) and erpL (BBO39)] have −10 regions virtually identical to that of PospF. Correspondingly, expression of gfp reporters based on the erpK and erpL promoters was RpoS‐dependent. Thus, the sequence of the PospF−10 region appears to serve as a motif for RpoS recognition, the first described for any B. burgdorferi promoter. Taken together, our data support the notion that B. burgdorferi utilizes sequence differences at the −10 region as one mechanism for maintaining the transcriptional integrity of RpoS‐dependent and ‐independent genes activated at the onset of tick feeding.
Involvement of the Escherichia coli folate‐binding protein YgfZ in RNA modification and regulation of chromosomal replication initiation
Authors: Ote Tomotake , Hashimoto Masayuki , Ikeuchi Yoshiho , Su’etsugu Masayuki , Suzuki Tsutomu , Katayama Tsutomu , Kato Jun‐Ichi
Published: February 2006

The Escherichia coli hda gene codes for a DnaA‐related protein that is essential for the regulatory inactivation of DnaA (RIDA), a system that controls the initiation of chromosomal replication. We have identified the ygfZ gene, which encodes a folate‐binding protein, as a suppressor of hda mutations. The ygfZ null mutation suppresses an hda null mutation. The over‐initiation and abortive elongation phenotypes conferred by the hda mutations are partially suppressed in an hda ygfZ background. The accumulation of the active form of DnaA, ATP‐DnaA, in the hda mutant is suppressed by the disruption of the ygfZ gene, indicating that YgfZ is involved in regulating the level of ATP‐DnaA. Although ygfZ is not an essential gene, the ygfZ disruptant grows slowly, especially at low temperature, demonstrating that this gene is important for cellular proliferation. We have identified mnmE (trmE) as a suppressor of the ygfZ disruption. This gene encodes a GTPase involved in tRNA modification. Examination of RNA modification in the ygfZ mutant reveals reduced levels of 2‐methylthio N 6‐isopentenyladenosine, indicating that YgfZ participates in the methylthio‐group formation of this modified nucleoside in some tRNAs. These results suggest that YgfZ is a key factor in regulatory networks that act via tRNA modification.
The intrinsic ATPase activity of Mycobacterium tuberculosis DnaA promotes rapid oligomerization of DnaA on oriC
Authors: Madiraju Murty V. V. S. , Moomey Meredith , Neuenschwander Pierre F. , Muniruzzaman Syed , Yamamoto Kohji , Grimwade Julia E. , Rajagopalan Malini
Published: February 2006

Oligomerization of the initiator protein, DnaA, on the origin of replication (oriC) is crucial for initiation of DNA replication. Studies in Escherichia coli (Gram‐negative) have revealed that binding of DnaA to ATP, but not hydrolysis of ATP, is sufficient to promote DnaA binding, oligomerization and DNA strand separation. To begin understanding the initial events involved in the initiation of DNA replication in Mycobacterium tuberculosis (Gram‐positive), we investigated interactions of M. tuberculosis DnaA (DnaATB) with oriC using surface plasmon resonance in the presence of ATP and ADP. We provide evidence that, in contrast to what is observed in E. coli, ATPase activity of DnaATB promoted rapid oligomerization on oriC. In support, we found that a recombinant mutant DnaATB proficient in binding to ATP, but deficient in ATPase activity, did not oligomerize as rapidly. The corresponding mutation in the dnaA gene of M. tuberculosis resulted in non‐viability, presumably due to a defect in oriC–DnaA interactions. Dimethy sulphate (DMS) footprinting experiments revealed that DnaATB bound to DnaA boxes similarly with ATP or ADP. DnaATB binding to individual DnaA boxes revealed that rapid oligomerization on oriC is triggered only after the initial interaction of DnaA with individual DnaA boxes. We propose that ATPase activity enables the DnaA protomers on oriC to rapidly form oligomeric complexes competent for replication initiation.
MLPA vs multiprobe FISH: comparison of two methods for the screening of subtelomeric rearrangements in 50 patients with idiopathic mental retardation
Authors: Palomares M , Delicado A , Lapunzina P , Arjona D , Amiñoso C , Arcas J , Martinez Bermejo A , Fernández L , López Pajares I
Published: February 2006

