bluuebunny/crossref_metadata_2025 huggingface dataset:
O‐6 RESPECTIVE ROLES OF FINE NEEDLE ASPIRATION CYTOLOGY AND CORE BIOPSY IN DIAGNOSIS OF SYMPTOMATIC BREAST LESIONS
Authors: Poon C. , Kocjan G.
Published: August 2006

Introduction:  To evaluate and compare the respective roles of fine needle aspiration cytology and core biopsy for diagnosis of symptomatic breast lesions.

Methods:  Retrospective study on 589 breast fine needle aspiration cytology (FNAC) cases and 88 core biopsies (CB) with no associated FNAC, performed between January and December 2004. A computer database was searched for initial results, subsequent investigations and outcomes.

Results:  Of the cases that had FNAC performed as an initial investigation, the final diagnosis was reached by FNAC alone in 81.8% of cases. Of these, 59.2% were benign, 6.1% malignant and 2.4% remaining suspicious with 14.1% inadequate samples. There were 31 cases reported as suspicious (C3/C4) on FNAC, of these 14% of C3 and all of C4 were malignant on CB. Of the 86 cases that had both FNAC and CB, CB improved on the FNAC diagnosis of malignancy in 19.8% of cases, half of which were considered inadequate on FNAC. The positive predictive value of malignant cases was 100%, and the negative predictive value 98%. The absolute sensitivity of FNAC in this study was 65% and complete sensitivity 72%. The false negative rate was 8% and false positive rate 0%. The diagnosis of 88 CB without FNAC showed 37.5% to be malignant and 60.2% as benign, with 2.3% as inadequate biopsies.

Discussion:  FNAC remains the first line investigation in symptomatic breast lesions. Its best use is in the diagnosis of benign disease which constitutes over two thirds of patients in our practice. In suspicious and clinically malignant lesions, it is complemented by CB which may provide additional information relevant to management. In conclusion, the majority benign findings in our patients who had CB without prior FNAC, does not justify the use of CB as a first line investigation. CB is indicated in cases of inadequate or suboptimal FNAC. The continuous use of suspicious categories (C3/C4) in breast cytology is justified by the subsequent outcomes, both benign and malignant.
O‐13 ENDOMETRIAL CARCINOMA DETECTED WITH SUREPATH LIQUID BASED CERVICAL CYTOLOGY: COMPARISON WITH CONVENTIONAL CERVICAL CYTOLOGY
Authors: Patel C. J. , Ullal A. , Roberts M. , Brady J. , Bulmer J. N. , Wadehra V.
Published: August 2006

Introduction:  Conventional Pap Smear (CPS) has had little impact on the detection of endometrial carcinoma (MC). Although Liquid Based Cytology (LBC) is replacing CPS in the UK, experience with identification of endometrial cancers with this is limited. A few studies of ThinPrep LBC show promise with reported increased detection rate, but to date, there has been no reported study of detection with SurePath LBC.

Aim:  The purpose of this 2‐year retrospective study was to compare the accuracy of the SurePath LBC with that of conventional smear in detecting endometrial cancers.

Methods:  Our study group consisted of all SurePath cases of endometrial atypia/carcinoma diagnosed between 1st Jan 2004 and 31st Dec 2005, following 100% conversion of our laboratory to the SurePath system in 2001. Conventional smears reported over a 6‐year period (1993–1998), comprised the control group. Histological follow up was obtained.

Results:  Endometrial lesions were reported in 95 (0.07%) of 130352 SurePath LBC smears. These included 70 (0.053%) reports of endometrial atypia, 05 (0.003%) suspicious and 20 (0.015%) diagnostic of endometrial carcinoma. A total of 58 (0.014%) cases of 409495 CPS were diagnosed as endometrial carcinoma. Adequate histological follow up was available in 47 (49.5%) SurePath LBC and 52 (89.6%) conventional cases. In these, the positive predictive value (PPV) for endometrial carcinoma of SurePath LBC was 73.3% compared to 55.4% of CPS. The PPV for endometrial carcinoma of the atypical and suspicious LBC categories was 14.3% and 40% respectively. No categorisation as atypical or suspicious in the conventional study was available for comparison. The sensitivity of the SurePath LBC, calculated from retrograde analysis of histologically diagnosed endometrial cancers during the same period was 40%.

Conclusion:  The SurePath LBC is at least an as accurate and sensitive method for detecting endometrial cancer as CPS.
P‐14 CERVICAL DYSPLASIA AND RISK FACTORS IN NORTHERN IRELAND SLE PATIENTS
Authors: McHenry M. T. , Cuschieri K. , Moore C. , Cubie H. A. , Clarke R. , Anderson N. , Bell A. L.
Published: August 2006

Introduction:  An increased risk of cervical dysplasia has previously been reported in lupus. The role of traditional related risk factors are unclear. Persistent infection with certain genotypes of Human Papilloma Virus termed high risk (HR‐HPV) is considered a prerequisite for the development of cervical cancer.

Methods:  A total of 141 SLE patients fulfilling the ACR criteria for lupus were enrolled into the study. They were compared to 138 control patients who were due to attend for a routine cervical smear. Each patient completed a cervical cancer risk factor questionnaire. A cervical smear was taken and residual material used to test for the presence of HR‐HPV using a hybridisation microplate assay. Positive samples were then genotyped.

