bluuebunny/crossref_metadata_2025 huggingface dataset:
Early life stage salinity tolerance of wild and hatchery‐reared juvenile pink salmon Oncorhynchus gorbuscha
Authors: Grant A. M. , Gardner M. , Hanson L. M. , Farrell A. P. , Brauner C. J.
Published: August 2010

Salinity tolerance in wild (Glendale) and hatchery (Quinsam) pink salmon Oncorhynchus gorbuscha (average mass 0·2 g) was assessed by measuring whole body [Na+] and [Cl−] after 24 or 72 h exposures to fresh water (FW) and 33, 66 or 100% sea water (SW). Gill Na+, K+‐ATPase activity was measured following exposure to FW and 100% SW and increased significantly in both populations after a 24 h exposure to 100% SW. Whole body [Na+] and whole body [Cl−] increased significantly in both populations after 24 h in 33, 66 and 100% SW, where whole body [Cl−] differed significantly between Quinsam and Glendale populations. Extending the seawater exposure to 72 h resulted in no further increases in whole body [Na+] and whole body [Cl−] at any salinity, but there was more variability among the responses of the two populations. Per cent whole body water (c. 81%) was maintained in all groups of fish regardless of salinity exposure or population, indicating that the increase in whole body ion levels may have been related to maintaining water balance as no mortality was observed in this study. Thus, both wild and hatchery juvenile O. gorbuscha tolerated abrupt salinity changes, which triggered an increase in gill Na+, K+‐ATPase within 24 h. These results are discussed in terms of the preparedness of emerging O. gorbuscha for the marine phase of their life cycle.
The NK1 receptor antagonist aprepitant does not alter the pharmacokinetics of high‐dose melphalan chemotherapy in patients with multiple myeloma
Authors: Egerer Gerlinde , Eisenlohr Kathrin , Gronkowski Martina , Burhenne Juergen , Riedel Klaus‐Dieter , Mikus Gerd
Published: August 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Nausea and vomiting are the most distressing side‐effects of a high dose melphalan regimen.

• Aprepitant in addition to an antiemetic standard regimen has been reported to improve significantly both acute and delayed chemotherapy‐induced nausea and vomiting.

WHAT THIS STUDY ADDS

• Anti‐emetic regimens including aprepitant have no clinically relevant effect on the pharmacokinetics of the anticancer agent melphalan when administered 1 h before high dose melphalan infusion.

AIMS

The objective of this investigation was to assess the effect of aprepitant on the pharmacokinetics of high‐dose melphalan used as conditioning therapy before blood stem cell transplantation in multiple myeloma.

METHODS

Aprepitant (125 mg) or placebo was administered 1 h before melphalan therapy (1 h infusion of 100 mg m−2). Eleven plasma samples were obtained over 8 h and melphalan was quantified using an LC/MS/MS method. Standard pharmacokinetic parameters were calculated and nonparametric testing was applied to assess the differences between aprepitant and placebo treatment.

RESULTS

Twenty patients received placebo and 10 patients aprepitant treatment. There were no differences observed for Cmax at the end of melphalan infusion (placebo 3431 ± 608 ng ml−1vs. aprepitant 3269 ± 660 ng ml−1). In addition, AUC and terminal elimination half‐life were not changed by aprepitant. Total clearance of melphalan was 304 ± 58 ml min−1 m−2 (placebo) which was not influenced by aprepitant (288 ± 78 ml min−1 m−2).

CONCLUSIONS

The administration of the NK1 receptor antagonist aprepitant 1 h before a high‐dose chemotherapy does not influence the exposure and the elimination of melphalan. Therefore, oral administration of 125 mg aprepitant 1 h before melphalan infusion does not alter the disposition of intravenously administered melphalan.
Polymorphisms in DNA repair genes and risk of non‐Hodgkin lymphoma in a pooled analysis of three studies
Authors: Shen Min , Menashe Idan , Morton Lindsay M. , Zhang Yawei , Armstrong Bruce , Wang Sophia S. , Lan Qing , Hartge Patricia , Purdue Mark P. , Cerhan James R. , Grulich Andrew , Cozen Wendy , Yeager Meredith , Holford Theodore R. , Vajdic Claire M. , Davis Scott , Leaderer Brian , Kricker Anne , Severson Richard K. , Zahm Shelia H. , Chatterjee Nilanjan , Rothman Nathaniel , Chanock Stephen J. , Zheng Tongzhang
Published: August 2010

Genetic variations in DNA repair genes are thought to play an important role in the pathogenesis and development of non‐Hodgkin lymphoma (NHL). To further explore this hypothesis, we genotyped 319 tag single nucleotide polymorphisms (SNPs) in 27 DNA repair gene regions in 1946 cases and 1808 controls pooled from three population‐based case‐control studies of NHL in the US and Australia. Relative risks of NHL and NHL subtypes in relation to SNP genotypes were assessed using logistic regression. Associations of gene regions and pathways with NHL or NHL subtypes were explored using the minP and tail‐strength statistics, respectively. Overall, genetic polymorphisms within the DNA repair pathway were associated with NHL (P = 0·005). Similar associations were seen with the double‐strand break repair (P = 0·02) and nucleotide excision repair (P = 0·04) pathways. Five SNPs (BLM rs441399, RAD50 rs2237060, FAM82A2 rs2304583, ERCC3 rs4150506, and XRCC4 rs13178127) were particularly noteworthy because their gene regions were significantly associated with NHL or NHL subtypes (minP ≤ 0·05), or because of high level of statistical significance (P ≤ 0·005) and consistent findings across the three studies. These results support the hypothesis that common genetic polymorphisms in human DNA repair genes may modify the risk of NHL.
Cardiac magnetic resonance in transfusion dependent thalassaemia: assessment of iron load and relationship to left ventricular ejection fraction
Authors: Chouliaras Giorgos L. , Kattamis Antonis , Berdoukas Vasilis , Gotsis Efstathios D. , Mavrogeni Sophie , Ladis Vassilis
Published: August 2010

