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Biomedical subjects

A Kiuru

Publications and source records attributed to A Kiuru.

At least 19 recordsLinked to original sources
PubMed2001

Substance P endopeptidase-like activity is altered in various regions of the rat central nervous system during morphine tolerance and withdrawal.

In this study the level of a substance P endopeptidase (SPE)-like activity was measured in different regions of the rat central nervous system (CNS) after chronic administration of morphine. Male rats (200-220 g) were randomly divided into four groups. Two groups were injected (s.c.) with morphine (10 mg/kg) twice daily, whereas the other two received saline under identical conditions. After 8 days, when animals were completely tolerant to morphine, one of the morphine-treated groups and one group of saline-injected rats were given naloxone (s.c. 2 mg/kg). Withdrawal signs were observed and recorded. The enzyme activity was measured in extracts of the various CNS tissues by following the conversion of synthetic substance P (SP) to its N-terminal fragment SP(1-7) using a radioimmunoassay detecting this product. In discrete CNS areas including periaqueductal grey, spinal cord, substantia nigra and ventral tegmental area (VTA) a significant increase in enzyme activity was observed in the withdrawal group, while tolerant rats exhibited decreased SPE-like activity in the striatum (see Table 1). The enhanced enzyme activity during withdrawal is in agreement with our previous observation that the levels of SP(1-7) in rat brain are affected following naloxone precipitated withdrawal. In some tissues, including VTA, a correlation between the SPE-like activity and the intensity of the opioid abstinence was observed. Our result suggests that the elevated SPE-like activity is responsible for enhanced release of SP(1-7) in rats during morphine withdrawal, affirming a modulatory or regulative role of this enzyme in this state of opioid dependence.

Animals↗
PubMed2001

Effectiveness of radiological image data compression.

This study was designed to evaluate effectiveness of radiological image data compression in terms of image quality and archiving material costs using DLT tapes, and to assess the relationship between loss of quality and cost savings. Six radiologists used Subjective Fidelity Criteria (SFC) in random fashion to evaluate the quality of 105 digitally acquired radiological images. In addition, 5 radiologists and 2 nonradiologists evaluated at random three phantom images exposed in conditions mimicking chest, bone, and colon examinations, displayed in five modes (a total of 15 images). Both patient images and phantom images were submitted to 3:1 (Ziv-Lempel method) and 10:1 compression (wavelet-based compression method). Cost information on material cost savings and the effect of compression on tape space requirements were compared. The results indicate that image quality was not degraded using either of the compression ratios. The interobserver proportion of agreement exceeded overwhelmingly the limit of a good proportion of agreement regarding each compression ratio and each image type. The divergence in the rest of the assessments was not consistent. The adoption of 10:1 compression would not bring a substantial decrease of archiving costs as compared to the total yearly operating costs, and especially as considering the consequences of possible image quality deterioration.

Chi-Square Distribution↗
PubMed2001

Comparison between direct ion storage and thermoluminescence dosimetry individual monitoring systems, and Internet reporting.

A new electronic direct ion storage (DIS) dosemeter allows accumulated personal dose equivalent Hp(d) at depths of 10 mm and 0.07 mm to be monitored in a few seconds by inserting the dosemeter into a local reader without deleting the accumulated dose. The DIS system meets general requirements on individual monitoring of hospital personnel using ionising radiation. It differs greatly from off-line thermoluminescence dosimetry systems and offers many additional benefits. The non-volatile reading takes only 5 s, is taken as often as needed, and the data are collected into a dose database, where background radiation is subtracted. Individual personnel doses are reported in Intranet as well as on the Internet at regular intervals to the National Regulatory Authorities.

Air Pollutants, Radioactive↗
PubMed2000

N-Hydroxyguanidine compound 1-(3,4-dimethoxy- 2-chlorobenzylideneamino)-3-hydroxyguanidine inhibits the xanthine oxidase mediated generation of superoxide radical.