Subtelomeric rearrangements not visible by conventional cytogenetic analysis have been reported to occur in approximately 5% of patients with unexplained mental retardation (MR). As the prevalence of MR is high, many patients need to be screened for these chromosomal abnormalities routinely. Multiplex ligation‐dependent probe amplification (MLPA) is a new technique for measuring sequence dosage, allowing large number of samples to be processed simultaneously and thus significantly reducing laboratory work. We have assessed its performance for the detection of subtelomeric rearrangements by comparing the results with those of our previous multiprobe fluorescence in situ hybridization (FISH) assay. We have tested 50 patients with idiopathic MR, dysmorphic features, congenital malformations, and/or familial history of MR. Our results show a high degree of concordance between the two techniques for the 50 samples tested. On the basis of these results, we conclude that MLPA is a rapid, accurate, reliable, and cost‐effective alternative to FISH for the screening of subtelomeric rearrangements in patients with idiopathic MR.
Clinical and molecular aspects of an informative family with neurofibromatosis type 1 and Noonan phenotype
Authors: Stevenson DA , Viskochil DH , Rope AF , Carey JC
Published: February 2006

Neurofibromatosis–Noonan syndrome (NFNS) has been described as a unique phenotype, combining manifestations of neurofibromatosis type 1 (NF1) and Noonan syndrome, which are separate syndromes. Potential etiologies of NFNS include a discrete syndrome of distinct etiology, co‐segregation of two mutated common genes, variable clinical expressivity of NF1, and/or allelic heterogeneity. We present an informative family with an unusual NF1 mutation with variable features of NF1 and Noonan syndrome. We hypothesize that an NF1 mutant allele can lead to diagnostic manifestations of Noonan syndrome, supporting the hypothesis that NF1 allelic heterogeneity causes NFNS.
A genetic model for determining MSH2 and MLH1 carrier probabilities based on family history and tumor microsatellite instability
Authors: Marroni F , Pastrello C , Benatti P , Torrini M , Barana D , Cordisco EL , Viel A , Mareni C , Oliani C , Genuardi M , Bailey‐Wilson JE , Ponz de Leon M , Presciuttini S
Published: February 2006

Mutation‐predicting models can be useful when deciding on the genetic testing of individuals at risk and in determining the cost effectiveness of screening strategies at the population level. The aim of this study was to evaluate the performance of a newly developed genetic model that incorporates tumor microsatellite instability (MSI) information, called the AIFEG model, and in predicting the presence of mutations in MSH2 and MLH1 in probands with suspected hereditary non‐polyposis colorectal cancer. The AIFEG model is based on published estimates of mutation frequencies and cancer penetrances in carriers and non‐carriers and employs the program MLINK of the FASTLINK package to calculate the proband's carrier probability. Model performance is evaluated in a series of 219 families screened for mutations in both MSH2 and MLH1, in which 68 disease‐causing mutations were identified. Predictions are first obtained using family history only and then converted into posterior probabilities using information on MSI. This improves predictions substantially. Using a probability threshold of 10% for mutation analysis, the AIFEG model applied to our series has 100% sensitivity and 71% specificity.
Severe Combined Immunodeficiency in a Fell Pony Foal
Authors: JelÌnek F. , Faldyna M. , Jasurkova‐Mikutova G.
Published: February 2006

Five days after birth of a viable Fell pony filly, yellow watery diarrhoea appeared without any signs of systemic disease. Four days later the diarrhoea ceased. On 11th day, the animal showed apathy, and a few days later, the foal was very lethargic, suffered from muscular weakness and severe watery diarrhoea that reappeared. The illness did not respond to therapy. At the age of 21 days the filly spontaneously died under symptoms of intestinal colic and pneumonia. Haematological examinations revealed lower numbers of erythrocytes as well as non‐selective lymphopenia. Phagocytic activity was slightly increased, lymphocyte activity was inhibited. Histopathology showed severe alteration of the lymphatic organs. T and B lymphocytes and antigen‐presenting macrophages were not arranged in characteristic areas, and the quantity of these cells was lower than would be expected. Histopathological changes in lymphatic organs resembled those described in the literature as severe combined immunodeficiency.
Effect of Anticholinergics (Atropine, Glycopyrrolate) and Prokinetics (Metoclopramide, Cisapride) on Gastric Motility in Beagles and Labrador Retrievers
Authors: Burger D. M. , Wiestner T. , Hubler M. , Binder H. , Keiser M. , Arnold S.
Published: February 2006