Cardiac Magnetic Resonance (CMR) has replaced all other surrogate measurements in the determination of transfusional cardiac iron overload in patients with thalassaemia major. We aimed to determine the diagnostic value of CMR T2* with respect to cardiac dysfunction (CD) as determined by CMR‐derived left ventricular ejection fraction (LVEF). Cardiac T2* values and LVEF measured by CMR were recorded in 303 patients with thalassaemia major, at the time of their first CMR. T2* was correlated with LVEF (regression coefficient: 0·57, P < 0·001). The prevalence of CD was 32·9% in patients with T2* ≤ 8 ms, 12·5% in patients with T2* > 8 ms and ≤14 ms and reduced to 9·1% in patients with T2* between 14–20 ms. As the probability of CD is progressively, and not suddenly, reduced with increasing values of T2*, CMR has a limited diagnostic value for CD (Receiver operating characteristic analysis, area under the curve = 0·68). Patients with cardiac T2* ≤ 8 ms require careful and intensive management. This risk decreases with increasing values of T2* but even in mildly loaded patients the probability of impaired LVEF is not negligible.
Negative changes in the scientific publication process in ecology: potential causes and consequences
Authors: STATZNER BERNHARD , RESH VINCENT H.
Published: August 2010

1. Increasingly viewed to have societal impact and value, science is affected by complex changes such as globalisation and the increasing dominance of commercial interest. As a result, technical advancements, financial concerns, institutional prestige and journal proliferation have created challenges for ecological and other scientific journals and affected the perception of both researchers and the public about the science that they publish.

2. Journals are now used for more than dissemination of scientific research. Institutions use journal rankings for a variety of purposes and often require a pre‐established number of articles in hiring and budgetary decisions. Consequently, journal impact factors have achieved greater importance, and the splitting of articles into smaller parcels of information (‘salami‐slicing’) to increase numbers of publications has become more frequent.

3. Journals may prescribe upper limits to article length, even though the average length of articles for several ecological journals examined has increased over time. There are clear signs, however, that journals without length limits for articles will become rarer. In contrast to ecological journals, taxonomic journals are not following this trend.

4. Two case histories demonstrate how splitting longer ecological articles into a series of shorter ones results in both redundancy of information and actually increases the journal space used overall. Furthermore, with current rejection rates of ecological journals (often ∼80%), many thin salami‐sliced articles jam the peer‐review system much longer (through resubmission after rejection) than unsliced articles previously did (e.g. when rejection rates were ∼50%). In our experience, the increased pressure to publish many articles in ‘high‐impact’ journals also may decrease the attractiveness of a future scientific career in ecology to young people.

5. ‘Gatekeeping’ of journal quality has shifted from editors to reviewers, and several recent trends are apparent including: bias about appropriate statistical methods; reviewers being more rigid overall; non‐native English writers being criticised for poor communications skills; and favourable reviews being signed more often than unfavourable ones. In terms of production, outsourcing of copy editing has increased the final error rate of published material.

6. We supplemented our perceptions with those of older colleagues (∼100 experienced ecologists) that responded to an informal survey on this topic (response rate: 81%). In the opinion of almost 90% of our respondents, the overall review process has changed and for 20% among them the professional quality of reviews has declined.

7. We, and many older colleagues, are convinced there have been some negative changes in the scientific publication process. If younger colleagues share this concern, we can collectively counter this deteriorating situation, because we are the key to the publishing and evaluation process.
Connective tissue growth factor expression is increased in collagenous colitis and coeliac disease
Authors: Günther Ute , Bateman Adrian C , Beattie R Mark , Bauer Michael , MacDonald Thomas T , Kaskas Berndt A
Published: August 2010

Günther U, Bateman A C, Beattie R M, Bauer M, MacDonald T T & Kaskas B A (2010) Histopathology 57, 427–435 Connective tissue growth factor expression is increased in collagenous colitis and coeliac disease

Aims:  Subepithelial collagen deposition is a classical feature of collagenous colitis (CC), but is also seen in untreated coeliac disease. The end‐stage mediator of excess cellular collagen production is connective tissue growth factor (CTGF). The aim of this study was to investigate CTGF expression by in situ hybridization (ISH) and polymerase chain reaction (PCR) in CC and coeliac disease as well as lymphocytic colitis (LC), Crohn’s colitis and ulcerative colitis (UC).

Methods and results:  For coeliac disease we analysed fresh frozen material by quantitative reverse transcription–polymerase chain reaction (RT–PCR) and archival material for ISH. PCR transcripts in coeliac disease were moderately elevated and labelled cells were significantly increased in the subepithelial zone. For CC, LC and UC we investigated archival material because of the rarity of the first two conditions. There was a marked increase in CTGF expression in the subepithelial zone in CC, localizing to cells with the morphology of smooth muscle cells, which was not seen in LC.

