bluuebunny/crossref_metadata_2025 huggingface dataset:
Kampo Medicines for Mite Antigen‐Induced Allergic Dermatitis in NC/Nga Mice
Authors: Gao Xiu Kun , Fuseda Kazutoshi , Shibata Tomonori , Tanaka Hiroyuki , Inagaki Naoki , Nagai Hiroichi
Published: March 2005

We have established an allergic dermatitis model in NC/Nga mice by repeated local exposure of mite antigen for analyzing atopic dermatitis. We examined how four Kampo medicines, Juzen‐taiho‐to, Hochu‐ekki‐to, Shofu‐san and Oren‐gedoku‐to, on the dermatitis model to obtain basic information on their usefulness for treating atopic dermatitis. Mite antigen (Dermatophagoides farinae crude extract) solution at a concentration of 10 mg/ml was painted on the ear of NC/Nga mice after tape stripping. The procedure was repeated five times, at 7 day intervals. An apparent biphasic ear swelling was caused after the fourth and fifth antigen exposures with elevated serum IgE levels and accumulation of inflammatory cells. In the cervical lymph nodes and ear lobes, the five procedures of antigen exposure induced interleukin‐4 mRNA expression but reduced interferon‐γ mRNA expression. Oral administration of all four Kampo medicines inhibited the formation of ear swelling and inflammatory cell accumulation. Juzen‐taiho‐to and Hochu‐ekki‐to apparently prevented the elevation of serum IgE level. Furthermore, the four Kampo medicines showed a tendency to prevent not only the increase in interleukin‐4 mRNA expression but also the decrease in interferon‐γ mRNA expression. The present results indicate that Juzen‐taiho‐to, Hochu‐ekki‐to, Shofu‐san and Oren‐gedoku‐to may correct the Th1/Th2 balance skewed to Th2, and this activity helps inhibit dermatitis in NC/Nga mice. The ability of the Kampo medicines to correct the Th1/Th2 balance seems to underlie their effectiveness in treating of atopic dermatitis.
Two Hundred Years of Political Theatre in Vienna
Authors: Yates W.E.
Published: March 2005

The intellectual and political climate of Vienna has long seemed hostile to political theatre, which was indeed forbidden for most of the nineteenth century. But Grillparzer's evocation of a public that perceived even the 1848 revolution as theatre exemplifies the centrality of theatre in cultural life, which has meant that even when politics was not its overt subject it has functioned as a showcase for political issues. Examples central to Viennese theatre tradition are cited to support the argument that historically this has indeed been one of the most important functions of theatre in Vienna, so qualifying in relation to the Burgtheater the kind of criticism developed in Eugen Klingenberg's recent polemical history. That in the Metternich period theatre reviews were the chief organ of public debate is exemplified by the reception of Nestroy and treatment of the emancipation of women. Later, implicitly political themes recur, as for instance in Hofmannsthal and Schnitzler. More recently, the controversy surrounding Claus Peymann's direction of the Burgtheater follows a long‐standing pattern whereby political issues, in this case centring on the identity of Austria, have been fought out at one remove in the theatrical culture of the city.
Plant strategies and trait trade‐offs influence trends in competitive ability along gradients of soil fertility and disturbance
Authors: FYNN R.W.S. , MORRIS C.D. , KIRKMAN K.P.
Published: March 2005

We present evidence of trade‐offs in competitive ability among five perennial C4grass species at different levels of soil fertility and disturbance in a garden experiment in KwaZulu‐Natal, South Africa.

Our goals were to examine plant strategy theory, using grass species that differed widely in various traits and in their response to environmental influences. More specifically, we wished to examine whether the importance of competition was less in low fertility or regularly disturbed environments (stressed environments) than in more fertile or undisturbed conditions, and whether species made trade‐offs in competitive ability along such stress gradients.

The trend in the competitive ability of two species in mixture along a soil fertility gradient tended to be inversely related if one had narrow and the other broad leaves or they differed in height, providing strong evidence for trait trade‐offs. Thus, a tall broad‐leaved species,Panicum maximum, was the most competitive species in fertile subplots, whereas a tall narrow‐leaved species,Hyparrhenia hirta, was the most competitive species in infertile subplots, but no difference in competitive ability across a fertility gradient was observed when both species in a mixture had similar traits.

Regular cutting altered competitive interactions amongst species resulting in a short species,Themeda triandra, having a greater competitive effect on neighbours and a better response to neighbours in cut than in the less stressed uncut treatments, suggesting a trade‐off for competitive ability in regularly disturbed habitats. However, cutting only improved the performance ofT. triandraagainstP. maximumin infertile subplots.

We demonstrated that for some, but not all, mixtures of species, competitive hierarchies may reverse along gradients of soil fertility and disturbance. Moreover, soil fertility and disturbance may interact in their effect on competitive interactions. Thus, soil fertility and disturbance form the major axes of an ecological framework for understanding plant competitive interactions.
Correlation between severity of thyroid dysfunction and renal function
Authors: Den Hollander Jan G. , Wulkan Remi W. , Mantel Mart J. , Berghout Arie
Published: March 2005

Objective  Renal function is profoundly influenced by thyroid status; however, this has not been studied in detail in human subjects. The purpose of the present study was to determine the relationship between renal function and thyroid status before and after treatment for hypothyroidism and hyperthyroidism, respectively.

