Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urinary excretion of deoxypyridinoline (D-Pyr) has been shown to be a useful marker for bone resorption. In this study, we investigated whether D-Pyr could be used to monitor the changes in bone resorption of the hind limb induced by tail-suspension. Male Wistar rats 5-weeks old were tail-suspended in a metabolic cage to unload the hind limbs. The control rats were not suspended. YH529 (YH), an inhibitor of bone resorption, or a vehicle (phosphate buffered saline=PBS) was administered daily starting 3 days before the commencement of tail-suspension. In the non-suspended rats receiving PBS, urinary excretion of D-Pyr did not show any significant change during the one-week experimental period. In the non-suspended rats receiving YH, D-Pyr excretion significantly decreased on day 5 and 7 when compared with that observed on day 0, in accordance with the systemic inhibition of bone resorption by YH. In the tail-suspended rats receiving PBS, D-Pyr excretion showed a tendency to increase on day 1, which is in agreement with our previous report that tail-suspension causes an early (on day 1 of suspension) and transient increase in bone-resorption of the hind limbs. In the tail-suspended rats treated with YH, the increase in D-Pyr excretion on day 1 was not observed, and a significantly lower excretion was noted from day 3 to 7 during the tail-suspension. It was suggested that D-Pyr excretion might reflect the transient increase in hind limb bone resorption induced by tail-suspension. As observed in-YH treated rats, D-Pyr excretion could serve as a good marker for the inhibition of systemic bone resorption.
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PMID:Changes in urinary excretion of deoxypyridinoline in tail-suspended rats: effects of a bisphosphonate, YH529. 1221 16

Human adenoviruses and adenoviral vectors are classified as Risk Group 2 agents and require BSL2 containment and practices. An additional consideration in using adenoviruses and viral vectors in laboratory animal studies is the possible transmission of these agents to other animals and/or personnel as a result of viral shedding in animal urine and feces. When handling BSL2 agents, cage-wash staff are required to wear appropriate personnel protective equipment, including scrubs, Tyvek suit, hair covering, dust mask, shoes covers, and gloves. Current decontamination procedures are to bag and autoclave soiled rodent cages containing bedding prior to washing in the cage washer to prevent possible adenoviral transmission. However, the practice of autoclaving softens the polycarbonate-based rodent cages, allowing damaging agents or conditions to affect the integrity of the plastic and degrade the cages. The objective of this study was to determine whether current rodent cage-cleaning practices produced virucidal effects for use in lieu of or prior to autoclaving the cages. We found that heating an Av3GFP vector in a test tube to a temperature of 74 degrees C (165 degrees F) for 6 min conditions equivalent to those of the cage washer resulted in greater than an 11-log reduction in infectivity of the vector as evaluated by its cytopathic effect on cells. The combination of heating and a liquid, phosphate-free alkaline detergent produced the same reduction in vector infectivity. However, common cage-cleaning solutions alone possessed no virucidal activity. The high temperatures used in cage-washing procedures alone or in combination with a cleaning solution reduced or eliminated the risk of transmission from viral shedding through urine and feces even at vector concentrations far greater than would ever be expected to be present. Autoclaving cages diminishes the stability and integrity of the polycarbonate cages without providing a further reduction in the risk of virus or vector transmission. On the basis of results from this study, new cage-wash recommendations include dumping the contaminated bedding into a HEPA-filtered waste disposal system and autoclaving the bags of bedding before disposal, then cleaning the cages in the rack washer at wash temperatures of 74 degrees C (165 F) and rinse temperatures of 82 degrees C (180 F).
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PMID:Virucidal effects of rodent cage-cleaning practices on the viability of adenovirus vectors. 1221 48