Conclusions:  The colocalization of CTGF transcripts with areas of excessive collagen deposition in coeliac disease and CC suggest that it might be the end‐stage mediator of local fibrosis in these conditions.
STAT3 modulates the DNA damage response pathway
Authors: Barry Seán P. , Townsend Paul A. , Knight Richard A. , Scarabelli Tiziano M. , Latchman David S. , Stephanou Anastasis
Published: August 2010

The STAT3 transcription factor is well known to function as an anti‐apoptotic factor, especially in numerous malignancies. Recently we showed that STAT3 is cytoprotective and that cells lacking STAT3 are more sensitive to oxidative stress. A key feature of oxidative stress involves activation of the DNA damage pathway. However, a role for STAT3 or its contribution in response to DNA damage has not been described. In the present study we show that cells lacking STAT3 are less efficient in repairing damaged DNA. Moreover, STAT3 deficient cells show reduced activity of the ATM‐Chk2 and ATR‐Chk1 pathways, both important pathways in sensing DNA damage. Finally we show that MDC1, a regulator of the ATM‐Chk2 pathway and facilitator of the DNA damage response, is modulated by STAT3 at the transcriptional level. These findings demonstrate that STAT3 is necessary for efficient repair of damaged DNA, partly by modulating the ATM‐Chk2 and ATR‐Chk1 pathways.
αB‐crystallin (HspB5) in familial amyloidotic polyneuropathy
Authors: Magalhães Joana , Santos Sofia Duque , Saraiva Maria João
Published: August 2010

The small heat shock protein αB‐crystallin (HspB5) is known to be overexpressed in several neurodegenerative disorders. In familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder characterized by extracellular deposition of mutated transthyretin (TTR), activation of heat shock factor 1 ‐HSF1‐ by extracellular TTR deposition has been shown as well as induction of the expression of heat shock proteins, HSP27 and HSP70. Here we investigate the expression of αB‐crystallin in FAP. We first detected αB‐crystallin in aggregates extracted from tissues of both FAP patients and transgenic mice for the human V30M mutant TTR; however, subsequent studies by confocal fluorescence microscopy did not confirm the association of αB‐crystallin with TTR aggregates; thus the presence of αB‐crystallin in aggregate extracts might derive from the extraction procedure. Increased levels of αB‐crystallin were observed by immunohistochemistry in human FAP skin, as compared to normal skin. Furthermore, skin, stomach and dorsal root ganglia from V30M transgenic mice showed increased expression of αB‐crystallin as compared to controls without deposition. A human neuroblastoma cell line incubated with TTR aggregates displayed increased expression of αB‐crystallin. Overall, these results show that extracellular TTR deposits induce an intracellular response of αB‐crystallin. This small heat shock protein (HSP), which is important for anti‐apoptotic and chaperone properties, may have a protective role in FAP.
Characteristic pattern of skeletal muscle remodelling in different mouse strains
Authors: Lagrota‐Candido Jussara , Canella Isabella , Pinheiro Douglas F. , Santos‐Silva Luana Paula , Ferreira Rafael. S. , Guimarães‐Joca Francisco J. , Lannes‐Vieira Joseli , Quirico‐Santos Thereza
Published: August 2010

Muscular injury associated with local inflammatory reaction frequently occurs in sports medicine, but the individual response and capacity of regeneration vary among subjects. Inflammatory cytokines are probably implicated in activation of repair mechanisms by specifically influencing tissue microenvironment. This work aimed to compare muscle tissue repair in different mouse lineages. We used C57BL/6 and BALB/c mice genetically predisposed to either Type1 or Type2 cytokine production. The role of Type1 cytokines was also investigated in C57IFN‐γ (IFNγ‐KO) and C57IL‐12 (IL12‐KO) knockout mice. Participation of T lymphocytes was assessed in athymic BALB/c nude (nu/nu) mice. Muscular lesion was induced with bupivacaine injection in the Triceps brachii muscle. BALB/c mice showed marked collagen deposition and increased TGF‐β mRNA content, contrasting with mild fibrosis observed in C57BL/6 mice. C57‐IFNγ‐KO mice, exhibited pronounced fibrosis, but IL12‐KO collagen deposition was similar to that of C57. Twenty‐four hours after lesion, C57BL/6 and BALB/cnu/nu presented numerous regenerating myofibres and marked increase of metalloprotease‐9 activity compared with BALB/c. These data support that skeletal muscle remodelling is greatly influenced by the genetic backgrounds, shedding light on the molecular mechanisms influencing differential muscular remodelling and tissue regeneration among individuals.
Review: bringing patient safety to the forefront through structured computerisation during clinical handover
Authors: Matic Jenelle , Davidson Patricia M , Salamonson Yenna
Published: August 2010

Aims and objectives.  This review aims to examine critically, the methods and modes of delivery of handover used in contemporary health care settings and explore the feasibility of a computerised handover system for improving patient safety.

Background.  Clinicians play a critical role in promoting patient safety, and the handover ritual is recognised as important in exchanging information and planning patient care. Communication failures have been identified as an important cause of adverse incidents in hospitals.

Design.  Integrative literature review.

Methods.  Search of multiple electronic databases using terms: nursing handover, handoff, shift‐to‐shift reporting and change of shift report.

Discussion.  To date, the focus of research has primarily been on the vehicle of the handover, rather than the content and processes involved in ensuring the reliability and quality of clinical information. Employing a computerised handover system in the clinical arena has the potential to improve the quality and safety of clinical care.

