bluuebunny/crossref_metadata_2025 huggingface dataset:
Late urodynamic findings after treating traumatic rupture of the posterior urethra in boys
Authors: ÖTGÜN IBRAHIM , KARNAK IBRAHIM , SENOCAK MEHMET EMIN , TANYEL FERIDUN CAHIT , CIFTCI ARBAY OZDEN , BÜYÜKPAMUKÇU NEBIL
Published: January 2006

OBJECTIVE

To investigate lower urinary tract (LUT) functions in a prospective study in boys treated for posterior urethral distraction (PUD), as posterior urethral stricture, erectile dysfunction and incontinence can occur after various treatments for this rare injury in children.

PATIENTS AND METHODS

Eleven boys were treated for PUD and resultant stricture between 1980 and 2000. Their age, the cause of trauma, extent of injury, previous treatment, and continence status were evaluated, and a urodynamic study conducted. Controls were 12 age‐matched males who underwent similar cystometrography (CMG) and uroflowmetry.

RESULTS

The mean (sd) age at injury was 8 (4) years and the cause was traffic accident in nine and crush injury in two boys. Seven boys had an isolated urethral rupture, two also had a bladder neck injury and two also had a perforated bladder. No gross neurological impairment developed after trauma. Voiding cysto‐urethrograms after initial therapy showed vesico‐ureteric reflux in five boys, but in only one at the time of the urodynamic studies. At the time of urodynamic study, the mean (sd) age of the patients was 15 (6) years; seven were fully continent, one had intermittent leakage, two were incontinent, and one had nocturnal enuresis. CMG‐electromyography (EMG) showed a reduced maximum cystometric capacity in nine patients, reduced compliance in 10, stable detrusor in 11, synergic detrusor‐sphincter activity in 11, and residual urine in one. The uroflowmetry‐EMG study showed prolonged voiding time and flow time, decreased maximum flow urinary rate (Qmax) and mean flow rate (Qavg). The shape of the flow curve showed an uninterrupted low‐amplitude pattern. Comparing these patients with age‐matched controls, CMG and uroflowmetry studies showed that the maximum cystometric bladder capacity, compliance, Qmax and Qavg were all significantly lower in patients with PUD, while voiding time and flow time were significantly higher.

CONCLUSION

The LUT deteriorates after treating PUD in boys. CMG and uroflowmetry findings are consistent with partial anatomical obstruction distal to the bladder. Our results are preliminary and full urodynamics, including pressure‐flow studies, will be useful to support this conclusion. A urodynamic study should be integral in the management of PUD.
Lymphadenectomy for invasive bladder cancer: I. historical perspective and contemporary rationale
Authors: STEIN JOHN P. , QUEK MARCUS L. , SKINNER DONALD G.
Published: January 2006

The role of extended lymphadenectomy in bladder cancer was introduced by Donald Skinner some years ago, and caused some controversy at the time. Since then, it has been reported by other influential urologists as being of benefit to patients with this condition. In this issue, two of the mini‐reviews are dedicated to a full description of this concept, giving a historical perspective, the rationale for the procedure, the technical aspects, and indicating important prognostic factors.
Distribution of neuropeptide Y‐containing nerves in the neurogenic and non‐neurogenic detrusor
Authors: HAFERKAMP AXEL , FREUND THOMAS , WAGENER NINA , REITZ ANDRE , SCHURCH BRIGITTE , DOERSAM JOACHIM , SCHUMACHER STEFAN , BASTIAN PATRICK J. , BUETTNER REINOLD J. , MUELLER STEFAN C. , HOHENFELLNER MARKUS
Published: January 2006

OBJECTIVE

To evaluate the role of neuropeptide Y in the detrusor of patients with neurogenic detrusor overactivity (NDO), as it has an important role in the neural regulation of the lower urinary tract by exerting differential effects on the release of cholinergic and adrenergic transmitters via autoinhibition and heterosynaptic interactions

MATERIALS AND METHODS

Detrusor biopsies were obtained from 38 patients; 31 had video‐urodynamically verified NDO, caused by meningomyelocele in 17 or spinal cord injury in 14. Seven had stress urinary incontinence (SUI) and this group served as a control. All specimens were fixed, paraffin wax‐embedded, sectioned and stained with a monoclonal antibody against neuropeptide Y and a general nerve marker protein‐gene‐product 9.5 (PGP 9.5). The number of PGP 9.5‐ and neuropeptide Y‐containing nerves was quantified by a standardized evaluation using image‐analysis software.

RESULTS

The median (range) number of neuropeptide Y‐containing nerves in the neurogenic detrusor, at 0.273 (0.126–0.639) per muscle cell nucleus (MCN), was significantly lower (P = 0.014) than that in patients with SUI, at 0.383 (0.267–0.728). In the neurogenic detrusor the number of PGP 9.5‐positive nerves, at 0.278 (0.054–0.641)/MCN was also lower (P = 0.111) than in patients with SUI, at 0.368 (0.258–0.497). The ratio of neuropeptide Y to PGP 9.5 counts per biopsy did not differ between the groups (P = 0.628).

CONCLUSIONS

The number of PGP 9.5‐positive nerves was not significantly and the number of neuropeptide Y‐containing nerves was significantly reduced in patients with NDO. This may have been caused by transynaptic nerve degeneration of the detrusor, as described by in patients with spinal cord injury. As neuropeptide Y inhibits the contractile response of the detrusor the reduction of neuropeptide Y‐containing nerves may play a role in the development and persistence of DO.
High‐dose interleukin‐2 immunotherapy is safe for patients with metastatic renal cell carcinoma on dialysis
Authors: BRUSKY JOHN P. , GAILANI FAWEZ , PATHAK APURBA , PATEL HATEL , ABOSEIF SHERIF
Published: January 2006

OBJECTIVE

To report our experience of high‐dose interleukin‐2 immunotherapy for patients with metastatic renal cell carcinoma (RCC) on haemodialysis.