The effect of atropine, glycopyrrolate, metoclopramide and cisapride on the antral motility was investigated in eight dogs (four Beagles and four Labradors) using passive telemetry. Both anticholinergics induced a pronounced and lasting reduction of the intensity and frequency of the contractions. A definite dose‐related inhibition of the antral motility was seen in Beagles, similar for both active substances. Low doses of atropine (0.02 mg/kg BW i.m.) and glycopyrrolate (0.005 mg/kg BW i.m.) completely inhibited the gastric motility for at least 30 min, whereas higher doses (0.04 or 0.01 mg/kg BW) caused a cessation of activity for more than 3 h. In Labradors, the effects of both active substances were not so dose related and the effect of glycopyrrolate lasted at least 6 h, whereas the effect of atropine gradually decreased after 3 h. A distinct breed difference regarding the effect of the two prokinetics on the antral motility was also observed. In Beagles, the prokinetics, at a low dose (metoclopramide 0.3 mg/kg BW, cisapride 0.2 mg/kg BW), resulted in a significant increase in the amplitude integral. Higher doses (metoclopramide 0.6 mg/kg BW, cisapride 0.5 mg/kg BW) also increased the integrals of the pressure profiles, but significantly less than with the lower doses. In Labradors, both medications, mainly at higher doses, resulted in an increase of the contraction amplitudes. The low dose had no (cisapride) or only a transient effect (metoclopramide). The frequency of the antral contractions was not at all influenced by cisapride, and only in Beagles metoclopramide resulted in a dose‐related increase. It is not clear if the different results in Labradors and Beagles are because of breed or body weight.
Immunohistochemical Expression of Mdm2 and p53 in Canine Cutaneous Mast Cell Tumours
Authors: Wu H. , Hayashi T. , Inoue M.
Published: February 2006

The objective of this study was to evaluate by immunohistochemical means nuclear reactivity for Mdm2 and p53 proteins in 71 canine cutaneous mast cell tumours. Detectable reactivity for Mdm2 was observed in 17 of 23 grade I tumours, 19 of 27 grade II tumours, and 14 of 21 grade III tumours, the grading method used was that byPatnaik et al. [Vet. Pathol., vol. 21, 1984, p. 469]. Increased reactivity for Mdm2 was detected in grade III tumours compared with grade I tumours. In contrast to Mdm2, detectable reactivity for p53 was observed in 17 tumours. Of 39 cases with moderate or marked Mdm2, 34 showed mild or no detectable p53, although only five showed moderate or marked p53. The results suggest that Mdm2 overexpression plays a crucial role in canine mast cell tumorigenesis and is consistent with the histologic grade, and its expression may be induced without p53 overexpression.
Chronic Progressive Autonomic Dysfunction in a Dog
Authors: Adamama‐Moraitou K. K. , Brellou G. D. , Rallis T. S. , Zavros N. , Pardali D. , Dinopoulos A. , Vlemmas I.
Published: February 2006

A 3.5‐year‐old intact male American Pit Bull was presented because of urinary incontinence and dysuria. Constipation, followed by diarrhoea, ocular disturbances and finally regurgitation developed over the next 4 years. Autonomic dysfunction was evidenced by clinical presentation, as well as positive ophthalmic pilocarpine test and subnormal Schirmer tear test. Diagnosis, however, was established through histopathological and immunohistochemical examination. Lesions attributable to inflammatory degenerative neuropathy of the autonomic ganglia, which represents one of the various types of human autonomic failure, were detected.
A Case of Suspected Lysosomal Storage Disease in a Neonatal Japanese Black Calf
Authors: Mikami O. , Anjiki T. , Yamato O. , Nakajima Y.
Published: February 2006

A 5‐day‐old Japanese black calf was necropsied and intracytoplasmic vacuolations were histologically observed in many tissues. In the central nervous system, intracytoplasmic inclusions and vacuoles were found in neuronal cells. Intracytoplasmic inclusions were more conspicuous in the nuclei containing large nerve cells, especially in the brain stem and spinal cord. These inclusions were stained weak positive to positive with alcian blue, Giemsa, Luxol fast blue and periodic acid–Schiff stains but not with oil red O. Ultrastructurally, neuronal inclusions were observed in lysosomes and consisted of an amorphous electron‐dense substance and occasional membranous structures. These findings seem to differ from the cases of bovine lysosomal diseases that have been reported, and this case may be another type of lysosomal storage disease.
Clinical Pharmacokinetics of Anti‐angiogenic Photodynamic Therapy with Benzoporphyrin Derivative Monoacid Ring‐A in Dogs Having Naturally Occurring Neoplasms
Authors: Osaki T. , Hoshino S. , Hoshino Y. , Takagi S. , Okumura M. , Kadosawa T. , Fujinaga T.
Published: February 2006