Design and patients  In 37 consecutive hypothyroid and 14 hyperthyroid patients renal function as measured by plasma creatinine and glomerular filtration rate (GFR) [based on the modification of diet in renal disease (MDRD) formula] was determined before treatment and after regaining euthyroidism.

Results  Renal function improved significantly during treatment of hypothyroidism and decreased during treatment of hyperthyroidism. There was a strong correlation between the change in thyroid status determined as the ratio log10(fT4 post‐treatment/fT4 pretreatment) and the change in renal function as a result of therapy expressed as serum creatinine (r2 = 0·81, P < 0·0001) and estimated GFR (0·69, P < 0·0001).

Conclusion  The kidney is an important target of thyroid hormone action.
Growth hormone response to arginine test distinguishes multiple system atrophy from Parkinson's disease and idiopathic late‐onset cerebellar ataxia
Authors: Pellecchia Maria Teresa , Pivonello Rosario , Salvatore Elena , Faggiano Antongiulio , Barone Paolo , De Michele Giuseppe , Lombardi Gaetano , Colao Annamaria , Filla Alessandro
Published: March 2005

Objective Multiple system atrophy (MSA) is difficult to distinguish from idiopathic Parkinson's disease (PD) and idiopathic late‐onset cerebellar ataxia (ILOCA). This study aimed to evaluate GH response to three different GH stimulation tests in order to establish a reliable test to differentiate these degenerative disorders.

Design Twelve patients with MSA, 10 with PD, eight with ILOCA and 30 healthy controls entered the study. They were submitted to clonidine, arginine, and GH‐releasing‐hormone (GHRH) + arginine tests in a random manner on three different nonconsecutive days. The peak serum GH response was used as a primary variable for analysis of stimulation tests. By ROC analysis, the optimum cut‐off level was considered as the cut‐off with the maximal sum of sensitivity and specificity.

Results After clonidine administration, GH peak was significantly lower in patients with MSA than in those with ILOCA (P < 0·05) and in the controls (P < 0·001). At the optimum cut‐off level of 5 mU/l, the clonidine test distinguished patients with MSA from those with PD with a sensitivity and specificity of 78%. Moreover, this test distinguished patients with MSA from those with ILOCA with a sensitivity of 100% and a specificity of 75% at a cut‐off level of 5  mU/l, and with a sensitivity of 75% and a specificity of 100% at the cut‐off level of 7·6 mU/l. After arginine administration, the GH peak was significantly lower in patients with MSA than in those with ILOCA (P = 0·001) and in controls (P < 0·001). At the optimum cut‐off level of 5 mU/l, the arginine test distinguished patients with MSA from those with PD with a sensitivity and a specificity of 100%. At a GH peak cut‐off value of 3·6 mU/l the arginine test distinguished patients with MSA from those with ILOCA with a sensitivity and specificity of 100%. After GHRH + arginine administration, a significant GH increase was found in all groups of patients and controls.

Conclusions The GH response to arginine administration is impaired in MSA. Therefore, the arginine test showed the highest diagnostic accuracy to distinguish MSA from both PD and ILOCA, and could be used in the clinical practice of these neurodegenerative diseases.
Circulating levels of angiogenic cytokines can predict tumour progression and prognosis in neuroendocrine carcinomas
Authors: Pavel Marianne E. , Hassler Gerda , Baum Ulrich , Hahn Eckhart G. , Lohmann Tobias , Schuppan Detlef
Published: March 2005

Objective The growth behaviour of well‐differentiated neuroendocrine carcinomas of the gastro‐entero‐pancreatic system varies greatly and parameters predicting their prognosis are lacking. The aim of our study was to investigate whether tumour growth could be correlated with the release of proangiogenic factors into the circulation.

Patients and methods Circulating vascular endothelial growth factor (VEGF), interleukin‐8 (IL‐8), basic fibroblast growth factor (bFGF) and angiogenin were measured in 38 patients with advanced neuroendocrine carcinomas and compared to healthy age‐matched controls. In 20 patients, angiogenic cytokine levels were measured at consecutive time points and correlated to tumour progression as assessed by abdominal CT scan, MRI and chromogranin A levels.

Results VEGF levels were elevated in patients compared to controls (P < 0·002) and clearly associated with tumour progression (P < 0·005). Angiogenin levels were significantly higher in patients than in controls (P < 0·003), while high IL‐8 levels were predictive of shorter survival. Angiogenin and bFGF levels were correlated neither with tumour growth nor with patient survival.

Conclusions VEGF and IL‐8 are associated with tumour progression and might qualify as markers of prognosis and therapy control in patients with neuroendocrine carcinomas. Our results support the notion that specific anti‐angiogenic therapies should be evaluated in neuroendocrine carcinoma patients.
Final adult height and body mass index after cure of paediatric Cushing's disease
Authors: Davies J. H. , Storr H. L. , Davies K. , Monson J. P. , Besser G. M. , Afshar F. , Plowman P. N. , Grossman A. B. , Savage M. O.
Published: March 2005

Objective  Linear growth data after cure of paediatric Cushing's disease (CD) have been reported infrequently. We evaluated final adult height (FH) and body mass index (BMI) in a cohort of paediatric patients treated successfully for CD.

Patients and Methods  Fourteen patients (10 male, age range 6·4–16·6 years) fulfilled the diagnostic criteria for CD. All had had transsphenoidal surgery (TSS), combined with pituitary irradiation (RT) (45 Gy in 25 fractions) in six. All were cured (post‐TSS cortisol < 50 nmol/l or mean cortisol post‐RT < 150 nmol/l). Subjects analysed had bone ages at diagnosis of < 15 ‘years’ (male) and < 13 ‘years’ (female).

