A mouse model for improving cell survival of bisected cattle embryos

Selostus: Hiiren alkio mallina solukestävyyden parantamiseksi naudan alkioiden halkaisussa

Production of fungal volatile organic compounds in bedding materials

Selostus: Haihtuvien orgaanisten yhdisteiden muodostuminen kuivikkeissa

Nursery Practices and Management of Fungal Diseases in Forest Nurseries in Finland : a review

Summary

Survival and early seedling growth of conifers with different shade tolerance in a Sitka spruce spacing trial and relationship to understorey light climate

Abstract

Pre-harvest soil acidification, liming or N fertilization did not significantly affect the survival and growth of young Norway spruce

Abstract

Survival-time analysis of white spruce during spruce budworm defoliation

Abstract

Survival and Quality of Life among Patients with Severe Lower Extremity Peripheral Arterial Disease

Lower extremity peripheral arterial disease (PAD) is associated with decreased functional status, diminished quality of life (QoL), amputation, myocardial infarction, stroke, and death. Nevertheless, public awareness of PAD as a morbid and mortal disease is low. The aim of this study was to assess the incidence of major lower extremity amputation due to PAD, the extent of reamputations, and survival after major lower extremity amputation (LEA) in a population based PAD patient cohort. Furthermore, the aim was to assess the functional capacity in patients with LEA, and the QoL after lower extremity revascularization and major amputation. All 210 amputees due to PAD in 1998–2002 and all 519 revascularized patients in 1998–2003 were explored. 59 amputees alive in 2004 were interviewed using a structured questionnaire of QoL. Two of each amputee age-, gender- and domicile-matched controls filled in and returned postal self-administered QoL questionnaire as well as 231 revascularized PAD patients (the amount of these patients who engaged themselves to the study), and one control person for each patient completed postal self-administered QoL questionnaire. The incidence rate of major LEA was 24.1/100 000 person-years and it was considerably high during the years studied. The one-month mortality rate was 21%, 52% at one-year, and the overall mortality rate was 80%. When comparing the one-year mortality risk of amputees, LEAs were associated with a 7.4-fold annual mortality risk compared with the reference population in Turku. Twenty-two patients (10%) had ipsilateral transversions from BK to AK amputation. Fifty patients (24%) ended up with a contralateral major LEA within two to four amputation operations. Three bilateral amputations were performed at the first major LEA operation. Of the 51 survivors returning home after their first major LEA, 36 (71%) received a prosthesis; (16/36, 44%) and were able to walk both in- and outdoors. Of the 68 patients who were discharged to institutional care, three (4%) had a prosthesis one year after LEA. Both amputees and revascularized patients had poor physical functioning and significantly more depressive symptoms than their controls. Depressive symptoms were more common in the institutionalized amputees than the home-dwelling amputees. The surviving amputees and their controls had similar life satisfaction. The amputees felt themselves satisfied and contented, whether or not they lived in long-term care or at home. PAD patients who had undergone revascularizations had poorer QoL than their controls. The revascularized patients’ responses on their perceived physical functioning gave an impression that these patients are in a declining life cycle and that revascularizations, even when successful, may not be sufficient to improve the overall function. It is possible that addressing rehabilitation issues earlier in the care may produce a more positive functional outcome. Depressive symptoms should be recognized and thoroughly considered at the same time the patients are recovering from their revascularization operation. Also primary care should develop proper follow-up, and community organizations should have exercise groups for those who are able to return home, since they very often live alone. In rehabilitation programs we should consider not only physical disability assessment but also QoL.

