Biomedical subjects

Paula Martikainen

Publications and source records attributed to Paula Martikainen.

5 recordsLinked to original sources

PubMed2006

Human brain tissue microarrays as a platform to investigate diseases of the nervous system.

We constructed tissue microarray (TMA) blocks containing post-mortem human brain tissue from subjects with clinically and neuropathologically verified Alzheimer's disease (AD), corticobasal degeneration (CBD), progressive supranuclear palsy, Lewy body disease, multisystem atrophy (MSA) as well as an age matched control. Fifteen donor blocks were merged into two TMA blocks containing 72, 2-mm punch core samples with representative brain regions generally affected in degenerative disorders. Hyperphosphorylated-gamma, alpha-synuclein and beta-amyloid-related pathologies were estimated. The diseases were easily recognized by evaluating the two TMA sections and the results assessing TMA sections were comparable with the assessment of the whole brain sections. The assessment of TMA sections revealed concomitant multifocal alpha-synuclein pathology in AD, mild tau-involvement in the case of MSA and a slight AD-type pathology in the case of CBD. These findings emphasize the importance of searching for a variety of pathologies in "the whole brain" rather than restricting the examination to a few vulnerable regions. Furthermore, the TMA methodology clearly reduced the number of sections needed for evaluating the whole brain, it increased the amount of research material generated and furthermore no detailed neuroanatomical knowledge was required for assessment of data.

Aged↗

PubMed2006

Human postmortem brain tissue and 2-mm tissue microarrays.

The authors constructed tissue microarray (TMA) blocks from human postmortem brain including numerous core samples measuring 2 mm in diameter from various anatomic regions. These TMA sections were then processed using various stainings and pretreatment techniques to evaluate their properties. The loss of core samples ranged from 2% to 100% and was significantly influenced by the type of glass slide used; it was lowest (2-8%) with SuperFrost Plus slides. The losses were not significantly altered when applying the most demanding pretreatment procedures or using human brain tissue with a long postmortem delay. A slight influence on the quality and the repeatability of some of the IHC stainings was seen by the postmortem delay, by the brain region, or by the glass slide used. One special feature of the constructed brain TMA block including many anatomic brain regions is that persons who lack skills in neuroanatomy can identify various brain structures simply by following the x-y coordinates. Thus, the applications of this brain TMA block in neurologic research by scientists with different skill bases remain to be determined.

Autopsy↗

PubMed2005

Web-based virtual microscopy in teaching and standardizing Gleason grading.

Gleason grading forms the basis of prognostic and therapeutic assessment in prostatic carcinoma despite its subjective nature and substantial interobserver variation. The accuracy of Gleason grading can be improved by the use of educational tools such as reference images. However, conventional microscopy images are of limited educational value because it is neither possible to view the sample at different magnifications nor to navigate into different areas of the specimen. This limitation can be overcome by the use of virtual microscopy, which allows viewing entire digitized microscope slides. We created an interactive Web site ( www.webmicroscope.net/gleason ) featuring a comprehensive set of prostatic needle biopsies as virtual slides, which can be viewed with a standard Web browser (Internet Explorer or Netscape). To evaluate the validity of Web-based virtual microscopy for Gleason grading, an experienced uropathologist (TK) scored a series of 62 biopsies from the original glass slides and 6 weeks later from virtual slides on the Web site using an ordinary desktop computer. The intraobserver agreement was excellent, with identical Gleason scores found in 48 of the 62 cases ( kappa = 0.73). The 14 remaining scores differed only by 1 point on the Gleason scale (2-10). The virtual slides were viewed by 2 other uropathologists (PM and HH), with interobserver kappa coefficients ranging from 0.55 to 0.62, which is within the range of previously reported studies using glass slides. The 3 uropathologists' Gleason scores were included as reference scores on the Web site, which now serves as a publicly open platform for self-testing and learning of Gleason grading. We conclude that Web-based virtual microscopy is a promising new tool for teaching and standardizing Gleason grading.

Biopsy, Needle↗

PubMed2004

Second round results of the Finnish population-based prostate cancer screening trial.

PURPOSE: Large randomized trials provide the only valid means of quantifying the benefits and drawbacks of prostate-specific antigen (PSA) screening, but the follow-up of ongoing studies is still too short to allow evaluation of mortality. We report here the intermediate indicators of screening efficacy from the second round of the Finnish trial. EXPERIMENTAL DESIGN: The Finnish trial, with approximately 80,000 men in the target population, is the largest component in the European Randomized Study of Screening for Prostate Cancer. The first round was completed in 1996-1999. Each year 8,000 men 55-67 years of age were randomly assigned to the screening arm, and the rest formed the control arm. Men randomized to the screening arm in 1996 were reinvited 4 years later, in 2000, and PSA was determined. RESULTS: Of the eligible 6415 men, 4407 (69%) eventually participated in the second round of screening. Of the first-round participants, up to 84% (3833 of 4556) attended rescreening. A total of 461 screenees (10.5%) had PSA levels of > or = 4 microg/liter. Altogether, 97 cancers were found, yielding an overall detection rate of 2.2% (97 of 4407). Seventy-nine cases were found among the 3833 second-time screenees (detection rate 2.1%) and 18 in those 574 men (3.1%) who had not participated previously. A PSA of > or = 4 microg/liter, but negative biopsy in the first screening round was associated with an up to 9-fold risk of cancer in rescreening relative to those with lower PSA levels at baseline. Ninety-one (94%) of all of the detected cancers were clinically localized. CONCLUSIONS: As surrogate measures of an effective screening program, both compliance as well as the overall and advanced prostate cancer detection rates remained acceptable. Men defined as screen-positive but with a negative confirmation of cancer at prevalence screen formed a high-risk group at rescreening.

Age Factors↗

PubMed2002

Antiproliferative action of vitamin D.

During the past few years, it has become apparent that vitamin D may play an important role in malignant transformation. Epidemiological studies suggest that low vitamin D serum concentration increases especially the risk of hormone-related cancers. Experimentally, vitamin D suppresses the proliferation of normal and malignant cells and induces differentiation and apoptosis. In the present review we discuss the mechanisms whereby vitamin D regulates cell proliferation and whether it could be used in prevention and treatment of hyperproliferative disorders like cancers.

Animals↗