PATIENTS AND METHODS

Two anephric patients with metastatic RCC on haemodialysis received interleukin‐2 (600 000 IU/kg) every 8 h for a maximum of 14 doses. The patients rested for 9 days and cycles were repeated as tolerated. A nephrologist followed the patients during treatment and they received nearly daily haemodialysis.

RESULTS

These two cases were treated with high‐dose interleukin‐2 and had no unusual toxicity or adverse events. The first patient tolerated five, five, four, four and one dose of interleukin‐2 over five cycles. He had a partial response to treatment with a decrease in size of a mediastinal mass, but ultimately developed progressive disease and died 32 months later. The second patient had four cycles of interleukin‐2 (13, 13, 14 and nine doses). He initially maintained stable disease throughout treatment, but the disease ultimately progressed and he died 19 months later.

CONCLUSIONS

We recommend considering high‐dose interleukin‐2 immunotherapy in highly selected dialysis patients with metastatic RCC. Further study is required to determine the safety, efficacy and optimum dosing in this group.
Urodynamic effects of propiverine hydrochloride in children with neurogenic detrusor overactivity: a prospective analysis
Authors: SCHULTE‐BAUKLOH HEINRICH , MÜRTZ GERD , HENNE THOMAS , MICHAEL THEODOR , MILLER KURT , KNISPEL HELMUT H.
Published: January 2006

The management of stones in children is often controversial; extracorporeal shock wave lithotripsy appears to be very successful, with excellent clearance rates, and probably better than in adults. For this reason, many maintain that percutaneous nephrolithotripsy might not be required in children. Authors from Pakistan retrospectively assessed their use of percutaneous nephrolithotripsy, finding that it too yields satisfactory results.

OBJECTIVES

To evaluate prospectively the efficacy and tolerability of propiverine for treating neurogenic detrusor overactivity (NDO) in children.

PATIENTS AND METHODS

Twenty children (mean age 8.9 years; median 5.6) with NDO due to an upper motor neurone lesion were enrolled (17 had myelomeningocele). In the urodynamic examination, reflex volume (RV), maximum detrusor pressure (MDP), maximum cystometric bladder capacity (MCBC) and bladder compliance (BC) before and after a twice‐daily propiverine hydrochloride regimen were determined. The urodynamic follow‐up was after 3–6 months. Incontinence was assessed by an incontinence score.

RESULTS

The mean (sem) RV increased from 103.8 (21.3) to 174.5 (33.7) mL (P < 0.005), MDP decreased from 52.5 (7.9) to 40.1 (6.2) cmH2O (P < 0.05), MCBC increased from 166 (28.8) to 231.9 (34.8) mL (P < 0.005), and BC improved from 11.2 (2.8) to 30.6 (9.7) mL/cmH2O (P < 0.01), with propiverine treatment. The incontinence score (scale 0–3) improved from 2.4 (0.2) to 1.6 (0.3) (P < 0.05). Propiverine was well tolerated, although some children were given higher doses than recommended.

CONCLUSIONS

Propiverine hydrochloride is effective and well tolerated in the treatment of children with NDO. Because of its dual mode of action, it is well tolerated even in children who need higher doses. Propiverine hydrochloride is a preferable alternative to oxybutynin, the anticholinergic most frequently used in children with NDO to date.
Location of a positive biopsy as a predictor of surgical margin status and extraprostatic disease in radical prostatectomy
Authors: TOUMA NAJI J. , CHIN JOSEPH L. , BELLA TONY , SENER ALP , IZAWA JONATHAN I.
Published: January 2006

OBJECTIVE

To investigate whether the location of preoperative biopsy positive cores can identify patients at higher risk of a positive surgical margin (SM) and extraprostatic extension (EPE) at radical retropubic prostatectomy (RRP).

PATIENTS AND METHODS

We retrospectively reviewed the clinical and pathological data of 371 patients who had a RRP for biopsy confirmed prostate cancer between January 2000 and October 2003.

RESULTS

A positive biopsy at the apex was not predictive of a positive apical SM or EPE. However, a positive biopsy at the base was predictive of a positive basal SM and EPE. A positive SM, in turn, correlated with EPE on final pathology. Positive basal SM correlated with EPE in 75% of cases whereas positive apical SM showed EPE in only 33% (P < 0.02).

CONCLUSION

A positive biopsy core at the base appears to correlate with a positive basal SM and EPE. A positive basal SM correlates with EPE at a higher rate than apical SMs.
A prospective analysis of the diagnostic yield resulting from the attendance of 4020 patients at a protocol‐driven haematuria clinic
Authors: EDWARDS TOM J. , DICKINSON ANDREW J. , NATALE SALVATORE , GOSLING JANE , MCGRATH JOHN S.
Published: January 2006

OBJECTIVE

To clarify the prevalence of disease as determined by age, sex and the degree of haematuria at presentation, and to ascertain the merits of using ultrasonography (US), i.v. urography (IVU) or both when imaging the upper urinary tract, in a prospective cohort of patients attending a protocol‐based haematuria clinic.

PATIENTS AND METHODS

In a two‐tier protocol, as a part of first‐line investigation, all 4020 patients attending the clinic between October 1998 and August 2003 had US and flexible cystoscopy. Subsequently, IVU was used where indicated following abnormal first‐line tests and in patients with persistent haematuria where no abnormality had been detected.