Conclusions.  Whilst the handover performed from shift‐to‐shift is a valuable communication strategy, ambiguities and incomplete information can increase the risks of adverse events. Given the importance of effective communication, its key link to patient safety and the frequency of nursing handover, it is imperative that clinical handover undergo increased scrutiny, development and research.

Relevance to clinical practice.  This review underscores the challenge in clinical handover and recommends the use of technological solutions to improve communication strategies.
A 350‐year tree‐ring fire record from Białowieża Primeval Forest, Poland: implications for Central European lowland fire history
Authors: Niklasson Mats , Zin Ewa , Zielonka Tomasz , Feijen Markus , Korczyk Adolf F. , Churski Marcin , Samojlik Tomasz , Jędrzejewska Bogumiła , Gutowski Jerzy M. , Brzeziecki Bogdan
Published: August 2010

1. Fires are nowadays small, yet frequent, in temperate Central European conifer forests, but little is known about the fire history in this region. This is likely due to the lack of intact forests that contain old trees and dead wood from which fire history may be reconstructed. An exception is the Białowieża Primeval Forest (BPF) in Poland for which we were able to reconstruct the fire history in detail.

2. From 886 tree ring samples collected in a 13‐ha conifer‐dominated area, we reconstructed fire events and tree establishment back to the mid 1600s. From 1653 to the late 1700s fires were very frequent, with mean point (single tree) fire intervals of 18 years and mean stand scale fire intervals of 6 years. After 1781, the intervals between the fires increased dramatically, and since 1874 no major fire was recorded.

3. Tree establishment underwent substantial changes, closely tracking shifts in fire frequency. When fires were frequent, Pinus sylvestris establishment occurred only sporadically. Later, less frequent fires promoted massive establishment of both P. sylvestris and Picea abies. At present, only P. abies and a few deciduous trees regenerate.

4. Synthesis. We present the first high‐resolution fire history in the Central European temperate lowland forest area. The discovery of old P. sylvestris trees and stumps with fire scars in many conifer‐dominated parts of BPF show that fire was a major component in the past dynamics of this forest. We also show that historically, fires were recurring at very close intervals, supporting an open, Pinus‐dominated forest. These result contrasts with the written history of BPF, which focus on a few, large fires from the past. Human influence on the fire regime was probably substantial, although the disentangling of climatic and human impacts needs further studies. We propose that fire should be increasingly taken into consideration in models of disturbance, vegetation development and forest openness in the whole Central European lowland forest region.
Seed dispersal by scatter‐hoarding rodents in arid environments
Authors: Beck Maurie J. , Vander Wall Stephen B.
Published: August 2010

1. The seeds of many plants are dispersed by animals, but the nature of these plant–animal mutualisms is often moulded by the abiotic environment. Here, we show that desert peach (Prunus andersonii), with dry fruits and large seeds, relies on scatter‐hoarding rodents for dispersal and that this form of seed dispersal maintains the effectiveness of dispersal while reducing water expenditure.

2. The fruit pulp of desert peach dries and dehisces at maturity in early summer. No vertebrate frugivores consumed the fruits, but rodents quickly harvested the nuts. Nearly 75% of the nut crop was removed from plant canopies by scansorial rodents like white‐tailed antelope squirrels (Ammospermophilus leucurus), which scatter‐hoarded nuts in 1–2 seed caches 10–30 mm deep. Deer mice (Peromyscus maniculatus) also made many shallow one‐nut caches.

3. Heteromyid rodents (Great Basin pocket mouse, Perognathus parvus; Panamint kangaroo rat, Dipodomys panamintinus) primarily larder‐hoarded nuts (c. 60%) in burrows too deep for seedling emergence, but also scatter‐hoarded nuts in a few, large caches 10–40 mm deep.

4. Antelope squirrels were the most effective dispersers and deer mice and Panamint kangaroo rats were less effective. Abiotically dispersed nuts had virtually no recruitment (<1% emergence), but nuts buried in soil to simulate rodent caches had 32% emergence and 5.6% survived after 1 year. Scatter‐hoarding rodents are responsible for virtually all recruitment in desert peach.

5. Synthesis. Desert peach arose from a fleshy‐fruited ancestor that was probably dispersed by endozoochorous frugivores. About 35 species of dry‐fruited Prunus occur in arid environments across North America and Eurasia. The most parsimonious explanation for the evolution of dry‐fruited Prunus is the loss of frugivory in a diplochorous ancestor (i.e. combined frugivore and scatter‐hoarding dispersal) to maintain the effectiveness of seed dispersal while reducing the demand for water in arid environments.
Response to Coomes & Allen (2009)‘Testing the metabolic scaling theory of tree growth’
Authors: Stark Scott C. , Bentley Lisa Patrick , Enquist Brian J.
Published: August 2010

1. Coomes & Allen (2009) propose a new statistical method to test the Metabolic Scaling Theory prediction for tree growth rate size scaling (scaling constant α = 1/3) presented in Enquist et al. (1999). This method finds values of the scaling constant that yield standardized major axis (SMA) slopes of one in a comparison of allometrically transformed diameter census data. This SMA ‘slope‐of‐one’ method produces results that contrast with those generated by maximum‐likelihood estimation (MLE; Russo, Wiser & Coomes 2007; Coomes & Allen 2009).

2. We hypothesize that the SMA slope‐of‐one method is inappropriate for this application because it assumes, unrealistically, that there is no biological or error variance in tree growth size scaling. To test our hypothesis, we simulate ‘allometric’ tree growth with biological and error variance in parameters and measurements. We find that the SMA slope‐of‐one method is sensitive to the amount of biological and error variance and consistently returns biassed parameter estimates, while the MLE method displays relatively little bias, particularly at larger sample sizes.