Results: 

VARIABLE
RR (95% CI)
P value

Ever conceived
2.52 (1.37–4.64)
P = 0.003

>1 sexual partner
3.46 (2.03–5.91)
P < 0.001

Age sexual active
0.98 (0.92–1.04)
NS

Smoking history
1.10 (0.64–1.90)
NS

STD
0.52 (0.20–1.40)
NS

SLE patients in this study had an increased lifetime occurrence of an abnormal cervical smear. Although a similar detection rate of HR‐HPV positivity was found in SLE (15.6%) and control women (17.4%), the mean age of the SLE HPV+ women was 43 years compared with 30 years for the HPV+ controls Co‐ Variate Analysis of traditional risk factors

Discussion:  Parity and number of sexual partners may be important traditional risk factors. HPV positive SLE patients tend to be older. HR‐HPV may represent an opportunistic infection in these women as in other immunosuppressed disease states. Genotyping results suggest the same HPV types as non‐SLE women and no single type predominated.
P‐17 FREQUENCY OF AFTER‐EFFECTS REPORTED BY WOMEN FOLLOWING A CERVICAL SMEAR TEST
Authors: Cochran C. , Cotton S. C. , Sharp L. , Gray N. M. , Cruickshank M. E. , Smart L.
Published: August 2006

Introduction:  Few studies have investigated after‐effects experienced by women immediately following a cervical smear test. We report the prevalence of women's self‐reported after‐effects following a smear test and identify factors associated with this.

Methods:  The study takes place within TOMBOLA (Trial Of Management of Borderline and Other Low‐grade Abnormal smears), a randomised‐controlled trial, nested within the NHS‐CSPs, comparing alternative follow‐up policies for women with low‐grade abnormal smears. This analysis includes 888 women aged 20–59 years randomised to cytological surveillance (ie 6‐monthly smears in primary care). Five weeks after their first surveillance smear, women completed questionnaires on any after‐effects they had experienced.

Results:  30% of women reported one or more after‐effects in the 5 weeks following their smear. 15% of women reported pain, 17% bleeding and 8% discharge. The median time these after‐effects were experienced was 1 day (mean = 2.5 days). The most commonly reported combination of after‐effects were bleeding and pain together (47 women; 18% of those reporting an after‐effect). In multivariate analysis of those reporting any after‐effect, younger women, those with a degree from college/university, women regularly undertaking physical activity and current pill users were significantly more likely to report any after‐effect than were older women, those without a degree, those who were never physically active and women not using the pill. In multivariate analysis of pain, bleeding and discharge separately, different factors were found to be associated with each after‐effect: the results of these analyses will be presented.

Discussion:  Almost one‐third of women experience after‐effects following a cervical smear test. Our results could help make the information that women receive prior to a smear test more relevant by, for example, providing guidance on the proportions of women who might experience specific types of after‐effects, and highlighting sub‐groups who might be more (or less) likely to experience them.
P‐18 WHICH IS THE CORRECT USE OF FINE‐NEEDLE ASPIRATION CYTOLOGY OF THE THYROID IN THE CLINICAL SETTING?
Authors: Standen J. M. , Dina R.
Published: August 2006

Thyroid fine needle aspiration (FNA) is the first choice procedure for differentiating between benign and malignant/suspicious lesions. Despite being highly sensitive and specific, it unfortunately has high inadequacy rates, with false‐negatives reported in most series. The fundamental contribution of the aspirator's skill, experience and expertise to inadequacy rates is well documented, differing between both individuals and aspirator groups. We performed a retrospective audit comparing inadequacy rates of cytopathologists and clinicians for all thyroid FNAs performed from 2002–2005 within the Hammersmith Hospitals Trust. A crude cost‐effectiveness was estimated, and using histological data where available, positive and negative powers (65.5% and 87.9% respectively), sensitivity (61.5%) and specificity (89.7%) were calculated. Pathologists were found to have significantly (P = 0.001) lower inadequacy rates (2.8%) than clinicians (16.1%) and were also more cost‐effective (non‐significant), with micropapillary carcinomas and lymphomas being identified as the main sources of false‐negatives. We thus propose updated protocols to reduce inadequacy and false‐negative rates, improve thyroid cancer diagnosis and the quality of patient care within our centre.
P‐2 COMPLETING THE AUDIT CYCLE OF NON‐GYNAECOLOGIC CYTOLOGY TURNAROUND TIMES
Authors: Li C. , Rana D. N. , Desai M.
Published: August 2006

Objective:  This is the re‐audit to examine whether the guidelines set after the last audit in 2002 have been implemented and followed. The initial audit concluded that the average turnaround time for reporting non‐gynaecologic cytology samples was 7 days and there was a wide variation in turnaround times between pathologists due to the practice of delayed electronic authorisation. It recommended that all cases should be electronically authorised by the reporting pathologist before a hard copy report was issued and guidelines for turnaround times should be set. These guidelines recommend turnaround times to report non‐gynaecologic cytology specimens of 3 days for urgent, 5 days for routine and 10 days for those specimens requiring ancillary tests.

Audit method:  Retrospective evaluation was carried out on non‐gynaecologic cytology specimens reported from 1st August to 31st October 2005.

