Search PubMed⌕ Search

Biomedical subjects

T O Rognum

Publications and source records attributed to T O Rognum.

At least 19 recordsLinked to original sources
PubMed2002

Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis.

Progression of colorectal cancer may follow either of two main genetic routes: the chromosome- or microsatellite-instability pathways. Association between the patients' prognosis and microsatellite instability has been questioned. Improved survival has previously been found in patients with expression of HLA-DR antigens on their tumour cells. In this study, the expression of HLA-DR antigen was investigated by immunohistochemistry in 357 large bowel carcinomas stratified by microsatellite instability status. Sixteen per cent of the tumours showed strong HLA-DR expression and 35% had weak DR expression. We confirmed that patients with strong positive HLA-DR staining had improved survival (P<0.001) compared to patients with no HLA-DR expression. Strong epithelial HLA-DR staining was significantly associated with high level of microsatellite instability (P<0.001). In the subgroup of tumours with characteristics typical of the chromosomal instability phenotype, i.e. in microsatellite-stable tumours, the patients positive for the HLA-DR determinants showed better survival than those without HLA-DR expression. The protective effect of HLA-DR expression on survival was confirmed by multivariate analysis, both in the whole patient group and in the microsatellite-stable/microsatellite instability-low group. This might be explained by enhanced T-cell mediated anti-tumour immune responses against tumour cells in the HLA-DR positive tumours. The finding of better patient survival in the subgroup of strong HLA-DR positive microsatellite-stable tumours may have clinical implications for these patients.

Age Factors↗
PubMed2002

Comparative epidemiology of sudden infant death syndrome and sudden intrauterine unexplained death.

BACKGROUND: Unexplained antepartum stillbirth and sudden infant death syndrome (SIDS) are major contributors to perinatal and infant mortality in the western world. A relation between them has been suggested. As an equivalent of SIDS, only cases validated by post mortem examination are diagnosed as sudden intrauterine unexplained death (SIUD). OBJECTIVE: To test the hypothesis that SIDS and SIUD have common risk factors. METHODS: Registration comprised all stillbirths in Oslo and all infant deaths in Oslo and the neighbouring county, Akershus, Norway during 1986-1995. Seventy six cases of SIUD and 78 of SIDS were found, along with 582 random controls surviving infancy, all singletons. Odds ratios were obtained by multiple logistic regression analysis. RESULTS: Whereas SIUD was associated with high maternal age, overweight/obesity, smoking, and low education, SIDS was associated with low maternal age, smoking, male sex, multiparity, proteinuria during pregnancy, and fundal height exceeding +2 SD. Thus the effects of maternal age were opposite in SIUD and SIDS (adjusted odds ratio 1.39 (95% confidence interval 1.17 to 1.66) per year, p < 0.0005). Heavy smoking, male sex, and a multiparous mother was less likely in SIUD than in SIDS (0.22 (0.06 to 0.83), 0.22 (0.07 to 0.78), and 0.03 (<0.01 to 0.17) respectively). Overweight/obesity and low fundal height were more common in SIUD than in SIDS (7.45 (1.49 to 37.3) and 13.8 (1.56 to 122) respectively). CONCLUSIONS: The differences in risk factors do not support the hypothesis that SIDS and SIUD have similar determinants in maternal or fetal characteristics detectable by basic antenatal care.

Adult↗
PubMed2001

Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study.

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P = 0.004, HR 1.3) and overall survival (P = 0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P = 0.008, HR 1.5; overall survival P = 0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P = 0.46, HR 1.12; overall survival P = 0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer.

Adolescent↗
PubMed2001

[Therapeutic cloning--future medicine or an ethical dead end?].

BACKGROUND: Treatment with stem cells has given promising results in animal experiments and may be relevant in a variety of diseases, including heart disease, cancer, diabetes, Parkinson's disease and Alzheimer's disease. However, the use of pluripotent stem cells grown from blastocysts available after in vitro fertilization or from fetuses raises difficult issues in medical ethics. The same goes for therapeutic cloning. RESULTS: Attitudes to this mode of treatment differ from country to country. In Britain, Parliament has accepted therapeutic cloning (February 2001), while the German Bundestag has banned the procedure. The EU Parliament has recommended European countries not to allow therapeutic cloning, and President George W. Bush takes a more critical stand than did the Clinton administration. DISCUSSION: The debate over embryonal cells and therapeutic cloning involves both scientists and politicians. In Norway, the Biotechnology Advisory Board wants to open up for research on fertilized eggs and for therapeutic cloning. The Storting, Norway's legislature, will have to reach a decision on these issues when the Biotechnology Act come up for revision, probably in 2002. In the debate in Norway, it has been claimed that accepting therapeutic cloning would be a violation of a traditional western norm: Man should always be an end onto himself, never be used as an instrument to other ends. Furthermore, some scientists think that one should use adult stem cells from adults--this also because the procedure seems less risky. Bone marrow transplantation with autologous bone marrow stem cells has been used for 30 years, and recent research has disclosed that such stem cells may be reprogrammed, for instance from bone marrow stem cells to nerve cells.

