bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cautionary tales in the clinical interpretation of studies of diagnostic tests
Authors: Scott I. A. , Greenberg P. B. , Poole P. J. 
Published: July 2007

AbstractThe use of investigational tests in making a diagnosis is a core activity of physicians and one that requires an understanding of the accuracy and usefulness of specific tests in discriminating between several diagnostic possibilities. Studies of diagnostic tests are frequently methodologically flawed and their results are often not well understood or applied in clinical practice. This article defines the performance characteristics of diagnostic tests, describes several commonly encountered deficiencies in study design which may invalidate reports of new diagnostic tests, and explains a Bayesian approach to interpreting test results in terms of disease probability.
Influence of PCPA and MDMA (ecstasy) on physiology, development and behavior in Drosophila melanogaster
Authors: Dasari Sameera , Viele Kert , Turner A. Clay , Cooper Robin L. 
Published: July 2007

AbstractThe effects of para‐chlorophenylalanine (PCPA) and 3,4 methylenedioxy‐methamphetamine (MDMA, ‘ecstasy’) were investigated in relation to development, behavior and physiology in larval Drosophila. PCPA blocks the synthesis of serotonin (5‐HT) and MDMA is known to deplete 5‐HT in mammalian neurons; thus these studies were conducted primarily to target the serotonergic system. Treatment with PCPA and MDMA delayed time to pupation and eclosion. The developmental rate was investigated with a survival analysis statistical approach that is unique for Drosophila studies. Locomotion and eating were reduced in animals exposed to MDMA or PCPA. Sensitivity to exogenously applied 5‐HT on an evoked sensory–central nervous system (CNS)–motor circuit showed that the CNS is sensitive to 5‐HT but that when depleted of 5‐HT by PCPA a decreased sensitivity occurred. A diet with MDMA produced an enhanced response to exogenous 5‐HT on the central circuit. Larvae eating MDMA from the first to third instar did not show a reduction in 5‐HT within the CNS; however, eating PCPA reduced 5‐HT as well as dopamine content as measured by high performance liquid chromatography from larval brains. As the heart serves as a good bioindex of 5‐HT exposure, it was used in larvae fed PCPA and MDMA but no significant effects occurred with exogenous 5‐HT. In summary, the action of these pharmacological compounds altered larval behaviors and development. PCPA treatment changed the sensitivity in the CNS to 5‐HT, suggesting that 5‐HT receptor regulation is modulated by neural activity of the serotonergic neurons. The actions of acute MDMA exposure suggest a 5‐HT agonist action or possible dumping of 5‐HT from neurons.
Embryonic depletion of serotonin affects cortical development
Authors: Vitalis Tania , Cases Olivier , Passemard Sandrine , Callebert Jacques , Parnavelas John G. 
Published: July 2007

AbstractCompelling evidence suggests that serotonin (5‐HT) is necessary for the refined organization of the cerebral cortex. Here we sought to analyse the short‐ and long‐term consequences of embryonic 5‐HT depletion on the development of the cerebral neocortex of the rat. We focused on the migration and differentiation of the pyramidal (projection) and nonpyramidal (interneuron) neuronal populations. Our paradigm used daily injection of DL‐P‐chlorophenylalanine (PCPA), a reversible inhibitor of 5‐HT synthesis, during the E12–17 stage of embryonic development, when major events in corticogenesis take place. We monitored the 5‐HT depletion induced by this treatment and showed that it led to subtle alterations in both the pyramidal and nonpyramidal neuronal populations. We found that E12–17 PCPA treatment altered the maturation of pyramidal neurons of layers III and V of the somatosensory cortex, with these cells displaying reduced dendritic arborization and complexity. These long‐lasting alterations were not associated with modification of cortical BDNF levels at postnatal stages. We also showed that PCPA treatment transiently altered the incorporation in the cortical plate of interneurons derived from the caudal ganglionic eminence, and persistently affected the differentiation of a subpopulation expressing calretinin and/or cholecystokinin.
The anandamide transport inhibitor AM404 reduces ethanol self‐administration
Authors: Cippitelli Andrea , Bilbao Ainhoa , Gorriti Miguel Angel , Navarro Miguel , Massi Maurizio , Piomelli Daniele , Ciccocioppo Roberto , De Fonseca Fernando Rodríguez 
Published: July 2007