The aim of this study was to examine the pharmacokinetics of clinically applied benzoporphyrin derivative monoacid ring‐A (BPD‐MA; Verteporfin®), a second‐generation photosensitizer, during a trial of photodynamic therapy (PDT) in nine dogs having naturally occurring neoplasms. After injecting BPD‐MA at 0.5 mg/kg intravenously, its mean half‐life (t1/2) was found to be 8.14 ± 5.34 h, mean clearance (Cl) 35.13 ± 9.62 ml/(h kg), the mean value of the volume of distribution (Vc) 0.08 ± 0.01 l/kg and the mean steady state volume of distribution (Vss) 0.38 ± 0.31 l/kg respectively. With the exception of a transitional increase in serum alkaline phosphatase activity, no other clinical abnormalities were observed. The t1/2 in dogs with naturally occurring tumours was longer than that in humans, but similar to that in rats. The values of Cl and Vss in dogs having naturally occurring neoplasms were lower than those in humans. It is suggested that the pharmacokinetics of BPD‐MA in tumour‐bearing dogs would be helpful in determining the protocol of a short drug‐light interval PDT with BPD‐MA that mainly targets the tumour vasculature.
Nosocomial bloodstream infections associated with Candida species in a Turkish University Hospital
Authors: Yapar Nur , Uysal Ulker , Yucesoy Mine , Cakir Nedim , Yuce Ayse
Published: February 2006

In recent years, a progressive increase in the frequency of nosocomial candidaemia has been observed, especially among the critically ill or immunocompromised patients. The aim of this study was to evaluate the trend in incidence of candidaemia together with potential risk factors in an 850‐bed Turkish Tertiary Care Hospital in a 4‐year period. A total of 104 candidaemia episodes were identified in 104 patients. The overall incidence was 0.56 per 1000 hospital admissions and the increase in incidence of candidaemia from 2000 to 2003 was found to be statistically significant (P = 0.010). Candida albicans was the most common species (57.7%) and non‐albicans species accounted for 42.3% of all episodes. The most common non‐albicans Candida sp. isolated was C. tropicalis (20.2%) followed by C. parapsilosis (12.5%). The most frequent risk factors possibly associated with the candidaemia were previous antibiotic treatment (76.9%), presence of central venous catheter (71.2%) and total parenteral nutrition (55.8%). Our results show the fact that the incidence of candidaemia caused by non‐albicans species is frequent and increasing significantly, although the most common isolated Candida species were C. albicans and further investigations are necessary to evaluate the mechanisms of increasing incidence of candidaemia caused by non‐albicans species.
In vitro adhesion of Candida species to denture base materials
Authors: He X. Y. , Meurman J. H. , Kari K. , Rautemaa R. , Samaranayake L. P.
Published: February 2006

Adhesion of Candida species to prosthetic acrylic resins is an essential first step in the pathogenesis of denture stomatitis. Data on the relative adhesion of pathogenic non‐albicans Candida species to different denture base materials are sparse. The purpose of the present study was to investigate in vitro adhesion of C. albicans, C. glabrata, C. krusei and C. dubliniensis to four different denture base materials. Specimens of both heat‐cured resins (VertexTM Rapid Simplified and ProBaseTM Hot) and cold‐cured resins (Paladur® A and Paladur® B) were prepared using a novel method and the adhesion of four strains each of the foregoing Candida species evaluated microscopically using a soft imaging system. There was a significant difference in yeast adherence between Vertex and the other resins. Only C. glabrata attached to Vertex, while all the remainder of the tested species adhered to all other resins tested except ProBase, which resisted C. krusei adhesion. There was a significant difference in candidal adhesion between cold‐cured and heat‐cured resins for three Candida species (C. albicans, P = 0.039; C. glabrata, P = 0.002 and C. krusei, P = 0.000). The type of denture base material and whether they are heat‐cured or cold‐cured play an important role in modifying candidal adhesion.
The glyoxylate cycle enzyme activities in the pathogenic isolates of Candida albicans obtained from HIV/AIDS, diabetic and burn patients
Authors: Lattif Ali Abdul , Prasad Rajendra , Banerjee Uma , Gupta Nivedita , Mohammad Sameer , Baquer Najma Z.
Published: February 2006