Results  At diagnosis, height SDS was [mean (range)]−2·5 (−4·2 to −0·8) and body mass index (BMI) SDS +2·7 (0·8–5·1). Following cure, 13 patients had GH deficiency (peak GH < 20 mU/l) and were treated with hGH (+ GnRH analogue in four). Height SDS at FH (n = 10) or latest assessment (n = 4) was −1·3 (−3·9–0·2) and increased compared to diagnosis (P < 0·01). The difference between final or latest height SDS and target height SDS was −1·2 (−3·3–0·5), that is less (P < 0·01) than the difference between the height SDS at diagnosis and target height SDS of −2·4 (−3·9 to −0·5). At final height or latest assessment, BMI SDS was +1·7 (0·4–6·2), being decreased compared to diagnosis (P < 0·05) but greater than the normal population (P < 0·01).

Conclusion  Catch‐up growth was demonstrated in paediatric patients cured from CD, with the majority achieving FH within target height range. Early diagnosis and treatment of GH deficiency is recommended to achieve optimal long‐term growth. Excess adiposity remains a potential long‐term complication.
Post‐dispersal predation ofTaraxacum officinale(dandelion) seed
Authors: HONEK ALOIS , MARTINKOVA ZDENKA , SASKA PAVEL
Published: March 2005

The importance of predation in determining the fate of post‐dispersal dandelion (Taraxacum officinale) seed was investigated. Flowering, seed dispersal, seedling establishment, seed predation and seed predator abundance were recorded in 2002 and 2003, at two sites. Number of flowers were counted in 1‐m2plots, wind‐borne seeds were collected in water traps, invertebrate seed predation was estimated from the rate of removal of dandelion seeds exposed on the ground and invertebrate activity density was determined by using pitfall traps. The censuses were made at 2‐ to 3‐day intervals.

Seed dispersal occurred 10 days after flowering. Although some seeds were blown away, 3.7–24.2 × 103seeds m−2fell to the ground. Four weeks after the peak in seed dispersal 0.7–3.1% of these seeds germinated. Three weeks later only 11–13% of the dispersed seed remained on the ground and most of these were damaged, the remainder presumably having been removed by predators.

Predation of exposed seeds was low before seed dispersal but increased after its onset, in parallel with increases in the number of seeds present on the ground and in the activity density of adults of a seed‐consuming carabid,Amara montivaga.

In cafeteria experiments in which the seeds of 28 perennial and annual herbs were providedA. montivagaconsumed the most dandelion seeds, followed by nine otherAmaraspecies. In no‐choice experiments, under field conditions,A. montivagaconsumed six seeds day−1.

Post‐dispersal predation, mainly due to aggregation of a single ground beetle species, was more important than that which occurred prior to dispersal. Although predators destroyedc. 97% of the seeds, the effect on dandelion population biology is likely to be small.

Post‐dispersal seed predation may nevertheless be important in other species, as aggregates of large invertebrate predators can consume large quantities of seed.
A kinase for light and time
Authors: Loros Jennifer
Published: March 2005

The eukaryotic filamentous fungus Neurospora crassa has proven to be a dependable model system for the analysis of light‐regulated gene expression and circadian rhythmicity. The molecular basis of the core circadian clock is a transcription/translation‐based feedback loop in which a heterodimer of the white‐collar 1 (WC‐1) and white‐collar 2 (WC‐2) proteins act as a transcription factor to promote expression of the negative elements in the clock, frq mRNA and FRQ protein. Additionally, WC‐1 is a flavoprotein that acts as the primary responder to environmental light and, in conjunction with WC‐2, is the major photoreceptor for the clock as well as other light‐regulated processes. Protein kinase C acts as a light‐dependent regulator of the WC‐1 protein.
Translation elongation factor EF‐Tu is a target for Stp, a serine‐threonine phosphatase involved in virulence of Listeria monocytogenes
Authors: Archambaud Cristel , Gouin Edith , Pizarro‐Cerda Javier , Cossart Pascale , Dussurget Olivier
Published: March 2005

Listeria monocytogenes is a pathogen that causes listeriosis, a severe food‐borne infection. This bacterium, in order to survive and grow in the multiple conditions encountered in the host and the environment, has evolved a large number of regulatory elements, in particular many signal transduction systems based on reversible phosphorylation. The genome sequence has revealed genes for 16 putative two‐component systems, four putative tyrosine phosphatases, three putative serine‐threonine kinases and two putative serine‐threonine phosphatases. We found that one of the latter genes, stp, encodes a functional Mn2+‐dependent serine‐threonine phosphatase similar to PPM eukaryotic phosphatases (Mg2+‐or Mn2+‐dependent protein phosphatase) and is required for growth of L. monocytogenes in a murine model of infection. We identified as the first target for Stp, the elongation factor EF‐Tu. Post‐translational phosphorylation of EF‐Tu had been shown to prevent its binding to amino‐acylated transfer RNA as well as to kirromycin, an antibiotic known to inhibit EF‐Tu function. Accordingly, an stp deletion mutant is less sensitive to kirromycin. These results suggest an important role for Stp in regulating EF‐Tu and controlling bacterial survival in the infected host.
Retrotransposition strategies of the Lactococcus lactis Ll.LtrB group II intron are dictated by host identity and cellular environment
Authors: Coros Colin J. , Landthaler Markus , Piazza Carol Lyn , Beauregard Arthur , Esposito Donna , Perutka Jiri , Lambowitz Alan M. , Belfort Marlene
Published: March 2005