3. Synthesis. The conclusions of Coomes & Allen (2009) should be reconsidered in the light of our findings. Investigations of tree growth rate size scaling must consider the influence of biological and error variance in model‐fitting procedures to ultimately unravel the effects of tree architecture and ecological factors on patterns of size‐dependent growth.
Improving diabetes care in a public hospital medical clinic: report of a completed audit cycle
Authors: Tan Florence , Liew Shan F. , Chan Grace , Toh Vivien , Wong See Y.
Published: August 2010

Rationale, aims and objectives  To evaluate the impact of clinical audit on diabetes care provided to type 2 diabetic patients attending our hospital general medical clinics.

Methods  Performances on diabetes‐related process measures and intermediate outcome measures were evaluated through structured review of outpatient medical records. The results were fed back to the doctors and measures were implemented to improve care. The performance indicators were re‐evaluated 2 years later to complete the audit cycle.

Results  Annual testing rates improved for HbA1c (68.4% vs. 87.4%; P < 0.001) and lipid profile (91.8% vs. 97%; P = 0.027). Enquiry on smoking improved from 45.9% to 82.3% (P < 0.001), eye screening rates from 68.9% to 78.8% (P = 0.020) and foot examinations from 22.4% to 64.1% (P < 0.001). Prescription rates for insulin increased from 17.3% to 31.8% (P = 0.001) and statin from 83.2% to 94.4% (P < 0.001). The use of aspirin (80.6% vs. 83.8%; P = 0.402) and angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker (92.3% vs. 88.9%; P = 0.239) remained high in both cycles. More patients achieved targets for HbA1c < 7% (38% vs. 26%; P = 0.006), blood pressure < 130/80 mmHg (43% vs. 32%; P = 0.071) and low‐density lipoprotein cholesterol < 2.6 mmol/L (71% vs. 52%; P < 0.001).

Conclusion  Clinical audit is a useful tool in improving diabetes care.
Pharmacist‐led intervention study to improve inhalation technique in asthma and COPD patients
Authors: Hämmerlein Andrea , Müller Uta , Schulz Martin
Published: August 2010

Rational and aims  Inhaled therapy is the mainstay of treatment in patients with asthma and chronic obstructive pulmonary disease (COPD). For effectiveness of pharmacotherapy, correct use of medication is required. The aims of this study were to survey the quality of inhalation technique in patients and to determine the effect of a single intervention in community pharmacies by means of standardized procedures.

Methods  A total of 757 patients with asthma or COPD were randomly selected by 55 community pharmacies. At baseline, patients were interviewed and their inhalation technique was assessed with a 21‐items checklist. Any error was recorded and, if necessary, patients were instructed in the proper use of their device. After 4–6 weeks, demonstration of inhalation technique was repeated in the community pharmacies and a pre–post comparison was performed.

Results  A total of 597 patients (78.9%) made at least one mistake in performing the inhalation technique at baseline. This number dropped to 214 (28.3%) from the first to the second appointment. All patients did benefit from the pharmacists' intervention regardless of their former training experiences.

Conclusions  Inhalation technique of asthma and COPD patients is poor. In daily practice, community pharmacy‐based pharmacists are well suited to significantly supplement doctor‐based education in inhalation technique.
Cell cycle and cell death in disease: past, present and future
Authors: Zhivotovsky B. , Orrenius S.
Published: August 2010

Abstract.  Zhivotovsky B, Orrenius S (Institute of Environmental Medicine, Division of Toxicology, Karolinska Institute, Stockholm, Sweden) Cell cycle and cell death in disease: past, present and future (Symposium). J Intern Med 2010; 268: 395–409.

Cell division and cell death are the two predominant physiological processes that regulate tissue homeostasis in the adult organism. The importance of dysregulation of these processes in the pathogenesis of major diseases, such as cancer, myocardial infarction, stroke, atherosclerosis, infection, inflammation and neurodegenerative disorders, is becoming increasingly evident. Hence, attempts to find modulators of the cell cycle and cell death programmes are being made with the hope of creating novel therapeutic approaches to the treatment of these diseases. It is clear that improved understanding of how cells balance life‐and‐death processes is crucial for this development. In view of this, a Nobel Symposium entitled ‘The Cell Cycle and Apoptosis in Disease’ was organized in conjunction with the celebration of the 200‐year anniversary of the Karolinska Institute in 2010. The symposium focused on the importance of dysregulation of cell cycle/cell death programmes in the pathogenesis of human disease. Three comprehensive reviews based on presentations at this symposium are presented in this issue of the Journal of Internal Medicine. They include a discussion of autophagy in anticancer therapy, the description of a role for type 2 transglutaminase in Huntington’s disease and the proposal that ‘redox‐sensing’ mechanisms might act as an orthogonal control in cell cycle and apoptosis signalling.
Electrophysiological Effects of Melatonin on MousePer1and non‐Per1Suprachiasmatic Nuclei NeuronesIn Vitro
Authors: Scott F. F. , Belle M. D. C. , Delagrange P. , Piggins H. D.
Published: August 2010

