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Biomedical subjects

C Page

Publications and source records attributed to C Page.

107 records · Page 6Linked to original sources

The dynamics of nerve growth factor-induced neurofilament and vimentin filament expression and organization in PC12 cells.

Monoclonal antibodies specific for neurofilament (NF) subunits or for vimentin filament (VF) protein were used to study nerve growth factor (NGF)-induced intermediate filament expression and organization in a rat pheochromocytoma cell line (PC12 cells). NGF induced increased amounts of NF subunits and VF protein, and they were, in part, differentially localized within PC12 cells. The relative expression of each of the NF subunits and of the VF protein was measured by an enzyme-linked immunosorbent assay which revealed that PC12 cells grown in the absence of NGF (PC12- cells) contained 3 times more VF than 68,000-dalton NF subunits and only barely detectable amounts of 150,000- and 200,000-dalton NF subunits. Exposure of these cells to NGF (PC12+ cells) increased the amount of 68,000-dalton NF subunits 8-fold, VF protein 3-fold, and 150,000- and 200,000-dalton NF subunits 2-fold. The ratio of VF to 68,000-dalton NF proteins in PC12- versus PC12+ cells decreased from 3.0 to 1.5. Both VF and 68,000-dalton NF subunits were arranged in juxtanuclear "ball-like" configurations and both were present in neurites of PC12+ cells. The distribution of 150,000- and 200,000-dalton NF subunits was diffuse with perinuclear stippling and only occasional, weakly fluorescent "balls." After perturbation of the PC12 cell cytoskeleton, 68,000-dalton NF subunits and VF redistributed together and, thus, may exist as heteropolymers. Finally, the increased expression of NF and VF proteins was specific for NGF since they could not be induced by other hormones or "growth" factors. We conclude that PC12 cells constitute a model system for studies of NF and VF expression, assembly, and interactions.

Animals↗

Leucotrienes, SRS-A and the vascular manifestations of PCA.

In order to study possible mediators of the vascular manifestations of passive cutaneous anaphylaxis (PCA), several arachidonic acid metabolites were injected into guinea-pig skin. SRS-A, LTB4, LTC and LTD increased vascular permeability, responses to LTs being enhanced by PGE2. Mepyramine inhibited responses to histamine, but not those to SRS-A and LTs; the latter were inhibited by the SRS-A antagonist FPL-55712. Both mepyramine and FPL-55712 exert limited inhibitory effects on vascular permeability during PCA. Leukotrienes may contribute towards vascular permeability during PCA.

Animals↗

Possible adverse effects from local anesthetics and the treatment of these reactions.

Adverse drug reactions are potentially serious and are becoming increasingly common. Although optometrists employ only a limited spectrum of drugs they may encounter such reactions among their patients. There is always a risk that a life threatening situation will develop in a pateint quite apart from the use of any drugs. An optometrist as a member of the health-care team must be competent to provide first-aid if an emergency occurs. Tables are provided listing possible reactions to topical anesthetics with the usual signs and the preferred treatment. Optometrists are reminded that many of these treatments are the responsibility of physicians. Optometrists should be prepared to provide artificial respiration and external cardiac massage and should plan in advance how they will obtain additional assistance if an emergency occurs in their office.

Affective Symptoms↗

Mitogen-activated protein kinase (MAPK) in cardiac tissues.

Mitogen-activated protein kinase (MAPK) has recently emerged as a prominent role player in intracellular signalling in the ventricular myocyte with attention being focussed on its possible role in the development of ventricular hypertrophy. It is becoming clear that MAPK is also active in other cells of cardiac origin such as cardiac fibroblasts and possible functions of this signalling pathway in the heart have yet to be explored. In this report the mammalian MAPK pathway is briefly outlined, before reviewing current knowledge of the MAPK pathway in cardiac tissue (ventricular myocytes, vascular smooth muscle cells and cardiac fibroblasts). New data is also presented on the presence and activity of MAPK in two additional cardiac celltypes namely atrial myocytes and vascular endothelial cells from the coronary microcirculation.

