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Biomedical subjects

K Tuppurainen

Publications and source records attributed to K Tuppurainen.

At least 19 recordsLinked to original sources
PubMed2006

Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis.

Serrated colorectal carcinomas (CRCs) are morphologically different from conventional CRCs and have been proposed to follow a distinct pathway of CRC formation. Despite studies of single molecular events in this tumor type, the diagnosis of serrated CRC relies on morphology and the putative unique biological character of these tumors has not been established. Here we show that the gene expression profiling of 37 CRCs separated serrated and conventional CRCs into two distinct branches in unsupervised hierarchical clustering (P-value 7.8 x 10(-7)), and revealed 201 differentially expressed genes representing potential biomarkers for serrated CRC. Immunohistochemistry was utilized to verify the key findings in the 37 CRCs examined by expression profiling, and a separate validation set of 37 serrated and 86 conventional CRCs was examined to evaluate the candidate biomarkers in an extended sample material. Ephrin receptor B2, hypoxia-inducible factor 1-alpha and patched appeared as proteins important for genesis of serrated CRC. This study establishes serrated CRCs as a biologically distinct subclass of CRC and represents a step forward in the molecular classification of these cancers. The study also provides a platform to understand the molecular basis of serrated CRC and in long term may contribute to the development of specific treatment options for this tumor type.

Adenocarcinoma, Mucinous↗
PubMed2006

Performance of multicomponent self-organizing regression (MCSOR) in QSAR, QSPR, and multivariate calibration: comparison with partial least-squares (PLS) and validation with large external data sets.

A novel method for underdetermined regression problems, multicomponent self-organizing regression (MCSOR), has been recently introduced. Here, its performance is compared with partial least-squares (PLS), which is perhaps the most widely adopted multivariate method in chemometrics. A potpourri of models is presented, and MCSOR appears to provide highly predictive models that are comparable with or better than the corresponding PLS models in large internal (leave-one-out, LOO) and pseudo-external (leave-many-out, LMO) validation tests. The "blind" external predictive ability of MCSOR and PLS is demonstrated employing large melting point, factor Xa, log P and log S data sets. In a nutshell, MCSOR is fast, conceptually simple (employing multiple linear regression, MLR, as a statistical tool), and applicable to all kinds of multivariate problems with single Y-variable.

Algorithms↗
PubMed2005

Improving the performance of SOMFA by use of standard multivariate methods.

Self-Organizing Molecular Field Analysis (SOMFA) comes with a built-in regression methodology, the Self-Organizing Regression (SOR), instead of relying on external methods such as PLS. In this article we present a proof of the equivalence between SOR and SIMPLS with one principal component. Thus, the modest performance of SOMFA on complex datasets can be primarily attributed to the low performance of the SOMFA regression methodology. A multi-component extension of the original SOR methodology (MCSOR) is introduced, and the performances of SOR, MCSOR and SIMPLS are compared using several datasets. The results indicate that in general the performance of SOMFA models is greatly improved if SOR is replaced with a more sophisticated regression method. The results obtained for the Cramer (CBG) dataset further underline the fact that it is a very poor benchmark dataset and should not be used to evaluate the performance of QSAR techniques.

Multivariate Analysis↗
PubMed2001

PCDD/F reduction in incinerator flue gas by adding urea to RDF feedstock.

The effect of urea on PCDD/F formation in a pilot incinerator was studied by incinerating urea with refuse-derived fuel (RDF) at three concentrations (0.1%, 0.5% and 1.0%, of the fuel feed). A distinct reduction in both PCDD/F and chlorophenol concentrations could be noticed when urea was introduced into the system. Partial-least-square (PLS) analysis of the data showed the importance of certain chlorophenol isomers as PCDD/F precursors, pointing to the possibility that the impact point of the urea inhibitor could be before the precursor molecules, i.e. chlorophenols, have been formed.

Air Pollutants↗
PubMed2001

Urea as a PCDD/F inhibitor in municipal waste incineration.