Group II introns are mobile retroelements that invade their cognate intron‐minus gene in a process known as retrohoming. They can also retrotranspose to ectopic sites at low frequency. Previous studies of the Lactococcus lactis intron Ll.LtrB indicated that in its native host, as in Escherichia coli, retrohoming occurs by the intron RNA reverse splicing into double‐stranded DNA (dsDNA) through an endonuclease‐dependent pathway. However, in retrotransposition in L. lactis, the intron inserts predominantly into single‐stranded DNA (ssDNA), in an endonuclease‐independent manner. This work describes the retrotransposition of the Ll.LtrB intron in E. coli, using a retrotransposition indicator gene previously employed in our L. lactis studies. Unlike in L. lactis, in E. coli, Ll.LtrB retrotransposed frequently into dsDNA, and the process was dependent on the endonuclease activity of the intron‐encoded protein. Further, the endonuclease‐dependent insertions preferentially occurred around the origin and terminus of chromosomal DNA replication. Insertions in E. coli can also occur through an endonuclease‐independent pathway, and, as in L. lactis, such events have a more random integration pattern. Together these findings show that Ll.LtrB can retrotranspose through at least two distinct mechanisms and that the host environment influences the choice of integration pathway. Additionally, growth conditions affect the insertion pattern. We propose a model in which DNA replication, compactness of the nucleoid and chromosomal localization influence target site preference.
Granulocytes govern the transcriptional response, morphology and proliferation of Candida albicans in human blood
Authors: Fradin Chantal , De Groot Piet , MacCallum Donna , Schaller Martin , Klis Frans , Odds Frank C. , Hube Bernhard
Published: March 2005

Survival in blood and escape from blood vessels into tissues are essential steps for the yeast Candida albicans to cause systemic infections. To elucidate the influence of blood components on fungal growth, morphology and transcript profile during bloodstream infections, we exposed C. albicans to blood, blood fractions enriched in erythrocytes, polymorphonuclear or mononuclear leukocytes, blood depleted of neutrophils and plasma. C. albicans cells exposed to erythrocytes, mononuclear cells, plasma or blood lacking neutrophils were physiologically active and rapidly switched to filamentous growth. In contrast, the presence of neutrophils arrested C. albicans growth, enhanced the fungal response to overcome nitrogen and carbohydrate starvation, and induced the expression of a large number of genes involved in the oxidative stress response. In particular, SOD5, encoding a glycosylphosphatidylinositol (GPI)‐anchored superoxide dismutase localized on the cell surface of C. albicans, was strongly expressed in yeast cells that were associated with neutrophils. Mutants lacking key genes involved in oxidative stress, morphology or virulence had significantly reduced survival rates in blood and the neutrophil fraction, but remained viable for at least 1 h of incubation when exposed to erythrocytes, mononuclear cells, plasma or blood lacking neutrophils. These data suggest that C. albicans genes expressed in blood were predominantly induced in response to neutrophils, and that neutrophils play a key role during C. albicans bloodstream infections. However, C. albicans is equipped with several genes and transcriptional programmes, which may help the fungus to counteract the attack of neutrophils, to escape from the bloodstream and to cause systemic infections.
Patterns of nucleosomal organization in the alc regulon of Aspergillus nidulans: roles of the AlcR transcriptional activator and the CreA global repressor
Authors: Mathieu Martine , Nikolaev Igor , Scazzocchio Claudio , Felenbok Béatrice
Published: March 2005

We have studied the chromatin organization of three promoters of the alc regulon of Aspergillus nidulans. No positioned nucleosomes are seen in the aldA (aldehyde dehydrogenase) promoter under any physiological condition tested by us. In the alcA (alcohol dehydrogenase I) and alcR (coding for the pathway‐specific transcription factor) promoters, a pattern of positioned nucleosomes is seen under non‐induced and non‐induced repressed conditions. While each of these promoters shows a specific pattern of chromatin restructuring, in both cases induction results in loss of nucleosome positioning. Glucose repression in the presence of inducer results in a specific pattern of partial positioning in the alcA and alcR promoters. Loss of nucleosome positioning depends absolutely on the AlcR protein and it is very unlikely to be a passive result of the induction of transcription. In an alcR loss‐of‐function background and in strains carrying mutations of the respective AlcR binding sites of the alcA and alcR promoters, nucleosomes are fully positioned under all growth conditions. Analysis of mutant AlcR proteins establishes that all domains needed for transcriptional activation and chromatin restructuring are included within the first 241 residues. The results suggest a two‐step process, one step resulting in chromatin restructuring, a second one in transcriptional activation. Partial positioning upon glucose repression shows a specific pattern that depends on the CreA global repressor. An alcR loss‐of‐function mutation is epistatic to a creA loss‐of‐function mutation, showing that AlcR does not act by negating a nucleosome positioning activity of CreA.
Enteropathogenic Escherichia coli EspG disrupts microtubules and in conjunction with Orf3 enhances perturbation of the tight junction barrier
Authors: Tomson Farol L. , Viswanathan V. K. , Kanack Kristen J. , Kanteti Rajani P. , Straub Kathryn V. , Menet Mark , Kaper James B. , Hecht Gail
Published: March 2005