AbstractThe endocannabinoid system mediates in the pharmacological actions of ethanol and genetic studies link endocannabinoid signaling to alcoholism. Drugs activating cannabinoid CB1 receptors have been found to promote alcohol consumption but their effects on self‐administration of alcohol are less clear because of the interference with motor performance. To avoid this problem, a novel pharmacological approach to the study of the contribution of the cannabinoid system in alcoholism may be to use drugs that locally amplify the effects of alcohol on endogenous cannabinoids. In the present study we addressed this model by studying the effects of the anandamide transport inhibitor N‐(4‐hydroxyphenyl) arachidonoyl‐ethanolamide (AM404) on both ethanol self‐administration and reinstatement of alcohol‐seeking behavior in rats. The results show that AM404 significantly reduced ethanol self‐administration in a dose‐dependent manner but failed to modify reinstatement for lever pressing induced by the stimulus associated with alcohol. This effect was not due to a motor depressant effect and was not related to a decrease in general motivational state, as it was not effective in other reward paradigms such as lever pressing for a saccharin solution. The mechanism of action of AM404 does not involve cannabinoid CB1 receptors as the CB1‐selective antagonist SR141716A did not block the reduction of ethanol self‐administration induced by the anandamide uptake blocker. Moreover, 3‐(1,1‐dimethylheptyl)‐(–)‐11‐hydroxy‐delta 8‐tetrahydrocannabinol (HU‐210), a classical cannabinoid receptor agonist, did not affect ethanol self‐administration. The effects of AM404 are not mediated by either vanilloid VR1 receptors or cannabinoid CB2 receptors because it is not antagonized by either the VR1 receptor antagonist capsazepine or the CB2 antagonist AM630. These results indicate that AM404 may be considered as an innovative approach to reduce alcohol consumption.
Neural activation state determines behavioral susceptibility to modified theta burst transcranial magnetic stimulation
Authors: Silvanto Juha , Muggleton Neil G. , Cowey Alan , Walsh Vincent 
Published: July 2007

AbstractTranscranial magnetic stimulation (TMS) allows one to investigate the effects of temporary interference of neural processing in neurologically intact subjects. In a previous study [J. Silvanto et al. (2007) Eur. J. Neurosci., 25, 1874–1881] we found that online TMS perceptually facilitates the attributes encoded by the least active neural populations. The objective of the present experiment was to extend this work to determine whether such state‐dependent effects can be observed when offline high‐frequency TMS is applied to suppress neural activity. The activity levels of direction‐selective neural populations in the V1/V2 region were modulated by asking subjects to passively view either leftward or rightward motion during offline TMS. In a subsequent motion direction‐discrimination task, their ability to discriminate motion direction was dependent on the type of motion they had passively viewed during offline TMS: detection of the congruent direction (i.e. direction viewed during offline TMS) was unaffected, whereas detection of the incongruent direction (i.e. opposite direction to the one viewed during offline TMS) was impaired. As the activity level of neurons tuned to the incongruent direction was presumably lower during the TMS than of those tuned to the congruent direction, this behavioral result demonstrates that the offline TMS preferentially suppressed attributes encoded by the least active neural populations. In contrast to direction discrimination, motion detection was not impaired in a direction‐specific manner. This shows that the requirements of the psychophysical task, in conjunction with the relative activity states of neuronal populations when TMS is applied, can be used to selectively interfere with overlapping neuronal populations.
The chemical component of the mixed GF‐TTMn synapse in Drosophila melanogaster uses acetylcholine as its neurotransmitter
Authors: Allen Marcus J. , Murphey R. K. 
Published: July 2007

AbstractThe largest central synapse in adult Drosophila is a mixed electro‐chemical synapse whose gap junctions require the product of the shaking‐B (shak‐B) gene. Shak‐B2 mutant flies lack gap junctions at this synapse, which is between the giant fibre (GF) and the tergotrochanteral motor neuron (TTMn), but it still exhibits a long latency response upon GF stimulation. We have targeted the expression of the light chain of tetanus toxin to the GF, to block chemical transmission, in shak‐B2 flies. The long latency response in the tergotrochanteral muscle (TTM) was abolished indicating that the chemical component of the synapse mediates this response. Attenuation of GAL4‐mediated labelling by a cha‐GAL80 transgene, reveals the GF to be cholinergic. We have used a temperature‐sensitive allele of the choline acetyltransferase gene (chats2) to block cholinergic synapses in adult flies and this also abolished the long latency response in shak‐B2 flies. Taken together the data provide evidence that both components of this mixed synapse are functional and that the chemical neurotransmitter between the GF and the TTMn is acetylcholine. Our findings show that the two components of this synapse can be separated to allow further studies into the mechanisms by which mixed synapses are built and function.
Susceptibility of Phthorimaea operculella Zeller (Lepidoptera; Gelechiidae) to its granulovirus PoGV with larval age
Authors: Sporleder Marc , Rodriguez Cauti Erica Maritza , Huber Jürg , Kroschel Jürgen 
Published: July 2007