Results:  A total of 718 non‐gynaecologic cases were reported during the 3‐month period by two cytopathologists. The largest proportion of the specimens was urine (40%), followed by FNA (24.9%), serous fluids (20.6%), respiratory specimens (7.4%), miscellaneous specimens (4.3%) including external referred cases, bile duct and oesophageal brushings, and peritoneal washings (2.8%). The mean turnaround time was 3.7 calendar days (Saturdays and Sundays were included). Over a quarter (25.2%) of the cases were reported within 1 day, and nearly half (48.6%) were reported within 2 days. Eighty‐four percent of the specimens had a turnaround time of 5 days or less and 95% were reported within 10 calendar days. Urine samples took the shortest time to report (2.6 days), followed by respiratory specimens (3.8 days), peritoneal washings and FNA (both 4 days), miscellaneous cases (4.2 days) and serous fluids (5.2 days). The reasons for the 5% specimens showing turnaround times of over 10 days were multifactoral, such factors included having to request cell blocks and/or immunohistochemical stains, having to contact the clinicians for additional information, having to retrieve prior case material for review, and external referred cases.

Conclusions:  These findings have demonstrated the value of completing the audit cycle. The re‐audit has demonstrated the improvement in the reporting time of non‐gynaecologic cytology specimens from 7 days to 3.7 days due to the guidelines produced following the initial audit.
P‐25 DOES THE PRESENCE OF KOILOCYTES IN A BNA SMEAR AFFECT CLINICAL OUTCOMES?
Authors: Alexander L. , Cotton S. C. , Gallager M. E. , Duncan I. , Henderson S. , Reid G. , Robertson A.
Published: August 2006

Introduction:  There is ongoing debate about the terminology used in the classification of dyskaryosis, including whether BNA smears should be classified according to whether koilocytes are present or not. We explored the effect of koilocytosis in the management experiences and clinical outcomes of women with a single BNA smear.

Methods:  This study includes 410 women aged 20–59 years, resident in Tayside who had an ‘baseline’ BNA smear between 31/10/1999 and 31/10/2002 who were eligible for the TOMBOLA trial but who did not participate. Recommended follow‐up for these women was a repeat smear in six months. Up to three‐years follow‐up data was collected on subsequent cytological smears, colposcopy examinations and any related histology. The baseline smear was re‐read for the presence or absence of koilocytes. Women were classified according to their clinical outcomes during their three years.

Results:  47% (192/410) of women were classified as having koilocytosis at baseline. The mean age was lower among these women (25 years) compared to those without koilocytosis (35 years). 55% (105/192) of women with koilocytosis at baseline had one or more negative smears and no further abnormal smears, compared to 63% (137/218) of those without koilocytosis, the difference was not statistically significant. 28% (53/192) of women with koilocytosis at baseline were referred to colposcopy after subsequent low‐grade or high‐grade smears compared to 19% (42/218) of those without koilocytosis; the difference was statistically significant. 14% (27/192) of women with koilocytosis at baseline were diagnosed with CIN2/3 or worse during follow‐up compared to 10% (21/218) of women without koilocytosis; the difference was not statistically significant.

Discussion:  Our results suggest that the presence or absence of koilocytosis has little impact on the clinical outcomes of women with a BNA smear.
P‐27 ATYPICAL GLANDULAR CELLS ON SMEAR – AGE RELATED IMPLICATIONS AND MANAGEMENT
Authors: Tan L. , McCarthy J. , Lyons D.
Published: August 2006

Introduction:  Atypical glandular cells on smear constitute 0.05–0.1% of all smears. The incidence appears to be rising and presents a diagnostic dilemma. The aim of our study was to assess the impact of age on disease distribution and management options.

Methods:  All patients presenting with atypical glandular cells on smear from January 2000 to December 2004 were analysed. All these smears were conventional smears (none LBC). Smear suggesting borderline changes in glandular cells were not included. We analysed the histopathological outcomes in patients with reference to age. Two groups were taken (a) Patients </= to 35 years old; (b) Patients > 36 years old. These age groups were taken as per BSCCP Guidelines, patients </= 35 years old are treated with conisation differently (1cm above SCJ) to patients >36 years olds (2 cm deep).

Results:  A total of 75 women were referred, 49 women > 36 years old, 26 women were </= 35 years old PPV for abnormal glandular cells was much higher in ladies >36 years old. 3/49 patients >36 years old showed no evidence of malignancy on further testing whereas 34% showed no evidence of malignancy in patients </= 35 years old. In women </= 35 years old no endometrial pathology was seen. There is an almost equal distribution of cervical versus extracervical disease women > 36 years old.

Conclusions:  This study suggests that ladies > 36 years old should have investigations to exclude extrauterine pathology whereas in ladies </= 35 years old may not require, these as cervical lesions were only identified in this group.
Modelling the impacts of removing seal predation from Atlantic salmon, Salmo salar, rivers in Scotland: a tool for targeting conflict resolution
Authors: BUTLER J. R. A. , MIDDLEMAS S. J. , GRAHAM I. M. , THOMPSON P. M. , ARMSTRONG J. D.
Published: August 2006