EspG, a secreted effector of enteropathogenic Escherichia coli (EPEC), as well as its homologue Orf3, has been shown to disrupt microtubules (MTs) in fibroblasts and non‐polarized epithelial cells. The roles of MTs and the effects of MT disruption in these cell types differ significantly. The aim of this study was to investigate the effects of EspG on polarized, host target intestinal epithelial cells. Immunofluorescent labelling of tubulin showed that EPEC caused progressive fragmentation and loss of the MT network in cells harbouring attached organisms. Immunoblots of proteins extracted from EPEC‐infected cells showed a corresponding loss of α‐tubulin. Type III secretion system (TTSS)‐deficient strains had no effect on MT suggesting TTSS dependence. Mutation of espG, but not espF or map, ablated EPEC's effects on MTs for up to 6 h. Ectopic expression of EspG in HeLa cells caused MT disruption. While deletion of espG alone had no effect on the EPEC‐induced decrease in transepithelial electrical resistance (TER), mutation of both espG and orf3 significantly delayed the kinetics of this response. Complementation of the double mutant with espG alone restored the kinetics of TER drop to that of wild type. Herein, we describe a previously unrecognized phenotype for the EPEC effectors EspG and Orf3.
Efficacy of the phosphorylation of synthetic peptides by purified catalytic subunit of PKA (PKAcat) from bovine lens depends on the amino acid sequence of the peptides
Authors: Samanta B. , Mezö G. , Das K.P. , Ghose A.C. , Hudecz F. , Sen P.C.
Published: March 2005

Abstract: Protein kinase (PK) A catalytic (PKAcat) subunit was purified to homogeneity from bovine lens using a 100‐kDa cut‐off membrane filtration followed by different chromatographic procedures. The molecular weight of PKAcat was found to be 41 kDa. The kinase phosphorylates histone IIIs and other synthetic modified peptides of VRKRTLRRL with different amino acid environment. The extent of phosphorylation depends not only on the presence of Ser or Thr (phosphorylating residues) but also on other surrounding amino acid residues. Although some peptides compete in phosphorylating histone, they are not very significant. The result suggests that the extent of phosphorylation depends on the amino acid residue(s) surrounding phosphorylable residue(s) on the peptide.
Differences between cation‐chloride co‐transporter functions in the visual cortex of pigmented and albino rats
Authors: Barmashenko Gleb , Schmidt Matthias , Hoffmann Klaus‐Peter
Published: March 2005

Albinism in mammals is accompanied by specific morphological and functional alterations of the visual system. To understand their cellular basis we studied the physiological characteristics and transmembrane currents of pyramidal neurons in 350‐µm‐thick slices of visual cortex from pigmented and albino rats using whole‐cell and gramicidin perforated patch‐clamp recordings. The resting membrane potential was significantly more positive and the rheobase was significantly lower in neurons of layers II/III and V in albinos as compared with pigmented rats. No significant differences were found in the input resistance, time constant and chronaxy. Whereas the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor‐mediated currents were not significantly different, the maximum γ‐aminobutyric acid (GABA)A receptor (GABAAR)‐mediated currents and miniature inhibitory postsynaptic currents showed significantly lower amplitudes in neurons of layer V in visual cortex of albinos as compared with pigmented rats. The reversal potential of the GABAAR‐mediated currents (EGABA) was significantly shifted to more positive values in albinos. Pharmacological experiments showed that this shift could be caused by an increased action of the inward chloride co‐transporter NKCC1 and reduced action of the outward chloride co‐transporter KCC2 in albino rats. This difference seems to be restricted to the visual cortex because in pyramidal neurons from frontal cortex EGABA was not significantly different in albinos as compared with pigmented rats. These results are discussed in relation to functional alterations in the albino visual system.
Impairment of conditioned freezing to tone, but not to context, in Fyn‐transgenic mice: relationship to NMDA receptor subunit 2B function
Authors: Kojima N. , Sakamoto T. , Endo S. , Niki H.
Published: March 2005

We previously demonstrated that transgenic mice overexpressing Fyn tyrosine kinase exhibit higher seizure susceptibility and enhanced tyrosine phosphorylation of several proteins, including the N‐methyl‐D‐aspartate (NMDA) receptor subunit 2B (NR2B). In the present study, we analysed behavioural phenotypes, especially conditioned fear responses, of Fyn‐transgenic (TG) mice to better understand the role of Fyn in learned emotional behaviour. Tone‐dependent conditioned freezing was significantly attenuated in Fyn‐TG mice, whereas context‐dependent freezing was unaffected. Neither massed nor spaced conditioning ameliorated the attenuation of tone‐dependent freezing. However, the selective NR2B antagonist ifenprodil, when administered before conditioning, restored tone‐dependent freezing in Fyn‐TG mice at a dose that did not affect freezing in wild‐type (WT) mice. These results suggest that impairment of tone‐dependent conditioned freezing in Fyn‐TG mice is caused by disruption of the NR2B‐containing NMDA receptor function. Tyrosine phosphorylation of brain proteins, including NR2B, was enhanced in Fyn‐TG mice compared with that in WT mice. We also found that ifenprodil significantly suppressed the enhanced tyrosine phosphorylation. Thus, our data support the notion that NMDA receptor activity is tightly correlated with protein tyrosine phosphorylation, and Fyn might be one key molecule that controls tone‐dependent conditioned freezing through the regulation of NMDA receptor function.
Endogenous enkephalins, not endorphins, modulate basal hedonic state in mice
Authors: Skoubis P. D. , Lam H. A. , Shoblock J. , Narayanan S. , Maidment N. T.
Published: March 2005

