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Comparison of Ki-ras gene mutation among simultaneously occurring multiple urethan-induced lung tumors in individual mice.

Mouse lung tumors were induced in C57BL/6J(female) x A/J(male) F1 mice by a single s.c. injection of urethan. About 6 months later, multiple small-sized lung tumors were detectable in almost all mice. After a further 6 months, some of these tumors became larger than the rest. We examined whether there were any mutational differences among multiple lung tumors in a single mouse. Direct DNA sequencing of a separately amplified Ki-ras gene by polymerase chain reaction (PCR) was carried out with 25 DNA samples from multiple tumors in four mice. Twenty-four of 25 tumors (96%) had mutations at the codon 61 of the Ki-ras gene. The major mutations involved were either AT to GC transition (44%) or AT to TA transversion (44%) at the second base of codon 61. We compared the types of these gene mutations among the tumors from each of two mice from two different groups of siblings and then compared the two groups. Interestingly, in the first group of siblings, we detected CTA in 5/6 tumors in the first mouse and again CTA in 4/6 tumors in the second one. In the second group of siblings, we detected CGA in 5/7 tumors in one mouse and CGA again in 3/5 tumors in the second mouse. These results show that the pattern of Ki-ras codon 61 mutations in urethan-induced lung tumors is similar in tumors developing in siblings, suggesting that host factors have an effect on the carcinogen-induced mutational pattern. There was no major mutational difference between small and large tumors. The results suggested that other event(s) in addition to the mutation of the Ki-ras gene might play a role during the development of large-sized tumors.

Amino Acid Sequence↗

Antithrombin and its deficiency states.

Antithrombin is the most important physiological proteinase inhibitor of thrombin and other coagulation proteinases. It is a single chain glycoprotein of MW 58,200 which has sequence homology with alpha 1-antitrypsin and other members of the serpin superfamily of inhibitors. Two functional domains of importance have been identified, the reactive centre that interacts with the proteinase and a heparin binding domain. Failure to maintain an adequate level of functional antithrombin in plasma results in an increased risk of thromboembolism: deficiency can be inherited or acquired. There is still uncertainty regarding the prevalence of inherited deficiency and the prevalence of thrombosis in affected individuals. The production of antithrombin is under the control of a single gene which is localized on chromosome 1q 23-25. Characterization of the coding sequence, which is distributed over seven exons, has allowed the analysis of the molecular basis for inherited antithrombin deficiency. To date more than 100 cases have been successfully investigated at the gene and/or protein sequence level and 40 novel mutations have been identified. Mutations causing amino acid substitutions solely affecting the heparin binding site have thus far been located primarily at the N-terminal region of the molecule, residues 7-129; this region has been postulated to align as a positive groove in the molecule that forms the primary contact region for the essential antithrombin binding pentasaccharide of heparin. Not all the residues in which substitutions have been found are basic and some serve to maintain the conformation of nearby basic regions. Examples of this are provided by the Pro-41 to Leu mutation and a recently investigated mutant, Leu-99 to Phe. The reactive site defects are an interesting group, including those that alter P1, P1' and P12-P10 residues. Perhaps more remote mutations can also be included such as Pro-429 to Leu. The P1 and P1' mutations directly block interaction of the proteinase with anti-thrombin, while P12-P10 mutants (which have mutations affecting serpin strand s4A) enable the substrate reaction to proceed to completion, i.e. the antithrombin-thrombin complex is not stabilized and the mutant inhibitor is transformed into a substrate. The effect of the Pro-429 to Leu substitution is impairment of the reactive site and heparin binding, and the finding that this variant is not completely recognized by some MAbs implies a conformational change at the C terminus. Another group (nine cases) of interesting mutations is emerging, that has its primary defect in or near serpin strand 1C, amino acid sequence 402-407.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Developing Online Communities with LAMP (Linux, Apache, MySQL, PHP) - the IMIA OSNI and CHIRAD Experiences.

Many health informatics organisations do not seem to use, on a practical basis, for the benefit of their activities and interaction with their members, the very technologies that they often promote for use within healthcare environments. In particular, many organisations seem to be slow to take up the benefits of interactive web technologies. This paper presents an introduction to some of the many free/libre and open source (FLOSS) applications currently available and using the LAMP - Linux, Apache, MySQL, PHP architecture - as a way of cheaply deploying reliable, scalable, and secure web applications. The experience of moving to applications using LAMP architecture, in particular that of the Open Source Nursing Informatics (OSNI) Working Group of the Special Interest Group in Nursing Informatics of the International Medical Informatics Association (IMIA-NI), in using PostNuke, a FLOSS Content Management System (CMS) illustrates many of the benefits of such applications. The experiences of the authors in installing and maintaining a large number of websites using FLOSS CMS to develop dynamic, interactive websites that facilitate real engagement with the members of IMIA-NI OSNI, the IMIA Open Source Working Group, and the Centre for Health Informatics Research and Development (CHIRAD), as well as other organisations, is used as the basis for discussing the potential benefits that could be realised by others within the health informatics community.