The pleura covers the lung parenchyma, chest wall, and diaphragm with a single layer of flat cells that are easy to genetically modify with adenovirus (Ad) vectors. Although intrapleural gene therapy has been used to treat intrapleural disorders, we hypothesized that it may also be used to deliver extracellular gene products to the lung parenchyma. In this context, this study is based on the concept that administration of adenovirus gene transfer vectors into the pleural cavity will mediate expression of gene products in mesothelial cells, and that the extracellular products produced by these genetically modified cells will reach the lung parenchyma. To assess this concept, Ad(beta)gal (expressing beta-galactosidase [beta-Gal]) or AdLuc (expressing luciferase) was administered into the right pleural cavity of BALB/c mice, as compared with intravenous injection via the jugular vein or the intratracheal route. Histologic assessment of lungs and pleural surface after intrapleural administration of Ad(beta)gal demonstrated beta-Gal expression limited to the pleural mesothelium and cells adjacent to the pleural surface. Right intrapleural administration of AdLuc showed higher level of luciferase in both the right and left lung (right vs. left, p > 0.8), compared with the intratracheal (p < 0.05) or intravenous routes (p < 0.02), that is, unilateral intrapleural administration is sufficient to transfer genes bilaterally to the pleura. To assess the ability of intrapleural gene transfer to modify lung parenchymal processes, CT26.CL25 tumor cells (3 x 10(5)) were injected via the jugular vein to generate tumor metastases in the lung parenchyma followed 24 hr later by administration to the right pleura of 5 x 10(8) PFU of Adsflt (an Ad "antiangiogenesis" vector expressing a soluble, secreted, extracellular portion of the Flt-1 receptor for vascular endothelial growth factor). Compared with phosphate-buffered saline, or the control vector AdNull (no transgene), mice receiving Adsflt by the intrapleural route had a marked suppression of tumor growth in the parenchyma of both lungs as assessed 12 days after tumor administration (p < 0.005). Treatment of preestablished lung metastases with Adsflt administered by the intrapleural route significantly improved long-term survival as compared with control animals (p < 0.0001). Thus, although intrapleural administration of an Ad vector encoding an intracellular protein mediates gene expression only in mesothelial cells and the local tissues, intrapleural delivery of a vector expressing a secreted protein can be used to modify processes throughout the lung parenchyma. In the context that intravascular gene transfer is an ineffective strategy to deliver gene products to the lung parenchyma, and that intratracheal administration is associated with alveolar inflammation secondary to host defenses against Ad vectors, these findings demonstrate that intrapleural administration represents a strategy that can be used to effectively deliver extracellular gene products to the lung parenchyma via a site that is readily accessible, and where inflammation against the vector will not have significant pathophysiologic consequences.
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PMID:Gene transfer to the pleural mesothelium as a strategy to deliver proteins to the lung parenchyma. 1221 68

Sediment oxygen consumption, TCO2 production and nutrient fluxes across the sediment-water interface were measured in sediments within and along a transect from four fish pens with production of milkfish (Chanos chanos) in the Bolinao area, The Philippines. The four fish pens were each representing a specific period in the production cycling. There was a positive linear relationship between the rates of sedimentation inside the fish pens and the sediment oxygen consumption indicating that the benthic processes were controlled by the input of organic matter from fish production. The nutrient fluxes were generally higher inside the fish pens, and nitrate was taken up (1.7-5.8 mmol m(-2) d(-1)) whereas ammonium (1-22 mmol m(-2) d(-1)) and phosphate (0.2-4.7 mmol m(-2) d(-1)) were released from the sediments. The sediments were enriched in organic matter with up to a factor 4 compared to outside. A mass balance for one crop of milkfish was constructed based on production data and on measured fluxes of nutrients in the fish pens to assess the loss of carbon and nutrients to the environment. There was a loss to the surroundings of carbon and nitrogen of 51-68% of the total input, whereas phosphorus was buried in the sediments inside the fish pens which acted as net sinks of phosphorus. The results obtained suggest that fish pen culture as practiced in the Bolinao area, leads to even greater impacts on benthic carbon and nutrient cycling than those found in suspended cage cultures.
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PMID:Impacts of milkfish (Chanos chanos) aquaculture on carbon and nutrient fluxes in the Bolinao area, Philippines. 1222 93

Nitric oxide (NO)-containing neurons have been localized in various parts of the central nervous system including the hypothalamus. NO plays an important role in the regulation of reproductive activities including sexual behavior and pituitary hormone secretion. To test the hypothesis that NO-containing neurons in specific brain areas may respond to the stimulus of mating and participate in integrating the tactile information in the hypothalamus, this study used Fos as a marker of neuronal activity. Proestrous rats receiving intromissions (mated group) from males or mounts-without-intromission (mounted group) were sacrificed along with rats taken directly from their home cage (control group) 90 min after the beginning of mating or mounting. NOergic neurons were labeled by histochemical reaction for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d). The presence of activated NO-producing (double-stained NADPH-d/Fos) neurons was quantitatively assessed in several brain areas before and after mating. The results showed that mating-with-intromissions induced a significant increase in the percentage of NADPH-d/Fos colabeled neurons in the medial preoptic area (mPOA) and the magnocellular component of the paraventricular nucleus (PVNm) compared to mounts-without-intromission or control treatment. Both mating and mounting induced Fos expression in NADPH-d-positive cells in the ventromedial nucleus of hypothalamus (VMN). In contrast, the expression of Fos in the NADPH-d-positive neurons in the supraoptic nucleus (SON) and the parvocellular portion of the paraventricular nucleus (PVNp) was not influenced by either mating or mounting although abundant NO-containing neurons were found in the two brain areas. The second experiment of the study examined whether NOergic neurons in these brain areas are influenced directly by estrogen by determining the number of NADPH-d-positive neurons that contained the estrogen receptor alpha (ERalpha), the classical ER. Double labeled NADPH-d/ERalpha neurons were observed in several brain areas including the mPOA and VMN while few, if any, NADPH-d-positive neurons in the SON, PVNm or PVNp contained ERalpha. The results suggest that the activated NOergic neurons in these brain areas may be involved in processing and integrating the mating stimulus. Further investigation is required to determine the physiological role of the mating-activated NOergic activity in specific mating-induced changes in reproductive neuroendocrinology.
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PMID:Mating-activated nitric oxide-producing neurons in specific brain regions in the female rat. 1223 Dec 31