Abstract1 Granulovirus PoGV is a strong candidate to substitute for chemical insecticides in integrated pest management (IPM) of the potato tuber moth Phthorimaea operculella Zeller (Lepidoptera: Gelechiidae). Generally, susceptibility to baculoviruses decreases with increasing larval age. For effective field applications, knowledge of the age‐related change in susceptibility is crucial.2 The relative susceptibility of various instars of P. operculella larvae to PoGV was studied by leaf‐disc bioassays in the laboratory at 26 °C incubation temperature. The LC50 increased from 4 × 106 granules/mL for neonate larvae to 1.2 × 107, 1.1 × 108, 4.4 × 108, and 4.2 × 109 granules/mL, signifying resistance ratios of 3, 29, 110, and 1051, for 5, 6, 7, and 9‐day‐old larvae, respectively.3 The relationship between log‐LC50 values and log‐larval weight was significantly linear. A logistic function described significantly the relation between larval weights and physiological age measured in degree‐days (DD  >  13.4 °C). Both functions allowed prediction of the activity ratio of PoGV for different larval ages by using temperature summation to express physiological age.4 PoGV was found to be highly active against P. operculella larvae up to a physiological age of approximately 50 DD (>13.4 °C) (i.e. the first third of the total larval development time). Thereafter, the virus rapidly lost its activity against older larvae. Prospects for applying this knowledge in the field are discussed.
Occurrence and effects of Nosema fumiferanae infections on adult spruce budworm caught above and within the forest canopy
Authors: Eveleigh Eldon S. , Lucarotti Christopher J. , McCarthy Peter C. , Morin Benoit , Royama Tomo , Thomas Anthony W. 
Published: July 2007

Abstract1 Nosema fumiferanae infections in populations of both sexes of spruce budworm Choristoneura fumiferana moths, collected live above the forest canopy (canopy moths), within the tree crown (crown moths) and in drop trays (dead moths), were examined over a 5‐year period in New Brunswick, Canada.2 The incidence of infection and of moderate–heavy infections in canopy and crown moths of both sexes increased concomitantly with moth eclosion, indicating that N. fumiferanae retards larval/pupal development, with infected moths, particularly those having higher disease loads, emerging later in the season.3 Infection rates differed among canopy, crown, and dead female, but not male, moths. Canopy (i.e. emigrating) females had a lower incidence of infection, lower incidence of moderate–heavy infections, and had longer forewings and higher dry weights, than crown females. These results suggest that N. fumiferanae infections negatively affect aspects of female, but not male, flight performance. Regardless of infection, forewing length and dry weight of both canopy and crown females declined over the moth flight period, but infected females in both moth types were smaller than their uninfected counterparts. Forewing lengths and dry weights of moderately–heavily infected females were most severely affected.4 Despite high annual infection rates in parents, only a small percentage of offspring (second‐instar larvae) that established feeding sites each spring were infected, indicating that high rates of horizontal transmission occurred annually throughout the larval period.5 The present study indicates that whether N. fumiferanae infections are a debilitating sublethal factor in spruce budworm populations depends more on the disease load than on the overall incidence of infection. The potential importance of N. fumiferanae infections on various fitness parameters related to host dispersal is discussed.
Structural changes in the spermatophore of the freshwater ‘red claw’ crayfish Cherax quadricarinatus (Von Martens, 1898) (Decapoda, Parastacidae)
Authors: López Greco Laura Susana , Lo Nostro Fabiana Laura 
Published: July 2007

