bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation through electrodes implanted near the subthalamic nucleus activates projections to motor areas of cerebral cortex in patients with Parkinson's disease
Authors: MacKinnon Colum D. , Webb Ruth M. , Silberstein Paul , Tisch Steven , Asselman Peter , Limousin Patricia , Rothwell John C.
Published: March 2005

High‐frequency electrical stimulation through electrodes implanted in the subthalamic nucleus (STN) has been shown to reduce significantly the cardinal symptoms of Parkinson's disease (PD). Despite the success of this treatment, the mechanisms of action of stimulation are poorly understood. To elucidate further the mechanisms of action of deep brain stimulation and its effects on cortical activity, we recorded electroencephalographic potentials from 61 scalp‐surface electrodes during low‐frequency (5–10 Hz) bipolar stimulation in 11 patients with advanced PD (14 implanted electrodes were tested). In all electrodes tested, stimulation through at least one of the four contacts produced a medium‐latency waveform with an average onset of 14 ± 3 ms and peak at 23 ± 4 ms. This potential typically increased in magnitude across contacts from ventral to dorsal. Within‐subject comparisons of median nerve somatosensory evoked potentials demonstrated that the generator of the medium‐latency potential was within the primary sensorimotor cortex or lateral premotor cortex ipsilateral to stimulation. The timing and topography of this potential were consistent with indirect activation of the cortex by excitation of pallido‐thalamic axons that traverse the dorsal aspect of the STN. The potential evoked by stimulation through the contact used for optimal clinical effect was highly variable across electrodes and frequently different from the medium‐latency potential described above, suggesting that the neuronal elements mediating the medium‐latency potential were different from those that mediate the clinical effects.
Type grouping in skeletal muscles after experimental reinnervation: another explanation
Authors: Vleggeert‐Lankamp C. L. A. M. , De Ruiter G. C. W. , Wolfs J. F. C. , Pêgo A. P. , Feirabend H. K. P. , Lakke E. A. J. F. , Malessy M. J. A.
Published: March 2005

Type grouping signifies clustering of muscle fibres of the same metabolic type, and is a frequent finding in reinnervated muscles. To elucidate the mechanism behind it, the rat sciatic nerve was either autografted or grafted with hollow synthetic nerve grafts. Twelve weeks later the number and fibre area of the type I and type II muscle fibres in the gastrocnemic and anterior tibial muscles were determined after ATP‐ase staining. The number and diameter of peroneal nerve fibres distal to the grafts were measured, and the number of Aα‐nerve fibres was derived. Nearly all nerve and muscle morphometrical parameters changed equally in both experimental groups. However, type grouping occurred frequently only after autografting, whereas the number of nerve fibres and the number of Aα‐nerve fibres increased in this group. Hence type grouping cannot be explained by increased intramuscular sprouting subsequent to a decrease in the number of innervating nerve fibres, as previously presumed. Regenerating axons branch along their course through the peripheral nerve. We propose that the probability of the occurrence of type grouping is related to the dispersion of sibling branches in the nerve. In the autograft, emerging branches are kept together by Schwann cell basal lamina scaffolds, in contrast to the hollow synthetic nerve grafts where the emerging branches become dispersed. Thus, in muscles reinnervated after autografting, the probability that nerve branches that arrive at a specific muscle territory are sibling branches is greater than after hollow tube grafting. Consequently, the probability that type grouping will occur is greater.
NR2 to NR3B subunit switchover of NMDA receptors in early postnatal motoneurons
Authors: Fukaya Masahiro , Hayashi Yasunori , Watanabe Masahiko
Published: March 2005

The NR3B NMDA receptor subunit is selective to somatic motoneurons in the adult nervous system. Here we report its developmental expression in the mouse brain and spinal cord by in situ hybridization. NR3B mRNA was detected in few neural regions during embryonic and neonatal periods. It first appeared in motoneurons at postnatal day (P)10−P14, and attained the maximal level at P21 and adult stage. This developmental profile was reciprocal with that of NR2 subunits, of which NR2A mRNA was most predominant in embryonic and neonatal motoneurons and downregulated by P14. Interestingly, mRNA of the NR1 subunit, which is required for functional NMDA receptors, displayed a ‘V’‐shaped change, decreasing with the early postnatal decline of NR2 mRNAs and increasing with the subsequent appearance of NR3B mRNA. Therefore, the major regulatory subunit of NMDA receptors is likely to switch from NR2 to NR3B in somatic motoneurons during the early postnatal period.
A single time‐window for protein synthesis‐dependent long‐term memory formation after one‐trial appetitive conditioning
Authors: Fulton Daniel , Kemenes Ildiko , Andrew Richard J. , Benjamin Paul R.
Published: March 2005

