Effect of increased lung expansion on lung growth and development near midgestation in fetal sheep

Obstruction of the fetal trachea is a potent stimulus for fetal lung growth and may have therapeutic potential in human fetuses with lung hypoplasia. However, the effects of increased lung expansion on lung development near midgestation, which is the preferred timing for fetal intervention, have not been well studied. Our aim was to determine the effects of increased lung expansion on lung development at 75-90 d of gestation in fetal sheep. In three groups of fetuses (n = 4 for each), the trachea was occluded for either 10 [10-d tracheal occlusion (TO) group] or 15 d (15-d TO group) or left intact (control fetuses). TO for both 10 and 15 d caused fetal hydrops, resulting in significantly increased fetal body weights. Both periods of TO significantly increased total lung DNA contents from 99.8 +/- 10.1 to 246.0 +/- 5.3 and 246.9 +/- 48.7 mg in 10- and 15-d TO fetuses, respectively. TO for 10 and 15 d also increased airspace diameter, although the percentage of lung occupied by airspace was not increased in 10-d TO fetuses due to large increases in interairway distances; this resulted from a large increase in mesenchymal tissue. The interairway distances at 15 d of TO were reduced compared with the 10-d value but were still similar to 30% larger than control values. We conclude that TO at

Development and standardization of the Self-regulation Skills Interview (SRSI): A new clinical assessment tool for acquired brain injury

The Self-regulation Skills Interview (SRSI) is a clinical tool designed to measure a range of metacognitive skills essential for rehabilitation planning, monitoring an individual's progress, and evaluating the outcome of treatment interventions. The results of the present study indicated that the SRSI has sound interrater reliability and test-retest reliability. A principle components analysis revealed three SRSI factors: Awareness, Readiness to Change, and Strategy Behavior. A comparison between a group of 61 participants with acquired brain injury (ABI) and a group of 43 non-brain-injured participants indicated that the participants with ABI had significantly lower levels of Awareness and Strategy Behavior, but that level of Readiness to Change was not significantly different between the two groups. The significant relationship observed between the SRSI factors and measures of neuropsychological functioning confirmed the concurrent validity of the scale and supports the value of the SRSI for post-acute assessment.

Computational chemistry on Fujitsu vector-parallel processors: Development and performance of applications software

In this and a preceding paper, we provide an introduction to the Fujitsu VPP range of vector-parallel supercomputers and to some of the computational chemistry software available for the VPP. Here, we consider the implementation and performance of seven popular chemistry application packages. The codes discussed range from classical molecular dynamics to semiempirical and ab initio quantum chemistry. All have evolved from sequential codes, and have typically been parallelised using a replicated data approach. As such they are well suited to the large-memory/fast-processor architecture of the VPP. For one code, CASTEP, a distributed-memory data-driven parallelisation scheme is presented. (C) 2000 Published by Elsevier Science B.V. All rights reserved.

Survival and development of Helicoverpa armigera (Hubner) (Lepidoptera : Noctuidae) on neem (Azadirachta indica A. Juss) leaves

The survival, development and feeding responses of Helicoverpa armigera (Hubner) on neem (Azadirachta indica A. Juss) leaflets were evaluated under choice and no-choice conditions. Neem leaflets provided to starving fourth-instar larvae were chewed, but larvae expectorated most of the material. The weight of surviving larvae decreased and no fourth instars completed development on neem leaflets alone. Larvae resumed feeding when transferred to cotton leaves after 5 days of feeding on neem leaflets. Fourth instars strongly discriminated between neem leaflets and cotton leaves when offered a choice. Early sixth instars decreased in weight and had delayed development when feet only on neem leaflets. Mure than one-half lived for more than 2 weeks and some completed development to adults. Neem is an unacceptable non-host plant species for H. armigera.

The development and evaluation of an incontinence screening questionnaire for female primary care

Although there is a high prevalence of leaking urine among Australian women, there are currently no standardized procedures for screening patients for incontinence in the primary care setting (known in Australia as general practice). In response to this, an incontinence screening questionnaire (ISQ) was developed and evaluated for use in general practice. Eighty-nine women completed an original compilation of 33 items that asked about situations associated with leaking urine, avoidance of leakage, and concern about leakage. Each item was assessed according to its acceptability for the population of female general practice patients, discriminative value, and test-retest reliability. These patients also underwent an objective test of incontinence, the 48-hour pad test, so that the screening items could be validated against an objective classification of incontinence. The study included women who had bladder control problems and those who did not. Eight items on the ISQ were shown to be acceptable to patients, discriminative, reliable, and valid indicators of objective incontinence. Five items were capable of predicting almost 70% of patients who showed objective leakage of urine and misclassified fewer than 15% of these patients. Those five items were selected for inclusion in the (refined) ISQ. (C) 2000 Wiley-Liss, Inc.