The master circadian pacemaker in the suprachiasmatic nuclei (SCN) regulates the nocturnal secretion of the pineal hormone melatonin. Melatonin, in turn, has feedback effects on SCN neuronal activity rhythms via high affinity G protein‐coupled receptors (MT1and MT2). However, the precise effects of melatonin on the electrical properties of individual SCN neurones are unclear. In the present study, we investigated the acute effects of exogenous melatonin on SCN neurones using whole‐cell patch‐clamp recordings in brain slices prepared fromPer1::d2EGFP‐expressing transgenic mice. In current‐clamp mode, bath applied melatonin, at near‐physiological concentrations (1 nm), hyperpolarised the majority (63.7%) of SCN neurones tested at all times of the projected light/dark cycle. In addition, melatonin depolarised a small proportion of cells (11.0%). No differences were observed for the effects of melatonin betweenPer1::GFPor non‐Per1::GFPSCN neurones. Melatonin‐induced effects were blocked by the MT1/MT2antagonist, luzindole (1 μm) and the proportion of SCN neurones responsive to melatonin was greatly reduced in the presence of either tetrodotoxin (200 or 500 nm) or gabazine (20 μm). In voltage‐clamp recordings, 1 nmmelatonin increased the frequency of GABA‐mediated currents. These findings indicate, for the first time, that exogenous melatonin can alter neuronal excitability in the majority of SCN neurones, regardless of whether or not they overtly express the core clock genePer1. The results also suggest that melatonin acts mainly by modulating inhibitory GABAergic transmission within the SCN. This may explain why exogenous application of melatonin has heterogenous effects on individual SCN neurones.
The making of a rapid plant invader: genetic diversity and differentiation in the native and invaded range of Senecio inaequidens
Authors: LACHMUTH SUSANNE , DURKA WALTER , SCHURR FRANK M.
Published: August 2010

To become invasive, exotic species have to succeed in the consecutive phases of introduction, naturalization, and invasion. Each of these phases leaves traces in genetic structure, which may affect the species’ success in subsequent phases. We examined this interplay of genetic structure and invasion dynamics in the South African Ragwort (Senecio inaequidens), one of Europe’s fastest plant invaders. We used AFLP and microsatellite markers to analyze 19 native African and 32 invasive European populations. In combination with historic data, we distinguished invasion routes and traced them back to the native source areas. This revealed that different introduction sites had markedly different success in the three invasion phases. Notably, an observed lag‐phase in Northern Germany was evidently not terminated by factors increasing the invasiveness of the resident population but by invasive spread from another introduction centre. The lineage invading Central Europe was introduced to sites in which winters are more benign than in the native source region. Subsequently, this lineage spread into areas in which winter temperatures match the native climate more closely. Genetic diversity clearly increases with population age in Europe and less clearly decreases with spread rate up to population establishment. This indicates that gene flow along well‐connected invasion routes counteracted losses of genetic diversity during rapid spread. In summary, this study suggests that multiple introductions, environmental preadaptation and high gene flow along invasion routes contributed to the success of this rapid invader. More generally, it demonstrates the benefit of combining genetic, historical, and climatic data for understanding biological invasions.
Weed community response to contrasting integrated weed management systems for cool dryland annual crops
Authors: THOMAS A G , LÉGÈRE A , LEESON J Y , STEVENSON F C , HOLM F A , GRADIN B
Published: August 2010

ThomasAG, LégèreA, LeesonJY, StevensonFC, HolmFA & GradinB (2011). Weed community response to contrasting integrated weed management systems for cool dryland annual crops.Weed Research 51, 41–50.

Contrasting approaches to integrated weed management (IWM) for prairie cropping systems were evaluated by measuring weed response to six IWM systems in a wheat–oilseed rape–barley–pea rotation at Saskatoon and Watrous, Saskatchewan, Canada. The six IWM systems (high herbicide/zero tillage; medium herbicide/zero tillage; low herbicide/zero tillage; low herbicide/low tillage; medium herbicide/medium tillage; no herbicide/high tillage) included various combinations of seeding rate and date, herbicide timing and rate, and tillage operations, in order to achieve similar weed management levels. Changes in weed communities were assessed over 4 years by monitoring species composition and abundance at various times during the growth season. Principal response curves indicated a gradual increase inThlaspi arvense,Chenopodium album,Amaranthus retroflexusandFallopia convolvulusin the no herbicide/high tillage system. Winter and early spring annuals and perennials increased in most systems, but particularly in the low herbicide/zero tillage and medium herbicide/zero tillage systems. Although five of the six IWM systems provided similar results, changes in weed communities would suggest that operations could be revised to improve the overall management of certain weed species and reduce seed return in the no herbicide/high tillage system and in systems with low herbicide inputs and zero tillage. This study confirms the potential of contrasting IWM systems under the challenging environmental conditions of the Canadian Prairies.
SHANK2 redemption: another synaptic protein for mental retardation and autism
Authors: Kumar RA
Published: August 2010

Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation

Berkel et al. (2010)

Nature Genetics 42(6):489–491
Treatment of respiratory syncytial virus infection in adult patients with hematologic malignancies based on an institution‐specific guideline
Authors: McCoy D. , Wong E. , Kuyumjian A.G. , Wynd M.A. , Sebti R. , Munk G.B.
Published: August 2010

D. McCoy, E. Wong, A.G. Kuyumjian, M.A. Wynd, R. Sebti, G.B. Munk. Treatment of respiratory syncytial virus infection in adult patients with hematologic malignancies based on an institution‐specific guideline. Transpl Infect Dis 2011: 13: 117–121. All rights reserved

Abstract: A total of 26 adults with hematologic malignancies and/or hematopoietic stem cell transplant were treated for respiratory syncytial virus (RSV) infection based on an institutional guideline. Thirteen patients received aerosolized ribavirin, and 13 received aerosolized ribavirin and intravenous palivizumab. Two deaths, not attributed to RSV infection, occurred within 90 days of diagnosis.
Template‐based lymphadenectomy in urothelial carcinoma of the upper urinary tract: Impact on patient survival
Authors: Kondo Tsunenori , Hashimoto Yasunobu , Kobayashi Hirohito , Iizuka Junpei , Nakazawa Hayakazu , Ito Fumio , Tanabe Kazunari
Published: August 2010

Objectives:  The benefit of lymphadenectomy (LND) in patients with urothelial carcinoma of the upper urinary tract (UCUUT) has remained controversial. The aim of this study was to examine the influence of the LND template and the total number of lymph nodes (LN) when increasing the number of patients undergoing complete dissection of regional nodes (CompLND).