RESULTS

In all, 2627 men and 1393 women presented with microscopic (53.2%) or macroscopic haematuria (46.8%). The overall prevalence of malignant disease was 12.1%, but for macroscopic haematuria it was 18.9% and for microscopic haematuria 4.8%. Age and sex also influenced the observed rates of disease. Of the upper tract tumours, 70 were identified after abnormal US, with three cases of transitional cell carcinoma identified on IVU after a normal US.

CONCLUSIONS

The study provides a rationale for the appropriate investigation of all patients, moderated by the age, sex and degree of haematuria, and the ubiquitous use of US with selective IVU based on age, sex and degree of (and persistence of) haematuria.
Family history, self‐perceptions, attitudes and cognitive abilities are associated with early adolescent reading skills
Authors: Conlon Elizabeth G. , Zimmer‐Gembeck Melanie J. , Creed Peter A. , Tucker Melinda
Published: January 2006

This study evaluated a model of reading skills among early adolescents (N=174). Measures of family history, achievement, cognitive processes and self‐perceptions of abilities were obtained. Significant relationships were found between family history and children's single‐word reading skills, spelling, reading comprehension, orthographic processing and children's perceived reading competence. While children with poor reading skills were five times more likely to come from a family with a history of reading difficulties, this measure did not account for additional variance in reading performance after other variables were included. Phonological, orthographic, rapid sequencing and children's perceived reading competence made significant independent contributions towards reading and spelling outcomes. Reading comprehension was explained by orthographic processing, nonverbal ability, children's attitudes towards reading and word identification. Thus, knowledge of family history and children's attitudes and perceptions towards reading provides important additional information when evaluating reading skills among a normative sample of early adolescents.
Genetic and environmental influences on reading and listening comprehension
Authors: Keenan Janice M. , Betjemann Rebecca S. , Wadsworth Sally J. , DeFries John C. , Olson Richard K.
Published: January 2006

We report preliminary behaviour genetic analyses of reading and listening comprehension from The Colorado Learning Disabilities Research Center. Although the twin sample with these new measures is still of limited size, we find substantial, and significant, genetic influences on individual differences in both reading and listening comprehension. In addition, word recognition and listening comprehension each accounted for significant independent genetic influences on reading comprehension. Together, they accounted for all the genetic influence on reading comprehension, indicating a largely genetic basis for the ‘simple model’ of individual differences in reading comprehension proposed by Hoover and Gough (1990).
Photosynthesis of Eucalyptus globulus with Mycosphaerella leaf disease
Authors: Pinkard E. A. , Mohammed C. L.
Published: January 2006

Mycosphaerella leaf disease (MLD) is a major cause of foliage damage in Eucalyptus globulus plantations. Our study is the first to describe the physiological effects of MLD on E. globulus leaves. It involved measurements on both field and potted plants.

Changes in photosynthetic parameters in response to MLD were quantified in a study using gas exchange techniques.

There was a negative linear relationship between light‐saturated photosynthesis (Amax) and leaf‐level damage from MLD. Reductions in Amax were proportionally greater than might be expected from the reduction in green leaf area as a result of the disease, indicating that asymptomatic tissue also was affected by MLD. The reductions in Amax were not related to increases in stomatal resistance, but were a result of reduced activity of ribulose bisphosphate carboxylase (Rubisco) and changes in the capacity for ribulose bisphosphate (RuBP) regeneration. Changes in mesophyll resistance to CO2 were also implicated.

The effect of MLD was similar at different sites and irrespective of tree‐level infection, suggesting a general leaf‐level response of E. globulus to MLD.
Does soil CO2efflux acclimatize to elevated temperature and CO2during long‐term treatment of Douglas‐fir seedlings?
Authors: Tingey D. T. , Lee E. H. , Waschmann R. , Johnson M. G. , Rygiewicz P. T.
Published: January 2006

We investigated the effects of elevated soil temperature and atmospheric CO2on soil CO2efflux (SCE) during the third and fourth years of study. We hypothesized that elevated temperature would stimulate SCE, and elevated CO2would also stimulate SCE with the stimulation being greater at higher temperatures.

The study was conducted in sun‐lit controlled‐environment chambers using Douglas‐fir (Pseudotsuga menziesii) seedlings grown in reconstructed litter‐soil systems. We used a randomized design with two soil temperature and two atmospheric CO2treatments. The SCE was measured every 4 wk for 18 months.

Neither elevated temperature nor CO2stimulated SCE. Elevated CO2increased the temperature sensitivity of SCE. During the winter, the relationship between SCE and soil moisture was negative but it was positive during the summer. The seasonal patterns in SCE were associated with seasonal changes in photosynthesis and above‐ground plant growth.

SCE acclimatized in the high‐temperature treatment, probably because of a loss of labile soil carbon. Elevated CO2treatment increased the temperature sensitivity of SCE, probably through an increase in substrate availability.
Activation of JAK/STAT signalling in neurons following spinal cord injury in mice
Authors: Yamauchi Katsuaki , Osuka Koji , Takayasu Masakazu , Usuda Nobuteru , Nakazawa Ayami , Nakahara Norimoto , Yoshida Mitsuhiro , Aoshima Chihiro , Hara Masahito , Yoshida Jun
Published: January 2006