Recently it has been found that Candida albicans harbours enzymes involved in the glyoxylate cycle (GC), which have a role in its virulence, especially the two key enzymes, isocitrate lyase (ICL) and malate synthase (MS). There are however, few studies on the GC enzyme activities isolated in the clinical isolates. Samples were collected from three groups of patients namely, HIV/AIDS, diabetic and burn patients suffering from candidiasis at different body locations. Isolation, identification and the antifungal susceptibility test of all the isolates of C. albicans were followed by the standard techniques. Measurements of all the GC enzyme activities were also carried out by the standard methods. Levels of the principal GC enzymes showed significant changes when calculated and compared taking control strains of C. albicans. The activity of the two key enzymes of the GC, ICL and MS were significantly higher in the isolates from diabetic patients. No significant relationship between the drug susceptibility and the level of enzymes of the GC was observed. As GC activity is absent in mammalian cells, a specific inhibitor for the GC could be developed and these enzymes therefore can be used as a new antifungal target.
A kerion celsi caused by Microsporum gypseum: unusual direct mycological examination
Authors: Baudraz‐Rosselet Florence , Bontems Olympia , Ninet Béatrice , Panizzon Renato G. , Monod Michel
Published: February 2006

A case of kerion celsi caused by Microsporum gypseum is documented. The patient was a 6‐year‐old girl with a 2‐cm purulent lesion on the scalp. Direct mycological examination of the hair showed hyphae with extremely numerous spindle‐shaped macrospores. The species identification was confirmed by 28S ribosomal DNA sequencing. The presence of numerous macrospores is unusual in direct mycological examination, but could be an indication for M. gypseum.
Intrinsic in vitro susceptibility of primary clinical isolates of Aspergillus fumigatus, Aspergillus terreus, Aspergillus nidulans, Candida albicans and Candida lusitaniae against amphotericin B
Authors: Singh Jagpal , Rimek Dagmar , Kappe Reinhard
Published: February 2006

A total of 60 clinical fungal isolates from patients without prior amphotericin B treatment and three control strains were evaluated for their intrinsic susceptibility to amphotericin B (AmB) using microdilution, Etest and disc diffusion assays, on three media each, Roswell Park Memorial Institute (RPMI) 1640, Antibiotic Medium 3 (AM3) and High Resolution Medium. The fungal strains included isolates of Aspergillus fumigatus (n = 10), Aspergillus terreus (n = 12), Aspergillus nidulans (n = 9), Candida albicans (n = 6) and Candida lusitaniae (n = 23). The A. terreus strains were significantly less susceptible to AmB than the A. fumigatus strains in all nine experimental settings (P‐values ranging from 0.009 to <0.00001). The A. nidulans strains were equally susceptible to AmB as the A. fumigatus strains in seven of nine experimental settings and less susceptible in two (microdilution performed on RPMI and AM3, P = 0.01 and 0.007). The C. lusitaniae strains were equally susceptible to AmB as the C. albicans strains in seven of nine experimental settings and more susceptible in two (microdilution and Etest, both performed on AM3, P = 0.01 and 0.0002). Thus, we confirmed that A. terreus is intrinsically less susceptible to AmB than A. fumigatus. In contrast, nine German clinical isolates of Aspergillus nidulans were found equally susceptible to AmB as 10 isolates of A. fumigatus. Furthermore, we found 23 German clinical isolates of C. lusitaniae from patients without prior treatment with AmB equally susceptible to AmB as C. albicans.
Risk factors and outcome for breakthrough candidaemia in patients with cancer
Authors: Chung Jin‐Won , Lee Sang‐Oh , Choi Sang‐Ho , Woo Jun‐Hee , Ryu Jiso , Kim Yang Soo , Kim Nam Joong
Published: February 2006