AbstractLópez Greco, L.S. and Lo Nostro, F.L. 2007. Structural changes in the spermatophore of the freshwater ‘red claw’ crayfish Cherax quadricarinatus (Von Martens, 1898) (Decapoda, Parastacidae). —Acta Zoologica (Stockholm) 88: 000–000The structure of the spermatophore was studied in Cherax quadricarinatus. Pieces of the distal vas deferens and transferred spermatophore from the females were fixed, cut and stained. Within the distal vas deferens, the primary layer and the secondary layer of the spermatophore were distinguishable. In the latter, two components were detected: cytoplasmic droplets and a homogeneous matrix. During the first 10 minutes post‐extrusion the cytoplasmic droplets drastically changed from looking like ‘empty droplets’; at this time the spermatophore changed from a liquid stage to a sticky one. One hour after extrusion the spermatophore began to harden and within the first 24–48 h post‐mating it was a solid and intense white structure tightly attached to the female; after 72 h it acquired a softer aspect, completely dehiscing between 96 and 120 h post‐mating. Histologically, the primary layer maintained its integrity surrounding the spermatozoa while the secondary layer lost the cytoplasmic droplets. The spermatophore began to hydrate between 24 and 48 h and by 72–96 h many sections of the sperm cord began to coalesce. From 48 h post‐mating some fissures appeared within the matrix that enlarged between 72 and 120 h. We propose that both manipulation by the female and hydration are the mechanisms involved in the release of the spermatozoa from the spermatophore.
The type 1 insulin‐like growth factor receptor is over‐expressed in bladder cancer
Authors: Rochester Mark A. , Patel Nilay , Turney Benjamin W. , Davies David R. , Roberts Ian S. , Crew Jeremy , Protheroe Andrew , Macaulay Valentine M. 
Published: July 2007

OBJECTIVETo analyse bladder cancer biopsies and investigate the pattern of expression of the type 1 insulin‐like growth factor receptor (IGF1R), a receptor tyrosine kinase that mediates tumour cell proliferation, motility and protection from apoptosis.MATERIALS AND METHODSFormalin‐fixed specimens of bladder cancer (40 whole‐mount, 80 cores on a tumour microarray) and normal bladder (15 samples) were stained immunohistochemically for the IGF1R. The IGF1R expression was also measured by quantitative reverse transcription‐polymerase chain reaction (Q‐RT‐PCR) on RNA extracted from fresh frozen bladder cancers (61) and benign bladder (12).RESULTSOf the 15 samples of normal bladder, 14 showed negligible (1+) or light (2+) IGF1R immunostaining. By contrast moderate (3+) or heavy (4+) staining for IGF1R was detected in 89 (74%) of the 120 samples of malignant urothelium. Q‐RT‐PCR showed significantly higher levels of steady‐state IGF1R mRNA in tumours (all cases, Ta–T4) than in normal bladder (P < 0.05), indicating up‐regulation at the transcriptional level. This difference was particularly evident when comparing normal urothelium with superficial (Ta–T1) or invasive (T2–4) tumours; only the latter showed significant IGF1R over‐expression at the RNA level (P < 0.05 vs normal bladder).CONCLUSIONThe IGF1R is up‐regulated in bladder cancer compared with non‐malignant bladder, and might contribute to a propensity for invasion.
Relationship between adult dark spermatogonia and secretory capacity of Leydig cells in cryptorchidism
Authors: Zivkovic Dragana , Bica Domingos T.G. , Hadziselimovic Faruk 
Published: July 2007

In a paper from Switzerland, the authors describe the relationship between adult dark spermatogonia and the secretory capacity of Leydig cells in cryptorchidism.OBJECTIVETo examine whether hormonal therapy before orchidopexy affects the histology of the testis and to assess the responsiveness of the Leydig cells, as it has been shown that although basal plasma testosterone levels are within the ‘normal’ range in cryptorchid boys there is an insufficient increase of testosterone after a human chorionic gonadotrophin (hCG) stimulation in ≈ 30% of cryptorchid boys.PATIENTS AND METHODSIn all, 55 boys (aged 1–7 years) with a unilateral undescended testis were included in the study and divided into two groups. Group I (32 boys) received hormonal therapy before orchidopexy; 17 boys received a long‐acting LHRH analogue (buserelin) administered as a nasal spray in doses of 20 µg/day for 28 days, followed by 1500 IU hCG intramuscularly (i.m.) once a week for 3 weeks, and the remaining 15 received 1500 IU hCG i.m. once a week for 3 weeks. Group II (33 boys) had orchidopexy alone. During orchidopexy biopsies were taken from the undescended and contralateral descended testes of the boys in both groups for histological analyses. Variations in the number of adult dark (Ad) spermatogonia per tubule (Ad/T) were assessed and testosterone levels were measured during the course of the hormonal therapy (before treatment, 14 days after initiation of buserelin administration, 24 h after each hCG injection, and 3 months after cessation of therapy).RESULTSIn group I, 17 boys (53%) had a ‘normal’ Ad/T after hormonal treatment vs only six (18%) in group II after orchidopexy alone (P = 0.019). In the hormonally treated boys (group I) we compared the testosterone values 24 h after the second injection of hCG (when the response was most pronounced). Those with a normal Ad/T had a mean (sd) testosterone level of 199.5 (97.6) ng/dL vs 99.6 (85) ng/dL in those with an inadequate Ad/T response to hormonal therapy (P < 0.003).CONCLUSIONWe have confirmed that there are two subgroups of cryptorchid boys. Patients with a sufficient Leydig cell secretory capacity will have normal testicular histology and Ad spermatogonia count after hormonal treatment. While those with a suboptimal Leydig cell capacity will have a low Ad spermatogonia count and consequently poor prognosis for future fertility, despite successful surgery. As to whether different types and durations of the hormonal therapy in patients with impaired Leydig cell response could lead to improved testicular histology and consequently improved prognosis for future fertility, remains to be answered.
Salvage cryotherapy for recurrent prostate cancer after radiation failure: a prospective case series of the first 100 patients
Authors: Ismail Mohamed , Ahmed Shwan , Kastner Christof , Davies John 
Published: July 2007