Protein synthesis is generally held to be essential for long‐term memory formation. Often two periods of sensitivity to blockade of protein synthesis have been described, one immediately after training and another several hours later. We wished to relate the timing of protein synthesis‐dependence of behavioural long‐term memory (LTM) formation to an electrophysiological correlate of the LTM memory trace. We used the snail Lymnaea because one‐trial appetitive conditioning of feeding using a chemical conditioned stimulus leads to a stable LTM trace that can be monitored behaviourally and then electrophysiologically in preparations made from the same animals. Anisomycin (an inhibitor of translation) injected 10 min after training blocked behavioural LTM formation. Actinomycin D (an inhibitor of transcription) was also effective at 10 min. When anisomycin, at doses shown to be effective in blocking central nervous system protein synthesis, was injected at 1, 2, 3, 4, 5 and 6 h after training there was no effect on recall. These results indicate that there is a single period of sensitivity to protein synthesis inhibition in Lymnaea lasting for between 10 min and 1 h after training with no evidence for a second window of sensitivity. An electrophysiological correlate of LTM was found to be sensitive to anisomycin injected 10 min after training. It is unusual to find only one period of protein synthesis‐dependence in detailed time‐course studies of LTM, and this suggests that the consolidation processes involving protein synthesis are relatively rapid in one‐trial appetitive conditioning and complete within 1 h of training.
Dopamine depletion increases the power and coherence of β‐oscillations in the cerebral cortex and subthalamic nucleus of the awake rat
Authors: Sharott Andrew , Magill Peter J. , Harnack Daniel , Kupsch Andreas , Meissner Wassilios , Brown Peter
Published: March 2005

Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) of untreated patients implanted with stimulation electrodes for the treatment of Parkinson's disease (PD) demonstrate strong coherence with the cortical electroencephalogram over the β‐frequency range (15–30 Hz). However, studies in animal models of PD emphasize increased temporal coupling in cortico‐basal ganglia circuits at substantially lower frequencies, undermining the potential usefulness of these models. Here we show that 6‐hydroxydopamine (6‐OHDA) lesions of midbrain dopamine neurons are associated with significant increases in the power and coherence of β‐frequency oscillatory activity present in LFPs recorded from frontal cortex and STN of awake rats, as compared with the healthy animal. Thus, the pattern of synchronization between population activity in the STN and cortex in the 6‐OHDA‐lesioned rodent model of PD closely parallels that seen in the parkinsonian human. The peak frequency of coherent activity in the β‐frequency range was increased in lesioned animals during periods of spontaneous and sustained movement. Furthermore, administration of the dopamine receptor agonist apomorphine to lesioned animals suppressed β‐frequency oscillations, and increased coherent activity at higher frequencies in the cortex and STN, before producing the rotational behaviour indicative of successful lesion. Taken together, these results support a crucial role for dopamine in the modulation of population activity in cortico‐basal ganglia circuits, whereby dopaminergic mechanisms effectively filter out synchronized, rhythmic activity at β‐frequencies at the systems level, and shift temporal couplings in these circuits to higher frequencies. These changes may be important in regulating movement.
The novel cytosolic RING finger protein dactylidin is up‐regulated in brains of patients with Alzheimer's disease
Authors: Von Rotz Ruth C. , Kins Stefan , Hipfel Rainer , Von Der Kammer Heinz , Nitsch Roger M.
Published: March 2005

Alzheimer's disease (AD) is characterized by a progressive degeneration of neurons along with deposition of amyloid plaques and the formation of neurofibrillary tangles. Neurodegeneration in AD follows both a spatial pattern of selective vulnerability and temporal staging of affected neurons. In order to address transcriptional changes associated with this selective vulnerability, we used subtractive hybridization of transcripts derived from human frontal cortex, which degenerates in late stages of AD, against transcripts of the inferior temporal cortex, which is affected both heavily and early in the course of AD. Moreover, we compared these to brain sections obtained from age‐matched control subjects. We isolated a differentially expressed novel gene encoding a polypeptide that contained an amino‐terminal C3HC4 RING finger domain, called dactylidin. It is ubiquitously expressed in all tissues examined and in situ hybridization of mouse brain sections revealed specific expression in neurons. Further, heterologous expression studies revealed a cytoplasmic localization of dactylidin and as all known cytoplasmic RING finger proteins function as ubiquitin protein ligases, an E3‐like ligase function of dactylidin is probable. However, the up‐regulation of dactylidin in highly vulnerable brain tissues of AD patients was confirmed by a quantitative PCR approach, suggesting that dactylidin may function early in the progression of neurodegenerative diseases.
Prostate‐specific antigen (PSA) complexed to α1‐antichymotrypsin improves prostate cancer detection using total PSA in Japanese patients with total PSA levels of 2.0–4.0 ng/mL
Authors: Kobayashi Takashi , Kamoto Toshiyuki , Nishizawa Koji , Mitsumori Kenji , Ogura Keiji , Ide Yoshihiro
Published: March 2005

OBJECTIVE

To assess the utility of prostate‐specific antigen (PSA) complexed to α1‐antichymotrypsin (PSA‐ACT) in prostate cancer screening in Japanese men with a total PSA level of 2.0–4.0 ng/mL, as improving cancer detection in men with these total PSA levels is a challenge for clinical urologists.

PATIENTS AND METHODS

Total PSA and PSA‐ACT were prospectively assessed and prostate biopsy recommended for patients who met either of two thresholds, i.e. a total PSA of ≥ 2.0 ng/mL or a PSA‐ACT of ≥ 1.5 ng/mL. The diagnostic ability of total PSA and PSA‐ACT, and free‐to‐total PSA ratio and prostate volume‐adjusted density were evaluated by receiver operating characteristic (ROC) analysis.

RESULTS

Of 1003 men enrolled, 547 met the biopsy criteria and a biopsy was taken in 315 (57.6%) patients. The area under the ROC curve for PSA‐ACT (0.679) was significantly greater than that for total PSA (0.601, P = 0.04) and equivalent to that for the free‐to‐total ratio (0.686, P = 0.911) in 116 men, including 27 with cancer with total PSA levels of 2.0–4.0 ng/mL. PSA‐ACT was more specific than the free‐to‐total ratio at a sensitivity of 95% (36% vs 18%, P < 0.05). The best variable for discriminating between cancer and benign disease in men with PSA levels of 2.0–4.0 ng/mL was PSA‐ACT density (area under the curve 0.852) which provided 66% specificity at a sensitivity of 90%.

