Reduced chondrogenic and adipogenic activity of mesenchymal stem cells from patients with advanced osteoarthritis.

Objective: Mesenchymal stem cells (MSCs) are resident in the bone marrow throughout normal adult life and have the capacity to differentiate along a number of connective tissue pathways, among them bone, cartilage, and fat. To determine whether functionally normal MSC populations may be isolated from patients with advanced osteoarthritis (OA), we have compared cells from patients undergoing joint replacement with cells from normal donors. Cell populations were compared in terms of yield, proliferation, and capacity to differentiate.

Determining the influence of biocompatible oxygenators during cardiopulmonary bypass by 99m Tc-DTPA aerosol assessment of pulmonary permeability.

Changes in pulmonary permeability provide a partial measure of the clinical impact of biocompatible oxygenator use during cardiopulmonary bypass surgery. Previous research has shown that the clearance rate of 99mTc-labelled diethylene triamine penta-acetic acid (99mTc-DTPA) aerosol from the lungs is increased following cardiopulmonary bypass, resulting from an increase in pulmonary permeability. The aerosol clearance rate has been shown to return to normal after a period of 7 days.

Effects of plant growth regulators on survival and recovery growth following cryopreservation.

Studies on the effects of plant growth regulators (PGRs) on survival, recovery and post-recovery growth of shoot apices following cryopreservation are limited. In this study, the effects of plant growth regulators in both the culture phase and the recovery phase of cryostorage were examined for the rare plant species, Anigozanthos viridis ssp terraspectans Hopper. Survival of shoot apices was not correlated to cytokinin or auxin treatments administered in culture media prior to cryostorage.

Accumulation of DDT and mercury in prothonotary warblers (Protonotaria citrea) foraging in a heterogeneously contaminated environment.

Foraging areas of adult prothonotary warblers (Protonotaria citrea) were determined using standard radiotelemetry techniques to determine if soil concentrations of p,p'dichlorodiphenyltrichloroethane (p,p'DDT) and mercury in foraging areas could be used to predict contaminant levels in diets and tissues of nestling warblers. Adult warblers were fitted with transmitters and monitored for approximately 2 d while foraging and feeding 6- to 8-d-old nestlings. Foraging ecology data were integrated with contaminant levels of soil, diets, and tissues into a comprehensive analysis of geographic variation in contaminant exposure and uptake using linear regression.

Conservation genetics of the rare and endangered Leucopogon obtectus (Ericaceae).

Leucopogon obtectus Benth. is a declared rare species found in the kwongan vegetation in Western Australia. Plants on a mineral sand mine and the rehabilitation area are subject to disturbance.

Constraints to symbiotic germination of terrestrial orchid seed in a mediterranean bushland.

•  The dependence of seeds of terrestrial orchids on specific fungi for germination provides a means of locating these fungi in the wild and to investigate the role of appropriate fungi in the germination of orchid seed and development of seedlings under natural field conditions. •  Seed baits, comprising orchid (Caladenia arenicola) seed enclosed in fine nylon mesh, were placed at sample points along four transects through two orchid populations in bushland in Western Australia. Seed germination was scored and compared with adult orchid plant distribution and soil factors.

Physiologic and clinical monitoring of spastic hypertonia.

Spasticity has been defined as "a motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks, resulting from hyperexcitability of the stretch reflex, as one component of the upper motor neuron syndrome." Increased motor neuron excitability and enhanced stretch-evoked synaptic excitation of motor neurons are potential neurophysiologic mechanisms to explain this phenomenon. The relative contribution of these two distinct mechanisms likely varies depending on the location of the lesion in the central nervous system.

Insights into UV-induced apoptosis: ultrastructure, trichrome stain and spectral imaging.

Nuclear substructures associated with apoptosis in HeLa cells have been examined using light-microscopic morphometry, trichrome staining, spectral imaging and transmission electron microscopy. This detailed analysis reveals several sites where alterations in the normal cellular ultrastructure occur during apoptotic progression. To correlate these ultrastructural changes with the underlying molecular processes, we have characterized and quantified apoptotic cell morphology with and without inhibition of two caspases, which are key effectors of the apoptotic program.

A single (6-4) photoproduct inhibits plasmid DNA replication in xeroderma pigmentosum variant cell extracts.

The human skin cancer-prone disease xeroderma pigmentosum variant (XPV) results from a mutation in the human RAD30 gene, which encodes the lesion bypass DNA polymerase eta. XPV cells are characterized by delayed completion of DNA replication and increased mutagenesis following UV-irradiation. Using extracts of an XPV lymphoblast cell line (GM2449C) that has a truncating mutation in the RAD30 gene, we investigated the effect of a (6-4) photoproduct and a cyclobutane pyrimidine dimer (CPD), at a unique -TT- site on either the leading or lagging strand, on plasmid DNA replication.

Inhibition of choroidal neovascularization by intravenous injection of adenoviral vectors expressing secretable endostatin.

Endostatin is a cleavage product of collagen XVIII that inhibits tumor angiogenesis and growth. Interferon alpha2a blocks tumor angiogenesis and causes regression of hemangiomas, but has no effect on choroidal neovascularization (CNV). Therefore, inhibitors of tumor angiogenesis do not necessarily inhibit ocular neovascularization.

Clinical efforts to modulate angiogenesis in the adult: gene therapy versus conventional approaches.

A gene therapy approach towards the modulation of neovascularization provides important advantages that could be crucial for the success of therapies that target blood vessels. These advantages include sustained local expression and the ability to supply multiple pro- or anti-angiogenic factors. There is potential near-term success in the application of this approach for the treatment of ischemic vascular diseases.

XPA protein alters the specificity of ultraviolet light-induced mutagenesis in vitro.