We here show that the novel N-hydroxyguanidine derivative PR5 (1-(3, 4-dimethoxy-2-chlorobenzylideneamino)-3-hydroxyguanidine) is acting as an alternative electron acceptor in xanthine oxidase catalyzed oxidation of xanthine. The reduction product is the corresponding guanidine derivative 1-(3, 4-dimethoxy-2-chlorobenzylideneamino)guanidine (PR9). The reaction occurs under both anaerobic and aerobic conditions. Moreover, EPR measurements show that the action of PR5 is associated with the inhibition of superoxide radical formation seen under aerobic conditions. PR5 also supports xanthine oxidase catalyzed anaerobic oxidation of NADH. Kinetic studies indicate that increasing xanthine concentration significantly increases the apparent K(m) of PR5, but it remains unaltered by changing NADH concentration. Moreover, the molybdenum center inhibitor allopurinol inhibits the PR5-sustained oxidation of xanthine and NADH equally well, whereas the flavin adenine dinucleotide site inhibitor diphenyliodonium (DPI) markedly inhibits only the PR5-sustained oxidation of NADH. We suggest that PR5 binds and becomes reduced at the molybdenum center of the xanthine oxidase. We also found that both PR5 and its reduction product PR9 can inhibit the oxygen-sustained xanthine oxidase reaction. The properties of PR5 suggest that it is a member of a novel class of compounds which we have termed xanthine oxidase electron acceptor-inhibitor drugs. The potential use of xanthine oxidase electron acceptor-inhibitors in the prevention of free radical mediated tissue damage in organ ischemia-reperfusion diseases is discussed.

Allopurinol↗
PubMed2000

Effects of the androgenic anabolic steroid, nandrolone decanoate, on adrenocorticotropin hormone, corticosterone and proopiomelanocortin, corticotropin releasing factor (CRF) and CRF receptor1 mRNA levels in the hypothalamus, pituitary and amygdala of the rat.

There is increasing abuse of androgenic anabolic steroids (AAS) by non-athletes. AAS abuse has been associated with psychiatric symptoms such as mania, major depression and aggression and the development of dependence. Little is known about the effects of AAS on hypothalamic-pituitary-adrenal axis function or corticotropin releasing factor, which may be involved in mediating some of the psychiatric symptoms associated with AAS abuse. Male Sprague-Dawley rats received one daily intra-muscular injection of the AAS nandrolone decanoate (ND, 15 mg/kg) or vehicle for 3 days. Animals were sacrificed either 1 h or 24 h after the last injection, brain regions dissected and trunk blood collected. Corticotropin releasing factor (CRF), CRF receptor1 (CRF-R1) and proopiomelanocortin (POMC) mRNAs were measured with solution hybridization/RNase protection. Circulating levels of corticosterone and adrenocorticotropin hormone (ACTH) were determined using radioimmunoassays. One hour following the last injection, ND significantly increased circulating levels of both corticosterone and ACTH levels. In the amygdala, CRF mRNA levels were unchanged 1 h after the last injection of ND but were significantly reduced at 24 h. The same was found for hypothalamic POMC. No significant AAS effects were observed on: hypothalamic CRF mRNA; POMC mRNA in the amygdala or CRF R1 mRNA in the anterior pituitary.

Adrenocorticotropic Hormone↗
PubMed2000

Localization of radiation-induced chromosomal breakpoints along human chromosome 1 using a combination of G-banding and FISH.

PURPOSE: To determine the exact location of radiation-induced chromosomal breakpoints along the euchromatic or heterochromatic regions: G-light and G-dark bands, respectively. MATERIALS AND METHODS: The distribution of radiation-induced chromosomal breakpoints was scored in human lymphocytes irradiated in vitro with 3 Gy of gamma-radiation. Image analysis was applied to combine G-banded and FISH-painted images of the human chromosome 1. RESULTS: A total of 195 chromosomal breakpoints in 176 cells with structural chromosomal aberrations was used for the present analysis. Radiation-induced breakpoints were found to be distributed randomly with respect to the p or q arms of chromosome 1 and specific band or band length, but more breakpoints were mapped to G-light than to G-dark bands, the difference being statistically significant. CONCLUSIONS: The results can well be interpreted in terms of concepts of existing models of nuclear architecture, chromatin structure and transcriptional activities of the chromatin, which can influence the induction of primary chromosomal aberrations by gamma-rays. Differential repair of randomly produced primary aberrations may also explain the non-random distribution of radiation-induced breakpoints.

Chromosome Aberrations↗
PubMed2000

p53 and K-ras gene mutations in carcinoma of the rectum among Finnish women.