While candidaemia that develops during systemic antifungal prophylaxis or therapy [breakthrough (BT) candidaemia] has been reported increasingly, the risk factors and outcome of BT candidaemia are not yet known definitely. We evaluated a consecutive series of cancer patients with candidaemia at Asan Medical Center during 6 years to identify risk factors and outcome in BT candidaemia comparing with non‐BT candidaemia. Fifty‐four episodes of candidaemia in cancer patients diagnosed during this period were reviewed retrospectively. There were 10 episodes (18.5%) of BT candidaemia in which the species distribution and frequency of catheter‐related infection in the BT and non‐BT groups were similar. BT candidaemia had a tendency to occur more frequently in patients with haematological than non‐haematological diseases. Profound neutropenia and disseminated candidiasis were more common in the BT group; however, these differences were not statistically significant (P = 0.17 and 0.07 respectively). The duration of prior antibiotic therapy and duration of profound neutropenia (<100 mm−3) were identified as risk factors for BT candidaemia (P < 0.01 and 0.02 respectively) in univariate analysis and the latter was the only risk factor in multivariate analysis. The death rates due to candidaemia were 85.7% in the BT group and 42.9% in the non‐BT group (P = 0.08); however, BT candidaemia alone did not increase mortality rate.
Dermatophytoses in Monterrey, México
Authors: Welsh Oliverio , Welsh Esperanza , Ocampo‐Candiani Jorge , Gomez Minerva , Vera‐Cabrera Lucio
Published: February 2006

In the present report we reviewed a total of 2397 cases of dermatophytosis from superficial cutaneous lesions between the years 1978 and 1990. The cases included were from the Department of Dermatology at the University Hospital located in the city of Monterrey, México. A total of 726 tinea pedis, 613 tinea unguium, 441 tinea capitis, 395 tinea corporis and 222 tinea cruris cases were observed. The most commonly isolated dermatophyte species was Trichophyton rubrum (45%), followed by Trichophyton mentagrophytes (23.7%), Trichophyton tonsurans (21%), Microsporum canis (7.1%) and Epidermophyton floccosum (2.5%). Less frequently we isolated Microsporum audouinii, Microsporum gypseum, Trichophyton violaceum and Trichophyton verrucosum. Most of the cases were observed in the warmest months of the year (from March to September), and were equally distributed in both genders, except for tinea cruris which was more prevalent in men (3.5 : 1 ratio).
Genotyping of Turkish environmental Cryptococcus neoformans var. neoformans isolates by pulsed field gel electrophoresis and mating type
Authors: Saracli M. A. , Yildiran S. T. , Sener K. , Gonlum A. , Doganci L. , Keller S. M. , Wickes B. L.
Published: February 2006

A total of 26 environmental Cryptococcus neoformans var. neoformans strains isolated from 634 samples of pigeon droppings collected from 54 different provinces of Turkey in 1996 and 1997 were included in this study. The results of pulsed‐field gel electrophoresis (PFGE) showed that the 26 strains could be separated into 24 different PFGE patterns. In a mating‐type study, of 26 strains, 20 were MATα, four were MATa, one was MATa/α and one was non‐typable by STE20 specific primers. By the polymerase chain reaction typing, all the isolates were serotype A. The extensive heterogeneity among these isolates suggests that a single clonal population may not be present in Turkey. Additionally, the presence of an AMATa/DMATα hybrid may indicate the existence of strains that are AMATa mating type in Turkish environment.
Concentric rings: an unusual presentation of tinea corporis caused by Microsporum gypseum
Authors: Sun Pei‐Lun , Ho Hsin‐Tsung
Published: February 2006

A case of tinea corporis with the unusual presentation of concentric erythematous rings on the abdomen is reported. The pathogen was identified as Microsporum gypseum. While a number of unusual lesions have been described in M. gypseum infections, we are unaware of any reports on concentric rings.
Necrotising cryptococcal vasculitis in an HIV‐negative woman
Authors: J. Sico Jason , Hughes Eric
Published: February 2006

An 84‐year‐old woman with a past medical history significant for haemolytic anaemia necessitating chronic steroid therapy presented with skin induration and erythema initially thought to be cellulitis. After a rapid progression of symptoms and failure to respond to antibiotics, a clinical diagnosis of necrotising vasculitis was made. Necrotising cryptococcal vasculitis was confirmed by histopathology and culture.
Vesicular glutamate transporter 3 (VGLUT3) identifies spatially segregated excitatory terminals in the rat substantia nigra
Authors: Martín‐Ibañez Raquel , Jenstad Monica , Berghuis Paul , Edwards Robert H. , Hioki Hiroyuki , Kaneko Takeshi , Mulder Jan , Canals Josep M. , Ernfors Patrik , Chaudhry Farrukh A. , Harkany Tibor
Published: February 2006