CONCLUSIONS

PSA‐ACT is better than total PSA and equivalent to the free‐to‐total ratio for detecting prostate cancer in men with PSA levels of 2.0–4.0 ng/mL, and is thus useful for reducing the number of unnecessary biopsies.
Testosterone recovery and changes in bone mineral density after stopping long‐term luteinizing hormone‐releasing hormone analogue therapy in osteoporotic patients with prostate cancer
Authors: Weston Robin , Hussain Asad , George Emmanuel , Parr Nigel J.
Published: March 2005

OBJECTIVE

To investigate the rate of testosterone recovery and changes in bone mineral density in patients found to be osteoporotic while receiving luteinizing hormone‐releasing hormone (LHRH) analogues after changing to antiandrogen monotherapy in an attempt to reduce further demineralization.

PATIENTS AND METHODS

Fifteen patients receiving LHRH analogue therapy for ≥ 1 year were identified as osteoporotic by distal forearm dual X‐ray densitometry. They were then converted to antiandrogen monotherapy, and prostate specific‐antigen (PSA) and total testosterone monitored at 3‐monthly intervals. The forearm densitometry was repeated at 1 year.

RESULTS

All patients had some testosterone recovery; the mean (range) duration to initial detectable testosterone was 12.8 (6–22) months. Six patients had a normal testosterone level after a mean of 17.5 (14–30) months. In the year after stopping LHRH analogue therapy the mean bone mineral density (t‐score) decreased by 7.2%.

CONCLUSIONS

Osteoporotic patients, after stopping LHRH analogues, continue to have suppressed levels of testosterone which have a detrimental effect on bone mineral density. We therefore would not advocate conversion to antiandrogen monotherapy to improve bone density, and suggest alternative therapeutic intervention e.g. bisphosphonate therapy, for these patients.
The assessment of patient life‐expectancy: how accurate are urologists and oncologists?
Authors: Wilson James R.M. , Clarke Michael G. , Ewings Paul , Graham John D. , MacDonagh Ruaraidh
Published: March 2005

OBJECTIVE

To assess the degree of accuracy, precision and consistency with which consultant urologists, oncologists and junior doctors predict a patient's 10‐year life‐expectancy.

SUBJECTS AND METHODS

Eighteen doctors of varying seniority independently examined 70 patient case scenarios containing detailed medical histories; 13 of these cases were duplicate scenarios. Bland‐Altman analyses were used to compare doctors’ estimates of the probability of each hypothetical patient surviving 10 years with that calculated using actuarial methods. Intra‐ and interdoctor reliability were also assessed.

RESULTS

Compared with actuarial estimates, doctors underestimated the 10‐year survival probability by an overall mean of 10.8% (95% confidence interval, 10.1–11.5%). The 18 individual doctors ranged from a mean underestimation of 33.2% to a mean overestimation of 3.9%. Variation around these means was considerable for each doctor, the standard deviations being 14.5–20.9%. Inter‐doctor reliability was 0.58, while overall intra‐doctor reliability was 0.74, but for individual doctors was 0.31–0.94. Junior doctors were less accurate in their predictions than the senior doctors. Five doctors tended to overestimate where life‐expectancy was poor and underestimate where it was good.

CONCLUSIONS

Doctors were poor at predicting 10‐year survival, tending to underestimate when compared with actuarial estimates. There was also substantial variability both within and between doctors. The inaccuracy, imprecision and inconsistency amongst the doctors in assessing patient life‐expectancy is an important finding and has significant implications for managing patients. Many patients may be denied treatment after a pessimistic assessment of life‐expectancy and (less commonly) some may inappropriately be offered treatment after an optimistic assessment. The particular inaccuracy in junior doctors compared with their senior colleagues also highlights the need for training. The development of a tool to assist in both training and clinical practice has the potential to improve doctors’ decision‐making and patient care.
Combined external urethral bulking and artificial urinary sphincter for urethral atrophy and stress urinary incontinence
Authors: Rahman Nadeem U. , Minor Thomas X. , Deng Donna , Lue Tom F.
Published: March 2005

OBJECTIVE

To describe a technique of externally bulking the urethra with a soft‐tissue graft before placing another artificial urinary sphincter (AUS), as when placing another AUS for recurrent male stress urinary incontinence (SUI) other manoeuvres, e.g. placing a tandem cuff or transcorporal cuff, must be used to obtain urinary continence in an atrophic urethra, and each is associated with morbidity.

PATIENTS AND METHODS

From January 2003 to July 2004, five patients (mean age 74 years, range 62–84) treated by radical prostatectomy were referred for recurrent SUI after placing an AUS (four, including one with urethral erosion) or a male sling (one, with a resulting atrophic urethra). Each patient was treated with an external urethral bulking agent (Surgisis® ES, Cook Urological, Spencer, Indiana) and had an AUS placed.

RESULTS

In each patient the greatest urethral circumference was <4 cm. To place a functional 4 cm cuff, the diameter of the urethra was enhanced by wrapping it with Surgisis ES. Continence was significantly improved in all patients except one 84‐year‐old man who had the replanted artificial sphincter removed because of erosion 14 months after surgery.