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway is one of the most important in transducing signals from the cell surface to the nucleus in response to cytokines. In the present study, we investigated chronological alteration and cellular location of JAK1, STAT3, phosphorylated (p)‐Tyr1022/1023‐JAK1, p‐Tyr705‐STAT3, and interleukin‐6 (IL‐6) following spinal cord injury (SCI) in mice. Western blot analysis showed JAK1 to be significantly phosphorylated at Tyr1022/1023 from 6 h after SCI, peaking at 12 h and gradually decreasing thereafter, accompanied by phosphorylation of STAT3 at Tyr705 with a similar time course. ELISA analysis showed the concentration of IL‐6 in injured spinal cord to also significantly increase from 3 h after SCI, peaking at 12 h, then gradually decreasing. Immunohistochemistry revealed p‐Tyr1022/1023‐JAK1, p‐Tyr705‐STAT3, and IL‐6 to be mainly expressed in neurons of the anterior horns at 12 h after SCI. Pretreatment with a JAK inhibitor, AG‐490, suppressed phosphorylation of JAK1 and STAT3 at 12 h after SCI, reducing recovery of motor functions. These findings suggest that SCI at the acute stage produces IL‐6 mainly in neurons of the injured spinal cord, which activates the JAK/STAT pathway, and that this pathway may be involved with neuronal response to SCI.
Norepinephrine transporter knockout‐induced up‐regulation of brain alpha2A/C‐adrenergic receptors
Authors: Gilsbach R. , Faron‐Górecka A. , Rogóz Z. , Brüss M. , Caron M. G. , Dziedzicka‐Wasylewska M. , Bönisch H.
Published: January 2006

The norepinephrine transporter (NET) is responsible for the rapid removal of norepinephrine released from sympathetic neurons; this release is controlled by inhibitory α2‐adrenergic receptors (α2ARs). Long‐term inhibition of the NET by antidepressants has been reported to change the density and function of pre‐ and postsynaptic ARs, which may contribute to the antidepressant effects of NET inhibitors such as desipramine. NET‐deficient (NET‐KO) mice have been described to behave like antidepressant‐treated mice. By means of quantitative real‐time PCR we show that mRNAs encoding the α2A‐adrenergic receptor (α2AAR) and the α2C‐adrenergic receptor (α2CAR) are up‐regulated in the brainstem, and that α2CAR mRNA is also elevated in the hippocampus and striatum of NET‐KO mice. These results were confirmed at the protein level by quantitative autoradiography. The NET‐KO mice showed enhanced binding of the selective α2AR antagonist [3H]RX821002 in several brain regions. Most robust increases (20–25%) in α2AR expression were observed in the hippocampus and in the striatum. Significant increases (16%) were also seen in the extended amygdala and thalamic structures. In an ‘in vivo’ test, the α2AR agonist clonidine (0.1 mg/kg) caused a significantly greater reduction of locomotor activity in NET‐KO mice than in wild‐type mice, showing the relevance of our findings at the functional level.
Alternative splicing of human metabotropic glutamate receptor 3
Authors: Sartorius Leah J. , Nagappan Guhan , Lipska Barbara K. , Lu Bai , Sei Yoshitatsu , Ren‐Patterson Renee , Li Zhen , Weinberger Daniel R. , Harrison Paul J.
Published: January 2006

The metabotropic glutamate receptor 3 (GRM3, mGluR3) is important in regulating synaptic glutamate. Here, we report the existence of three splice variants of GRM3 in human brain arising from exon skipping events. The transcripts are expressed in prefrontal cortex, hippocampus and cerebellum, and in B lymphoblasts. We found no evidence for alternative splicing of GRM2. The most abundant GRM3 variant lacks exon 4 (GRM3Δ4). In silico translation analysis of GRM3Δ4 predicts a truncated protein with a conserved extracellular ligand binding domain, absence of a seven‐transmembrane domain, and a unique 96‐amino acid C‐terminus. When expressed in rat hippocampal neurons, GRM3Δ4 is translated into a 60 kDa protein. Immunostaining and cell fractionation data indicate that the truncated protein is primarily membrane‐associated. An antibody developed against the GRM3Δ4 C‐terminus detects a protein of approximately 60 kDa in human brain lysates and in B lymphoblasts, suggesting translation of GRM3Δ4 in vivo. The existence of the GRM3Δ4 isoform is relevant in the light of the reported association of non‐coding single nucleotide polymorphisms (SNPs) in GRM3 with schizophrenia, and with the potential of GRM3 as a therapeutic target for several neuropsychiatric disorders.
Hydrogen ion concentration differentiates effects of methamphetamine and dopamine on transporter‐mediated efflux
Authors: Wilhelm Clare J. , Johnson Robert A. , Eshleman Amy J. , Janowsky Aaron
Published: January 2006

Methamphetamine (METH) causes release of stored intracellular dopamine (DA). We explored the interactions of METH with the recombinant human vesicular monoamine (hVMAT2) and/or human DA transporters (hDAT) in transfected mammalian (HEK293) cells and compared the findings with those for DA. In ‘static’ release assays at 37°C, less than 20% of pre‐loaded [3H]DA was lost after 60 min, while nearly 80% of pre‐loaded [3H]METH was lost at 37°C under non‐stimulated conditions. Results obtained by measuring substrate release using a superfusion apparatus revealed an even greater difference in substrate efflux. At pH 7.4, nearly all of the pre‐loaded [3H]METH was lost after just 6 min, compared with the loss of 70–80% of pre‐loaded [3H]DA (depending on cell type) after superfusion for 32 min. Increasing the extracellular pH from 7.4 to 8.6 had opposite effects on [3H]DA and [3H]METH retention. At pH 8.6, [3H]METH was retained more effectively by both hDAT and hDAT‐hVMAT2 cells, compared with results obtained at extracellular pH 7.4. [3H]DA, however, was more effectively retained at pH 7.4 than at pH 8.6. These data suggest that DA and METH interact differently with the DAT and VMAT2, and require different H+concentrations to exert their effects.
Galanin attenuates cyclic AMP regulatory element‐binding protein (CREB) phosphorylation induced by chronic morphine and naloxone challenge in Cath.a cells and primary striatal cultures
Authors: Hawes Jessica J. , Narasimhaiah Roopashree , Picciotto Marina R.
Published: January 2006