Methods:  A total of 109 UCUUT patients with clinically negative nodes underwent nephroureterectomy with concomitant lymphadenectomy at our center. Patients' survival was examined according to the type of LND and the number of removed LN. Univariate analysis was performed to find the cut‐off value of LN influencing survival.

Results:  Seventy‐eight patients underwent CompLND. Incomplete lymphadenectomy was performed in an additional 41 patients. In the patients with pT2 or higher who were clinically negative for nodal metastasis, any cut‐off value for the total number of LN removed showed no statistical significance. In contrast, CompLND had a significant impact on patient survival. The Cox proportional hazard model showed that CompLND was a significant factor after adjusting for adjuvant chemotherapy. The total number of removed LN was not significant.

Conclusions:  In patients with muscle‐invasive clinical node‐negative UCUUT, the number of LN removed shows minimal influence on their survival. In contrast, the influence of the particular type of lymphadenectomy is statistically significant. These findings suggest that the extent of lymphadenectomy should be determined by the template and not by the number of removed LN.
Hetero‐Transplantation of Human Embryonal Carcinoma into the Nude Mouse Functional and Morphologic Examination
Authors: Ohkawa Kiyoshi , Koike Kiyoshiko , Amasaki Hirofumi , Tohtake Takayasu , Nakata Hironobu , Dohsono Haruhiko
Published: August 2010

Human embryonal carcinoma, adult type, free from any components of endodermal sinus tumor was successfully transplanted into a nude mouse designated JTG‐1. The tumor formed a large unilocular cyst in the mouse containing various concentrations of alpha‐fetoprotein and carcinoembryonic antigen. Histologically it was composed of three patterns, such as endodermal sinus (Schiller‐Duval body), reticular and solid patterns and was compatible with an endodermal sinus tumor. Fine structural observation revealed two major types of tumor cells, namely, a spindle‐shaped stellate cell with numerous glycogen granules and many cytoplasmic processes, and an endodermal‐like large cell including voluminous cytoplasm with well‐developed microvilli situated on basal laminalike electron‐dense materials. Immunofluorescent study revealed a localization of both alpha‐fetoprotein and carcinoembryonic antigen in the tumor tissue. These findings suggest that the transplantation procedure induced both a morphologic and functional transformation of the adult embryonal carcinoma in the direction of an endodermal sinus tumor proving that the carcinoma had maintained the character of a multi‐potential cell.
Tumor‐Antigen (TA‐4) of Squamous Cell Carcinomaits Tissue Distribution and its Relationship to Serum TA‐4 Concentrations
Authors: Morioka Hitoshi
Published: August 2010

Tissue concentrations of the tumor‐antigen (TA‐4) in squamous cell carcinoma were determined in several malignant and non‐malignant tissues utilizing a radioimmunoassay method, and the relationship between tissue TA‐4 concentrations and serum TA‐4 concentrations was investigated in patients with cervical squamous cell carcinoma. Squamous cell carcinoma tissue contained 1,080.5 + 208.7 μu/mg of TA‐4 activities, which was significantly greater than those in normal squamous epitheliums of the uterine cervix (219.1 + 21.7 μu/mg), vagina (280.1 + 26.6 μu/mg) and vulva (264, 324 μu/mg). Neither adenocarcinomas of the uterine cervix, endometrium and ovary nor normal columnar epithelium, stroma and endometrium of the uterus showed TA‐4 activities. There was no direct correlation between tumor TA‐4 contents and serum TA‐4 concentrations, suggesting that circulating TA‐4 levels were not solely attributable to the antigen content of the tumor but also to other factors.
Evaluation of the Health and Nutritional Status of Women in Sri Lanka
Authors: Chinnatamby Siva , Basnayake Sriani , Nichoalds George E.
Published: August 2010

Certain aspects of the general health and nutritional status of 489 women of child‐bearing age living in Colombo and the surrounding vicinity have been evaluated by several criteria. Although women with chronic and/or acute medical problems were not included in the study, the sample population was typical of the average woman living in the area. Medical histories and physical examinations revealed a low incidence of severe clinical abnormalities. The latter did indicate public health problems concerning dental caries and probable deficiencies of riboflavin and vitamin A. Dietary data confirmed the clinical findings in that the corfsumption of riboflavin and vitamin A were grossly inadequate. Total calorie intake was also very low and accounts for the limited fat stores observed in this population. In contrast, protein status was quite adequate. There was some parasite infestation but it did not appear to be severe enough to have an impact on health and nutritional status. Liver function and lipid levels of cholesterol and triglyceride were normal. Approximately half of the women exhibited abnormal glucose tolerance tests. Anemia was present in 15% of the participants; iron deficiency was the most common cause of the anemia with deficiencies of folacin and vitamin B12 contributing to a lesser degree. Body levels of vitamin C and iodine were found to be normal whereas riboflavin nutriture was inadequate in 54% of the women.
Prenatal Fetal Heart Structures Identified by Two‐Dimensional Echocardiography
Authors: Hata Toshiyuki , Yamamoto Kazuhiko , Kitao Manabu
Published: August 2010