CONCLUSION

In cases of severe recurrent SUI from urethral atrophy after placing an AUS, externally bulking the urethra with Surgisis ES before placing another AUS is well tolerated, and gives satisfactory results.
The effect on erectile function of 103palladium implantation for localized prostate cancer
Authors: Ponholzer Anton , Oismüller Renée , Somay Canatay , Büchler Felix , Maier Ulrich , Hawliczek Robert , Rauchenwald Michael , Madersbacher Stephan
Published: March 2005

OBJECTIVE

To determine in a prospective study the effect on erectile function of 103Pd brachytherapy for localized prostate cancer, using a validated questionnaire.

PATIENTS AND METHODS

Between July 1999 and April 2003, 113 men with localized prostate cancer were treated by permanent implantation of 103Pd seeds, of whom 78 with a follow‐up of 30 months were included in this study. No patient received supplemental external beam radiation therapy. At baseline and 3‐month intervals, erectile function (EF) was assessed by the EF domain score of the International Index of Erectile Function‐15 (IIEF‐15); 77% received (neo)adjuvant antiandrogen therapy for up to 3 months.

RESULTS

At baseline, 27 (35%) patients had no erectile dysfunction (ED; EF domain score 26–30), 24 (31%) had mild/moderate ED (score 11–25) and 27 (35%) severe ED (score 6–10). The mean EF domain score decreased from 17 to 12 (P < 0.001) after 30 months. Overall, 52 men (67%, including those with severe ED at baseline) remained in the same ED category at 30 months after therapy as before, 12 (15%) deteriorated by one category, 14 (18%) by two or more, and no patient improved. Of the 27 patients fully potent (score 26–30) at baseline, 37% remained so after 30 months, 19% developed mild and the remaining 44% moderate/severe ED. In a multivariate analysis, neither age nor preoperative prostate‐specific antigen level, prostate volume, D90, hormonal treatment, diabetes, smoking or hypertension were predictive of preserving potency (P > 0.05).

CONCLUSIONS

There was a high prevalence of pre‐existing ED in these men; 57% of men fully potent or with mild ED at baseline remained so 30 months after brachytherapy.
Synergistic inhibitory effect of high‐intensity focused ultrasound combined with chemotherapy on Dunning adenocarcinoma
Authors: Paparel Philippe , Curiel Laura , Chesnais Sabrina , Ecochard Rene , Chapelon Jean‐Yves , Gelet Albert
Published: March 2005

OBJECTIVE

To evaluate the therapeutic effect of high‐intensity focused ultrasound (HIFU) combined with chemotherapy (paclitaxel + estramustine) on AT2 Dunning adenocarcinoma, as no satisfactory treatment for localized prostate cancer is available for patients with a poor prognosis, e.g. stage T3, a high Gleason score, or a prostate‐specific antigen level of >15 ng/mL.

MATERIALS AND METHODS

Forty‐one Dunning AT2 tumour‐bearing Copenhagen rats were divided into four groups, i.e. control, chemotherapy, HIFU, and chemotherapy + HIFU (the last three treated for 1 week). The growth in tumour volume was recorded for 3 weeks, the point at which tumour volume was considered to have doubled (doubling time). The growth curves of each group were plotted and evaluated statistically.

RESULTS

At 30 days of follow‐up the distributions of tumour volume with treatment group were significantly different (P < 0.001); volumes were significantly greater in the control than in the chemotherapy‐only or in the HIFU‐only group (both P = 0.006). The greatest difference was between the chemotherapy + HIFU and the control group. The tumour doubling times were 13.2 days for HIFU‐only, 31.2 days for chemotherapy + HIFU and 7.7 days for the controls.

CONCLUSION

These results suggest that this combined therapy could be useful for treating patients with high‐risk prostate cancer.
Stereotactic electrical stimulation of the pontine micturition centre in the pig
Authors: Dalmose Asger L. , Bjarkam Carsten R. , Djurhuus Jens Christian
Published: March 2005

OBJECTIVE

To apply stereotactic electrical stimulation of the pig brainstem and thus identify a pontine micturition centre.

MATERIALS AND METHODS

In 10 anaesthetized female Vietnamese minipigs a needle‐electrode was positioned in the pontine region. Pressure responses in the lower urinary tract identified the micturition centre functionally during electrical stimulation. Stereotactic coordinates were recorded, and the needle visualized by fluoroscopy, magnetic resonance imaging (MRI) or histologically.

RESULTS

The stimulation evoked responses similar to voiding, i.e. a urethral pressure decrease followed by a bladder pressure increase; or similar to a continence manoeuvre, i.e. urethral pressure increase and no change in bladder pressure. In a few cases a continence response was evoked by stimulating a site 1 mm away from the site where a voiding response was evoked. The electrode position was detected by the fluoroscopy‐based stereotactic procedure followed by subsequent MRI (one animal), and by histological analysis, verifying it to be in the dorsolateral pontine region.

CONCLUSIONS

These results show that a pontine micturition centre exists in pigs similar to that described in rats, cats, dogs and humans.
Assessment of microheterogeneity of blood flow in the rat urinary bladder by high‐resolution digital radiography
Authors: Kimura Takahiro , Yamamoto Tokunori , Sone Atsushi , Takenaka Atsushi , Fujisawa Masato
Published: March 2005

OBJECTIVES

To assess high‐resolution digital radiography for measuring blood flow and thus examine the microheterogeneity of bladder microcirculation in a rat model.

MATERIALS AND METHODS

Microheterogeneity of blood flow in both mucosa and detrusor muscle of eight anaesthetized rats was investigated using an imaging technique with very high spatial resolution (0.1 × 0.1 mm2) using digital radiography combined with the deposition of 3H‐labelled desmethylimipramine. The spatial pattern of blood flow was quantified by the coefficient of variation of the regional flow (CV = sd/mean).