The aversive response to naloxone administration observed in human and animal studies suggests the presence of an endogenous opioid tone regulating hedonic state but the class(es) of opioid peptides mediating such opioid hedonic tone is uncertain. We sought to address this question using mice deficient in either beta‐endorphin or pro‐enkephalin in a naloxone‐conditioned place aversion paradigm. Mice received saline in the morning in one chamber and either saline or naloxone (0.1, 1 or 10 mg/kg, s.c.) in the afternoon in another chamber, each day for 3 days. On the test day they were given free access to the testing chambers in the afternoon and the time spent in each chamber was recorded. Whereas wild‐type and beta‐endorphin‐deficient mice exhibited a robust conditioned place aversion to naloxone, pro‐enkephalin knockout mice failed to show aversion to naloxone at any dose tested. In contrast, these mice showed a normal conditioned aversion to the kappa opioid receptor agonist, U50,488 (5 mg/kg), and to LiCl (100 mg/kg) indicating that these mice are capable of associative learning. In a separate experiment, pro‐enkephalin knockout mice, similar to wild‐type and beta‐endorphin‐deficient mice, demonstrated a significant conditioned place preference to morphine (2.5, 5 and 10 mg/kg s.c.). These data suggest that enkephalins, but not endorphins, may mediate an endogenous opioid component of basal affective state and also indicate that release of neither endogenous enkephalins nor endorphins is critical for the acquisition or expression of the association between contextual cues and the rewarding effect of exogenously administered opiates.
Behavioural phenotypes of hypomorphic KCC2‐deficient mice
Authors: Tornberg Janne , Voikar Vootele , Savilahti Harri , Rauvala Heikki , Airaksinen Matti S.
Published: March 2005

Hyperpolarizing fast inhibitory neurotransmission by γ‐aminobutyric acid and glycine requires an efficient chloride extrusion mechanism in postsynaptic neurons. A major effector of this task in adult animals is the potassium‐chloride co‐transporter KCC2 that is selectively and abundantly expressed postsynaptically in most CNS neurons. Yet, the role of KCC2 in adult brain at the systems level is poorly known. Here, we characterize the behaviour of mice doubly heterozygous for KCC2 null and hypomorphic alleles that retain 15–20% of normal KCC2 protein levels in the brain. These hypomorphic KCC2‐deficient mice were viable and fertile but weighed 15–20% less than wild‐type littermates at 2 weeks old and thereafter. The mice displayed increased anxiety‐like behaviour in several tests including elevated plus‐maze and were more susceptible to pentylenetetrazole‐induced seizures. Moreover, the mice were impaired in water maze learning and showed reduced sensitivity to tactile and noxious thermal stimuli in von Frey hairs, hot plate and tail flick tests. In contrast, the mice showed normal spontaneous locomotor activity in open field and Y‐maze tests, and intact motor coordination in rotarod and beam tests. The results suggest that requirements for KCC2‐dependent fast hyperpolarizing inhibition may differ among various functional systems of the CNS. As shunting inhibition is expected to be intact in KCC2‐deficient neurons, these mice may provide a useful tool to study the specific functions and relative importance of hyperpolarizing fast synaptic inhibition in adult CNS that may have implications for human neuropsychiatric disorders, such as epilepsy, pain and anxiety.
Synaptic contacts between an identified type of ON cone bipolar cell and ganglion cells in the mouse retina
Authors: Lin Bin , Masland Richard H.
Published: March 2005

We surveyed the potential contacts between an identified type of bipolar cell and retinal ganglion cells in the mouse. By crossing two existing mouse strains (line 357 and line GFP‐M), we created a double transgenic strain in which GFP is expressed by all members of a single type of ON cone bipolar cell and a sparse, mixed population of retinal ganglion cells. The GFP‐expressing bipolar cells appear to be those termed CB4a of Pignatelli & Strettoi [(2004) J. Comp. Neurol., 476, 254–266] and type 7 of Ghosh et al. [(2004) J. Comp. Neurol., 469, 70–82 and J. Comp. Neurol., 476, 202–203]. The labelled ganglion cells include examples of most or all types of ganglion cells present in the mouse. By studying the juxtaposition of their processes in three dimensions, we could learn which ganglion cell types are potential synaptic targets of the line 357 bipolar cell. Of 12 ganglion cell types observed, 10 types could be definitively ruled out as major synaptic targets of the line 357 bipolar cells. One type of monostratified ganglion cell and one bistratified cell tightly cofasciculate with axon terminals of the line 357 bipolar cells. Double labelling for kinesin II demonstrates colocalization of bipolar cell ribbons at the sites of contact between these two types of ganglion cell and the line 357 bipolar cells.
Short‐term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus
Authors: Hajszan Tibor , MacLusky Neil J. , Leranth Csaba
Published: March 2005