Repeated morphine administration leads to molecular alterations of the neural circuitry in the locus coeruleus and nucleus accumbens. These changes include increased activity of several components of the cAMP signaling pathway that are thought to be associated with psychological and somatic signs of opiate withdrawal. The neuropeptide galanin has been shown to attenuate cAMP signaling in multiple cell types. The current study demonstrates that acute galanin treatment blocks the consequences of increased cAMP signaling following chronic opiate administration and withdrawal in Cath.a cells and primary cultures of striatal neurons as measured by phosphorylation of the transcription factor cAMP regulatory element‐binding protein (CREB). In addition, galanin‐mediated attenuation of CREB phosphorylation is independent of galanin‐induced extracellular signal‐regulated kinase (ERK) 1/2 phosphorylation in Cath.a cells. These data suggest that galanin receptors may serve as an additional potential therapeutic target for the treatment of opiate withdrawal.
Altered neuropeptide processing in prefrontal cortex of Cpefat/fat mice: implications for neuropeptide discovery
Authors: Lim Jihyeon , Berezniuk Iryna , Che Fa‐Yun , Parikh Rishi , Biswas Reeta , Pan Hui , Fricker Lloyd D.
Published: January 2006

The biosynthesis of most neuropeptides and peptide hormones requires a carboxypeptidase such as carboxypeptidase E, which is inactive in Cpefat/fat mice due to a naturally occurring point mutation. To assess the role of carboxypeptidase E in the processing of peptides in the prefrontal cortex, we used a quantitative peptidomics approach to examine the relative levels of peptides in Cpefat/fat versus wild‐type mice. Peptides representing internal fragments of prohormones and other secretory pathway proteins were decreased two‐ to 10‐fold in the Cpefat/fat mouse prefrontal cortex compared with wild‐type tissue. Degradation fragments of cytosolic proteins showed no major differences between Cpefat/fat and wild‐type mice. Based on this observation, a search strategy for neuropeptides was performed by screening for peptides that decreased in the Cpefat/fat mouse. Altogether, 32 peptides were identified, of which seven have not been previously reported. The novel peptides include fragments of VGF, procholecystokinin and prohormone convertase 2. Interestingly, several of the peptides do not fit with the consensus sites for prohormone convertase 1 and 2, raising the possibility that another endopeptidase is involved with their biosynthesis. Taken together, these findings support the proposal that carboxypeptidase E is the major, but not the only, peptide‐processing carboxypeptidase and also demonstrate the feasibility of searching for novel peptides based on their decrease in Cpefat/fat mice.
The cytoplasmic sequence of E‐cadherin promotes non‐amyloidogenic degradation of Aβ precursors
Authors: Agiostratidou Georgia , Muros Rosa Miñana , Shioi Junichi , Marambaud Philippe , Robakis Nikolaos K.
Published: January 2006

The presenilin (PS)/γ‐secretase system promotes production of the Abeta (Aβ) peptides by mediating cleavage of amyloid precursor protein (APP) at the γ‐sites. This system is also involved in the processing of type‐I transmembrane proteins, including APP, cadherins and Notch1 receptors, at the ɛ‐cleavage site, resulting in the production of peptides containing the intracellular domains (ICDs) of the cleaved proteins. Emerging evidence shows that these peptides have important biological functions, raising the possibility that their inhibition by γ‐secretase inhibitors may be detrimental to the cell. Here, we show that peptide E‐Cad/CTF2, produced by the PS1/γ‐secretase processing of E‐cadherin, promotes the lysosomal/endosomal degradation of the transmembrane APP derivatives, C99 and C83, and inhibits production of the APP ICD (AICD). In addition, E‐Cad/CTF2 decreases accumulation of total secreted Aβ. These data suggest a novel method to promote the non‐amyloidogenic degradation of Aβ precursors and to inhibit Aβ production.
Transcriptional response to the neuroleptic‐like compound Ampullosporin A in the rat ketamine model
Authors: Krügel Hans , Becker Axel , Polten Andreas , Grecksch Gisela , Singh Ram , Berg Albrecht , Seidenbecher Constanze , Saluz Hans‐Peter
Published: January 2006

Psychotic disorders affecting up to 1% of the human population represent pathological changes to the metabolic homeostasis of the brain. Increasing evidence in the literature suggests complex biochemical and/or transcriptional alterations accompanying schizophrenia‐like phenomena. Sub‐chronic treatment with sub‐anaesthetic doses of ketamine induces schizophrenia‐related psychotic alterations that can be used as an animal model in the study of this disorder. Ampullosporin A belongs to a specific group of pore‐forming fungal peptides, peptaibols. We focused on the analysis of molecular events occurring in the brain of ketamine‐pre‐treated rats after administration of Ampullosporin A with neuroleptic‐like activity. The complex experimental approach allowed us to correlate the use of low molecular weight substances with a transcriptome fingerprint in the prefrontal cortex. We found 63 genes to be up‐regulated and 22 genes suppressed, with transthyretin, syndecan‐1 and NeuroD1 showing the highest degree of up‐regulation. Our results suggest the possibility that Ampullosporin A belongs to the group of neuroleptic‐like compounds, inducing massive changes in neurotransmitter receptor composition, calcium signalling cascades and second messenger systems, and leading to the plastic reorganization of brain tissue, metabolic pathways and synapses.
Editorials: Recombinant Human Erythropoietin: Has Treatment Reached its Full Potential?
Authors: Fishbane Steven
Published: January 2006