RESULTS

Muscle blood flow was less than mucous blood flow (muscle : mucosa, 2.9 : 5) in the empty bladder. In the muscle layer the blood flow distribution was more heterogeneous than that in the mucosa, with a mean (sd) CV in muscle and mucosa of 0.33 (0.033) and 0.16 (0.019), respectively (P < 0.001) at the capillary level.

CONCLUSION

There was a heterogeneous distribution of blood flow in the microcirculation to capillary vessels in the muscular layer, possibly reflecting a difference in dynamic blood flow of regional perfusion of the emptied bladder.
Pinealectomy impairs adipose tissue adaptability to exercise in rats
Authors: Borges‐Silva Cristina N. , Alonso‐Vale Maria I. C. , Franzói‐De‐Moraes Solange M. , Takada Julie , Peres Sidney B. , Andreotti Sandra , Skorupa Ana L. , Cipolla‐Neto José , Pithon‐Curi Tânia C. , Lima Fábio B.
Published: March 2005

Abstract:  This study investigated the effects of pinealectomy and exercise training on rat adipose tissue metabolism. Pinealectomized (PINX) and sham‐operated (CONTROL) adult male Wistar rats were subdivided into four subgroups, including PINX untrained, PINX trained, CONTROL untrained and CONTROL trained. At the end of the training period (8 wk), the rats were killed and peri‐epididymal adipocytes were isolated for in vitro insulin‐stimulated glucose uptake, conversion of d‐[U‐14C]‐glucose, l‐[U‐14C]‐lactate, [2‐14C]‐acetate and [1‐14C]‐palmitate into 14CO2, and insulin binding. Pinealectomy resulted in a significantly decreased insulin‐stimulated glucose uptake in adipocytes without affecting insulin‐binding capacity. However, in intact control animals only, training promoted a higher baseline glucose uptake in adipocytes. Training influenced the adipocyte ability to oxidize the different substrates: the rates of glucose and palmitate oxidation increased while the rates of lactate and acetate diminished. Nevertheless, these effects of exercise training were not seen in pinealectomized rats. Additionally, an increase in palmitate oxidation was observed in sedentary pinealectomized animals. In conclusion, these data show that the pineal gland alters the patterns of substrate utilization by the adipocyte, in such a way that its absence disrupts the ability to adapt to the metabolic demands evoked by exercise training in rats.
Localization and interactions of melatonin in dry cholesterol/lecithin mixed reversed micelles used as cell membrane models
Authors: Bongiorno David , Ceraulo Leopoldo , Ferrugia Mirella , Filizzola Felice , Ruggirello Angela , Liveri Vincenzo Turco
Published: March 2005

Abstract:  The state of melatonin confined in dry cholesterol/lecithin mixed reversed micelles dispersed in CCl4 was investigated using 1H‐NMR and FT‐IR spectroscopies as a function of the melatonin to lecithin molar ratio (RMLT) and of the cholesterol to lecithin molar ratio (RCHL). An analysis of experimental results leads to the hypothesis that, independent of RMLT and as a consequence of anisotropic melatonin/lecithin, melatonin/cholesterol and cholesterol/lecithin interactions, melatonin is totally solubilized in reversed micelles. Melatonin is mainly located in and oriented in the nanodomain constituted by the hydrophilic groups of cholesterol and lecithin. A competition of melatonin and cholesterol for the hydrophilic binding sites of the reversed micelles was observed by changing the RCHL. Some possible biological implications of the specific interactions governing the solubilization process, the preferential location and the peculiar properties of melatonin confined in cholesterol/lecithin mixed reversed micelles are discussed.
Patient perceptions of privacy infringements in an emergency department
Authors: Karro Jonathan , Dent Andrew W , Farish Stephen
Published: March 2005

Objective:  To identify the nature, severity, impact, frequency and risk factors for patient perceived privacy infringements in the ED of St Vincent's Health Melbourne with 32 000 emergency attendances per annum.

Methods:  Patients 18 years and older attending emergency over a 2‐week period were offered a nine‐item questionnaire using a Likert scale. A privacy incident was defined as: (i) overhearing medical or personal information; (ii) being overheard; (iii) having private body parts exposed or (iv) seeing others’ body parts. Differences between demographic, emergency environment, length of stay and other factors suspected of affecting patient privacy were quantified.

Results:  From 1169 emergency presentations, 235 patients returned questionnaires, with 105 of these (45%) reporting a total of 159 privacy incidents. Seventy‐eight patients (33%, 95% CI 28–36%) reported a definite privacy incident and 81 (35%, 95% CI 29–37%) reported a probable privacy incident. Ninety‐six patients (41%, 95% CI 35–47%) reported overhearing other patient's conversations with the staff whereas 36 (15%, 95% CI 11–21%) felt their conversations with staff were overheard by others. Twenty‐seven patients (11%, 95% CI 6–14%) experienced or observed inappropriate exposure of private body parts. Ten patients (4%, 95% CI 2–7%) changed or withheld information from staff because they felt others may overhear it and two refused part of their physical examination because they felt they may be seen by inappropriate people. Twenty‐four patients (10%, 95% CI 6–14%) did not have their expectations of privacy met. The longer a patient was in emergency the greater the number of privacy incidents they experienced (Spearman correlation P < 0.01). Patients in walled cubicles experienced fewer privacy incidents than those in curtained cubicles (P < 0.05).

