Browsing by department "Haartman Institute"

Accurate pre-operative identification and grading of soft tissue sarcomas is required for their correct treatment. While core needle biopsy has been recognized accurate for identifying and grading soft tissue sarcomas, data is still lacking on diagnostic errors, their underlying reasons and the effects any errors may have on patient treatment. We retrospectively analysed data on all 313 patients treated for soft tissue sarcomas of the trunk and extremities whose core needle biopsies were analysed between 2000 and 2012 at Helsinki University Central Hospital. The final analysis included 297 patients with a primary soft tissue sarcoma who had their surgical specimen evaluated at Helsinki University Central Hospital. We found 48 diagnostic errors with the ability to affect subsequent treatment: 19 nonsarcomatous, 25 incorrect low-grade and five pre-operative diagnoses with errors in subtype. Core needle biopsies of myxoid soft tissue sarcomas appeared challenging to interpret. Twenty-five treatment inaccuracies were found in 18 patients, twelve of these were related to inadequate surgery and one had not received chemotherapy. On re-examination of the core needle biopsy, we reached the correct diagnosis in 20 patients. In addition six patients got a more correct diagnosis. Core needle biopsy is reliable for identifying mesenchymal malignancy and guiding treatment planning at our institution. We recommend it for diagnosis of all soft tissue sarcoma suspicious tumours with interpretation done by an experienced soft tissue sarcoma pathologist. Special caution must be taken when evaluating myxoid tumours.

The aim of this study was to find temperature-regulated genes in Yersinia pseudotuberculosis. They might contribute to its virulence. A library of Y. pseudotuberculosis strains with the luxCDABE operon added to different promoter regions was screened. First, we calculated a correction factor of 3.1 for the luxCDABE-coded luciferase enzyme between room (25 degrees C) and body temperature (37 degrees C). For the screening the different strains of bacteria were grown at these temperatures. We then compared the luminescence to find the strains that showed at least a three-fold difference in light emission. The temperature-regulated promoters were identified. Up-regulated ones coded a glycoside hydroxylase and a hypothetical operon. Down-regulated were ribosomal proteins, a glycoprotease, a methyltransferase, an exodeoxyribonuclease and an abortive infection protein. These results are preliminary and can be validated by further research.

Komplementti on tärkeä osa luontaista immuunipuolustusta. Komplementtia voivat aktivoida esimerkiksi erilaiset mikrobien pinnan proteiinit. Mikrobit ovat kuitenkin kehittäneet keinoja suojautua komplementilta. On tärkeää oppia tuntemaan näitä mekanismeja erityisesti mikrobilääkekehityksen kannalta. Yksi ryhmä bakteerien seerumiresistenssiä välittävistä proteiineista ovat autotransportteri-adhesiineihin kuuluvat Oca-proteiinit (Oligomeric coiled-coil adhesin). YadA (Yersinia–adhesiini A) on prototyyppi Oca-perheen proteiineista. Sen on todettu sitovan liukoisia komplementin säätelijäproteiineja FH:ta (faktori H) ja C4BP:tä (C4 b binding protein) ja se on merkittävä Yersinia enterocolitican seerumiresistenssiä välittävä proteiini. Tässä tutkimuksessa selvitettiin Oca-proteiineihin kuuluvien meningokokin NadA:n (Neisseria-adhesiini A) ja hemofiluksen HadA:n (Hemofilus-adhesiini A) kykyä sitoa FH:ta ja C4BP:tä. Aikaisempia tutkimuksia samasta aiheesta ei ole tiedossa. Tutkimusmenetelminä olivat ELISA (Enzyme-Linked Immunosorbent Assay) -testi, SDS-Page (Sodium Dodecyl Sulfate Polyacrylamide gel electrophoresis) ja Western blotting, geelivärjäys, sekä vasta-aineleimaus ja virtaussytometria. Lisäksi tutkittiin käytettyjen bakteerikantojen seerumiresistenssiä. Tutkimuksen perusteella ei saatu osoitettua, että NadA tai HadA sitoisivat FH:ta tai C4BP:tä, toisin kuin YadA. Seerumiresistenssitutkimuksessa NadA ja HadA näyttivät suojaavan bakteeria komplementin vaihtoehtoiselta tieltä.