Basic fibroblast growth factor (bFGF) is a potent tumor angiogenesis factor which lacks an amino-terminal signal sequence and does not normally circulate in serum from normal subjects. Naturally-occurring autoantibodies which mimicked basic fibroblast growth factor were described in serum from patients with multiple endocrine neoplasia type 1 prolactinoma or sporadic growth-hormone-secreting adenoma associated with increased bFGF. Since bFGF was increased in serum from a variety of cancers, we used endothelial cell proliferation assay(s) to test for bioactivity in the IgG fraction of serum from 56 patients with cancer-associated hypercalcemia, and normal or control subjects. We now report increased IgG-like endothelial cell activity in serum from a hyper prolactinemic subset (4/19 breast cancer; 1/14 renal cancer; 0/23 lung cancer) of cancer-associated hypercalcemic subjects. Highest activity was found in serum from three breast cancer patients who suffered spinal cord compression/metastases. The activity had properties of antiidiotype bFGF antibodies including reaction with anti-human IgG antibodies, and complete neutralization by rabbit antibodies to intact bFGF. The activity in endothelial cells persisted after storage at 0-4 C for 5 yrs; and [prepared by SDS-PAGE and immunoblotting with anti-human IgG] had apparent mol wt corresponding to the heavy chains of IgG. Serum IgG-like activity from 5 of 5 breast cancer patients and 2 of 2 prostate cancer subjects tested [prepared by anti-bFGF antibody, protein-A immunoaffinity, and hydroxyapatite (HA) chromatography] yielded peak HA-adsorbed activity that eluted with 0.4 M sodium phosphate, and was neutralized 70% by antibodies to intact bFGF. Cancer sera mean peak specific activity (12.0 ng-eq bFGF/ug protein) (n = 7) significantly exceeded (P < 0.001) normal sera mean peak specific activity (0.46 ng-eq bFGF/ug protein) (n = 6) in the 0.4 M sodium phosphate eluate fraction from hydroxyapatite columns. These results imply that long-lasting, bioactive FGF-like autoantibodies may arise spontaneously (and contribute to pathophysiology) in subsets of cancer patients with osseous metastases.
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PMID:Increased fibroblast growth factor-like autoantibodies in serum from a subset of patients with cancer-associated hypercalcemia. 1238 79

The in vitro and in vivo degradation of poly-L-lactic acid cages used as an adjunct to spinal arthrodesis was investigated. In the in vitro experiments cages were subjected to aging up to 73 weeks in phosphate-buffered solution (pH 7.4) at 37 degrees C. Inherent viscosity, crystallinity, and mechanical strength were determined at different time points. In the in vivo study, the poly-L-lactic acid cages were packed with bone graft and implanted in the L3-L4 spinal motion segment of 18 Dutch milk goats. At 12, 26, and 52 weeks, the motion segments were isolated and poly-L-lactic acid samples retrieved. On evaluation, the in vivo implanted cages showed an advanced decline in inherent viscosity compared to the cages subjected to in vitro degradation experiments. At 6 months of implantation, the geometrical shape and original height of 10 mm was maintained during 6 months of follow up. This finding fits well with the observation that mechanical strength was maintained for a period of 6 months in vitro. At 12 months, the poly-L-lactic acid cage had been disintegrated into multiple fragments with signs of absorption. Despite the high-load-bearing conditions, the poly-L-lactic acid cage allowed interbody fusion to occur without collapse of the cage.
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PMID:In vitro and in vivo degradation of bioabsorbable PLLA spinal fusion cages. 1241 20