Abstract  Bioenergetics were used to model the potential impacts on adult Atlantic salmon, Salmo salar L., stocks and rod fisheries of removing harbour seals, Phoca vitulina L., from three rivers of different scales in the Moray Firth, Scotland, viz: the Spey (large), Conon (medium) and Moriston (small). Overall, seals had the greatest impact on the Moriston, where removal of a single animal could increase cumulative catch by 17% during the fishing season. On the Conon and Spey the impacts were negligible, and resulted in increased catches of <1% annually. On all rivers eliminating seal predation had the greatest impact during the spring due to the smaller size of spring salmon sub‐stocks. A generalised model of seal removal illustrated that stocks and catches increased by >33% in rivers with monthly rod catches ≤10 fish, but declined to <10% for rivers with catches >34 fish. The outputs of the models are qualitative, but provide a management tool for targeting action to resolve seal‐salmon fishery conflict. Smaller salmon population units, and spring salmon sub‐stocks and fisheries in particular, are most vulnerable to predation. The merit of this approach is discussed regarding the management of Special Areas of Conservation for salmon and seals.
Eradicating the invasive topmouth gudgeon, Pseudorasbora parva, from a recreational fishery in northern England
Authors: BRITTON J. R. , BRAZIER M.
Published: August 2006

Abstract  An established population of the invasive topmouth gudgeon, Pseudorasbora parva (Temminck & Schlegel), was discovered in a recreational fishery in Northwest England in 2002. As the lake was seasonally connected to a river catchment, providing potential for dispersal, a containment and eradication programme was initiated. Containment involved screening of outfalls and preventing fish movements off site. Eradication involved the fishery being treated twice with a rotenone‐based piscicide, in March and April 2005. The mean P. parva density prior to rotenone application was 6.1 m−2; following the application, none were recorded. Non‐target species in the fishery were removed prior to the application; following rotenone degradation, they were re‐introduced and subsequently spawned, with recording of young‐of‐the‐year. This contrasts with 2004 when only young‐of‐the‐year of P. parva were recorded. As the eradication appeared to be successful, the method is considered suitable for use on other populations posing a similar threat of dispersal of the species into rivers and on other invasive fish populations in undesirable locations.
Root canal morphology of mandibular incisors in a Jordanian population
Authors: Al‐Qudah A. A. , Awawdeh L. A.
Published: August 2006

Aim  To investigate the root canal morphology of mandibular incisors in a Jordanian population using a canal staining and tooth‐clearing technique.

Methodology  Four hundred and fifty extracted mandibular incisors were collected from dental clinics within north Jordan. Following pulp tissue removal and staining of the canal systems, the teeth were decalcified with 5% nitric acid, dehydrated with ascending concentrations of alcohol and rendered clear by immersion in methyl salicylate. Cleared teeth were examined by eye and the following features were evaluated: (i) number and type of root canals; (ii) presence and location of lateral canals and intercanal communications; (iii) location of apical foramina; and (iv) frequency of apical deltas.

Results  The majority of mandibular incisors had a single canal (73.8% of teeth possessed a Type I canal system). Although 26.2% of the roots possessed two canals, only 8.7% had two separate apical foramina.

Conclusions  The prevalence of two canals in this group of mandibular incisors was 26.2% and is within the range of previous studies performed on populations of different racial origin.
Microsatellite variation and differentiation in African and non‐African populations of Drosophila simulans
Authors: SCHÖFL GERHARD , SCHLÖTTERER CHRISTIAN
Published: August 2006

Drosophila simulans originated in sub‐Saharan Africa or Madagascar and colonized the rest of the world after the last glaciation about 10 000 years ago. Consistent with this demographic history, sub‐Saharan African populations have been shown to harbour higher levels of microsatellite and sequence variation than cosmopolitan populations. Nevertheless, only limited information is available on the population structure of D. simulans. Here, we analysed X‐linked and autosomal microsatellite loci in four sub‐Saharan African, one North African, one Israeli, and two European D. simulans populations. Bayesian clustering algorithms combined the North African, Israeli, and European populations into a single cosmopolitan group. The four sub‐Saharan populations were split into two separate groups. Pairwise FST analysis, however, indicated significant population differentiation between all eight populations surveyed. A significant signal for population reduction in cosmopolitan populations was found only for X‐linked loci.
The response regulator ResD modulates virulence gene expression in response to carbohydrates in Listeria monocytogenes
Authors: Larsen Marianne H. , Kallipolitis Birgitte H. , Christiansen Janne K. , Olsen John E. , Ingmer Hanne
Published: August 2006

Listeria monocytogenes is a versatile bacterial pathogen that is able to accommodate to diverse environmental and host conditions. Presently, we have identified a L. monocytogenes two‐component response regulator, ResD that is required for the repression of virulence gene expression known to occur in the presence of easily fermentable carbohydrates not found inside host organisms. Structurally and functionally, ResD resembles the respiration regulator ResD in Bacillus subtilis as deletion of the L. monocytogenes resD reduces respiration and expression of cydA, encoding a subunit of cytochrome bd. The resD mutation also reduces expression of mptA encoding the EIIABman component of a mannose/glucose‐specific PTS system, indicating that ResD controls sugar uptake. This notion was supported by the poor growth of resD mutant cells that was alleviated by excess of selected carbohydrates. Despite the growth deficient phenotype of the mutant in vitro the mutation did not affect intracellular multiplication in epithelial or macrophage cell lines. When examining virulence gene expression we observed traditional induction by charcoal in both mutant and wild‐type cells whereas the repression observed in wild‐type cells by fermentable carbohydrates did not occur in resD mutant cells. Thus, ResD is a central regulator of L. monocytogenes when present in the external environment.
Epigenetic mechanisms are involved in the control of Giardia lamblia antigenic variation
Authors: Kulakova Liudmila , Singer Steven M. , Conrad John , Nash Theodore E.
Published: August 2006