Amino Acid Sequence↗

Effects of resistance training on bone parameters in young and mature rats.

1. Osteoporosis is a major public health problem that is predicted to worsen over the next decade and preventative strategies that increase bone strength have become the focus of substantial research. 2. Although mechanical load is a primary factor in the acquisition and maintenance of skeletal tissue, the type of exercise used and when in life it is most effectively prescribed remain inconclusive. 3. The present study compared 10 weeks of resistance training in both young and mature female Sprague-Dawley rats and measured bone density and body composition by dual energy X-ray absorptiometry and biomechanical properties by three point bending tests of the tibia and femur. 4. No significant differences were observed for any of the bone parameters when comparing exercise and control groups at either age. This was despite using a comparable training protocol to that in humans and using loads of approximately 150% bodyweight. 5. The present study concludes that more intensive work programmes of resistance training or different outcome measures are required when using animal models for skeletal research.

Age Factors↗

Stopping bacterial adhesion: a novel approach to treating infections.

Adhesion and colonization are prerequisites for the establishment of bacterial pathogenesis. The prevention of adhesion is an attractive target for the development of new therapies in the prevention of infection. Bacteria have developed a multiplicity of adhesion mechanisms commonly targeting surface carbohydrate structures, but our ability to rationally design effective antiadhesives is critically affected by the limitations of our knowledge of the human 'glycome' and of the bacterial function in relation to it. The potential for the future development of carbohydrate-based antiadhesives has been demonstrated by a significant number of in vitro and in vivo studies. Such therapies will be particularly relevant for infections of mucosal surfaces where topical application or delivery is possible.

Animals↗

Overexpression of Akt/AKT can modulate chemotherapy-induced apoptosis.

The AKT oncogenes are amplified or AKT kinase activity is constitutively elevated in several types of human malignancy. We sought to determine whether AKT might play a role in the development of resistance to apoptosis induced by chemotherapy. We showed that ovarian cancer cells either overexpressing constitutively active Akt/AKT1 or containing AKT2 gene amplification were highly resistant to paclitaxel than cancer cells express low AKT levels. The Akt/AKT1 clones also contained higher levels of phospho-Bad protein than parental cells. Further, the complexes between the endogenous proapoptotic protein, Bad, and the anti-apoptotic protein, BC1-XL were undetectable in Akt/AKT1 clones. These results suggest that Akt/AKT1 expressed in these clones can phosphorylate Bad and prevent it from binding to Bcl-XL. Furthermore, overexpression of Akt/AKT1 can inhibit the release of cytochrome c induced by paclitaxel. Therefore, our findings provide evidence that aberrant expression or activation of AKT in cancer cells may confer resistance to paclitaxel.

Adenocarcinoma↗

Suppression activity of pro-apoptotic gene products in cancer cells, a potential application for cancer gene therapy.

Overexpression of anti-apoptotic Bcl-2 and Bcl-XL proteins may play a role in the development of resistance to cancer therapy. We examined the expression of these proteins in prostate, breast, and ovarian cancer cells. We found that some of these cancer cell lines expressed high levels of Bcl-XL or Bcl-2., In order to develop an effective strategy to overcome the potential inhibition of cancer therapy by Bcl-2 and Bcl-XL, we tested the inhibitory ability of several pro-apoptotic or tumor suppressor genes in these cells. The expression of these genes induced apoptosis or suppressed cell growth with variable efficiency in these cells. Harakiri (Hrk) appears to result in the greatest induction of apoptosis or inhibition of cell growth Mtd, bax and bcl-XS were also effective in inhibiting cell growth. Furthermore, transfection of Hrk, bax, or Mtd into these cells caused significantly less colony formation than in cells transfected with p53 or BRCA1. Therefore, these results suggest that Hrk, bax, and Mtd are potent therapeutic agents for cancers expressing high levels of Bcl-2 and Bcl-XL.

Apoptosis↗