Conclusions:  Patient privacy incidents occur frequently in an ED, risk factors being length of stay and absence of a walled cubicle. Patients who have their conversations overheard are more likely to withhold information from staff and less likely to have had their expectations of privacy met.
A double‐blind, randomized trial of intravenous versus intramuscular antivenom for Red‐back spider envenoming
Authors: Ellis Rodney M , Sprivulis Peter C , Jelinek George A , Banham Neil DG , Wood Simon V , Wilkes Garry J , Siegmund Andrew , Roberts Brigit L
Published: March 2005

Objective:  To compare the efficacy of intravenous versus intramuscular antivenom (AV) in the treatment of Red‐back spider (RBS) envenoming.

Methods:  Randomized, double‐dummy, double‐blind, multicentre trial of patients with red‐back spider envenoming requiring AV treatment recruited from five hospital EDs in Western Australia.

Results:  Thirty‐five patients were recruited; two were excluded; 33 were available for initial analysis, but two who were unblinded after one ampoule of trial AV and given i.v. AV had limited data; 31 remained in the study and had more complete data. After AV, pain scores for both i.m. and i.v. groups improved rapidly. At 24 h, the i.v. group was better with a 55% absolute difference (76% vs. 21%; 95% CI 25–85% difference) in the proportion pain‐free. There were no safety issues.

Conclusions:  Red‐back spider antivenom was initially effective by both i.m. and i.v. routes. The study generates the hypothesis that at 24 h, significantly more patients are pain‐free with i.v. administration. Definitive recommendations on the optimal route of administration of RBS AV await the results of further studies.
Mix and Mismatch
Authors: Leslie Mitch
Published: March 2005

DNA is as predictable as a bad sitcom--adenine lines up opposite thymine, and cytosine faces guanine. But occasionally nucleotides don't pair correctly, a flaw that can lead to cancer. A protein implicated in some tumors disrupts cells' ability to fix these errors, according to a new study. The work reveals a new function for the protein and might allow doctors to refine cancer treatments.
New Age
Authors: Davenport R. John
Published: March 2005

A stopwatch is the best tool for assessing yeast aging, according to a new study. Timing how long a yeast cell squeezes out offspring is a better gauge of its life span than standard measures, the authors suggest. But other researchers caution that further work is necessary to validate the technique and doubt that it will supplant current approaches.
Coming Back for Seconds
Authors: Davenport R. John
Published: March 2005

Frequent trips through the buffet line can contribute to obesity. For mice, additional servings of a different kind--copious amounts of a protein called lipin--promote corpulence, new results reveal. Previous studies had shown that deficiencies in the protein prevent animals from making fat tissue, and the new work clarifies how it controls fat storage and metabolism.
Plugged Up
Authors: Davenport R. John
Published: March 2005

Without a good bilge pump, ships can flood and sink--and so can cells. After a stroke, a cellular pump protein breaks down, allowing a deadly accumulation of calcium, new results reveal. The study uncovers a protein-eating molecule that dismantles the channel and suggests that preventing the razing might stave off stroke damage.
Ageless No More
Authors: Leslie Mitch
Published: March 2005

They don't develop wrinkles in their cell walls or sprout gray flagella, but intestinal bacteria do grow old, new research suggests. The work shows that senior bacteria grow and reproduce more slowly than do their youthful counterparts, a result that defies long-held beliefs about which organisms decay over time.
More Is Less: Neurogenesis and Age-Related Cognitive Decline in Long-Evans Rats
Authors: Bizon Jennifer L. , Gallagher Michela
Published: March 2005

A reduction in the ability to generate new neurons in the brain has been suggested to contribute to cognitive decline with advanced age. In an outbred model strain of Long-Evans rats, cognitive performance as a function of age is variable in assessments of hippocampal-dependent spatial memory. Recent research indicates that greater hippocampal neurogenesis accompanies diminished cognitive abilities in older Long-Evans rats. These findings imply that the role of neurogenesis might change between youth and old age, and that further work is needed to understand the potential benefits and liabilities that new neurons may afford an aging brain.
Oxidative Mutagenesis, Mismatch Repair, and Aging
Authors: Skinner Amy M. , Turker Mitchell S.
Published: March 2005

A PubMed search for the term "oxidative stress" yields over 29,000 articles published on the subject over the past 10 years; more than 2000 of these articles also include the term "aging" in their title or abstract. Many theories of aging predict causal roles for oxidative stress in the myriad of pathological changes that occur as a function of age, including an increasing propensity to develop cancer. A possible link between aging and cancer is the induction and accumulation of somatic mutations caused by oxidative stress. This Review focuses on small mutational events that are induced by oxidative stress and the role of mismatch repair (MMR) in preventing their formation. It also discusses a possible inhibitory effect of oxidative stress on MMR. We speculate that a synergistic interaction between oxidative damage to DNA and reduced MMR levels will, in part, account for an accumulation of small mutational events, and hence cancer, with aging.
Host-Bacterial Mutualism in the Human Intestine
Authors: Bäckhed Fredrik , Ley Ruth E. , Sonnenburg Justin L. , Peterson Daniel A. , Gordon Jeffrey I.
Published: March 2005