AIMS/BACKGROUND: The aim of this study was to identify p53 and K-ras gene mutations in carcinoma of the rectum among Finnish women. Mutation patterns might give clues to aetiological factors when comparisons are made with other human tumours. METHODS: Of 134 women with carcinoma of the rectum, paraffin wax embedded specimens of the tumour tissue were obtained from 118 patients. Genomic DNA was extracted, and exons 4-8 of the p53 gene and codons 12/13 and 61 of the K-ras gene were amplified, and analysed for mutations by single strand conformation polymorphism and direct sequencing. The production of p53 and K-ras proteins was studied by immunohistochemistry. RESULTS: The overall crude frequency for mutations in the p53 gene was 35% but the true frequency appears to be higher (up to 56%). In the K-ras gene, the mutation frequency (15%) was significantly lower than that reported for colon cancer. In the p53 gene, the mutation frequency increased significantly with patient age. In a high proportion of patients (14%) the rectal tumours contained small subclones of tumour cells that displayed extremely rare mutations at codons 110 and 232 of the p53 gene. Hot spot codon 175 mutations were significantly less common in rectal cancer than in cancer of the colon. CONCLUSIONS: Rectal cancer among Finnish women has characteristics in the mutations of the p53 and K-ras genes that are uncommon in other human tumours, including cancer of the colon. A biological explanation of these findings is not clear at present, but might be associated with an unidentified genetic factor in Finland.

Age Factors↗
PubMed1998

Sublethal damage repair capacity in carcinoma cell lines with p53 mutations.

BACKGROUND: The previous findings that sublethal damage repair (SLDR) capacity varies between carcinoma cell lines and that the inherent radiosensitivity of these lines tends to be higher in connection with p53 mutations lead us to study the possible role of p53 gene in the regulation of SLDR. The activation of p53 gene by irradiation is known to cause changes in cell cycle progression. Thus, p53 status probably has effects on cellular radiosensitivity, theoretically through modulating repair processes. METHODS: The SDLR capacity of 17 head and neck carcinoma cell lines was determined in split-dose experiments using a 96-well plate clonogenic assay. The SLDR capacity as well as the inherent radiosensitivity were compared with the p53 status of the cells. RESULTS: The SLDR capacity varied markedly also between cell lines of similar radiosensitivity, but there was a tendency of the more sensitive cells to be more SLDR proficient .(r = -.69; p = .0016). The (beta-values obtained from linear quadratic equation correlated well with the observed amount of SLDR (r = .73; p = .0006). With one exception, those cell lines having p53 mutations showed higher SLDR than those with no mutations (p = .0017). In many of these cell lines, the mutations caused either total loss of the p53 protein or major, probably functional changes in it. The cell line UT-SCC-16A, showing no SLDR in the experiments, had two mutation points in different alleles, perhaps having less effect on the protein function. CONCLUSION: This extended material confirmed the previous result that the SLDR capacity tends to increase with increasing radiosensitivity in carcinoma cell lines. A clear correlation between p53 mutations and SLDR capacity was found. The SLDR depended, however, on loss of normal p53 function, which implies that the p53-mediated G1 arrest is not as important in this repair process, as would have been expected.

Carcinoma↗
PubMed1997

p53 mutations in human head and neck cancer cell lines.

The p53 tumour suppressor gene is commonly mutated in human cancers. We performed a molecular analysis of the frequency and spectrum of p53 gene mutations in 40 cell lines (23 from oral cavity tumours and 17 from larynx tumours) derived from 33 patients with squamous cell carcinoma of the head and neck (SCCHN). Using PCR, SSCP, and sequence analysis, we detected the mutated p53 gene in 26 patients (79%); in 23 patients (70%) the wild-type allele of the p53 gene was deleted. Four patients had 2 p53 gene mutations each, and thus the total number of p53 mutations observed was 30. Seven patients had 2 cell lines each, established from the primary and recurrent/metastatic tumour, and the status of the p53 gene (mutant or normal) was identical in both cell lines. Forty percent of the mutations were transitions, 33% transversions, and 27% deletions, insertions and other more complicated changes. In oral cavity tumours the predominant mutation type was G:C-->A:T transition at a CpG site (50% of mutations), and in larynx tumours the predominant type was G:C-->T:A transversion (50% of mutations). These suggest endogenous and exogenous factors in tumour etiology. The G:C-->T:A transversions in larynx tumours are probably associated with mutagenic components in the cigarette smoke, but the causative factor in G:C-->A:T transitions (apparent oxidative damage) remains to be identified.

Carcinoma, Squamous Cell↗
PubMed1997

The bcl-2 gene status of human head and neck cancer cell lines.