The pathomechanism of major depressive disorder and the neurobiological basis of antidepressant therapy are still largely unknown. It has been proposed that disturbed hippocampal activity could underlie some of the cognitive and vegetative symptoms of depression, at least in part because of loss of pyramidal cell synaptic contacts, a process that is likely to be reversed by antidepressant treatment. Here we provide evidence that daily administration of the antidepressant fluoxetine to ovariectomized female rats for 5 days induces a robust increase in pyramidal cell dendritic spine synapse density in the hippocampal CA1 field, with similar changes appearing in CA3 after 2 weeks of treatment. This rapid synaptic remodelling might represent an early step in the fluoxetine‐induced cascade of responses that spread across the entire hippocampal circuitry, leading to the restoration of normal function in the hippocampus. Hippocampal synaptic remodelling might provide a potential mechanism to explain certain aspects of antidepressant therapy and mood disorders, especially those associated with changes in reproductive state in women, that cannot be reconciled adequately with current theories for depression.
The influence of bladder neck mucosal eversion and early urinary extravasation on patient outcome after radical retropubic prostatectomy: a prospective controlled trial
Authors: Srougi Miguel , Paranhos Mario , Leite Kátia M. , Dall’oglio Marcos , Nesrallah Luciano
Published: March 2005

OBJECTIVE

To evaluate the role of bladder neck (BN) mucosal eversion during retropubic radical prostatectomy (RRP) on the rate of BN sclerosis and urinary incontinence, with the hypothesis that BN mucosal eversion is not essential to improve the clinical outcome after RRP.

PATIENTS AND METHODS

One hundred patients with stage T1c–T2c prostate cancer had RRP by the same surgeon and were randomly divided in two equal groups; one had a vesico‐urethral anastomosis with and one with no BN mucosal eversion. The patients were assessed by retrograde cysto‐urethrography 4 days after surgery to evaluate the presence of urinary leakage. The occurrence of BN sclerosis and the rate of urinary incontinence (more than one pad/day) was assessed by double‐blind interviews at 2 days, 2 months and 6 months after catheter removal, and the incidence of BN sclerosis was also assessed after 12 months.

RESULTS

In the groups with or with no BN mucosal eversion, 48 and 47 patients, respectively, fulfilled the selection criteria. Urinary leakage after vesico‐urethral anastomosis was more common after mucosal eversion (33% vs 21%), but not significantly (P = 0.251). BN sclerosis occurred in only one patient, with no mucosal eversion. The rate of urinary continence was similar in both groups at 2 days (69% vs 68%, respectively), 2 months (90% vs 87%) and 6 months (92% vs 92%) after surgery. Urinary extravasation at 4 days after surgery was followed by same rate of BN sclerosis and urinary continence as in patients with no urinary extravasation.

CONCLUSION

BN mucosal eversion before vesico‐urethral anastomosis during RRP is not essential to reduce the frequency of BN sclerosis or urinary incontinence. Early radiological urinary extravasation at the vesico‐urethral anastomosis did not increase the risk of BN sclerosis or urinary incontinence.
A novel technique for approaching the endopelvic fascia in retropubic radical prostatectomy, based on an anatomical study of fixed and fresh cadavers
Authors: Takenaka Atsushi , Hara Ryoei , Soga Hideo , Murakami Gen , Fujisawa Masato
Published: March 2005

OBJECTIVE

To present the anatomical basis and details of a technique for an approach to the endopelvic fascia devised to preserve urinary continence.

PATIENTS, MATERIALS AND METHODS

For cross‐sectional macroscopic observation, seven formalin‐fixed specimens of the male pelvic contents including the pelvic wall were serially sectioned at a 5‐mm thickness. Semi‐serial sections from eight other specimens were examined histologically. Eight fresh cadavers were dissected to mimic the various steps in a retropubic radical prostatectomy. After approaching the endopelvic fascia in an anatomically determined manner to reach the paraprostatic space, the pubic bone was removed and nerves near the rhabdosphincter dissected. To assess the clinical implication of this approach, we examined the time to achieve continence in 23 consecutive patients who had a radical retropubic prostatectomy using the new technique.

RESULTS

Sectional macroscopic observation depicted the fascia of the levator ani as a definite structure adherent to but not fused with the lateral pelvic fascia. The thin fascia overlying the levator ani fascia and lateral pelvic fascia represented the true endopelvic fascia. Microscopically, the lower part of the fascia of the levator ani was rich in smooth muscle, which interdigitated with the framework of the rhabdosphincter. In fresh cadavers, the levator ani muscle was removed laterally still covered by its fascia, without visualizing the muscle fibres. Small branches from the pudendal nerve entered the rhabdosphincter. The mean (sd, range) distance from the lowest point of the endopelvic fascia to the point where the sphincteric branch entered the rhabdosphincter was 5.5 (1.8, 3–8) mm. The continence rate at 1, 3, 6 and 9 months after surgery using the new technique was 44%, 83%, 96% and 100%, respectively.

CONCLUSIONS

Preserving the fascia of the levator ani helps to protect the levator ani muscle, rhabdosphincter and pudendal nerve branches to the rhabdosphincter. In retropubic radical prostatectomy, this anatomical approach to the endopelvic fascia should preserve or allow the earlier recovery of urinary continence.
The incidence and treatment of lymphoceles after radical retropubic prostatectomy
Authors: Pepper Ruth J. , Pati Jhumur , Kaisary Amir V.
Published: March 2005

OBJECTIVE

To determine the incidence and treatment of lymphoceles after retropubic radical prostatectomy (RP).

PATIENTS AND METHODS

Up to January 2004, 260 patients who had a retropubic RP in one institution by one surgeon were assessed retrospectively, using the patients’ notes or the computerized results system to determine whether a lymphocele was suspected and then confirmed by imaging studies (computed tomography or ultrasonography).