Humans↗

Priorities for understanding and managing occupational allergy: a Delphi consensus.

Limiting factors in the understanding, clinical management, and prevention of occupationally related allergic disease should be identified, since these dictate the tasks that need to be undertaken and/or important research questions that warrant an answer. Through an adaptation of the Delphi technique, a working group of the Special Interest Group on Occupational Allergy of the British Society of Allergy and Clinical Immunology addressed these issues. The consensus categorized and ranked the limiting factors and tasks needed in relation to epidemiology and natural history, mechanisms, clinical diagnosis, statute and education, and the workplace environment. This report should help focus the debate regarding which issues are perceived to be most relevant and timely for research and good practice in the field of occupational allergy.

Delphi Technique↗

osni.info-Using free/libre/open source software to build a virtual international community for open source nursing informatics.

Many health informatics organizations seem to be slow to take up the advantages of dynamic, web-based technologies for providing services to, and interaction with, their members; these are often the very technologies they promote for use within healthcare environments. This paper aims to introduce some of the many free/libre/open source (FLOSS) applications that are now available to develop interactive websites and dynamic online communities as part of the structure of health informatics organizations, and to show how the Open Source Nursing Informatics Working Group (OSNI) of the special interest group in nursing informatics of the International Medical Informatics Association (IMIA-NI) is using some of these tools to develop an online community of nurse informaticians through their website, at . Some background introduction to FLOSS applications is used for the benefit of those less familiar with such tools, and examples of some of the FLOSS content management systems (CMS) being used by OSNI are described. The experiences of the OSNI will facilitate a knowledgeable nursing contribution to the wider discussions on the applications of FLOSS within health and healthcare, and provides a model that many other groups could adopt.

Database Management Systems↗

An important role of corticotropin-releasing hormone in electroacupuncture normalizing the subnormal function of hypothalamus-pituitary-ovary axis in ovariectomized rats.

In the present study, the effects of electroacupuncture (EA) at a group of specific acupoints on corticotropin-releasing hormone (CRH) and gonadotropin-releasing hormone (GnRH) immunoreactivity (ir) in the hypothalamuses of ovariectomized rats were observed. Meanwhile the blood E2 level was detected. The results showed that EA might significantly increase the blood level of E2 and GnRH cell number in the ovariectomized rats. The number of CRH neurons was higher in the group ovariectomized with EA than that in the ovariectomized and intact groups. Interestingly enough, only in the group ovariectomized with EA was observed the co-localization of CRH-ir and GnRH-ir substances in one cell of hypothalamic nucleus paraventricularis by immunofluorescent double-labeling histochemistry combining laser con-focal scanning microscope. The results suggest that CRH might be an important factor in EA normalizing the subnormal function of hypothalamus-pituitary-ovary axis.

Animals↗

Genetic analysis of PHIP intestinal mutations in MutaMouse.

The mutagenicity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) was investigated in male MutaMouse mice administered 20 mg/kg per o.s. for 4 days and killed 7 days later. Genomic DNA was extracted from liver, kidney and small and large intestine and the mutation frequency (MF) at the lacZ locus was determined using a positive selection assay. Mutant lacZ clones from the intestine were characterized further by direct PCR amplification and DNA sequencing. A total of 57 lacZ mutants from PhIP-treated (40) and untreated (18) mice were analysed. In mutants from the PhIP group, 33% were G:C-->T:A transversions from a total of 65% base substitutions (cf. 17% in the vehicle control group). In untreated control mice, 39% of mutants were G:C-->A:T transitions from a total of 72 % base substitutions (cf. 25 % in the PhIP group). Interestingly, 20% of the PhIP group mutations were due to G:C base pair (-G) deletions (cf. none in controls). This study confirms that PhIP is mutagenic to the intestine of the MutaMouse and induces a spectrum of mutations which are clearly distinct from those spontaneously generated. Also, the PhIP mutation signature in vivo is very similar to that observed for the HPRT and DHFR loci in hamster and human cells in vitro. This suggests that the mutational characteristics of PhIP are well conserved over different reporter genes and between species and that the mutation signature could be of value in molecular epidemiology studies.

Animals↗

Occupational therapy and physiotherapy for the patient with burns: principles and management guidelines.

Clinical practice guidelines are a tool to assist with clinical decision making. They provide information about the care for a condition and make recommendations based on research evidence, which can be adapted locally. A focus group within the Allied Health Interest Group of the Australian and New Zealand Burn Association has compiled the "Occupational Therapy and Physiotherapy for the Patient with Burns--Principles and Management Guidelines." These guidelines are designed as a practical guide to the relevant clinical knowledge and therapy intervention techniques required for effective patient management. Content areas include respiratory management, edema management, splinting and positioning, physical function (mobility, function, exercise), scar management, and psychosocial and mutual elements. The document has undergone extensive review by members of the Australian and New Zealand Burn Association to ensure clarity, internal consistency, and acceptability. The guidelines have been endorsed by the Australian and New Zealand Burn Association. An abridged version of the guidelines is included in this article, with the full document available from www.anzba.org.au.