Adult↗
PubMed2001

[Intracytoplasmic sperm injection--risk of abnormalities].

BACKGROUND: Intracytoplasmic sperm injection (ICSI) is performed in a large number of fertility clinics; since 1991, several thousand children have been conceived by this method. Intracytoplasmic sperm injection is different than traditional in vitro-fertilization (IVF) in that a single spermatozoon is mechanically transferred into a mature oocyte using a glass pipette. Concern has been raised as to whether intracytoplasmic sperm injection damages the chromosomes and/or the spindle apparatus in the oocyte, leading to an increased risk of congenital abnormalities. MATERIAL AND METHODS: We have reviewed the literature on congenital abnormalities in children conceived by intracytoplasmatic sperm injection. RESULTS AND INTERPRETATION: Although the reports are methodologically heterogeneous, most articles conclude that intracytoplasmatic sperm injection does not cause a statistically significant increased risk of congenital abnormalities compared to traditional in vitro fertilization or normally conceived children. However, some studies do report an increased risk. The issue cannot be finally settled until even larger studies on children conceived by intracytoplasmatic sperm injection are published.

Congenital Abnormalities↗
PubMed2001

A strategy combining flow sorting and comparative genomic hybridization for studying genetic aberrations at different stages of colorectal tumorigenesis in ulcerative colitis.

BACKGROUND: DNA aneuploidy has been shown to increase the risk of developing dysplasia in ulcerative colitis (UC) and is related to tumorigenesis in the colorectum. Therefore, it is of particular interest to study genetic aberrations behind DNA aneuploidization during colorectal carcinogenesis. We wanted to elucidate further the relationship between mucosal morphology and DNA aberrations in UC. METHODS: DNA flow cytometry was applied to multiple lesions including regenerative, dysplastic, and carcinomatous mucosa from the colectomy specimen of a male patient with long-standing UC. The lesions harbored multiple DNA aneuploid stemlines that were subjected to flow sorting. We analyzed gene alterations by degenerate oligonucleotide primer (DOP; universal primers) polymerase chain reaction (PCR)-based comparative genomic hybridization (CGH) and fluorescent in situ hybridization (FISH) in diploid and aneuploid sorted cells. RESULTS: DOP-PCR-based CGH shows gains and losses that can be verified by FISH. We show that with this approach one can study genetic evolution of distinct DNA diploid and aberrant subpopulations through defined stages of colorectal tumorigenesis. This includes getting information related to tumor heterogeneity that cannot be obtained by CGH with DNA extracted from nonsorted cell populations. Genetic imbalance was also detected in diploid nondysplastic flow-sorted mucosal cells from the same bowel. CONCLUSIONS: Similar gains and losses were found in aneuploid dysplasias and carcinomas at widely separated locations in the same bowel, indicating a common selection pressure in different areas of the same bowel. The common aberrations may be of importance for progression from dysplasia to carcinoma.

Aged↗
PubMed2001

WNT1 inducible signaling pathway protein 3, WISP-3, a novel target gene in colorectal carcinomas with microsatellite instability.

BACKGROUND & AIMS: Microsatellite instability (MSI) is the phenotype of colorectal carcinomas with defect mismatch repair. Genes with repetitive sequences within their coding regions are targets for mutations in these tumors. We have evaluated 2 novel candidate genes for potential involvement in development of MSI colorectal carcinomas and compared them with alterations in known target genes. METHODS: The MSI status was determined by multiplex polymerase chain reactions (PCRs) of 5-17 markers in a Norwegian series of 275 colorectal carcinomas. All MSI tumors were analyzed for gene mutations using fluorescence PCR followed by capillary electrophoresis. Two novel candidate genes, WNT1-inducible signaling pathway protein 3 (WISP-3) and caspase-1, and 9 known target genes were analyzed. RESULTS: Thirteen percent of the tumors were MSI-high (H) and 12% were MSI-low (L). Thirty-three of 37 MSI-H vs. 1 of 34 MSI-L tumors showed mutations in the target genes (P < 0.001). WISP-3 was mutated in 31% of the MSI-H tumors. The frequencies of frameshift mutations in the known target genes were comparable with other studies. CONCLUSIONS: The relative high frequency of mutation, higher than those seen for other known target genes, the predicted truncation of the protein product, and the homology with WISP-1 and WISP-2, 2 proteins induced downstream of WNT1 signaling, strongly suggest WISP-3 as a novel target in development of MSI-H colorectal carcinomas.

Aged↗
PubMed2001

Changes in the epidemiological pattern of sudden infant death syndrome in southeast Norway, 1984-1998: implications for future prevention and research.