RESULTS

Nine patients developed symptomatic lymphoceles; eight of these were detected by imaging. Four lymphoceles required intervention while the remainder regressed spontaneously. No complications were reported in the group that was treated.

CONCLUSION

The rate of symptomatic lymphocele formation was low after RP, with an overall incidence of 3.5%. Ultrasonography was effective in detecting lymphoceles and ultrasonographically guided percutaneous drainage an effective treatment.
Sexual, psychological and dyadic qualities of the prostate cancer ‘couple’
Authors: Soloway Cynthia T. , Soloway Mark S. , Kim Sandy S. , Kava Bruce R.
Published: March 2005

OBJECTIVES

To examine the levels of sexual, psychological and dyadic functioning of the prostate cancer ‘couple’ (as studies have shown that spouses/partners play an integral role in the patient's adjustment to prostate cancer treatment), to encourage the creation of innovative psychosexual interventions to be used in the outpatient setting, and to offer insights into a novel area of prostate cancer research.

PATIENTS AND METHODS

In all, 103 men newly diagnosed with prostate cancer, and their partners, were assessed in an academic outpatient setting using instruments measuring sexual function, depressed mood, psychological distress and dyadic adjustment.

RESULTS

The partners’ mean scores on sexual function questions were 55.75, significantly higher than those of the patients (51.7, P = 0.018), showing that partners perceived their sexual performance at a better level. Partners’ mean scores on the depression and distress measures were also significantly higher. On those items that monitored the accuracy of the patients’ perceptions of their sexual function, partners rated the patients significantly lower in ability to gain erections (patient/partner means 2.67/4.52; P < 0.001) and to perform sexually (patient/partner means 1.38/4.68; P < 0.001) than they rated themselves.

CONCLUSIONS

Information from this study could be useful in constructing interventions that allow the physician and the prostate cancer ‘couple’ to reflect on issues of sexual function and psychological distress that might once have been considered taboo. The results characterize the disparities between patients with prostate cancer and their partners on self‐reported questionnaires, and underscore how important it is to hear the voice of the ‘couple’.
A comparison of the pathology of transitional cell carcinoma of the bladder and upper urinary tract
Authors: Stewart Grant D. , Bariol Simon V. , Grigor Ken M. , Tolley David A. , McNeill S. Alan
Published: March 2005

OBJECTIVE

To clarify the histopathological patterns of upper and lower urinary tract transitional cell carcinomas (TCCs), as previous reports suggest that upper urinary tract TCCs have a greater tendency towards high‐grade disease than bladder TCCs, of which most are low‐grade and low‐stage tumours.

PATIENTS AND METHODS

All patients presenting with TCC of bladder or upper urinary tract between February 1991 and December 2001 at one institution were identified. Further patient information was obtained from the hospital database and case‐note review.

RESULTS

In all, 164 patients with upper urinary tract TCC and 2197 with bladder TCC were identified. There was a correlation between grade and stage of both upper urinary tract and bladder TCCs. 35% of the upper tract TCCs were classified as grade 2 and 44% as grade 3, while for bladder TCCs, 31% of lesions were classified as grade 2 and 35% as grade 3 (P = 0.003). Of the upper urinary tract lesions 33% were stage pT2–T4, compared with only 20% of bladder TCCs (P = 0.001).

CONCLUSIONS

Upper urinary tract TCC is a higher grade and stage disease than bladder cancer, a finding that emphasizes the need for aggressive treatment of upper urinary tract TCC. If endourological management of upper urinary tract TCC is considered, histopathological determination of tumour grade before treatment is essential.
The laparoscopic management of intersex patients: the preferred approach
Authors: Dénes Francisco T. , Cocuzza Marcelo A.S. , Schneider‐Monteiro Edison D. , Silva Frederico A.Q. , Costa Elaine M.F. , Mendonca Berenice B. , Arap Sami
Published: March 2005

In the world's largest series of patients with intersex treated by laparoscopy, authors from Sao Paulo found that this technique allowed easy identification and removal of gonads. They also found that other organs could be removed and genitoplasty performed.

OBJECTIVE

To present possibly the largest series of the use of laparoscopy for treating intersex patients.

PATIENTS AND METHODS

Fifty intersex patients (34 with male and two with female pseudohermaphroditism, nine with gonadal dysgenesis, four with true hermaphroditism, and one with complex hypospadias), aged 0.5–46 years (mean 18.3), underwent laparoscopy to remove gonads and/or ductal structures incompatible with the social gender, or for gonadal tumour or a potential risk for malignancy. When necessary, genitoplasty was performed concomitantly.

RESULTS

At the laparoscopic evaluation, 10 gonads of six patients were absent, while four were identified as ‘vanishing’; 72 gonads (46 dysgenetic, 17 normal testes, one normal ovary, one ovotestis, seven gonadoblastomas or dysgerminomas) were removed; two ovotestes were replaced in the scrotum after removing the ovarian segment, as was one normal testis. Twelve patients with a urogenital sinus had its vaginal component removed, 11 including a hysterectomy. Three of these patients had a combined perineal approach to complete its removal, together with masculinizing genitoplasty. There were no intraoperative complications or conversions; two patients had complications after surgery.

CONCLUSIONS

Laparoscopy allows the straightforward identification and removal of gonads. All abnormal ductal structures must be removed, as this increases the chance of resecting unidentified gonads. Removing the uterus and vaginal component of the urogenital sinus in patients with male social sex is feasible, with low morbidity. Genitoplasty, according to the social sex, can be performed in the same procedure.