For more than 15 years recombinant human erythropoietin (r‐HuEPO) has been used for the treatment of renal anemiabenefiting patients with improved quality of life and reduced need for blood transfusions. It is still early in the history of r‐HuEPO treatment; therapy has changed little and there have been few investigations into whether current treatment strategies are optimal. Of notecurrent therapy makes little attempt to mimic normal erythropoietin biology. Large doses of drug are administered episodicallyresulting in great fluxes in serum erythropoietin levels. It is unlikely that this approach is very efficient from the erythropoietic standpoint. Furthermorethe effects of these nonbiologic kinetics on extraerythroid organs that express erythropoietin receptors are unknown. In this reviewthe current state of r‐HuEPO treatment is compared to the normal biology of erythropoietin and potential pitfalls caused by divergences are explored.
Dynamics and Function of Phospholipase D and Phosphatidic Acid During Phagocytosis
Authors: Corrotte Matthias , Chasserot‐Golaz Sylvette , Huang Ping , Du Guangwei , Ktistakis Nicholas T. , Frohman Michael A. , Vitale Nicolas , Bader Marie‐France , Grant Nancy J.
Published: January 2006

Phospholipase D (PLD) produces phosphatidic acid (PA), an established intracellular signalling lipid that has been also implicated in vesicular trafficking, and as such, PLD could play multiple roles during phagocytosis. Using an RNA interference strategy, we show that endogenous PLD1 and PLD2 are necessary for efficient phagocytosis in murine macrophages, in line with results obtained with wild‐type constructs and catalytically inactive PLD mutants which, respectively, enhance and inhibit phagocytosis. Furthermore, we found that PA is transiently produced at sites of phagosome formation. Macrophage PLD1 and PLD2 differ in their subcellular distributions. PLD1 is associated with cytoplasmic vesicles, identified as a late endosomal/lysosomal compartment, whereas PLD2 localizes at the plasma membrane. In living cells undergoing phagocytosis, PLD1 vesicles are recruited to nascent and internalized phagosomes, whereas PLD2 is only observed on nascent phagosomes. These results provide evidence that both PLD isoforms are required for phagosome formation, but only PLD1 seems to be implicated in later stages of phagocytosis occurring after phagosomal internalization.
From Sermon to Play: Literary Representations of ‘Turks’ in Renaissance England 1550–1625
Authors: Schmuck Stephan
Published: January 2006

This article explores the figure of ‘Turks’ in a number of texts ranging from sermon to play. More specifically, it addresses a variety of available representations of ‘Turks’ and considers the ways in which literary critics and cultural historians have assessed their role and significance in early modern English writings. Whether as ambassadors, partners in trade, demonised infidels, potential military allies or as characters on the commercial stage, English writers invested ‘Turks’ with controversial and frequently contradictory meanings that were both real and imagined. As a result, this cultural ‘other’ emerges as a complex construct, an idea through which Englishmen and women could reflect on their own culture and which defies easy critical categorisation.
British Romanticism in the Museum Age: A Review of Recent Scholarship
Authors: Gidal Eric
Published: January 2006

This essay surveys recent scholarship in British Romantic literature and culture that emphasizes the interrelations between collections, exhibitions, and museums and the poetry, novels, and aesthetic philosophy of the late eighteenth and early nineteenth centuries. It summarizes the scope and argument of important works of literary and cultural criticism and lists many related studies from other disciplines while providing a general overview of the historical and theoretical issues governing current discussions of Romantic‐era exhibitionary culture.
A Brief History of the Edited Shakespearean Text
Authors: Paul Gavin
Published: January 2006

This essay won the 2005 Literature Compass Graduate Essay Prize, Shakespeare Section.

This essay will involve a historical survey of the underlying theories and principles that have been instrumental in determining the formative scholarly editions of Shakespeare since the early eighteenth century. By examining representations of editorial practice – specifically representations as expressed in prefatory material as well as other editorial apparatuses such as notes and commentary in influential editions from Nicholas Rowe's (1709) through to those of the late twentieth century – this paper is aimed at providing a clear sense of the fundamental principles shaping the edited Shakespearean text.
The hemoglobin genes of Drosophila
Authors: Burmester Thorsten , Storf Joachim , Hasenjäger Anne , Klawitter Sabine , Hankeln Thomas
Published: January 2006

We recently reported the unprecedented occurrence of a hemoglobin gene (glob1) in the fruitfly Drosophila melanogaster. Here we investigate the structure and evolution of the glob1 gene in other Drosophila species. We cloned and sequenced glob1 genes and cDNA from D. pseudoobscura and D. virilis, and identified the glob1 gene sequences of D. simulans, D. yakuba, D. erecta, D. ananassae, D. mojavensis and D. grimshawi in the databases. Gene structure (introns in helix positions D7.0 and G7.0), gene synteny and sequence of glob1 are highly conserved, with high ds/dn ratios indicating strong purifying selection. The data suggest an important role of the glob1 protein in Drosophila, which may be the control of oxygen flow from the tracheal system. Furthermore, we identified two additional globin genes (glob2 and glob3) in the Drosophilidae. Although the sequences are highly derived, the amino acids required for heme‐ and oxygen‐binding are conserved. In contrast to other known insect globin, the glob2 and glob3 genes harbour both globin‐typical introns at positions B12.2 and G7.0. Both genes are conserved in various drosophilid species, but only expression of glob2 could be demonstrated by western blotting and RT‐PCR. Phylogenetic analyses show that the clade leading to glob2 and glob3, which are sistergroups, diverged first in the evolution of dipteran globins. glob1 is closely related to the intracellular hemoglobin of the botfly Gasterophilus intestinalis, and the extracellular hemoglobins from the chironomid midges derive from this clade.
Increased amylosucrase activity and specificity, and identification of regions important for activity, specificity and stability through molecular evolution
Authors: van der Veen Bart A. , Skov Lars K. , Potocki‐Véronèse Gabrielle , Gajhede Michael , Monsan Pierre , Remaud‐Simeon Magali
Published: January 2006