Articular cartilage has limited capacity for repair. In the present study, tissue-engineered two-phase composite material was used for the repair of osteochondral defects in young adult rabbit knee. This composite material is composed of an injectable calcium phosphate (ICP) and a hyaluronan (HA) derivate of either ACP or HYAFF 11 sponge. The osteochondral defect, 3 mm in diameter and 3 mm deep, was created in the weight-bearing region of the medial femoral condyle. The bone portion of the defect was first filled with ICP to a level approximately 1 mm below the articular surface. HA sponge (3 mm in diameter and 1-1.2 mm thick), with or without loading of autologous bone marrow-derived progenitor cells (MPCs), was then inserted into the defect on top of the ICP as it hardened. Animals were allowed free cage activity postoperatively, and killed 4 or 12 weeks (for the HYAFF 11 sponge group) after the surgery. At 4 weeks, histological examination showed that the defect was filled up to 90-100% of its depth. Whitish repair tissue on the top appeared to be integrated with the surrounding articular cartilage. Four distinct zones of repair tissue were identified: a superficial layer, a chondroid tissue layer, an interface between HA sponge and ICP, and the ICP material. Evidence of extensive osteoclastic and osteoblastic activities was observed in the bone tissue surrounding the defect edge and in ICP material. By 12 weeks, the zonal features of the repair tissue became more distinct; chondrocytes were arranged in a columnar array, and a calcified layer of cartilage was formed beneath the chondroid tissue in some specimens. The healing tissue of the HA sponge material loaded with MPCs had higher cellular density and better integration with the surrounding cartilage than HA sponge material not loaded with MPCs. This study suggests that using a two-phase composite graft may hold potential for the repair of osteochondral defects by providing mechanical support that mimicks subchondral bone, while also providing a chondrogenic scaffold for the top cartilage repair.
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PMID:Repair of osteochondral defect with tissue-engineered two-phase composite material of injectable calcium phosphate and hyaluronan sponge. 1245 61

The in vivo host response to two gelatin-based hydrogel systems of varying crosslinking modalities and loaded with the anti-inflammatory agent dexamethasone sodium phosphate was investigated. Either gelatin was chemically crosslinked with glutaraldehyde, or polyethyleneglycol diacrylate was photopolymerized around gelatin to form interpenetrating networks. The subcutaneous cage implant system was utilized to determine differential leukocyte concentrations in the inflammatory exudate surrounding the materials as indices for biocompatibility and drug efficacy in vivo. Most of the crosslinked gelatin-based materials, either via glutaraldehyde fixation or interpenetrating network formation, elicited stronger inflammatory responses than either of the starting materials, gelatin and polyethyleneglycol diacrylate. In general, dexamethasone delayed and intensified the inflammatory response. The loss of material mass did not correlate directly with the degree of cellular inflammatory response, but increased with longer implantation time and decreased with more extensive fixation.
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PMID:In vivo biocompatibility of gelatin-based hydrogels and interpenetrating networks. 1255 1

Forty-eight Wistar rats were treated for 3 weeks with water containing 0.7% ethylene-glycol and divided into four groups. The first group, used as control, has received sodium chloride at 1 ml/100 g BW daily. The second group was intraperitoneally injected with selenium at 10 micrograms/d per 100 g BW as NaSeO3 for 3 weeks. The third group was intraperitoneally administered with 15 mg Vit E/d per 100 g BW as alpha-tocopherol acetate for 3 weeks. The last group was simultaneously administered vitamin E and Se at the same doses and periods as the precedent groups. One day before the end of the treatment, each animal was placed in a metabolic cage for collection of 24 h urine samples and determination of urinary creatinin, urea, calcium, magnesium, phosphate and oxalate levels. Immediately thereafter, all the rats were anesthetized and aortic blood was collected to determine the same parameters as in urine. The kidneys were also removed to determine calcium oxalate deposits, dry weight and to conduct a histological examination. Our results showed decreased ionic product and increased magnesium fractional reabsorption in the group receiving only selenium and in the group receiving selenium in combination with vitamin E, in comparison with the control animals. In view of the knowledge concerning the same protective action of Vit E and selenium, regardless of tubular membrane alteration, the absence of any inhibitory effect of Vit E on calcium oxalate formation suggests that selenium, like other minerals, could be stuck onto the crystal surface and would inhibit induction of new crystals, growth and aggregation.
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PMID:Effects of intraperitoneally administered vitamin E and selenium on calcium oxalate renal stone formation: experimental study in rat. 1274 Nov 89


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