The distal human intestine represents an anaerobic bioreactor programmed with an enormous population of bacteria, dominated by relatively few divisions that are highly diverse at the strain/subspecies level. This microbiota and its collective genomes (microbiome) provide us with genetic and metabolic attributes we have not been required to evolve on our own, including the ability to harvest otherwise inaccessible nutrients. New studies are revealing how the gut microbiota has coevolved with us and how it manipulates and complements our biology in ways that are mutually beneficial. We are also starting to understand how certain keystone members of the microbiota operate to maintain the stability and functional adaptability of this microbial organ.
Temporal Relationships of Carbon Cycling and Ocean Circulation at Glacial Boundaries
Authors: Piotrowski Alexander M. , Goldstein Steven L. , Hemming Sidney R. , Fairbanks Richard G.
Published: March 2005

Evidence from high-sedimentation-rate South Atlantic deep-sea cores indicates that global and Southern Ocean carbon budget shifts preceded thermohaline circulation changes during the last ice age initiation and termination and that these were preceded by ice-sheet growth and retreat, respectively. No consistent lead-lag relationships are observed during abrupt millennial warming events during the last ice age, allowing for the possibility that ocean circulation triggered some millenial climate changes. At the major glacial-interglacial transitions, the global carbon budget and thermohaline ocean circulation responded sequentially to the climate changes that forced the growth and decline of continental ice sheets.
Immunity, Inflammation, and Allergy in the Gut
Authors: MacDonald Thomas T. , Monteleone Giovanni
Published: March 2005

The gut immune system has the challenge of responding to pathogens while remaining relatively unresponsive to food antigens and the commensal microflora. In the developed world, this ability appears to be breaking down, with chronic inflammatory diseases of the gut commonplace in the apparent absence of overt infections. In both mouse and man, mutations in genes that control innate immune recognition, adaptive immunity, and epithelial permeability are all associated with gut inflammation. This suggests that perturbing homeostasis between gut antigens and host immunity represents a critical determinant in the development of gut inflammation and allergy.
Soft-Tissue Vessels and Cellular Preservation in
Tyrannosaurus rex
Authors: Schweitzer Mary H. , Wittmeyer Jennifer L. , Horner John R. , Toporski Jan K.
Published: March 2005

Soft tissues are preserved within hindlimb elements of
Tyrannosaurus rex
(Museum of the Rockies specimen 1125). Removal of the mineral phase reveals transparent, flexible, hollow blood vessels containing small round microstructures that can be expressed from the vessels into solution. Some regions of the demineralized bone matrix are highly fibrous, and the matrix possesses elasticity and resilience. Three populations of microstructures have cell-like morphology. Thus, some dinosaurian soft tissues may retain some of their original flexibility, elasticity, and resilience.
Ready for Their Close-Up
Authors: Sues Hans
Published: March 2005

Mammals from the Age of Dinosaurs
Origins, Evolution, and Structure.
By Zofia Kielan-Jaworowska, Richard L. Cifelli, and Zhe-Xi Luo
. Columbia University Press, New York, 2004. 648 pp. $195, £126. ISBN 0-231-11918-6.

Building on the wealth of fossil discoveries from the past quarter century, the authors provide a comprehensive synthesis of our current understanding of the anatomy, ecology, and evolution of Mesozoic mammals.
TRK
ing Signals Through the Golgi
Authors: Sorkin Alexander
Published: March 2005

The subcellular localization of transmembrane receptors and other signaling proteins has emerged as a key component in the regulation of the intensity and specificity of their activity. Recent research indicates that immature TrkA neurotrophin receptors are transactivated in the Golgi apparatus after stimulation of neuropeptide pituitary adenylate cyclase–activating polypeptide PAC1 receptors or adenosine A
2A
receptors. Transactivation occurs independently of the TrkA extracellular ligand, nerve growth factor (NGF), through a signaling pathway that is distinct from that used in the transactivation of other receptor tyrosine kinases and has consequences distinct from those elicited by NGF at the plasma membrane.
Focus Issue: Diabetes—Fighting Fat on Multiple Fronts
Authors: Adler Elizabeth M.
Published: March 2005

Diabetes, an increasing problem worldwide, involves both insulin resistance and deficiencies in insulin secretion. This week’s issues of
Science
and
Science’s
STKE explore genetic factors that predispose to the development of diabetes as well as the links between diabetes and obesity.
Ser/Thr Phosphorylation of IRS Proteins: A Molecular Basis for Insulin Resistance
Authors: Zick Yehiel
Published: March 2005

S6K1, like other serine and threonine kinases activated by insulin (such as mTOR and PKCζ), has recently been shown to participate in negative feedback mechanisms aimed at terminating insulin signaling through IRS (insulin receptor substrate) phosphorylation. Such homeostatic mechanisms can also be activated by excess nutrients or inducers of insulin resistance (such as fatty acids and proinflammatory cytokines) to produce an insulin-resistant state that often leads to the development of diabetes. Identification of the specific kinases involved in such insulin resistance pathways can help lead to the rational design of novel therapeutic agents for treating insulin resistance and type 2 diabetes.
Cell Signaling Systems: A Course for Graduate Students
Authors: Iyengar Ravi , Diverse-Pierluissi Maria , Weinstein Daniel , Devi Lakshmi A.
Published: March 2005

This course uses the primary literature to develop a systems-level understanding of the information flow through the various cell signaling pathways and networks. Current areas of research activities in the experimental and theoretical understanding of cell signaling research are highlighted. This Teaching Resource describes a sample syllabus and organization for this course. Each lecture is 2 hours. After each set of lectures, there is a 2-hour discussion period during which students present an in-depth analysis of a primary literature article, selected in consultation with the lecturer.
Protein Interfaces in Signaling Regulated by Arginine Methylation
Authors: Boisvert François-Michel , Chénard Carol Anne , Richard Stéphane
Published: March 2005