Studies of ultraviolet (UV) light mutagenesis have demonstrated mutations at common sites in the target genes of shuttle vector plasmids replicated in cultured cells or by cellular extracts. The reasons for the specific pattern of mutagenesis are largely unknown. We have examined the specificity of UV-induced mutagenesis by replicating plasmid pLS189, irradiated with 40 J/m(2) UVC or unirradiated, in either xeroderma pigmentosum group A (XP-A) or HeLa cellular extracts.

UV-induced hyperphosphorylation of replication protein a depends on DNA replication and expression of ATM protein.

Exposure to DNA-damaging agents triggers signal transduction pathways that are thought to play a role in maintenance of genomic stability. A key protein in the cellular processes of nucleotide excision repair, DNA recombination, and DNA double-strand break repair is the single-stranded DNA binding protein, RPA. We showed previously that the p34 subunit of RPA becomes hyperphosphorylated as a delayed response (4-8 h) to UV radiation (10-30 J/m(2)).

In vitro replication and mutagenesis of a novel reversion vector with selective DNA damage in the supF gene.

The ability to detect the most common type of UV-induced mutation, the C to T transition, at the previously characterized hotspot at position 99 of the supF gene has been demonstrated in a selectively irradiated reversion vector, pLS189(Rev). The supF region was amplified, irradiated with 500J/m(2) UVC or unirradiated, and ligated into the pLS189(Rev) plasmid. A portion of ligated product plasmid containing the irradiated fragment was sensitive to nicking by T4 endonuclease V, indicating the presence of the most common type of UV-induced damage, the pyrimidine dimer.

Anthropogenic warming of Earth's climate system.

We compared the temporal variability of the heat content of the world ocean, of the global atmosphere, and of components of Earth's cryosphere during the latter half of the 20th century. Each component has increased its heat content (the atmosphere and the ocean) or exhibited melting (the cryosphere). The estimated increase of observed global ocean heat content (over the depth range from 0 to 3000 meters) between the 1950s and 1990s is at least one order of magnitude larger than the increase in heat content of any other component.

Glucokinase gene locus transgenic mice are resistant to the development of obesity-induced type 2 diabetes.

Transgenic mice that overexpress the entire glucokinase (GK) gene locus have been previously shown to be mildly hypoglycemic and to have improved tolerance to glucose. To determine whether increased GK might also prevent or diminish diabetes in diet-induced obese animals, we examined the effect of feeding these mice a high-fat high-simple carbohydrate low-fiber diet (HF diet) for 30 weeks. In response to this diet, both normal and transgenic mice became obese and had similar BMIs (5.

Expression of ATM in ataxia telangiectasia fibroblasts rescues defects in DNA double-strand break repair in nuclear extracts.

Ataxia telangiectasia (A-T) is a human genetic disorder characterized by progressive cerebellar degeneration, hypersensitivity to ionizing radiation (IR), immunodeficiency, and high cancer risk. At the cellular level, IR sensitivity and increased frequency of spontaneous and IR-induced chromosomal breakage and rearrangements are the hallmarks of A-T. The ATM gene, mutated in this syndrome, has been cloned and codes for a protein sharing homology with DNA-PKcs, a protein kinase involved in DNA double-strand break (DSB) repair and DNA damage responses.

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions.

Stereochemical arrangement of hydroxyl groups in sugar and polyalcohol molecules as an important factor in effective cryopreservation.

The efficacy of several sugars and polyalcohols in preculture medium was investigated using Anigozanthos viridis ssp terraspectans Hopper (Haemodoraceae), a threatened plant species endemic to the south west of Western Australia. A vitrification protocol involving preculturing of shoot apices for 3 days on different concentrations of sugars and polyalcohols, followed by incubation in plant vitrification solution 2 (PVS2) for 25 min, prior to immersion in liquid nitrogen (LN) and warming resulted in shoot tip survival ranging from 34 to 84%. High levels of survival were obtained with polyalcohols, compared to sucrose, glucose, trehalose and raffinose when used at the same molarity (0.

Effects of threonine injections in the lateral hypothalamus on intake of amino acid imbalanced diets in rats.

Previous work from this laboratory suggests that animals decrease their intake of an amino acid imbalanced diet (IMB), due in part to a drop in the concentration of the dietary limiting amino (DLAA) in the anterior piriform cortex (APC). Administration of the DLAA, but not of a non-limiting amino acid into the APC, blocks the anorectic response to IMB. To our knowledge, the effects of DLAA injections on intake of a diet devoid of the DLAA (DEV), have not been examined in areas outside the APC.

Chromium(VI)-induced mutagenesis in the lungs of big blue transgenic mice.

The mutagenic activity of the hexavalent chromium [Cr(VI)] compound potassium dichromate was examined in the Big Blue transgenic mouse lung, the target organ for Cr(VI) carcinogenesis in humans. Mice were exposed to Cr(VI) by intratracheal instillation of a potassium dichromate (K2Cr2O7) solution. Analysis of the deposition of Cr in mouse lungs revealed that the procedure reproducibly resulted in about 5% retention of the Cr in the lung.

Differential effects of selective vagotomy and tropisetron in aminoprivic feeding.

Both total subdiaphragmatic vagotomy (TVAGX) and serotonin(3) receptor blockade with tropisetron or ondansetron attenuate amino acid-imbalanced diet (Imb) anorexia. Total vagotomy is less effective than tropisetron in reducing Imb-induced anorexia and also blunts the tropisetron effect. With the use of electrocautery at the subdiaphragmatic level of the vagus, we severed the ventral and dorsal trunks as well as the hepatic, ventral gastric, dorsal gastric, celiac, and accessory celiac branches separately or in combination to determine which vagal branches or associated structures may be involved in these responses.