Introduction: Merkel cell carcinoma (MCC) is a rare neuroendocrine cancer of the skin that has a strong propensity to relapse and metastasize. Exposure to ultraviolet radiation and immunosuppression contribute to MCC. Merkel cell polyomavirus (MCV) is detected in 70% to 80% of MCC tumors, but the significance of MCV infection is not yet understood. MicroRNAs (miRNA) have been reported to associate with many types of cancer, and miRNA profiles of other cancers with a virus etiology have been defined. The aim of this study was to compare the expression of five miRNAs, miR-34a, miR-30a, miR-1539, miR-142-3p and miR-181d in formalin fixed paraffin embedded MCC tumor samples according to MCV status using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Materials and methods: Sufficient RNA was extracted from 26 tumor samples and from control skin sample using the miRNeasy FFPE Kit (QIAGEN, Valencia, CA, USA). Reverse transcription of the RNA was done using the miScript II RT Kit (50) (QIAGEN). QRT-PCR was executed with miScript SYBR Green PCR Kit (QIAGEN).and LightCycler 480 instrument (Roche Diagnostics GmbH, Mannheim, Germany). Student's t-test and Mann-Whitney U-test were used to evaluate differences in miRNA expression. Results: We found a statistically significant underexpression of mir-34a in MCV-negative tumors compared to MCV-positives. The other four miRNAs studied did not show significant expression differences according to MCV-status. There was no statistically significant difference in miRNA expression according to tumor location or metastasizing. Conclusion: The difference in miRNA expression according to MCV-status suggests distinct pathogenesis of the tumors. The role of underexpressed miR-34a in MCV-negative tumor pathogenesis remains unclear but it might be consequential in the tumorigenesis of MCV-negative tumors.

Johdanto Reumataudit ovat yleisiä, mutta esiintyvyydeltään, kuormittavuudeltaan ja kustannuksiltaan erilaisia. Tautien kuormittavuuden vertailuun ei ole käytössä yksinkertaista menetelmää. Tutkimuksemme tavoitteena oli määrittää reumatautien yleisyys erikoissairaanhoidossa ja tuottaa kuormittavuuskerroin, joka voidaan laskea helposti saatavilla olevista tiedoista. Menetelmät Aineisto kerättiin kattavilla ATK-hauilla HUS:n tietojärjestelmistä ja kattaa vuosina 2011 ja 2012 Meilahden, Peijaksen Jorvin ja Hyvinkään sairaaloissa reumatologista erikoissairaanhoitoa saaneet potilaat. Potilaita oli 12 000 ja potilaskontakteja 51 000. Aineisto analysoitiin tutkimuksessa Python-ohjelmointikielellä kirjoitetulla ohjelmalla. Tulokset Tulokset on laskettu diagnooseittain. Yleisin ja kuormittavin reumadiagnoosi oli muu seropositiivinen nivelreuma, jota sairasti 28 % potilaista, joka aiheutti 38 % potilaskontakteista ja jonka kuormittavuusosuus oli 28 % reumatologisesta kokonaiskuormasta. Potilasmäärään suhteutettuna kuormittavimpia olivat lastenreumat, joista muuta lasten niveltulehdusta sairastavat potilaat kuormittivat eniten, keskivertopotilaisiin nähden 2,9-kertaisesti. Pohdinnat Kuormittavuuskertoimillamme erottuivat sekä harvinaiset että yleiset kuormittavat diagnoosit. Kertoimien soveltaminen diagnoosien sijaan taudeille ja tautiryhmille on käynnissä. Kertoimia kehitetään myös hyödyntämään aineistoa laajemmin. Periaate on sovellettavissa laajasti myös muille erikoisaloille.

Schistosomiasis and soil-transmitted helminthiasis (STH) are major public health problems in tropical and subtropical countries. In 2006, the World Health Organization launched a new strategy against helminth infections, based on the concept of preventive chemotherapy. Ac-cording to this recommendation, anthelminthic drugs should be distributed to all at risk of infection, with the aim of reducing morbidity and the intensity of infection. This report describes the process of constructing an epidemiological database, which attempts to incorporate all information available on the global prevalence of STH, schistosomiasis and other helminthiases. This database can be used as a tool for the implementation of preventive chemotherapy. The aim is also to gather information on the availability of epidemiological data on helminth infections. I found out that data on STH and schistosomiasis are lacking especially in Sub-Saharan Africa. Better data collection and communication between WHO and endemic countries should therefore be developed.