The excitability of dopaminergic (DA) neurons in the substantia nigra is controlled by the convergent activity of multiple glutamatergic afferents. Here, we show that vesicular glutamate transporter 3 (VGLUT3)‐immunoreactive (ir) terminals segregate to the perisomatic region of DA neurons in the substantia nigra pars compacta, and VGLUT3 decorates a synapse population distinct from those marked by vesicular glutamate transporters 1 and 2. VGLUT3‐ir nerve endings form asymmetric terminals on DA neurons. Retrograde tracing suggests the superior colliculus as an origin of excitatory VGLUT3‐ir afferents. Collectively, our data indicate that VGLUT3 identifies a novel excitatory terminal subset that contributes to the tuning of DA cell excitability in the substantia nigra.
NMDA receptor‐mediated transmission contributes to network ‘hyperexcitability’ in the rat insular cortex
Authors: Inaba Yuji , De Guzman Philip , Avoli Massimo
Published: February 2006

The insular cortex (IC) plays distinct roles under physiological and pathological conditions. However, the mechanisms regulating excitability in this area remain unknown. By employing field potential and sharp‐electrode intracellular recordings in horizontal rat brain slices comprising the IC and the perirhinal cortex, we studied here the intrinsic and network characteristics of neurons in the agranular IC. These cells generated regular action potential firing with weak adaptation during intracellular injection of depolarizing current pulses, and were pyramidal in shape when neurobiotin filled. Spontaneous, field events (duration = 2.3 ± 0.25 s; intervals of occurrence = 44.9 ± 6.3 s) were identified in 22/52 slices and corresponded in IC neurons to intracellular depolarizations with action potential firing. Similar field and intracellular discharges were elicited in all slices by electrical stimuli. Antagonizing N‐methyl‐d‐aspartate (NMDA) receptors blocked the spontaneous activity and reduced or abolished the stimulus‐induced discharges. In the latter cases, stimuli elicited depolarizing events that became hyperpolarizing at about −64 mV, suggesting the contribution of γ‐aminobutyric acid (GABA)A receptor‐mediated conductances. Our findings identify for the first time some functional properties of agranular IC neurons and point at a powerful NMDA receptor‐mediated mechanism implementing network hyperexcitability. This feature may contribute to the role of IC in neurological disorders.
1H MRS identifies lactate rise in the striatum of MPTP‐treated C57BL/6 mice
Authors: Koga Keiko , Mori Atsushi , Ohashi Satoshi , Kurihara Naoki , Kitagawa Hisashi , Ishikawa Makoto , Mitsumoto Yasuhide , Nakai Masami
Published: February 2006

Mitochondrial dysfunction has been implicated in the death of nigrostriatal dopaminergic neurons in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated experimental models of Parkinson's disease (PD). Here we utilized proton magnetic resonance spectroscopy (1H MRS) to identify changes in energy metabolism in the striatum of MPTP‐treated C57BL/6 mice. Remarkable increases in lactate/creatine (Lac/Cr) ratio were observed at 2 h and then quickly returned to about the basal level by 7 h after injection of MPTP. Neurochemical and Western blot analyses revealed that dopamine contents and protein levels of tyrosine hydroxylase and dopamine transporter in the striatum were profoundly decreased at 3 days after MPTP treatment. Pretreatment with deprenyl, a monoamine oxidase B inhibitor, or GBR‐12909, a dopamine uptake inhibitor, almost completely attenuated both the increases in striatal Lac/Cr ratio and the subsequent loss of dopaminergic nerve terminals in MPTP‐treated mice. The present study indicates that 1H MRS is a sensitive measure of biochemical alterations of the brain in a mouse model of PD, and further shows that the increases in striatal Lac/Cr ratio induced by MPTP may be associated with mitochondrial energy crisis, followed by dopaminergic neurotoxicity.
Evening exposure to blue light stimulates the expression of the clock gene PER2 in humans
Authors: Cajochen Christian , Jud Corinne , Münch Mirjam , Kobialka Szymon , Wirz‐Justice Anna , Albrecht Urs
Published: February 2006

