Mies, talli ja moottoripyörä : Etnografinen tutkimus Misfit MC:stä ja bikerkulttuurin eetoksesta

Tutkimuksen punaisena lankana kulkee kysymys siitä, millainen on bikerkulttuurin eetos? Miten se on syntynyt, miten sitä ylläpidetään ja miten Misfit MC:n jäsenet sitä tulkitsevat ja toteuttavat omassa elämässään? Tarkastelen eetosta kahdenlaisen aineiston valossa. i) Kenttätyöllä (vuosina 1995-1998 ja 2000-2001) kerätyn aineiston valossa tarkastelen yhtä pääkaupunkiseudulla toimivaa HD-moottoripyöräkerhoa, vuonna 1989 toimintansa aloittanutta Misfit MC:tä. Jäsenet kutsuvat kerhoaan useimmiten talliksi, joskus pajaksi, kerhoksi tai klubiksi. Puhuessaan tallista, miehet voivat viitata kerhorakennukseen ("tuut sä tallille?") mutta myös ryhmään ("meidän talli") ja sen olemassaoloon ajallisesti ja paikallisesti. Aloittaessani kenttätyön vuonna 1995 Misfit MC:n kuului kymmenen 25-30-vuotiasta miestä. ii) Kenttätyöllä kerätyn aineiston lisäksi käytän materiaalia, joka koostuu Harley-Davidson-moottoripyörän ympärille rakentuneen bikerkulttuurin historiasta ja kulttuurituotteista, kuten kertomuksista, elokuvista, musiikista, kuvataiteesta ja moottoripyörälehdistä. Aineiston avulla valotan bikerkulttuurin eetoksen syntyä, alkuvaiheita, leviämistä ja keskeisiä elementtejä. Lähdeaineiston monimuotoisuus ja runsaus palautuu kenttätyöhöni jolloin vakuutuin siitä, että tutkimusmatka bikerkulttuurin historiaan, perinteisiin ja median välittämiin (mieli)kuviin on välttämätöntä, sillä menneisyys ja Harrikkaan ajan kuluessa varastoituneet merkitykset vaikuttavat ja ovat vahvasti läsnä Misfit MC:n toiminnassa ja talliin kuuluvien miesten elämäntyylissä. Tutkimus etenee seuraavanlaisesti. Luku I on Johdanto. Luvussa II Etnografia käsittelen etnografisen tiedon luonnetta niin tutkimusasenteena kuin kenttätyön valossa. Pohdin kenttätyötä ja sen suhdetta etnografian kirjoittamiseen eli miten kenttätyöllä kerätty aineisto muuntuu etnografiseksi monografiaksi. Käsittelen myös kenttätyöni reunaehtoja, kuten tyttöystävyyden ja sukupuolen merkitystä, ja tarkastelen tutussa kulttuurissa tehdyn kenttätyön ominaispiirteitä. Reunaehtojen kuvailu toimii myös johdatuksena bikerkulttuuriin sellaisena kuin se ilmenee Misfit MC:n tallielämässä ja käytänteissä. Lopuksi pohdin "tiheän kuvauksen" mahdollisuuksia ja vaateita aineistoni puitteissa. Luvussa III Bikerkulttuurin eetosta kartoittamassa, kuvailen Harley-Davidson-moottoripyörän ympärille rakentuneen elämäntavan syntyä, levittäytymistä ja keskeisiä elementtejä. Tarkastelen media- ja populaarikulttuurisia tekstejä (elokuvien kertomat tarinat, musiikkikappaleiden sanoitukset ja HD- ja bikerlehtien artikkelit) ja kuvia (elokuvien audiovisuaaliset aspektit, kuvataide ja HD- ja bikerlehtien kuvitus), jotka ovat vaikuttaneet bikerkulttuurin eetokseen. Luvun keskeisiä - aineistosta nousevia ja miessukupuoleen vahvasti sidoksissa olevia - käsitteitä ovat biker, outlaw ja chopper, jotka ovat bikerkulttuurissa säilyneet alkuperäisessä muodossa maantieteellisestä tai kielialueesta riippumatta. Luvussa IV Misfit MC ja bikerkulttuurin eetos temaattinen painopiste siirtyy Suomeen ja Misfit MC:hen. Aluksi käyn läpi suomalaisen bikerkulttuurin muotoutumista ja ominaispiirteitä. Alkukappaleiden jälkeen keskityn Misfit MC:n jäsenten elämäntyylin sävyihin ja heidän käsityksiinsä bikerkulttuurin eetoksesta. Analyysin kiintopisteitä ovat Misfit MC:n jäsenten näkemys bikeriydestä ja tallitoiminnasta, miesten elämäntyylin moraaliset ja esteettiset sävyt, tallirakennus miesyhteisöllisyyttä ja bikerkulttuurin eetosta luovana ja ylläpitävänä sosiaalisena tilana ja Misfit MC miesten yhteisönä. Luvussa V Eetoksen ytimessä: mies ja Harley-Davidson keskityn bikerkulttuurin ytimeen: miehen ja Harley-Davidson-moottoripyörän väliseen suhteeseen. Luvun alussa esittelen ruotsalaisen yhteiskuntatieteilijä Lars Lagergrenin moottoripyörään soveltamaa työkalu - leikkikalu - toteemi - välittäjä -typologiaa ja tarkastelen moottoripyörän olemusta sukupuolittavana ja sukupuolittuvana artefaktina. Johdanto-osion jälkeen siirryn kuvailemaan Misfit MC:n jäsenten suhdetta Harley-Davidson-moottoripyörään. Lähestyn miesten ja moottoripyörien suhdetta kahden toiminnan - moottoripyörän kunnostamisen ja rakentamisen sekä moottoripyörällä ajamisen - kautta. Avainsanat: aineellinen kulttuuri, arvot, biker, bikerkulttuuri, chopper, eetos, elämäntapa, etnografia, Harley-Davidson-moottoripyörä, Harley-Davidson-moottoripyöräkerho, kenttätyö, maskuliinisuus, mieskulttuuri, mieskuva, moottoripyöräily, osakulttuurit, outlaw, populaarikulttuuri, sukupuoliroolit, yhteisöt