The bcl-2 oncogene was originally found in the translocation in a pre-B cell acute lymphocytic leukemia cell line. Since then a high expression of Bcl-2 has been found in many types of cancer. The bcl-2 gene encodes an intracellular membrane-associated protein. Overexpression of bcl-2 inhibits apoptosis induced by many drugs and radiation. In this study the bcl-2 gene status of 9 human head and neck squamous cell carcinoma cell lines was studied. Mutations of the bcl-2 gene were studied at mRNA and DNA levels. The presence and abundance of the Bcl-2 protein in cells were also investigated. In earlier studies the p53 tumour suppressor gene was screened for point mutations, and the radiosensitivity of these cell lines was measured. We were able to amplify bcl-2 cDNA from 5 of the 9 cell lines, which shows that bcl-2 was expressed in these cells. No point mutations were found in the bcl-2 gene in any of these cell lines. Loss of heterozygosity was observed in 2 cell lines at the bcl-2 locus, and these cell lines had no detectable levels of bcl-2 mRNA or Bcl-2 protein. The Bcl-2 protein was abundant in the cell lines with the wild-type p53 gene, and these cell lines were radioresistant. The Bcl-2 protein was also found in many other cell lines in mitotic cells. It seems that cells expressing bcl-2 are radioresistant, and even functional p53 cannot induce apoptosis in these cells.

Apoptosis↗
PubMed1996

p53 mutations associated with increased sensitivity to ionizing radiation in human head and neck cancer cell lines.

The p53 tumour suppressor gene is activated following cellular exposure to DNA-damaging agents. The functions of wild-type p53 protein include transient blocking of cell cycle progression, direct or indirect stimulation of DNA repair machinery and triggering of apoptosis if DNA repair fails. Therefore, the status of p53 protein may be critically associated with tumour cell radiosensitivity. In the present study we examine the intrinsic radiosensitivity of 20 human carcinoma cell lines derived from 15 patients with different types of head and neck tumour. Radiosensitivities were measured in a 96-well plate clonogenic assay in terms of the mean inactivation dose, surviving fraction at 2 Gy, and constants alpha and beta in the linear quadratic survival curve. The p53 allele status was determined by amplifying exons 4-10 by the polymerase chain reaction (PCR), screening for mutations using single-strand conformation polymorphism (SSCP) analysis and determining the exact type and location of a mutation by direct sequencing. The results showed that prevalence of p53 mutations in squamous cell carcinoma (SCC) cell lines is high (80%), and that deletion of one or both wild-type alleles is common (75%). Intrinsic radiosensitivity of the cell lines varied greatly in terms of mean inactivation dose, from 1.4 +/- 0.1 to 2.6 +/- 0.2 Gy. Radiosensitivity correlated well with the p53 allele status so that cell lines carrying a wild-type p53 allele were significantly (P < 0.01) more radioresistant (mean inactivation dose 2.23 +/- 0.15 Gy) than cell lines which lacked a wild-type gene (1.82 +/- 0.24 Gy). Evaluation of our own results and those published in the literature lead us to conclude that absence of the wild-type p53 allele in human head and neck cancer cell lines is associated with increased radiosensitivity. However, the sensitivity is also strongly dependent on the exact type and location of the p53 mutation.

Adult↗
PubMed1996

Increased radiosensitivity is associated with p53 mutations in cell lines derived from oral cavity carcinoma.

The curability of oral cavity carcinomas, as well as of other head and neck cancers, varies remarkably especially in more advanced disease. Radiotherapy and surgery, including large operations, are currently combined, but as new radiotherapy regimens are being introduced, the need for predictive assays has increased in order to plan a suitable individual treatment for the patient. Variations in intrinsic radiation sensitivity of cancer cells cannot alone explain differences in therapy outcome, and thus additional predictive variables have to be searched. Mutations in the p53 tumor suppressor gene are found in most head and neck tumors, which has led us to study the possible association between these mutations and radiation sensitivity. We analyzed 16 cell lines from oral cavity carcinomas and found a remarkable variation in radiosensitivity (AUC 1.7-2.3 Gy and SF2 0.31-0.51). The p53 gene was mutated in 11/16 cell lines, and these cells were also significantly more sensitive than those with wildtype p53 (AUC 1.9 +/- 0.2 Gy and 2.3 +/- 0.2 Gy, respectively, p = 0.023). Structural alterations in the p53 gene were also observed in three of the relatively resistant cell lines, which indicates that not all mutations are critical in this respect.

Carcinoma, Squamous Cell↗
PubMed1994

Standardization of medical imaging in Europe: an integrated initiative.

The successful implementation of PACS (or IMACS) depends on the integration of image and image related data handling systems in an overall hospital information system (HIS) and other departmental information systems (DIS), one of which is radiology information system (RIS). With respect to standardization in the medical imaging field, this integration cannot be looked at separately from the overall prospect of standardization in medical informatics. All relevant standardization work done outside health care should be taken into account. This paper gives an overview of the work within Technical Committee TC 251 'Medical Informatics', of the European Standardization Committee, CEN, with special focus on its Working Group 4 'Medical Imaging and Multimedia'. An indication of the overall framework and relations towards ongoing work is given, with emphasis on short-term targets. The standards to be proposed are collectively called MEDICOM, standing for medical image communication.