Emissions of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from municipal waste incineration have been widely studied because of their extensive toxicity, and many efforts have been made to restrict their emissions. Although a number of chemical compounds have been shown in laboratory-scale tests to inhibit the formation of PCDD/Fs, few have been tested in pilot- or full-scale plants. This work evaluates the effect of urea as a PCDD/F inhibitor in a pilot-scale incinerator that uses refuse-derived fuel (RDF). The decomposition of urea under the test conditions was also studied using detailed kinetic modeling. An aqueous solution of urea was injected into the flue gas stream after the furnace at approximately 730 degrees C, with varied urea concentrations and flue gas residence times used between the furnace and the sampling point. The results demonstrate that urea can successfully inhibit PCDD/F formation in waste incineration if concentrations and injection points are properly adjusted. The kinetic model showed that urea can be rapidly decomposed under appropriate flue gas conditions, indicating that in addition to the urea molecule itself, decomposition products of urea can also be responsible for the reduction of PCDD/F production during incineration.

Benzofurans↗
PubMed2000

Electronic eigenvalue (EEVA): a new QSAR/QSPR descriptor for electronic substituent effects based on molecular orbital energies. A QSAR approach to the Ah receptor binding affinity of polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs).

A new descriptor of molecular structure for use in the derivation of predictive QSAR and QSPR models, electronic eigenvalue (EEVA), is described. This is a modification of the recently proposed EVA approach, but is based on computationally-derived molecular orbital energies instead of vibrational frequencies. Like EVA, it is also invariant as to the alignment of the structures concerned. Its performance has been tested with respect to the Ah receptor binding of PCBs, PCDDs and PCDFs, and its predictive ability has been clearly demonstrated. In particular, it seems to be suitable for 'pure' electronic substituent effects. i.e., for cases in which both hydrophobic and steric factors are of minor importance.

Algorithms↗
PubMed1999

Cataract in traffic.

BACKGROUND: To obtain a driver's licence to drive a private passenger car, the binocular visual acuity required is 0.5 or better, and the minimum horizontal width of the visual field is 120 degrees . Persons who fulfill these requirements can obtain a driver's licence even if they have an eye disease such as cataract. However, contrast sensitivity and visual acuity in glare can be considerably decreased in eyes with cataract, and this may create a risk factor in traffic. METHODS: Examinations of the eyes, visual fields, contrast sensitivity and glare sensitivity (visual acuity in glare and macular photostress test) were performed for 35 cataract patients aged 60 to 87 years (mean 70.1 years+/-6.1 SD). They had cataract in one or both eyes. In spite of the cataract, the visual acuity was > or =0.5 in 50 of the eyes. Twenty-two control eyes of persons within the same age range were similarly tested. RESULTS: The results in the contrast sensitivity test were significantly worse in the cataract eyes than in the control eyes. Contrast sensitivity decreased significantly as the visual acuity became worse. In the glare test, none of the control eyes lost any of the lines in the visual acuity chart. In the cataract eyes, the loss of lines with the highest glare varied from 0 to 6 lines (mean 1.4+/-1.5). The recovery time in the macular photostress test was longer, but not significantly, in cataract eyes than in normal eyes. There was no significant correlation between the loss of visual chart lines and visual acuity or between the recovery time in the macular photostress test and visual acuity. CONCLUSION: It would be advisable for traffic safety if simple tests for contrast and glare sensitivity were added to the requirements for a driver's licence, at least for older drivers. The age and test result limits should be defined.

Aged↗
PubMed1999

Effect of liquid inhibitors on PCDD/F formation. Prediction of particle-phase PCDD/F concentrations using PLS modelling with gas-phase chlorophenol concentrations as independent variables.

Emissions of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) from municipal waste incineration are currently a subject of considerable public concern because of their extreme toxicity. PCDD/F formation in incineration processes is being studied widely, but little work has been done on their inhibition. We studied the effect of two liquid inhibitors, sodium ammonium hydrogen phosphate (NAHF) and urea (H2NCONH2), on PCDD/F formation in the combustion of liquid fuel doped with copper and chlorine using a pilot-scale plant. The inhibitors were injected into the flue gas stream at a temperature of 725 degrees C, whereupon both the chlorophenol and PCDD/F concentrations decreased. Particle-phase PCDD/F concentrations in particular decreased by up to 90% with NAHF and 70% with urea, but gas phase reduction took place only with urea. The results suggest that the formation of PCDD/Fs is hindered in the particle phase at the early stages of the PCDD/F formation chain, probably even before precursors such as chlorophenols have been formed. As a consequence, particle-phase PCDD/F concentrations can be predicted by a PLS (partial least-squares) approach with the gas-phase chlorophenol concentrations as independent variables. The structure and partial charges of Cu(+)-urea complex were calculated by the HF/3-21G basis set.