Giardia lamblia, an intestinal dwelling protozoan parasite, undergoes surface antigenic variation where only one of an estimated 150 variant‐specific surface proteins (VSPs) is expressed and present on the surface at any one time. Transcriptional switching between VSPs results in replacement of one VSP by another. The mechanisms that control antigenic variation are poorly understood and difficult to study because there are multiple copies of each VSP and strong similarity with other VSPs. In order to study transcriptional regulation of one specific vsp, a haemagglutinin (HA) epitope‐tagged h7 was integrated into the G. lamblia GS genome. We show that HA‐tagged H7 undergoes antigenic variation in the same manner as native H7, also present in the GS genome. Control of expression of both HA‐tagged H7 and native H7 is independent of each other even though the genes and their surrounding 5′ and 3′ flanking sequences are virtually identical. Analysis of expressing and non‐expressing clones revealed an absence of HA‐tagged h7 gene rearrangements upon switching and acetylation of histone lysine residues within the 167 nucleotides 5′ to the expressed HA‐tagged h7 gene. Lack of vsp rearrangements and acetylation of expressed immediate upstream regions implicates involvement of epigenetic mechanisms in antigenic variation.
Polypeptide binding proteins: what remains to be discovered?
Authors: Fischer Gunter , Wawra Stephan
Published: August 2006

Many proteins have developed the potential to sequester a client polypeptide chain in its various folding states as a specific intermolecular ligand and, thus, exhibit the properties of a holding chaperone. The resulting complexes can be of a diverse nature in terms of structure and reaction dynamics and are characterized on the basis of various microscopic properties including formation and decay of encounter and Michaelis complexes as well as reactant and product stability. Interpretation of the functional consequences of complex formation in the cell generally tends to be rather complicated, with notable exceptions including complexes formed during the reaction pathways of proteases, protein kinases and protein phosphatases. Peptide bond cis/trans isomerases take up an intermediate position among the poly(oligo)peptide binding proteins because, although the relationship between chain sequestration and catalysis of isomerization can easily be delineated in vitro, it is sometimes difficult to resolve in the cell. Time‐resolved studies on interactions involving peptide bond cis/trans isomerases have led to the establishment of generally applicable methods for studying protein–poly(oligo)peptide interactions that are capable of identifying new types of biocatalysis.
The role of nutrient regulation and the Gpa2 protein in the mating pheromone response of C. albicans
Authors: Bennett Richard J. , Johnson Alexander D.
Published: August 2006

Although traditionally classified as asexual, the human fungal pathogen Candida albicans can undergo highly efficient mating. A key component of this mating is the response to pheromone, which is mediated by a conserved kinase cascade that transduces the signal from the pheromone receptor to a transcriptional response in the nucleus. In this paper we show (i) that the detailed response of C. albicans to the alpha pheromone differs among clinical isolates, (ii) that the response depends critically on nutritional conditions, (iii) that the entire response is mediated by the Ste2 receptor, and (iv) that, in terms of genes induced, the response to alpha pheromone in C. albicans shows only marginal overlap with the response in Saccharomyces cerevisiae. We further investigated the nutritional control of pheromone induction and identify the GPA2 gene as a critical component. We found that Δgpa2/Δgpa2 mutants are hypersensitive to pheromone and, unlike wild‐type strains, show efficient cell cycle arrest (including the formation of characteristic halos on solid medium) in response to mating pheromone. These results indicate that C. albicans, like several other fungal species but unlike S. cerevisiae, integrates signals from a nutrient‐sensing pathway with those of the pheromone response MAP kinase pathway to generate the final transcriptional response.
Ultrasonography in filaria‐infected rodents: detection of adult Litomosoides sigmodontis and Brugia malayi filariae
Authors: Mand S. , Specht S. , Zahner H. , Hoerauf A.
Published: August 2006

Objective  To evaluate the usefulness of ultrasonography (USG) in the detection of adult filariae in rodents. Wuchereria bancrofti are frequently detected using USG in humans, whereas adult Brugia malayi have not been so far.

Methods  A Meriones unguiculatus with Litomosoides sigmodontis infection was examined to visualize adult filariae of a similar length as W. bancrofti. Similarly, three Mastomys coucha, infected with B. malayi, were examined using USG to verify whether the adult worms, which are far smaller than W. bancrofti and L. sigmodontis, can be located using USG in the animals.

Results  Adult L. sigmodontis were detected using USG in the pleural cavity of M. unguiculatus, and in M. coucha adult B. malayi were visualized in the hearts, lungs, axillary lymph nodes and scrotum. Ultrasound findings were verified by dissection of the rodents.

Conclusions  Although adult B. malayi are far smaller than L. sigmodontis and W. bancrofti, they can be detected using USG in rodents. USG may serve as an adjunctive tool to support parasitological examinations and can add information on filarial infections at any time point of an observation period, particularly in cryptic infections and without the need for invasive measures or killing of the rodent. Thus, USG can support the early detection of macrofilaricidal activities of new compounds and can be used to determine the location of adult worms in the animals. It is possible to give a rough estimate of the number of adult worms, but determination of the exact numbers of adult filariae in various locations is impossible with USG.
Species diversity causing human cutaneous leishmaniasis in Rio Branco, state of Acre, Brazil
Authors: Tojal da Silva Anna Christina , Cupolillo Elisa , Volpini Ângela Cristina , Almeida Roque , Sierra Romero Gustavo Adolfo
Published: August 2006

Objective  Information on Leishmania species diversity in western Brazilian Amazon and the clinical picture of human cutaneous leishmaniasis it causes is scarce. We describe clinical findings, diagnostic procedures and identification of Leishmania species in patients from that region.