OBJECTIVETo report the short‐ to intermediate‐term experience of using salvage targeted cryoablation of the prostate (TCAP) for the recurrence of localized prostate cancer after radiotherapy.PATIENTS AND METHODSBetween May 2000 and November 2005, 100 patients had salvage TCAP for recurrent prostate cancer after radiotherapy; the mean follow‐up was 33.5 months. All patients had biopsy‐confirmed recurrent prostate cancer. Biochemical recurrence‐free survival (BRFS) was defined using a prostate specific antigen (PSA) level of <0.5 ng/mL and by applying the American Society for Therapeutic Radiology and Oncology (ASTRO) definition for biochemical failure. Patients were stratified into three risk groups, i.e. high‐risk (68 men), intermediate‐risk (20) and low‐risk (12).RESULTSThere were no operative or cancer‐related deaths; the 5‐year actuarial BRFS was 73%, 45% and 11% for the low‐, intermediate‐ and high‐risk groups, respectively. Complications included incontinence (13%), erectile dysfunction (86%), lower urinary tract symptoms (16%), prolonged perineal pain (4%), urinary retention (2%), and recto‐urethral fistula (1%).CONCLUSIONSalvage TCAP is a safe and effective treatment for localized prostate cancer recurrence after radiotherapy.
Detrusor glycogen reflects the functional history of bladders with partial outlet obstruction
Authors: De Jong Bas W.D. , Wolffenbuttel Katja P. , Arentshorst Marlous E. , Lodder Petra , Kok Dirk‐Jan 
Published: July 2007

OBJECTIVETo assess the relationship between glycogen content in bladder detrusor tissue and historical bladder function in a guinea‐pig model of partial bladder outlet obstruction (PBOO).MATERIALS AND METHODSIn male immature guinea pigs PBOO was created with a silver ring around the proximal urethra; a control group had a sham operation for comparison. Longitudinal individual urodynamic data were obtained weekly, so that guinea pigs were killed at different levels of bladder dysfunction. Bladder sections were stained with periodic acid‐Schiff (PAS) to assess overall morphology and glycogen granule density, scored from 0 (no glycogen) to 3. Glycogen scores were related to both the end‐stage and historical extremes of bladder function values.RESULTSGlycogen granules were seen only in the detrusor; as their number increased their location expanded from only close to the serosa (glycogen score 1), through the detrusor (score 2) up to the urothelium (score 3). A glycogen score of 0 correlated with normal values for all urodynamic variables. Compared with a glycogen score of 0 a score of 1 correlated with significant (P < 0.05) changes in end‐stage compliance (decrease) and contractility (increase) and significantly higher historical values for contractility, pressure and number of unstable contractions (NUC). In the group with a glycogen score of 2 there were significant changes in both the end‐stage values and historical extremes for compliance, pressure, contractility and NUC (all P < 0.05). In the group with a glycogen score of 3 all these changes were even more dramatic, except for the end‐stage contractility, for which the increase was not significant. From glycogen score 0 to score 3 all changes increased in magnitude.CONCLUSIONA high glycogen content reflects a history of abnormal urodynamic function. This finding exemplifies the added value of structural analysis to urodynamic studies. Further studies are needed to relate bladder structure to the potential for functional recovery.