Benzofurans↗
PubMed1999

Frontier orbital energies, hydrophobicity and steric factors as physical QSAR descriptors of molecular mutagenicity. A review with a case study: MX compounds.

A review on QSARs (Quantitative Structure-Activity Relationships) in modelling molecular mutagenicity is given. The importance of hydrophobicity, frontier orbital (HOMO and LUMO) energies and steric factors as physical descriptors of mutagenicity is emphasized. In addition, some possible connections between QSAR models and the general electrophilic theory of genotoxic activity are discussed. As a detailed example, QSARs for the Ames Salmonella typhimurium TA100 mutagenicity of halogenated hydroxyfuranones including MX, one of the most potent bacterial mutagens ever identified, are discussed and a plausible mechanism for their mutagenic activity is proposed.

Animals↗
PubMed1999

Clinical features of Goldmann-Favre syndrome.

A 21-year-old woman complained of progressive loss of visual acuity. She had also had night blindness since she was ten years old. At the eye examination, the vitreous was found to be degenerated in both eyes. The fundus findings were a large retinoschisis in the right macula, edema resembling retinoschisis in the left macula and annular degenerative changes in the midperiphery. ERG and dark adaption were abnormal. This vitreoretinal degeneration was diagnosed as Goldmann-Favre syndrome.

Adult↗
PubMed1998

Visual function in professional truck drivers.

OBJECTIVES: The purpose of this study was to examine the visual function of professional truck drivers at working age to find out whether older drivers had any defective function and should therefore be given less demanding duties at work. METHODS: Of the 100 drivers invited to the study, 77 came to the examination, including 74 men and 3 women aged from 30 to 66 years (mean 50.3+/-10.3 years). In addition to the basic eye examination, visual fields, dark adaptation, contrast sensitivity, color vision, and glare sensitivity were studied. RESULTS: Two drivers (2.6%) had an incipient cataract in one eye, four (5.2%) had slight fundus abnormalities, five (6.5%) had exo- or esotropia, and five (6.5%) had amblyopia. Visual acuity in the better eye varied from 0.4 to 1.2 (mean 1.06+/-0.17) and in the other eye from 0.1 to 1.2 (mean 0.96+/-0.23). Five drivers (6.5%) had inadequate visual acuity for a professional driver's license. Visual fields were interpreted as normal in all drivers. The results of the dark-adaptation, contrast-sensitivity, and glare testing showed values within normal ranges for all drivers. In the color-vision tests, five male drivers (6.8% of the men) had a slight congenital green defect, and two drivers had an acquired blue defect in one eye because of cataract and diabetes. CONCLUSIONS: According to the present study, there is no need to give older drivers less demanding duties because of their eyes. However, one serious finding in the present study needs attention: the visual acuity was lower than that required for a professional driver's license in five drivers. Evidently, more regular checkups of visual acuity are needed for a professional driver's license.

Adaptation, Ocular↗
PubMed1998

Colour vision in gyrate atrophy.

A follow-up study of colour vision in two patients with gyrate atrophy was performed. Gyrate atrophy was diagnosed in the first patient at the age of 17 years. Her colour vision was first tested at the age of 25 years; at the follow-up examination 7 years later, she correctly interpreted the Standard Pseudoisochromatic Plates part 2, however, with one mistake due to lens opacity. In the Farnsworth-Munsell 100 hue test and in the Color Vision Meter 712 (CVM) anomaloscope, the results were within normal ranges. In the second patient, gyrate atrophy was diagnosed at the age of 4 years. At the ages of 4 and 5 years, he correctly interpreted the Ishihara, AO H-R-R, and Lanthony Tritan Album plates as well as the City University test. At the ages of 6, 7, and 8 years, he correctly interpreted the plate tests, the Farnsworth Panel D 15, and Lanthony's Desaturated Panel. The CVM anomaloscope results were normal.

Adult↗
PubMed1998

Stargardt disease: linkage to the ABCR gene region on 1p21-p22 in Scandinavian families.