Methods  The sample consisted of 50 patients, prospectively evaluated for epidemiological and clinical characteristics by means of a structured questionnaire. Conventional and molecular tools were applied to confirm the parasitological diagnosis and identify the species responsible for the disease.

Results  Patients were predominantly male (76.5%) and living in rural areas. Median average age was 18 years and median average disease evolution was 8 weeks. For the diagnostic procedures of leishmanin skin test, direct visualization of amastigotes in dermal scrapings and parasite culture of aspirates of the ulcer border were positive for 98%, 52% and 34%, respectively. Molecular methods applied to DNA extracted from skin biopsies of the 50 patients yielded 100%, 82% and 44% positivity by PCR minicircle kDNA, PCR‐RFLP ITS1rDNA and PCR‐glucose‐6‐phosphate (G6P), respectively. Fourteen samples from 13 patients were successfully isolated and identified. Multilocus enzyme electrophoresis, PCR‐RFLP ITS1rDNA and PCR‐G6P permitted identification of the Leishmania species responsible for the aetiology of American tegumentary leishmaniasis in 60% of the examined patients: 16 Leishmania (Viannia) braziliensis, 12 Leishmania (Viannia) lainsoni, 1 Leishmania (Viannia) guyanensis and 1 putative hybrid of Leishmania (Viannia) naiffi and L. (V.) lainsoni.

Conclusion  The clinical and epidemiological behaviour of cutaneous leishmaniasis in Acre, Brazil, is similar to other Amazon scenarios previously described; however Acre's complex parasite diversity may be contributed to the concomitant circulation of at least three distinct Leishmania species. The implementation of control interventions in the studied area must take into consideration the possibility of various expected phlebotomine vectors and reservoirs.
Repeated fluorescence in situ hybridization by a microwave‐enhanced protocol
Authors: Kitayama Yasuhiko , Igarashi Hisaki , Kozu Taeko , Nagura Kiyoko , Ohashi Yohei , Sugimura Haruhiko
Published: August 2006

A novel re‐hybridization protocol for pathology archive sections that uses microwave‐assisted fluorescence in situ hybridization (FISH) is described. Stripping the probe from the pathology archive sections with HCl and re‐hybridizing with the next probe by intermittent microwave irradiation generated clear signals without background noise. Repeated stripping and hybridization with numerous bacterial artificial chromosome (BAC)‐derived probes would identify the profile of genome‐wide changes in small lesions on sections.
Desmoplastic small cell tumor of soft tissue: Molecular variant of EWS‐WT1 chimeric fusion
Authors: Hamazaki Minoru , Okita Hajime , Hata Jun‐ichi , Shimizu Shin‐ichi , Kobayashi Hiroshi , Aoki Katsuhiko , Nara Taemi
Published: August 2006

A 7‐year‐old girl was hospitalized because of a tumorous mass in her left periorbital region. The tumor was removed by local excision. The soft‐part tumor recurred in the parotid gland region 4 months later, and a second recurrence was noted on the left side of the neck 3 years and 3 months thereafter. The patient had not received chemotherapy or local irradiation. Histological and immunohistochemical examinations of the recurrent masses revealed morphological characteristics of small cell proliferation with desmoplastic stroma that were similar to those of the initial tumor. The cellular components showed immunoreactivity for desmin, cytokeratin, vimentin, and epithelial membrane antigen in part, but the cells were negative for myogenin, CD99, and neuron‐specific enolase. These findings suggested a diagnosis of desmoplastic small cell tumor, despite its extra‐abdominal location. The histological diagnosis was confirmed by reverse transcriptase polymerase chain reaction, which demonstrated an EWS‐WT1 chimeric fusion gene. An in‐frame fusion of EWS exon 9 and WT1 exon 8 was subsequently identified by cloning and sequencing. The chimeric fusion gene might be related to the tissue‐specific phenotype of desmoplastic small cell tumors, although further investigation of this speculation is necessary.
Adaptive changes in serotonin neurons of the raphe nuclei in 5‐HT4 receptor knock‐out mouse
Authors: Conductier Grégory , Dusticier Nicole , Lucas Guillaume , Côté Francine , Debonnel Guy , Daszuta Annie , Dumuis Aline , Nieoullon André , Hen René , Bockaert Joël , Compan Valérie
Published: August 2006