Assessing perceived need for mental health care in a community survey: development of the Perceived Need for Care Questionnaire (PNCQ)

Background: The Perceived Need for Care Questionnaire (PNCQ) was designed for the Australian National Survey of Mental Health and Wellbeing. The PNCQ complemented collection of data on diagnosis and disability with the survey participants' perceptions of their needs for mental health care and the meeting of those needs. The four-stage design of the PNCQ mimics a conversational exploration of the topic of perceived needs. Five categories of perceived need are each assigned to one of four levels of perceived need (no need, unmet need, partially met need and met need). For unmet need and partially met need, information on barriers to care is collected, Methods: Inter-rater reliabilities of perceived needs assessed by the PNCQ were examined in a study of 145 anxiety clinic attenders. Construct validity of these items was tested, using a multi-trait multi-method approach and hypotheses regarding extreme groups, in a study with a sample of 51 general practice and community psychiatric service patients. Results: The instrument is brief to administer and has proved feasible for use in various settings. Inter-rater reliabilities for major categories, measured by the kappa statistic, exceeded 0.60 in most cases; for the summary category of all perceived needs, inter-rater reliability was 0.62. The multi-trait multi-method approach lent support to the construct validity of the instrument, as did findings in extreme groups. Conclusions: The PNCQ shows acceptable feasibility, reliability and validity, adding to the range of assessment tools available for epidemiological and health services research.

Analysis of Mouse Keratin 6a Regulatory Sequences in Transgenic Mice Reveals Constitutive, Tissue-Specific Expression by a Keratin 6a Minigene

The analysis of keratin 6 expression is complicated by the presence of multiple isoforms that are expressed constitutively in a number of internal stratified epithelia, in palmoplantar epidermis, and in the companion cell layer of the hair follicle. In addition, keratin 6 expression is inducible in interfollicular epidermis and the outer root sheath of the follicle, in response to wounding stimuli, phorbol esters, or retinoic acid. In order to establish the critical regions involved in the regulation of keratin 6a (the dominant isoform in mice), we generated transgenic mice with two different-sized mouse keratin 6a constructs containing either 1.3 kb or 0.12 kb of 5' flanking sequence linked to the lacZ reporter gene. Both constructs also contained the first intron and the 3' flanking sequence of mouse keratin 6a. Ectopic expression of either transgene was not observed. Double-label immunofluorescence analyses demonstrated expression of the reporter gene in keratin 6 expressing tissues, including the hair follicle, tongue, footpad, and nail bed, showing that both transgenes retained keratinocyte-specific expression. Quantitative analysis of beta -galactosidase activity verified that both the 1.3 and 0.12 kb keratin 6a promoter constructs produced similar levels of the reporter. Notably, both constructs were constitutively expressed in the outer root sheath and interfollicular epidermis in the absence of any activating stimulus, suggesting that they lack the regulatory elements that normally silence transcription in these cells. This study has revealed that a keratin 6a minigene contains critical cis elements that mediate tissue-specific expression and that the elements regulating keratin 6 induction lie distal to the 1.3 kb promoter region.

Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination

Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4-9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged similar to 171 mg/dl and in the ETHD animals similar to 430 mg/dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection or ketamine and xylazine, and killed by intracardiac perfusion with phosphate-buffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of similar to 145000-165000 axons in MRC, SC and ETLD animals. About 4 % of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75000 optic nerve axone (P < 0.05) of which about 2.8 % were myelinated. By 30 d of age there was a total of between 75000 90000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P < 0.001) in the ETHD animals (similar to 77 %) than in the other groups (about 98 %). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9.

Structure development in octadecyl trimethylammonium templated silicate films grown at the air/water interface

The mechanism of growth of silicate films at the air/liquid interface has been investigated in situ by a series of grazing incidence diffraction experiments using a 20 x 25 cm(2) imaging plate as the detector. C(18)TAX (X = Br- or Cl-) has been used as the film templating surfactant. The formation of a layered phase, prior to growth of the hexagonal mesophase in C(18)TABr templated films. has been seen. This layered structure has a significantly shorter d spacing compared to the final hexagonal film (43 versus 48 Angstrom, respectively). The correlation lengths associated with the development of the hexagonal in-plane diffraction spots are much longer in-plane than perpendicular to the air/liquid interface (300 Angstrom versus 50 Angstrom). This implies that the film forms via the growth or aggregation of islands that are initially only a micelle or two thick. which then grow down into the solution.