Burns↗

Clinicians' attitudes to prostate cancer peer-support groups.

OBJECTIVE: To assess clinicians' knowledge and attitudes to prostate cancer peer-support groups, essential in improving support services for men with prostate cancer, as patients' perceptions of their clinicians' attitudes to such groups predict patients' positive and negative perceptions of their experiences at such groups. SUBJECTS AND METHODS: In all, 36 clinicians (75% response) across Australia, of whom 27 were urologists and nine were radiation oncologists, were interviewed in-depth using a key-informant approach. Nine clinicians were from regional Australia, with the remaining 27 from major metropolitan settings. Subsequently, 30 clinicians (69% response) completed surveys to confirm identified themes. RESULTS: Peer support was rated positively by most clinicians and most report a fair to good knowledge of such groups. However, less than a quarter regularly refer their patients to these groups. While clinicians can describe positive aspects of peer support, many are concerned that biased viewpoints and misinformation within these groups might potentially contribute to patients' decisional uncertainty and regret. CONCLUSIONS: Further research is needed to establish for whom these support groups are most helpful. Concerns about misleading information that might be proffered in support groups is a barrier to clinician referral to these groups. Dialogue between prostate cancer interest groups and clinicians to resolve concerns presents as a key strategy to improve support for men with prostate cancer.

Attitude of Health Personnel↗

Effects of Time-Based and Distance-Based Repeated Sprint Training on Physical and Physiological Adaptations in Collegiate Basketball Players.

PURPOSE: This study aimed to compare the effects of time-based (TB) and distance-based (DB) repeated-sprint training (RST) on athletic performance adaptations in collegiate basketball players during preseason and to examine whether the 2 training prescriptions produce different levels of homogeneity in the magnitude of individual adaptations. METHODS: Thirty young male basketball players (age = 21.3 [1.4]&#xa0;y) were randomly and equally assigned to 3 groups (n = 10): DB-RST, TB-RST, and an active control group. Participants completed a 7-week RST program performed 3 times per week, consisting of 4 sets of 4 to 9 repetitions per session. The DB-RST group completed each sprint by covering a fixed 35-m distance, whereas the TB-RST group performed each sprint maximally for a fixed 5-second duration. Performance assessments including countermovement vertical jump, 20-m sprint, Illinois change-of-direction speed, reactive strength index, Wingate anaerobic power, and cardiorespiratory fitness were conducted before and after the 7-week training period. RESULTS: Both training groups demonstrated significant performance improvements over the 7-week intervention and relative to the control group (P < .05). Similar gains were observed in the magnitude of adaptations in the countermovement vertical jump, 20-m sprint, Illinois change-of-direction speed, and reactive strength index for the DB-RST and TB-RST groups. Interestingly, the TB-RST group showed more gains than the DB-RST in the magnitude of adaptations in the peak and mean power outputs, as well as cardiorespiratory fitness. Moreover, the TB-RST group showed lower intersubject variability in adaptive responses across the measured performance outcomes following the training intervention. CONCLUSION: Our findings indicate that RST effectively enhances the performance of basketball players, and that implementing a TB-RST protocol is more effective than a DB-RST approach for producing greater adaptations in physiological variables-specifically anaerobic power output and cardiorespiratory fitness-over the 7-week preseason period.

Humans↗

Data collection by acute pain services in Australia and New Zealand.

Forty-three Acute Pain Service units in Australia and New Zealand were surveyed regarding data they collected on their daily rounds. The survey sought to determine what data each unit actually collected and what they considered to be a set of data that would be an acceptable minimal standard for the purpose of audit. The scoring or scaling mechanisms that were used in auditing the various parameters were also ascertained in an attempt to derive a consistent means of comparing data from the various Acute Pain Service groups. The Acute Pain Special Interest Group is currently developing suggestions for a standard data set and associated scoring mechanisms in line with the results of this survey.

Acute Disease↗

Pre-treatment with all-trans retinoic acid accelerates polymorphonuclear recovery after chemotherapy in patients with acute promyelocytic leukemia.

All-trans retinoic acid (ATRA) is currently being used as remission induction treatment for acute promyelocytic leukemia (APL). Conventional chemotherapy is added both during and after ATRA treatment, in order to avoid the occurrence of hyperleukocytosis, and to improve the duration of complete remission. In this study we analysed the hematopoietic recovery of 18 consecutive APL patients after standard Idarubicin or Daunorubicin +/- Cytosine-Arabinoside regimens. 9 of the patients were at the onset of the disease, (CHT group) while 9 had been pre-treated with ATRA 45 mg/sqm/day for at least 3 months (ATRA group). 500 PMN/mmc were reached after 20.8 day from the end of treatment in CHT group and after 12.0 days in ATRA group (p = 0.007). Platelets recovery was faster, even though not significantly in ATRA group. Interestingly, PMN recovery in ATRA group was even shorter (p = 0.004) than that obtained in CHT group, after the first course of chemotherapy (treatment in CR vs treatment in CR). If these results are confirmed in a larger study, a protective effect of ATRA on normal residual hemopoiesis should be postulated.

Adult↗