Decreased serotonin (5‐HT) transmission is thought to underlie several mental diseases, including depression and feeding disorders. However, whether deficits in genes encoding G protein‐coupled receptors may down‐regulate the activity of 5‐HT neurons is unknown currently. Based on recent evidence that stress‐induced anorexia may involve 5‐HT4receptors (5‐HT4R), we measured various aspects of 5‐HT function in 5‐HT4R knock‐out (KO) mice. When compared to dorsal raphe nucleus (DRN) 5‐HT neurons from wild‐type mice, those from 5‐HT4R KO mice exhibited reduced spontaneous electrical activity. This reduced activity was associated with diminished tissue levels of 5‐HT and its main metabolite, 5‐hydroxyindole acetic acid (5‐HIAA). Cumulative, systemic doses of the 5‐HT uptake blocker citalopram, that reduced 5‐HT cell firing by 30% in wild‐type animals, completely inhibited 5‐HT neuron firing in the KO mice. This effect was reversed by administration of the 5‐HT1A receptor (5‐HT1AR) antagonist, WAY100635, in mice of both genotypes. Other changes in DRN of the KO mice included increases in the levels of 5‐HT plasma membrane transporter sites and mRNA, as well as a decrease in the density of 5‐HT1AR sites without any change in 5‐HT1A mRNA content. With the exception of increased 5‐HT turnover index in the hypothalamus and nucleus accumbens and a decreased density of 5‐HT1AR sites in the dorsal hippocampus (CA1) and septum, no major changes were detected in 5‐HT territories of projection, suggesting region‐specific adaptive changes. The mechanisms whereby 5‐HT4R mediate a tonic positive influence on the firing activity of DRN 5‐HT neurons and 5‐HT content remain to be determined.
Contribution of spike timing to the information transmitted by HVC neurons
Authors: Huetz Chloé , Del Negro Catherine , Lebas Nicolas , Tarroux Philippe , Edeline Jean‐Marc
Published: August 2006

In many species, neurons with highly selective stimulus‐response properties characterize higher order sensory areas and/or sensory motor areas of the CNS. In the songbird nuclei, the responses of HVC (used as a proper name) neurons during playback of the bird's own song (BOS) are probably one of the most striking examples of selectivity for natural stimuli. We examined here to what extent spike‐timing carries information about natural and time‐reversed versions of the BOS. From a heterogenous population of 107 HVC neurons recorded in long‐day or short‐day conditions, a standard indicator of stimulus preference based on spike‐count (the d′ index) indicates that a limited proportion of cells can be classified as selective for the BOS (20% with a |d′| > 1). In contrast, quantifying the information conveyed by spike trains with the metric‐space of J.D. Victor & K.P Purpura [(1996) J. Neurophysiol., 76, 1310–1326] indicates that 62% of the cells display significant amounts of transmitted information, among which 77% are ‘temporal cells’. ‘Temporal cells’ correspond to cells transmitting significant amounts of information when spike‐timing is considered, whereas no information, or lower amounts of transmitted information, is obtained when only spike‐count is considered. Computing a correlation index between spike trains [S. Schreiber et al. (2003) Neurocomputing, 52–54,925–931] revealed that spike‐timing reliability is higher for the forward than for the reverse BOS, whatever the day length and the cell type are. Cells classified as selective in terms of spike‐counts (d′ index) had greater amounts of transmitted information, but cells classified as non‐selective (d′ < 0.5) can also transmit significant amounts of information. Thus, information theory methods demonstrate that a much larger proportion of neurons than expected based on spike‐count only participate in the discrimination between stimuli.
Brain‐derived neurotrophic factor and neurotrophin receptors modulate glutamate‐induced phase shifts of the suprachiasmatic nucleus
Authors: Michel S. , Clark J. P. , Ding J. M. , Colwell C. S.
Published: August 2006

Light information reaches the suprachiasmatic nucleus (SCN) through a subpopulation of retinal ganglion cells. Previous work raised the possibility that brain‐derived neurotrophic factor (BDNF) and its high‐affinity tropomyosin‐related receptor kinase may be important as modulators of this excitatory input into the SCN. In order to test this possibility, we used whole‐cell patch‐clamp methods to measure spontaneous excitatory currents in mouse SCN neurons. We found that the amplitude and frequency of these currents were increased by BDNF and decreased by the neurotrophin receptor inhibitor K252a. The neurotrophin also increased the magnitude of currents evoked by application of N‐methyl‐d‐aspartate and amino‐methyl proprionic acid. Next, we measured the rhythms in action potential discharge from the SCN brain slice preparation. We found that application of K252a dramatically reduced the magnitude of phase shifts of the electrical activity rhythm generated by the application of glutamate. By itself, BDNF caused phase shifts that resembled those produced by glutamate and were blocked by K252a. The results demonstrate that BDNF and neurotrophin receptors can enhance glutamatergic synaptic transmission within a subset of SCN neurons and potentiate glutamate‐induced phase shifts of the circadian rhythm of neural activity in the SCN.
Altered sodium currents in auditory neurons of congenitally deaf mice
Authors: Leão Richardson N. , Naves Marcell M. , Leão Katarina E. , Walmsley Bruce
Published: August 2006

Sodium currents are essential for action potential generation and propagation in most excitable cells. Appropriate tuning of these currents can be modulated both developmentally and in response to activity. Here we use a mouse model of congenital deafness (dn/dn– asymptomatic deafness associated with hair cell degeneration) to investigate the effect of lack of activity in the expression of Na+ currents in neurons from the medial nucleus of the trapezoid body (MNTB). Patch‐clamp recordings show that at postnatal day (P) 14, both normal and deaf mice display a significant amount of persistent and resurgent Na+ currents. However, the persistent current is greater in deaf mice than in normal mice, and resurgent current kinetics are slower in deaf mice. At P7, resurgent currents are not present in either group. MNTB immunohistochemistry demonstrates that Nav1.1 subunits are expressed postsynaptically in both P14 normal and deaf mice, while postsynaptic Nav1.6 staining was only observed in deaf mice. Labelling of Nav1.6 subunits in different age groups revealed that at younger ages (P7), both normal and deaf mice express this protein. Nav1.6 staining was not observed in MNTB neurons of P28 normal mice, whereas it is maintained in deaf mice cells until much later (P28). At P7, none of the groups displayed resurgent currents (despite the detection of Nav1.6 subunits at this age group); this suggests that factors other than alpha subunits are important for modulating these currents in MNTB cells. Our results emphasize the importance of activity during development in regulating Na+ channels.
Expression of a truncated tau protein induces oxidative stress in a rodent model of tauopathy
Authors: Cente Martin , Filipcik Peter , Pevalova Miroslava , Novak Michal
Published: August 2006