Exploratory research: Citizen participation, local government and sustainable development in Australia

Exploratory research reported in this paper was undertaken in Adelaide, Australia during 1998/99. The purpose of the research is to explore local development practice as evidenced through the experiences and actions of local citizens, community based groups and local government (Neuman, 1994). Results from this first stage research suggest that sustainability initiatives in Australia might best be implemented through a collaborative approach at the local community level involving local citizens working in partnership with local government. Copyright (C) 2002 John Wiley & Sons, Ltd and ERP Environment.

Increased generation of dendritic cells from myeloid progenitors in autoimmune-prone nonobese diabetic mice

Aberrant dendritic cell (DC) development and function may contribute to autoimmune disease susceptibility. To address this hypothesis at the level of myeloid lineage-derived DC we compared the development of DC from bone marrow progenitors in vitro and DC populations in vivo in autoimmune diabetes-prone nonbese diabetic (NOD) mice, recombinant congenic nonbese diabetes-resistant (NOR) mice, and unrelated BALB/c and C57BL/6 (BL/6) mice. In GM-CSF/IL-4-supplemented bone marrow cultures, DC developed in significantly greater numbers from NOD than from NOR, BALB/c, and BL/6 mice. Likewise, DC developed in greater numbers from sorted (lineage(-)IL-7Ralpha(-)SCA-1(-)c-kit(+)) NOD myeloid progenitors in either GM-CSF/IL-4 or GM-CSF/stem cell factor (SCF)/TNF-alpha. [H-3]TdR incorporation indicated that the increased generation of NOD DC was due to higher levels of myeloid progenitor proliferation. Generation of DC with the early-acting hematopoietic growth factor, flt3 ligand, revealed that while the increased DC-generative capacity of myeloid-committed progenitors was restricted to NOD cells, early lineage-uncommitted progenitors from both NOD and NOR had increased DC-gencrative capacity relative to BALB/c and BL/6. Consistent with these findings, NOD and NOR mice had increased numbers of DC in blood and thymus and NOD had an increased proportion of the putative myeloid DC (CD11c(+)CD11b(+)) subset within spleen. These findings demonstrate that diabetes-prone NOD mice exhibit a myeloid lineage-specific increase in DC generative capacity relative to diabetes-resistant recombinant congenic NOR mice. We propose that an imbalance favoring development of DC from myeloid-committed progenitors predisposes to autoimmune disease in NOD mice.

Efficacy of Lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy for ovarian cancer

Transfer of the herpes simplex virus type I thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. Effective gene therapy,, depends on the efficient transfer and specific targeting of therapeutic genes and their protein products to target cells. The purpose of this study was to investigate the anti-tumor effect of Lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy in animal models. Mouse models were generated with intraperitoneal injection of human epithelial ovarian cancer cells 3AO, which are MUC1-positive. HTV-1-based lentiviral vectors carrying VP22-TK or scFv-VP22-TK were prepared. The animals were injected intraperitoneally with lentivirus containing scFv-VP22-TK, VP22-TK followed by GCV treatment. Combined treatment of lentivirus-expressed scFv-VP22-TK or VP22-TK with GCV inhibited the proliferation and prolonged survival times compared with the control vector. The survival time of animals treated with scFv-VP22-TK/GCV was significantly longer than that of animals treated with VP22-TK/GCV (p = 0.006). Conclusion: Our results suggest that MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy can efficiently inhibit ovarian tumor growth and increase survival in a nude mouse model of ovarian carcinoma. These data support the development of this method for human clinical trials.

Cytokine-related genes identified from the RIKEN full-length mouse cDNA data set

To identify novel cytokine-related genes, we searched the set of 60,770 annotated RIKEN mouse cDNA clones (FANTOM2 clones), using keywords such as cytokine itself or cytokine names (such as interferon, interleukin, epidermal growth factor, fibroblast growth factor, and transforming growth factor). This search produced 108 known cytokines and cytokine-related products such as cytokine receptors, cytokine-associated genes, or their products (enhancers, accessory proteins, cytokine-induced genes). We found 15 clusters of FANTOM2 clones that are candidates for novel cytokine-related genes. These encoded products with strong sequence similarity to guanylate-binding protein (GBP-5), interleukin-1 receptor-associated kinase 2 (IRAK-2), interleukin 20 receptor alpha isoform 3, a member of the interferon-inducible proteins of the Ifi 200 cluster, four members of the membrane-associated family 1-8 of interferon-inducible proteins, one p27-like protein, and a hypothetical protein containing a Toll/Interleukin receptor domain. All four clones representing novel candidates of gene products from the family contain a novel highly conserved cross-species domain. Clones similar to growth factor-related products included transforming growth factor beta-inducible early growth response protein 2 (TIEG-2), TGFbeta-induced factor 2, integrin beta-like 1, latent TGF-binding protein 4S, and FGF receptor 4B. We performed a detailed sequence analysis of the candidate novel genes to elucidate their likely functional properties.