Superoxide dismutase 3-mediated cell survival and proliferation

This dissertation studies the signaling events mediated by the extracellular superoxide dismutase (SOD3). SOD3 is an antioxidant enzyme which converts the harmful superoxide into hydrogen peroxide. Overproduction of these reactive oxygen species (ROS) in the cellular environment as a result of tissue injury or impaired antioxidant defense system has detrimental effects on tissue integrity and function. However, especially hydrogen peroxide is also an important signaling agent. Ischemic injury in muscle causes acute oxidative stress and inflammation. We investigated the ability of SOD3 to attenuate ischemia induced inflammation and to promote recovery of skeletal muscle tissue. We found that SOD3 can downregulate the expression of several inflammatory cytokines and cell adhesion molecules thus preventing the accumulation of oxidant-producing inflammatory cells. Secondly, SOD3 was able to promote long-term activation of the mitogenic Erk pathway, but increased only briefly the activity of pro-survival Akt pathway at an early stage of ischemic inflammation, thus reducing apoptosis. SOD3 is a prominent antioxidant in the thyroid gland where oxidative stress is constantly present. We investigated the role of SOD3 in normal thyroid follicular cells and the changes in its expression in various hyperproliferative disorders. We first showed that SOD3 is TSH-responsive which indicated its participation in thyroid function. Its principal function seems to be in follicular cell proliferation since knockdown cells were deficient in proliferation. Additionally, it was overexpressed in goiter tissue. However, SOD3 was consistently downregulated in thyroid cancer cell lines and tissues. In conclusion, SOD3 is involved in tissue maintenance, cell proliferation and inflammatory cell migration. Its mechanisms of action are the activation of known proliferation/survival pathways, inhibition of apoptosis and regulation of adhesion molecule expression.

The Dual Role of HIF Hydroxylase PHD3 in Cancer Cell Survival

Most advanced tumours face periods of reduced oxygen availability i.e. hypoxia. During these periods tumour cells undergo adaptive changes enabling their survival under adverse conditions. In cancer hypoxia-induced cellular changes cause tumour progression, hinder cancer treatment and are indicative of poor prognosis. Within cells the main regulator of hypoxic responses is the hypoxia-inducible factor (HIF). HIF governs the expression of over a hundred hypoxia-inducible genes that regulate a number of cellular functions such as angiogenesis, glucose metabolism and cell migration. Therefore the activity of HIF must be tightly governed. HIF is regulated by a family of prolyl hydroxylase enzymes, PHDs, which mark HIF for destruction in normoxia. Under hypoxic conditions PHDs lose much of their enzymatic activity as they need molecular oxygen as a cofactor. Out of the three PHDs (PHD1, 2 and 3) PHD2 has been considered to be the main HIF-1 regulator in normoxic conditions. PHD3 on the other hand shows the most robust induction in response to oxygen deprivation and it has been implied as the main HIF-1 regulator under prolonged hypoxia. SQSTM1/p62 (p62) is an adaptor protein that functions through its binding motifs to bring together proteins in order to regulate signal transduction. In non-stressed situations p62 levels are kept low but its expression has been reported to be upregulated in many cancers. It has a definitive role as an autophagy receptor and as such it serves a key function in cancer cell survival decisions. In my thesis work I evaluated the significance of PHD3 in cancer cell and tumour biology. My results revealed that PHD3 has a dual role in cancer cell fate. First, I demonstrated that PHD3 forms subcellular protein aggregates in oxygenated carcinoma cells and that this aggregation promotes apoptosis induction in a subset of cancer cells. In these aggregates an adaptor protein SQSTM1/p62 interacts with PHD3 and in so doing regulates PHD3 expression. SQSTM1/p62 expression is needed to keep PHD3 levels low in normoxic conditions. Its levels rapidly decrease in response to hypoxia allowing PHD3 protein levels to be upregulated and the protein to be diffusely expressed throughout the cell. The interaction between PHD3 and SQSTM1/p62 limits the ability of PHD3 to function on its hydroxylation target protein HIF-1alpha. Second, the results indicate that when PHD3 is upregulated under hypoxia it protects cancer cells by allowing cell cycle to proceed from G1 to S-phase. My data demonstrates that PHD3 may either cause cell death or protect the cells depending on its expression pattern and the oxygen availability of tumours.