Amylosucrase is a transglycosidase which belongs to family 13 of the glycoside hydrolases and transglycosidases, and catalyses the formation of amylose from sucrose. Its potential use as an industrial tool for the synthesis or modification of polysaccharides is hampered by its low catalytic efficiency on sucrose alone, its low stability and the catalysis of side reactions resulting in sucrose isomer formation. Therefore, combinatorial engineering of the enzyme through random mutagenesis, gene shuffling and selective screening (directed evolution) was applied, in order to generate more efficient variants of the enzyme. This resulted in isolation of the most active amylosucrase (Asn387Asp) characterized to date, with a 60% increase in activity and a highly efficient polymerase (Glu227Gly) that produces a longer polymer than the wild‐type enzyme. Furthermore, judged from the screening results, several variants are expected to be improved concerning activity and/or thermostability. Most of the amino acid substitutions observed in the totality of these improved variants are clustered around specific regions. The secondary sucrose‐binding site and β strand 7, connected to the important Asp393 residue, are found to be important for amylosucrase activity, whereas a specific loop in the B‐domain is involved in amylosucrase specificity and stability.
Cholesterol and its anionic derivatives inhibit 5‐lipoxygenase activation in polymorphonuclear leukocytes and MonoMac6 cells
Authors: Aleksandrov Dmitry A. , Zagryagskaya Anna N. , Pushkareva Marina A. , Bachschmid Markus , Peters‐Golden Marc , Werz Oliver , Steinhilber Dieter , Sud'ina Galina F.
Published: January 2006

5‐Lipoxygenase (5‐LO) is the key enzyme in the biosynthesis of leukotrienes (LTs), biological mediators of host defense reactions and of inflammatory diseases. While the role of membrane binding in the regulation of 5‐LO activity is well established, the effects of lipids on cellular activity when added to the medium has not been characterized. Here, we show such a novel function of the most abundant sulfated sterol in human blood, cholesterol sulfate (CS), to suppress LT production in human polymorphonuclear leukocytes (PMNL) and Mono Mac6 cells. We synthesized another anionic lipid, cholesterol phosphate, which demonstrated a similar capacity in suppression of LT synthesis in PMNL. Cholesteryl acetate was without effect. Cholesterol increased the effect of CS on 5‐LO product synthesis. CS and cholesterol also inhibited arachidonic acid (AA) release from PMNL. Addition of exogenous AA increased the threshold concentration of CS required to inhibit LT synthesis. The effect of cholesterol and its anionic derivatives can arise from remodeling of the cell membrane, which interferes with 5‐LO activation. The fact that cellular LT production is regulated by sulfated cholesterol highlights a possible regulatory role of sulfotransferases/sulfatases in 5‐LO product synthesis.
Manipulation of prenyl chain length determination mechanism of cis‐prenyltransferases
Authors: Kharel Yugesh , Takahashi Seiji , Yamashita Satoshi , Koyama Tanetoshi
Published: January 2006

The carbon backbones of Z,E‐mixed isoprenoids are synthesized by sequential cis‐condensation of isopentenyl diphosphate (IPP) and an allylic diphosphate through actions of a series of enzymes called cis‐prenyltransferases. Recent molecular analyses of Micrococcus luteus B‐P 26 undecaprenyl diphosphate (UPP, C55) synthase [Fujihashi M, Zhang Y‐W, Higuchi Y, Li X‐Y, Koyama T & Miki K (2001) Proc Natl Acad Sci USA98, 4337–4342.] showed that not only the primary structure but also the crystal structure of cis‐prenyltransferases were totally different from those of trans‐prenyltransferases. Although many studies on structure–function relationships of cis‐prenyltransferases have been reported, regulation mechanisms for the ultimate prenyl chain length have not yet been elucidated. We report here that the ultimate chain length of prenyl products can be controlled through structural manipulation of UPP synthase of M. luteus B‐P 26, based on comparisons between structures of various cis‐prenyltransferases. Replacements of Ala72, Phe73, and Trp78, which are located in the proximity of the substrate binding site, with Leu − as in Z,E‐farnesyl diphosphate (C15) synthase − resulted in shorter ultimate products with C20−35. Additional mutation of F223H resulted in even shorter products. On the other hand, insertion of charged residues originating from long‐chain cis‐prenyltransferases into helix‐3, which participates in constitution of the large hydrophobic cleft, resulted in lengthening of the ultimate product chain length, leading to C60−75. These results helped us understand reaction mechanisms of cis‐prenyltransferase including regulation of the ultimate prenyl chain‐length.
COMPARISON OF A REAL‐TIME POLYMERASE CHAIN REACTION ASSAY WITH A CULTURE METHOD FOR THE DETECTION OF SALMONELLA IN RETAIL MEAT SAMPLES
Authors: CATARAME T.M.G. , O'HANLON K.A. , MCDOWELL D.A. , BLAIR I.S. , DUFFY G.
Published: January 2006