We developed a non‐invasive method to measure and quantify human circadian PER2 gene expression in oral mucosa samples and show that this gene oscillates in a circadian (= about a day) fashion. We also have the first evidence that induction of human PER2 expression is stimulated by exposing subjects to 2 h of light in the evening. This increase in PER2 expression was statistically significant in comparison to a non‐light control condition only after light at 460 nm (blue) but not after light exposure at 550 nm (green). Our results indicate that the non‐image‐forming visual system is involved in human circadian gene expression. The demonstration of a functional circadian machinery in human buccal samples and its response to light opens the door for investigation of human circadian rhythms at the gene level and their associated disorders.
The Acinetobacter outer membrane protein A (OmpA) is a secreted emulsifier
Authors: Walzer Gil , Rosenberg Eugene , Ron Eliora Z.
Published: February 2006

Acinetobacter strains use hydrophobic carbon sources and most of them are efficient oil degraders. They secrete a variety of emulsifiers which are efficient in producing and stabilizing oil‐in‐water emulsions. The bioemulsifier of Acinetobacter radioresistens KA53 (Alasan) is a high‐mass complex of proteins and polysaccharides. The major emulsification activity of this complex is associated with a 45 kDa protein (AlnA), which is homologous to the outer membrane protein OmpA. The emulsification ability of AlnA depends on the presence of hydrophobic residues in the four loops spanning the transmembrane domains. The finding of a secreted OmpA was unexpected, in view of the fact that this protein is essential in all Gram‐negative bacteria, has four trans‐membrane domains and is considered to be an integral structural component of the outer membrane. However, secretion of an OmpA with emulsifying ability could be of physiological importance in the utilization of hydrophobic substrates as carbon sources. Here we examined the possibility that secretion of OmpA with emulsifying activity is a general property of the oil‐degrading Acinetobacter strains. The results indicate that OmpA is secreted in five strains of Acinetobacter, including strain Acinetobacter sp. ADP1 whose genome has been sequenced. The ompA genes of ADP1 and an additional strain, Acinetobacter sp. V‐26 were cloned and sequenced. Structure analysis of the sequence of the two proteins indicated the existence of the hydrophobic regions, previously shown to be responsible for the emulsification activity of AlnA. Further examination of the recombinant OmpA proteins indicated that they are, indeed, strong emulsifiers, even when produced in Escherichia coli. The finding that Acinetobacter OmpA has emulsifying activity and that it is secreted in five strains of Acinetobacter may be physiologically significant and suggests the involvement of this protein in biodegradation of hydrophobic substrates, including hydrocarbons.
Analysis of fimbrial gene clusters and their expression in enterohaemorrhagic Escherichia coli O157:H7
Authors: Low Alison S. , Holden Nicola , Rosser Tracy , Roe Andrew J. , Constantinidou Chrystala , Hobman Jon L. , Smith David G. E. , Low J. Christopher , Gally David L.
Published: February 2006

The sequence of two enterohaemorrhagic Escherichia coli (EHEC) O157:H7 strains reveals the possession of at least 16 fimbrial gene clusters, many of the chaperone/usher class. The first part of this study examined the distribution of these clusters in a selection of EHEC/EPEC (enteropathogenic E. coli) serotypes to determine if any were likely to be unique to E. coli O157:H7. Six of the clusters, as determined by the presence of amplified main subunit or usher gene sequences, were detected only in the E. coli O157 and O145 serotypes tested. With the exception of one serotype O103 strain that contained an lpf2 cluster, lpf sequences were only detected in E. coli O157 of the serotypes tested. Expression from each cluster was measured by the construction of chromosomally integrated lacZ promoter fusions and plasmid‐based eGFP fusions in E. coli O157:H7. This analysis demonstrated that the majority (11/15) of main fimbrial subunit genes were not expressed under the majority of conditions tested in vitro. One of the clusters showing promoter activity, loc8, has a temperature expression optimum indicating a possible role outside the host. From the presence of pseudogenes in three of the clusters, the lack of FimH‐like minor adhesins in the clusters and their limited expression in vitro, it would appear that E. coli O157:H7 has a limited repertoire of expressed functional fimbriae. This restricted selection of fimbriae may be important in bringing about the tropism E. coli O157:H7 demonstrates for the terminal rectum of cattle.