UNLABELLED: Stargardt disease (STGD) or fundus flavimaculatus (FFM) is one of the most frequent causes of macular degeneration in childhood. The disease is inherited as an autosomal recessive trait and the corresponding gene has been localized to chromosome 1p21-22 and subsequently identified as the ATP-binding cassette transporter (ABCR) gene. PURPOSE: To characterize Finnish and Swedish STGD families genetically, with special reference to chromosome region 1p21-22. METHODS: We performed genetic linkage and haplotype analyses in five families of Finnish and Swedish origin with members affected by STGD or FFM. RESULTS: Evidence for linkage between STGD and the ABCR gene region on chromosome 1p was found with a maximum cumulative two-point lod score for marker D1S188 (Z=4.04, theta=0.001). The affected individuals of all families, including the offspring of a consanguineous family, were found heterozygous for haplotypes spanning the ABCR gene. CONCLUSION: The results support genetic homogeneity for a STGD/FFM gene defect on chromosome 1p21-22. A variety of haplotypes tightly linked to the ABCR gene region were found among affected individuals which indicate the presence of several independent STGD mutations in the Scandinavian population.

ATP-Binding Cassette Transporters↗
PubMed1997

A plausible mechanism for the mutagenic activity (Salmonella typhimurium TA100) of MX compounds: a formation of CG-CG(+)-CG radical cation by one-electron reduction.

Combining our previous QSAR work with recent high-level quantum mechanical calculations, a plausible mechanism for the mutagenic activity of halogenated furanones (so called MX compounds) in Salmonella typhimurium TA100 tester strain is proposed. The mechanism involves one-electron reduction as a key step and it seems reasonable to suggest that the mutagenicity of these direct-acting compounds may be a purely thermodynamic phenomenon, rather than the result of site-specific binding or adduct formation. Overall, the proposed model is consistent with the most experimental findings.

Amino Acid Sequence↗
PubMed1997

Colour vision through intraocular lens.

Fifty patients aged from 30 to 69 years (mean 54.7 +/- 11.3 years, SD) with a UV-protected monofocal polymethylmethacrylate intraocular lens (IOL) were examined with the Farnsworth-Munsell 100 hue (FM 100) test and the Color Vision Meter 712 anomaloscope. The spectral transmission of the same kind of IOLs as was used surgically was measured with Lambda 2 UV/VIS Spectrometer. In the FM 100 test, there was no significant difference between the results of the IOL eyes and normal eyes. However, the IOL eyes showed better error scores than the normal eyes in the blue-purple box IV in the FM 100 test. In the anomaloscope testing, the Rayleigh (red-green) equation showed no differences between the IOL patients and controls. In the Moreland (blue) equation, however, the mid matching point was significantly shifted towards more green (meaning better blue colour sensitivity) in the IOL eyes than in the control eyes. This is due to the spectral transmission of the IOLs which showed 80-90% transmission already starting at the wavelength of about 420 nm. In comparison, the transmission of the normal human lens reaches those percentages near 500 nm or even further at advanced age.

Adult↗
PubMed1997

Wooden foreign particles in the orbit--spontaneous recovery.

A six-year-old boy consulted an ophthalmologist, because another boy had hit his right eye with a tree branch. There were slight corneal erosions, and a superficial small wound in the oedematous upper lid. The erosions healed in 2 days, but the lid showed progressive ptosis and oedema. Computed tomography revealed a hyperdense, tight structure, which was suspected to be a foreign particle. An orbital exploration was made three times, but the foreign body was not found. After prolonged suppuration, two wooden particles appeared spontaneously 4 and 5.5 months after the trauma. After that, the suppuration subsided and the wound healed.

Blepharoptosis↗
PubMed1997

Contrast sensitivity in patients with silicone intraocular lenses.

Contrast sensitivity in 64 patients aged from 50 to 69 years with an intraocular lens (IOL) was studied. There were 23 eyes with a silicone and 31 eyes with a polymethylmethacrylate (PMMA) IOL. Ten patients had a silicone IOL in one eye and a PMMA IOL in the other. Contrast sensitivity was examined with the Vistech far vision VCTS 6500 test. The contrast sensitivity test results in silicone and PMMA IOL eyes were in all cpd (cycles per degree) lines significantly worse than in normal eyes except in the 60-year-old group in the 18-cpd line. The contrast sensitivity test results were in all cpd lines better in the silicone IOL eyes than in the PMMA IOL eyes, but it reached significantly only in the 3-cpd line. In the 10 patients with the silicone lens in one and the PMMA lens in the other eye, the test results were also better in the silicone IOL eye; it also reached significance only in the 3-cpd line.

Aged↗