A real‐time polymerase chain reaction (PCR) method developed in this study was compared with a conventional International Organization for Standardization culture method for the detection of Salmonella in Irish beef, chicken, pork and turkey. This also provided a snapshot of the incidence of Salmonella in such products. After selective enrichment, all meat samples (n = 100) were: (1) subjected to DNA extraction and real‐time PCR analysis using primers against Salmonella spp. specific gene (16S rRNA) or the invA virulence gene; and (2) plated on differential media and identified as Salmonella using immunological and sub‐typing methods. Retail samples (5/100) were shown to contain Salmonella using the 16S rRNA gene‐based real‐time PCR assay and the standard culture method. However, only two (of five) samples were shown to contain Salmonella using the invA gene‐based real‐time PCR assay. For the sample set examined, the developed 16S rRNA gene‐based real‐time PCR assay demonstrated comparable specificity and sensitivity to the currently used standard culture method but was considerably more rapid.
EFFECTS OF SODIUM LACTATE, SODIUM ACETATE AND SODIUM DIACETATE ON MICROBIOLOGICAL QUALITY OF VACUUM‐PACKED BEEF DURING REFRIGERATED STORAGE
Authors: SERDENGECTI NEJLA , YILDIRIM IBRAHIM , GOKOGLU NALAN
Published: January 2006

Beef samples were cut into the pieces and treated with solutions of 1.8 and 2.5% sodium lactate (SL), 0.1% sodium acetate (SA), 0.1 and 0.2% sodium diacetate (SDA) and their combinations, packed under vacuum and stored in a refrigerator at 4C. Microbiological quality of the samples was investigated during their storage for 21 days. Sodium salts and their combinations significantly (P < 0.05) affected the aerobic plate count (APC). Although growth of lactic acid bacteria (LAB), psychrotrophs and coliforms was delayed in treated samples, they were not completely inhibited. The most effective treatment to delay the growth of microorganisms was the combination of 2.5% SL + 0.2% SDA. The count of bacteria of the samples reached and exceeded the spoilage limit (107−108log cfu/g) after 14 days at 4C.
INCIDENCE AND CHARACTERIZATION OF BACILLUS CEREUS IN MEAT AND MEAT PRODUCTS CONSUMED IN TURKEY
Authors: GÜVEN KIYMET , MUTLU MEHMET BURÇİN , AVCI ÖZGÜR
Published: January 2006

A total of 100 retail samples of meat and meat products were examined for Bacillus cereus using mannitol egg yolk polymyxin (MYP) agar as a selective isolation medium. Only 22.4% of the samples contained detectable levels of B. cereus, with counts ranging from log10 0.69 to 4.80 cfu/g, but a large number of other organisms up to log10 9.06 cfu/g were sometimes observed on the plates and may have masked the presence of B. cereus or inhibited growth. Two samples of soudjouck contained significant levels of B. cereus, sufficient enough to create a public health hazard. Selected isolates were tested for diarrheal enterotoxin production by a reversed passive latex agglutination (RPLA) test kit. Results showed no difference in the toxin production of B. cereus between beef, ground meat, soudjouck and pastrami samples. Plasmid‐profile analysis and susceptibility to the six commonly used antimicrobial agents were done on selected B. cereus isolates. About 96.4% of the isolates contained plasmids. Plasmid sizes ranged between 2.5 and 3.5 kb. The isolates showed a high rate of resistance to oxacillin (OXA) and amoxicillin (AMC) and a low frequency of resistance to the other antimicrobial agents, with all of them being susceptible to vancomycin (VAN). Approximately 54% of the isolates showed multiple resistance. There was no apparent relationship between drug resistance and carriage of plasmids.
Experimentally probing the shape of extra dimensions
Authors: Sher Marc , Sullivan Kelly A.
Published: January 2006

Theories with compact extra dimensions have become increasingly popular. In some theories the standard model particles are confined to our four-dimensional world and only gravity can propagate in the extra dimensions. In these models the size of the extra dimensions can be as large as hundreds of microns. The functional dependence of the gravitational force on distance is well known at both large and small distances compared to the size of the extra dimensions; for two extra dimensions, for example, it varies from 1∕r2 to 1∕r4 as the distance decreases. However, the dependence for intermediate distances has not been fully calculated. We determine this dependence as a function of both the size of the extra dimensions and the possible angle between the extra dimensional unit vectors and show that high precision measurements of the gravitational force would make possible the determination of the shape of the extra dimensions.
Teaching the principles of statistical dynamics
Authors: Ghosh Kingshuk , Dill Ken A. , Inamdar Mandar M. , Seitaridou Effrosyni , Phillips Rob
Published: January 2006

We describe a simple framework for teaching the principles that underlie the dynamical laws of transport: Fick’s law of diffusion, Fourier’s law of heat flow, the Newtonian viscosity law, and the mass-action laws of chemical kinetics. In analogy with the way that the maximization of entropy over microstates leads to the Boltzmann distribution and predictions about equilibria, maximizing a quantity that E. T. Jaynes called “caliber” over all the possible microtrajectories leads to these dynamical laws. The principle of maximum caliber also leads to dynamical distribution functions that characterize the relative probabilities of different microtrajectories. A great source of recent interest in statistical dynamics has resulted from a new generation of single-particle and single-molecule experiments that make it possible to observe dynamics one trajectory at a time.
The Genus
Hafnia
: from Soup to Nuts
Authors: Janda J. Michael , Abbott Sharon L.
Published: January 2006

The genus
Hafnia
, a member of the family
Enterobacteriaceae
, consists of gram-negative bacteria that are occasionally implicated in both intestinal and extraintestinal infections in humans. Despite the fact that the genus currently contains only a single species (
H. alvei
), more extensive phylogenetic depth (two or more species) is apparent based upon DNA relatedness and 16S rRNA gene sequencing studies.
Hafnia
causes a variety of systemic infections, including septicemia and pneumonia; however, its role as a gastrointestinal pathogen is controversial. Many of the data supporting a role for hafniae as enteric pathogens were incorrectly attributed to this genus rather than to the actual pathogen,
Escherichia albertii
. There are numerous gaps in our understanding of this genus, including ecologic habitats and population genetics, disease-producing role in animals, phenetic and genetic methods useful in distinguishing genomospecies within the
H. alvei
complex, and bona fide pathogenicity factors.