Computer Communication Networks↗
PubMed1992

Diagnosis of Duchenne and Becker muscular dystrophies by polymerase chain reaction. A multicenter study.

OBJECTIVE--To assess the efficiency, reliability, and ease of use of DNA diagnosis for Duchenne and Becker muscular dystrophies (DMD/BMD) using the polymerase chain reaction (PCR). DESIGN--DNA from the patients was screened for deletion mutations using multiplex PCR, and the results were compared with those obtained by Southern blot analysis. The PCR multiplex reaction detects nine specific "hot-spot" exons in the dystrophin gene while the Southern analysis detects 66 specific dystrophin gene restriction fragments. The multiplex reaction requires 50-fold less DNA than Southern analysis and thus is considerably more sensitive. SETTING--Fourteen university-affiliated and private genetic disease diagnostic laboratories. PATIENTS--Male patients with clinical signs of DMD/BMD. Cases were selected for analysis randomly, without knowledge of whether a deletion was present within the dystrophin gene. MAIN OUTCOME MEASURES--The percentage of cases that were detectable by multiplex PCR in comparison with Southern analysis, the frequency, extent, and location of the detected deletion mutations. In some cases, duplication mutations were monitored. RESULTS--The accuracy of a single PCR multiplex amplification (nine exons) was compared with Southern analysis with 10 cDNA probes that cover the full length of the gene. The multiplex PCR analytic method detected 82% of those deletions detected by Southern analysis methods. In one of 745 analyses, the multiplex method suggested a single exon deletion, which was not confirmed by Southern analysis, representing a false-positive rate of 0.013%. CONCLUSIONS--Multiplex PCR represents a sensitive and accurate method for deletion detection of 46% of all cases of DMD/BMD. The method requires 1 day for analysis, is easy to perform, and does not use radioactive tracers. As such, multiplex PCR represents an efficient and rapid method for prenatal or postnatal diagnosis of DMD/BMD.

Blotting, Southern↗
PubMed1992

User requirements and standards for PACS. 2nd Japan-Nordic PACS Symposium.

PACS has been regarded as a system which will bring a new era to image handling, radiology departments and its services to other departments of the hospital. However, many recently held international conferences indicate that a worldwide consensus on 'what is PACS, why is PACS needed and who is PACS for' has not been established. Although the actual PACS implementation will vary among the countries and according to each situation, a worldwide consensus of PACS should be possible. This would help those involved to speed up the implementation of PACS. It is suggested that this consensus needs to be developed by convergence of three points of view; the availability, maturity and cost of the technologies on which PACS is built, the user requirements for PACS and standardization in PACS. These themes were the topics of the 2nd Japan-Nordic PACS Symposium which was arranged in Tampere, Finland, June 9-11th 1991. A summary of the papers and discussions of the symposium is produced in this paper.

Cost-Benefit Analysis↗
PubMed1992

Information compression in dynamic radiological studies.

The large volumes of digital image data from radiological examinations demand further research and practical solutions in image compression before PACS solutions in large radiological departments are plausible. But another type of compression of image information is also possible, which has, in fact, been somewhat utilized already in analog form, but which has far better possibilities in the digital world. The number of essential images in dynamic X-ray, nuclear medicine, examinations etc. can be greatly reduced. These examinations producing image series are reviewed in terms of compression of information. 3-D displays are very useful in slice imaging, because they provide a means to see easier inside the human body than a number of slice images side by side. We also provide a new method, dynamic pulmonary imaging with digital fluoroscopy, as an example of the digital possibilities to compress a number of images into parametric images, numbers, histograms and curves. These processes also have other positive consequences information is transformed into a more easily perceptible form.

Diagnostic Imaging↗
PubMed1991

Dynamic imaging of pulmonary ventilation. Description of a novel digital fluoroscopic system.

A new fluoroscopic imaging device consisting of an AT-microcomputer and a digital image memory unit has been used in experimental and clinical ventilation studies during a 2-year period. Digital images with 256 shades of gray were collected during one to 3 ventilation cycles at the rate of 6 to 25 images/s and stored on an optical laser disc. Both subtracted time interval difference (TID-) images and images relative, for example, to the mean image of the cycle (REL-images) were produced. The series of images could also be evaluated dynamically using animation sequences or analyzed using region of interest calculations. The method gave dynamic information with adequate spatial resolution and was easy to use in clinical practice. The radiation dose was kept low due to the high kilovoltage and heavy beam filtration technique. In experimental studies the software enabled flexible measurements of physiological pulmonary parameters.

Animals↗