Endoplasmic reticulum stress and cell death mechanisms in the cell model of Huntington’s disease

This thesis clarifies important molecular pathways that are activated during the cell death observed in Huntington’s disease. Huntington’s disease is one of the most common inherited neurodegenerative diseases, which is primarily inherited in an autosomal dominant manner. HD is caused by an expansion of CAG repeats in the first exon of the IT15 gene. IT15 encodes the production of a Huntington’s disease protein huntingtin. Mutation of the IT15 gene results in a long stretch of polyQ residues close to the amino-terminal region of huntingtin. Huntington’s disease is a fatal autosomal neurodegenerative disorder. Despite the current knowledge of HD, the precise mechanism behind the selective neuronal death, and how the disease propagates, still remains an enigma. The studies mainly focused on the control of endoplasmic reticulum (ER) stress triggered by the mutant huntingtin proteins. The ER is a delicate organelle having essential roles in protein folding and calcium regulation. Even the slightest perturbations on ER homeostasis are effective enough to trigger ER stress and its adaptation pathways, called unfolded protein response (UPR). UPR is essential for cellular homeostasis and it adapts ER to the changing environment and decreases ER stress. If adaptation processes fail and stress is excessive and prolonged; irreversible cell death pathways are engaged. The results showed that inhibition of ER stress with chemical agents are able to decrease cell death and formation of toxic cell aggregates caused by mutant huntingtin proteins. The study concentrated also to the NF-κB (nuclear factor-kappaB) pathway, which is activated during ER stress. NF-κB pathway is capable to regulate the levels of important cellular antioxidants. Cellular antioxidants provide a first line of defence against excess reactive oxygen species. Excess accumulation of reactive oxygen species and subsequent activation of oxidative stress damages motley of vital cellular processes and induce cell degeneration. Data showed that mutant huntingtin proteins downregulate the expression levels of NF-κB and vital antioxidants, which was followed by increased oxidative stress and cell death. Treatment with antioxidants and inhibition of oxidative stress were able to counteract these adverse effects. In addition, thesis connects ER stress caused by mutant huntingtin to the cytoprotective autophagy. Autophagy sustains cellular balance by degrading potentially toxic cell proteins and components observed in Huntington’s disease. The results revealed that cytoprotective autophagy is active at the early points (24h) of ER stress after expression of mutant huntingtin proteins. GADD34 (growth arrest and DNA damage-inducible gene 34), which is previously connected to the regulation of translation during cell stress, was shown to control the stimulation of autophagy. However, GADD34 and autophagy were downregulated at later time points (48h) during mutant huntingtin proteins induced ER stress, and subsequently cell survival decreased. Overexpression GADD34 enhanced autophagy and decreased cell death, indicating that GADD34 plays a critical role in cell protection. The thesis reveales new interesting data about the neuronal cell death pathways seen in Huntington’s disease, and how cell degeneration is partly counteracted by various therapeutic agents. Expression of mutant huntingtin proteins is shown to alter signaling events that control ER stress, oxidative stress and autophagy. Despite that Huntington’s disease is mainly an untreatable disorder; these findings offer potential targets and neuroprotective strategies in designing novel therapies for Huntington’s disease.