Two‐dimensional echocardiograms of 141 fetuses ranging from 18 to 42 weeks of gestational age were examined retrospectively to identify fetal heart structures. Many different views of the fetal heart were clearly evident, and the structures were well delineated. As four chamber views were seen in many cases, this plane may be suitable for a standardized observation of the fetal heart. This approach is expected to lead toward a prenatal diagnosis of congenital heart diseases.
Outcome of Pregnancy and Follow‐up of Children Conceived by Ovulation Induction
Authors: Seki Katsuyoshi , Seki Mitsunori , Kato Koichi
Published: August 2010

Evaluation of gestational outcome was attempted in 271 pregnancies achieved with various methods of ovulation induction (gonadotropin, clomiphene, Sexovid and epimestrol). The overall abortion rate was 18.4%. Although the incidence of multiple pregnancy was high (20.0%) after human nemopausal gonadotropin therapy, it was not after clomiphene when used alone. The overall male/female ratio of the neonates and fetuses was 117.7/100, and the incidence of malformation found at birth was 1.8%. Body lengths and weights of the neonates at birth were similar to standard values in Japan, though body weights of those after gonadotropin therapy were slightly lighter. In an attempt to follow‐up later developments of children born of mothers treated with ovulation‐inducing agents, questionnaires were sent to 141 mothers and 113 replies were obtained. No particular tendency was observed in the malformations and/or abnormalities found at the time of follow‐up or diseases suffered during the course of development. Body heights and weights of the children at the time of follow‐up fitted well with the physical developmental curves for children throughout Japan.
Clinical Implication of Hyperprolactinemias, Especially with Prolactinoma and Luteal Insufficiency
Authors: Tamaya Teruhiko , Murakami Toshiki , Ohno Yousuke , Wada Keisuke , Higashiyama Shusei , Mizukawa Norio , Okada Hiroji
Published: August 2010

The incidence of prolactinoma was 23 out of 64 hyperprolactinemic anovulatory patients (35.9%). The basal plasma prolactin (PRL) level showed a positive correlation to prolactinoma size. The turn of height in the increment ratio of PRL in the TRH test was prolactinomatous < hyperprolactinemic (except prolactinoma) < normoprolactinemic in anovulatory patients. This progression had statistical significance. The TSH release in the TRH test seemed to decrease with increase in tumor size. Gonadotropin secretion and the gonadotropin release in the LHRH test were independent of tumor size. ΔLH in the LHRH test in the patients with prolactinomas was significantly lower than ΔLH in the other anovulatory patients. The basal FSH level in hyperprolactinemic patients with or without prolactinomas tended to be lower than that in normoprolactinemic patients. The hyperprolactinemia associated with luteal insufficiency was 9.3 per cent in the incidence. In 9 out of 15 confirmed luteal hyperprolactinemic patients (60%), the endometrium appeared out‐of‐phase without any difference of basal gonadotropin level. Bromocriptine therapy of women with hyperprolactinemia, irrespective of the etiology, lead easily to restoration of ovulation, sometimes with clomiphene citrate. Clomiphene citrate induced ovulation in 4 out of 10 cases of prolactinoma (40%) and in 11 out of 16 cases of idiopathic hyperprolactinemia (68.8%). hMG‐hCG induced ovulation in 10 out of 10 cases in both groups (100%).
The Effect of Maternal Glucose Administration upon Fetal Myocardial Glycogen Change During Acute Blood Loss in the Term Pregnant Dog
Authors: Takeda Yoshihiko , Hongo Motohiro , Gabel Paul V. , Romney Seymour L.
Published: August 2010

(1) To evaluate the effect of maternal glucose loading upon myocardial glycogen and cardiovascular function in induced fetal distress, acute maternal hemorrhage was caused in term pregnant dogs pretreated with 1.5 gm/Kg of glucose 15 minutes before initiating hemorrhage.

(2) Myocardial glycogen depletion followed almost the same pattern as in the untreated group, reaching a level a little below half of the control at the end of the experiment.

(3) Fetal heart rate changes were altered by glucose administration in two respects: prolonged initial techycardia and less severe progressive bradycardia when this occurred.

(4) Other main effects of glucose during the hypotensive period were significantly higher increases in both fetal and maternal plasma glucose compared to the untreated group and a tremendous increase of fetal pCO2 and decrease of fetal pH.

(5) It may be concluded that glucose pretreatment is effective in providing oxidative energy to hypoxic cardiac muscle for its contractile activity.
Experimental Microsurgical Utero‐Ovarian and Tubal Transplantation
Authors: Iwasa Yoshihiko , Yanagino Kazuo
Published: August 2010

Animal experiments of utero‐ovarian and tubal homo‐transplantation with vascular anastomosis using hamsters, rabbits and dogs were carried out by the microscopic technique. The homografted dogs survived but are apparently not fertile. The homografts of hamsters and rabbits were not viable, chiefly due to poor anesthetic management. However, this experiment clearly proved the technical feasibility of this transplantation. The operative procedures used in these experiments, the possibility of their clinical application for human tubal transplantation and methods of immunosuppression are discussed in detail.