Truncation of tau protein and oxidative stress have been implicated as important pathogenetic events in tauopathies including Alzheimer's disease (AD). We have generated a transgenic rat model that expresses a human truncated tau protein analogous to a variant form derived from sporadic AD. We employed this model to investigate the relationship between tau protein truncation and oxidative stress. We have found that rat cortical neurons (derived from transgenic animals) that had been cultured in vitro for 16 days showed an increased accumulation of reactive oxygen species (up to 1.4‐fold increase; P < 0.01) when compared to neurons derived from nontransgenic control animals. Transgene‐expressing neurons treated with inducers of oxidative stress, such as glucose oxidase (GO) and buthionine sulfoximine (BSO), displayed dramatically reduced survival (31.4 ± 3.3 and 24.9 ± 3.6%, respectively; both P < 0.001) compared to neurons from control animals (79.9 ± 7.1%, survival following treatment with GO and to 98.2 ± 3.8%, survival following treatment with BSO). The number of mitochondria in processes of neurons from transgenic animals was decreased by about one‐third from that present in neurons from control animals. The results reveal that expression of a human truncated variant form of tau protein leads to the accumulation of reactive oxygen species and sensitizes rat cortical neurons to cell death induced by oxidative stress. This indicates that truncation of tau may precede oxidative stress in the pathogenesis of neurodegenerative diseases such as AD and other tauopathies. These findings may have implications for therapeutic strategies aiming at prevention of neurofibrillary degeneration and cognitive decline, and identify potential new targets for drug development.
External tufted cells in the main olfactory bulb form two distinct subpopulations
Authors: Antal Miklós , Eyre Mark , Finklea Bryson , Nusser Zoltan
Published: August 2006

The glomeruli of the main olfactory bulb are the first processing station of the olfactory pathway, where complex interactions occur between sensory axons, mitral cells and a variety of juxtaglomerular neurons, including external tufted cells (ETCs). Despite a number of studies characterizing ETCs, little is known about how their morphological and functional properties correspond to each other. Here we determined the active and passive electrical properties of ETCs using in vitro whole‐cell recordings, and correlated them with their dendritic arborization patterns. Principal component followed by cluster analysis revealed two distinct subpopulations of ETCs based on their electrophysiological properties. Eight out of 12 measured physiological parameters exhibited significant difference between the two subpopulations, including the membrane time constant, amplitude of spike afterhyperpolarization, variance in the interspike interval distribution and subthreshold resonance. Cluster analysis of the morphological properties of the cells also revealed two subpopulations, the most prominent dissimilarity between the groups being the presence or absence of secondary, basal dendrites. Finally, clustering the cells taking all measured properties into account also indicated the presence of two subpopulations that mapped in an almost perfect one‐to‐one fashion to both the physiologically and the morphologically derived groups. Our results demonstrate that a number of functional and structural properties of ETCs are highly predictive of one another. However, cells within each subpopulation exhibit pronounced variability, suggesting a large degree of specialization evolved to fulfil specific functional requirements in olfactory information processing.
Transient synaptic zinc‐positive thalamocortical terminals in the developing barrel cortex
Authors: Ichinohe Noritaka , Potapov Daniel , Rockland Kathleen S.
Published: August 2006

In rat barrel cortex, layer 4 has a transiently high density of zinc‐positive terminations from postnatal day (P)9 to P12 [P.W. Land & L. Shamalla‐Hannah (2002)J. Comp. Neurol., 447, 43–56]. These terminations have been proposed to originate from cortico‐cortical connections, but their exact origin is unknown. To determine their sources, we injected sodium selenite into the barrel cortex of two adult rats and 32 pups, from P5 to P28. As predicted, abundant zinc‐positive cortically projecting neurons were visible around the injection sites and in distant cortical areas. From P9 to P13, however, neurons retrogradely labeled by zinc selenite occurred in the thalamus, in topographically appropriate regions of the ventroposterior medial (VPM) and posterior nuclei (Po). Because there are no previous reports of zinc‐positive sensory thalamocortical connections, we sought corroboration of this unexpected finding by electron microscopy. This revealed a subset of boutons in layers 4 and 1, positive for both zinc and vesicular glutamate transporter 2, a protein used by thalamocortical terminations. Finally, in an additional nine rats, we carried out in situ hybridization for zinc transporter 3 mRNA. Moderate signal was detected in VPM and Po at P10, but this disappeared by P28. In contrast, a strong signal was apparent in the anterodorsal nucleus, which projects to limbic areas, and this persisted at P28. The timing of the transient zinc‐positive terminations in the sensory thalamus roughly coincides with the onset of exploratory and whisking behavior in the middle of the second postnatal week; and this suggests zinc is important for activity‐related refinement of circuitry.