Thrombophilia and direct thrombin inhibitor lepirudin clinical and monitoring aspects

Thrombophilia (TF) predisposes both to venous and arterial thrombosis at a young age. TF may also impact the thrombosis or stenosis of hemodialysis (HD) vascular access in patients with end-stage renal disease (ESRD). When involved in severe thrombosis TF may associate with inappropriate response to anticoagulation. Lepirudin, a potent direct thrombin inhibitor (DTI), indicated for heparin-induced thrombocytopenia-related thrombosis, could offer a treatment alternative in TF. Monitoring of narrow-ranged lepirudin demands new insights also in laboratory. The above issues constitute the targets in this thesis. We evaluated the prevalence of TF in patients with ESRD and its impact upon thrombosis- or stenosis-free survival of the vascular access. Altogether 237 ESRD patients were prospectively screened for TF and thrombogenic risk factors prior to HD access surgery in 2002-2004 (mean follow-up of 3.6 years). TF was evident in 43 (18%) of the ESRD patients, more often in males (23 vs. 9%, p=0.009). Known gene mutations of FV Leiden and FII G20210A occurred in 4%. Vascular access sufficiently matured in 226 (95%). The 1-year thrombosis- and stenosis-free access survival was 72%. Female gender (hazards ratio, HR, 2.5; 95% CI 1.6-3.9) and TF (HR 1.9, 95% CI 1.1-3.3) were independent risk factors for the shortened thrombosis- and stenosis-free survival. Additionally, TF or thrombogenic background was found in relatively young patients having severe thrombosis either in hepatic veins (Budd-Chiari syndrome, BCS, one patient) or inoperable critical limb ischemia (CLI, six patients). Lepirudin was evaluated in an off-label setting in the severe thrombosis after inefficacious traditional anticoagulation without other treatment options except severe invasive procedures, such as lower extremity amputation. Lepirudin treatments were repeatedly monitored clinically and with laboratory assessments (e.g. activated partial thromboplastin time, APTT). Our preliminary studies with lepirudin in thrombotic calamities appeared safe, and no bleeds occurred. An effective DTI lepirudin calmed thrombosis as all patients gradually recovered. Only one limb amputation was performed 3 years later during the follow-up (mean 4 years). Furthermore, we aimed to overcome the limitations of APTT and confounding effects of warfarin (INR of 1.5-3.9) and lupus anticoagulant (LA). Lepirudin responses were assessed in vitro by five specific laboratory methods. Ecarin chromogenic assay (ECA) or anti-Factor IIa (anti-FIIa) correlated precisely (r=0.99) with each other and with spiked lepirudin in all plasma pools: normal, warfarin, and LA-containing plasma. In contrast, in the presence of warfarin and LA both APTT and prothrombinase-induced clotting time (PiCT®) were limited by non-linear and imprecise dose responses. As a global coagulation test APTT is useful in parallel to the precise chromogenic methods ECA or Anti-FIIa in challenging clinical situations. Lepirudin treatment requires multidisciplinary approach to ensure appropriate patient selection, interpretation of laboratory monitoring, and treatment safety. TF seemed to be associated with complicated thrombotic events, in venous (BCS), arterial (CLI), and vascular access systems. TF screening should be aimed to patients with repeated access complications or prior unprovoked thromboembolic events. Lepirudin inhibits free and clot-bound thrombin which heparin fails to inhibit. Lepirudin seems to offer a potent and safe option for treatment of severe thrombosis. Multi-centered randomized trials are necessary to assess the possible management of complicated thrombotic events with DTIs like lepirudin and seek prevention options against access complications.

Long-term results of operative treatment for Hirschsprung's disease and internal anal sphincter achalasia

The aim of the study was to evaluate long-term results of operative treatment for Hirschsprung's disease(HD) and internal anal sphincter achalasia. Fecal continence and quality of life were evaluated by a questionnaire in 100 adult patients who had undergone surgery for HD, during 1950-75. Fecal continence was evaluated using a numerical scoring described by Holschneider. Fifty-four of the 100 patients underwent clinical examination, rigid sigmoidoscopy and manometric evaluation. In anorectal manometry basal resting pressure(BRP)and maximal squeeze pressure(MSP) were measured and voluntary sphincter force(VSF) was calculated by subtracting the BRP from MSP. The results of operative treatment for adult HD were compared with the results of the patients operated in childhood. In adult HD the symptoms are such mild that the patients attain adolescence or even adulthood. The patients with HD and cartilage-hair-hypoplasia were specifically evaluated. The outcome of the patients with internal anal sphincter achalasia operated on by myectomy was evaluated by a questionnaire and continence was evaluated using a numerical scoring described by Holschneider. Of the 100 patients operated on for HD 38 patients had completely normal bowel habits. A normal or good continence score was found in 91 our of 100 patients. Nine patients had fair continence. One of the patients with fair continence had Down's syndrome and two were mentally retarded for other reasons. Only one patient suffered from constipation. In anorectal manometry the difference in BRP between patients with normal and good continence was statistically significant, whereas the difference between good and fair continence groups was not statistically significant. The differences on MSP and VSF between patient groups with different continence outcome were not statistically significant. The differences between patient groups and normal controls were statistically significant in BRP and MSP. In VSF there was not statistically significant difference between the patients and the normal controls. The VSF reflects the working power of the muscles including external sphincter, levator ani and gluteal muscles. The patients operated at adult age had as good continence as patients operated in childhood. The patients with HD and cartilage-hair-hypoplasia had much more morbidity and mortality than non-cartilage-hair-hypoplasia HD patients. The mortality was as high as 38%. In patients with internal anal sphincter achalasia the constipation was cured or alleviated by myectomy whereas a significant number suffered from soiling-related social problems.