Posttranslational modifications are well-known effectors of signal transduction. Arginine methylation is a covalent modification that results in the addition of methyl groups to the nitrogen atoms of the arginine side chains. A probable role of arginine methylation in signal transduction is emerging with the identification of new arginine-methylated proteins. However, the functional consequences of arginine methylation and its mode of regulation remain unknown. The identification of the protein arginine methyltransferase family and the development of methylarginine-specific antibodies have raised renewed interest in this modification during the last decade. Arginine methylation was mainly observed on abundant proteins such as RNA-binding proteins and histones, but recent advances have revealed a plethora of arginine-methylated proteins implicated in a variety of cellular processes, including signaling by interferon and cytokines, and in T cell signaling. We discuss these recent advances and the role of arginine methylation in signal transduction.
Protein Kinases
Authors: Caplan Avrom
Published: March 2005

This Teaching Resource provides lecture notes and slides for a class covering the structure and function of protein kinases and is part of the course "Cell Signaling Systems: A Course for Graduate Students." The lecture begins with a discussion of the genomics and evolutionary relationships among kinases and then proceeds to describe the structure-function relationships of specific kinases, the molecular mechanisms underlying substrate specificity, and selected issues in regulation of kinase activity.
Protein Phosphatases
Authors: Salton Stephen R.
Published: March 2005

This Teaching Resource provides lecture notes and slides for a class covering the structure and function of protein phosphatases and is part of the course "Cell Signaling Systems: A Course for Graduate Students." The lecture begins with a discussion of the importance of phosphatases in physiology, recognized by the award of a Nobel Prize in 1992, and then proceeds to describe the two types of protein phosphatases: serine/threonine and tyrosine phosphatases. The information covered includes the structure, regulation, and substrate specificity of protein phosphatases, with an emphasis on their importance in disease and clinical settings.
IgM colocalises with complement and C reactive protein in infarcted human myocardium
Authors: Krijnen P A J , Ciurana C , Cramer T , Hazes T , Meijer C J L M , Visser C A , Niessen H W M , Hack C E
Published: March 2005

Aims:Reperfusion of ischaemic myocardium after acute myocardial infarction (AMI) can induce ischaemia/reperfusion (I/R) injury, as a result of local activation of the complement system. C reactive protein (CRP) is involved in this activation. This study analysed the potential role of IgM in complement activation in the infarcted human myocardium.

Methods:Immunochemical analysis was carried out on heart specimens from 59 patients who died from AMI. Serial slides of frozen tissue from the infarction site were stained for IgM, complement factors C3d and C5b–9 (membrane attack complex), and CRP.

Results:IgM deposits were found on the plasma membrane, cross striations, and in the cytoplasm of jeopardised cardiomyocytes in infarcts of one to five days duration. IgM depositions were remarkably similar to those of CRP and both complement factors. The relative staining intensities of IgM and CRP varied greatly among patients.

Conclusions:Similar to CRP, IgM targets complement locally to jeopardised cardiomyocytes in the human heart after AMI. Localisation patterns and relative staining intensities suggest that IgM and CRP recognise similar epitopes in the ischaemic heart, but that the relative contribution of each protein to complement activation in the ischaemic myocardium differs among patients.
VARIATIONAL MONTE CARLO FOR MICROSCOPIC CLUSTER MODELS
Authors: LEONTIOU THEODOROS , WALET NIELS R.
Published: March 2005

We examine the application of the Variational Monte Carlo (VMC) method to a cluster model for halo nuclei. Particular attention is paid to the error estimate in the presence of correlations in the underlying random walk. We analyze the required steps for a reliable application of the VMC in the case of a complicated many-body problem, such as the direct solution of the nuclear Hamiltonian with realistic interactions. We also examine the possibility of variance reduction through the "zero variance principle", paying particular attention to the complexity of the many-body problem.
A POINT-LIKE PICTURE OF THE HYDROGEN ATOM
Authors: FAGHIHI F. , JANGJOO A. , KHANI M.
Published: March 2005

A point-like picture of the Schrödinger solution for hydrogen atom is worked to emphasize that "point-like particles" may describe as "probability wave function". In each case, the three-dimensional shape of the |Ψnlm(rn, cos θ)|2 is plotted and the paths of the point-like electron (it is better to say reduced mass of the pair particles) are described in each closed shell. Finally, the orbital shape of the molecules are given according to the present simple model. In our opinion, "interpretations of the Correspondence Principle", which is a basic principle in all elementary quantum text, seems to be reviewed again!
PARTICLE DYNAMICS SIMULATIONS OF THE NAVIER–STOKES FLOW WITH HARD DISKS
Authors: ISHIWATA TATSUYA , MURAKAMI TERUYOSHI , YUKAWA SATOSHI , ITO NOBUYASU
Published: March 2005

Flow simulation with a particle dynamics method is studied. The fluid is made of hard particles which obey the Newtonian equations of motion and the collisions between particles are elastic, that is, energy and momentum are conserved. The viscosity appears autonomously together with the local equilibrium state. When a particle collides with a nonslip boundary, a new velocity is given randomly from the thermal distribution if the wall is isothermal, or a random reflection angle is selected if the wall is adiabatic. Shear viscosity is estimated from simulations of plane Poiseuille flow together with the confirmation that the system obeys the Navier–Stokes equation. Flows past a cylinder are also simulated. Depending on the Reynolds number up to 106, flow patterns are properly reproduced, and Kármán vortex shedding is observed. The estimated values of drag coefficient show quantitative agreement with experiments.