AIM: To look for changes in risk factors for sudden infant death syndrome (SIDS) after decrease and stabilisation of the SIDS rate. METHODS: Questionnaires were distributed to parents of 174 SIDS infants, dying between 1984 and 1998, and 375 age and sex matched controls in southeast Norway. RESULTS: The proportion of infants sleeping prone has decreased, along with the decrease in SIDS rate for the region during the periods studied, but over half of the SIDS victims are still found in the prone position. As the number of SIDS cases has decreased, additional risk factors have become more significant. Thus, after 1993, a significantly increased risk of SIDS is seen when the mother smokes during pregnancy. After 1993, young maternal age carries an increased risk. Maternal smoking and young maternal age are associated with each other. For SIDS victims, an increase in the number of infants found dead while co-sleeping is seen, and the age peak between 2 and 4 months and the winter peak have become less pronounced. CONCLUSION: Changes in risk factor profile following the decrease in SIDS rate in the early 1990s, as well as consistency of other factors, provides further clues to SIDS prevention and to the direction of further studies of death mechanisms.

Adolescent↗
PubMed1999

[Crib death or cot death in the Nordic countries. A forensic pathologist's point of view].

In the 15 years between 1975 and 1989 approximately 5,000 infants succumbed to SIDS in the Nordic countries. Denmark and Norway were most seriously hit, with SIDS rates amounting to 2 and 2.5 per 1,000 live births in 1989. During the 1970's and 1980's especially Denmark and Norway experienced a significant increase in SIDS rates. In 1990 a co-operative study was initiated by Nordic Council of Ministers. Part of the study consisted of forensic pathologists examining SIDS victims. They showed that neither the increase during the 1980's nor the decrease during the 1990's was due to changes in the classification or diagnostic practise. A correlation between prone sleeping position and SIDS rates is now well recognised. However, neither an explanation for the great discrepancy in SIDS rates between the Nordic countries nor a possible explanation for the risk of prone sleeping position has been achieved.

Autopsy↗
PubMed1999

Inflammatory responses in sudden infant death syndrome -- past and present views.

Sudden infant death syndrome (SIDS) is sudden unexpected death in infancy for which there is no explanation based on commonly accepted diagnostic criteria; however, half of the victims have had slight signs of infection prior to death. Such slight infection with fever is an important risk factor in combination with a prone sleeping position, especially in infants between 2 and 4 months of age. The purpose of this review is to summarise findings that support the theory that a significant part of cot deaths may be due to an overreaction to otherwise harmless infections. Such factors are mucosal immune stimulation, cytokines in the cerebrospinal fluid and hypoxanthine levels in vitreous humour. The review aims at explaining why we believe that a slight infection combined with a prone position, a warm environment and a vulnerable age period may trigger a vicious circle leading to death.

Cytokines↗
PubMed1999

The complement component C4 in sudden infant death.

UNLABELLED: The aim of the present study was to compare partial deletions of the complement C4 gene in victims of totally unexplained sudden infant death (SID) (n = 89) and borderline SID (n = 15) with and without slight infections prior to death, in cases of infectious death (n = 19), and in living infants with and without infections (n = 84). The SID and borderline SID groups were pooled. In this total SID group slight infections prior to death was associated with deletion of either the C4A or the C4B gene (P = 0.033), and the SID victims with such infections had a higher deletion frequency than the controls (P = 0.039). There were no differences between the living infants with and without upper airway infections. CONCLUSION: The present study confirms that partial deletions of the C4 gene in combination with slight upper airway infections may be a risk factor in sudden infant death.

Child, Preschool↗
PubMed1999

Germline and somatic mutations in exon 15 of the APC gene and K-ras mutations in duodenal adenomas in patients with familial adenomatous polyposis.

BACKGROUND: In sporadic colorectal adenomas mutations in the adenomatous polyposis gene (APC) are among the first gene aberrations to appear. In familial adenomatous polyposis (FAP) the patients already have a germline mutation in the APC gene. To investigate the natural history of duodenal adenomas in FAP patients, we examined germline and somatic mutations of the APC gene and K-ras mutations in these lesions. METHODS: Frozen sections from 54 duodenal polyps from 31 FAP patients were used to histologically verify the presence of adenomatous growth in the mucosa; the rest of each biopsy specimen was processed for DNA extraction. APC exon 15 was investigated with the protein truncation test (PTT), using four overlapping polymerase chain reaction (PCR) fragments, and samples showing an APC mutation were thereafter sequenced. The adenomas were examined for K-ras mutations by use of a combination of the 'enriched PCR method' and temporal temperature gradient electrophoresis. RESULTS: APC germline mutations in exon 15 were found in 19 of 31 (61%) patients, whereas somatic mutations were localized to 12 of 54 (22%) duodenal adenomas. In seven adenomas both the germline and the somatic mutations were found, whereas five small adenomas showed somatic mutations only. There was no tendency for more mutations to be detected in large and severely dysplastic adenomas compared with small and mildly dysplastic ones. K-ras mutations were found in four (7%) duodenal adenomas. CONCLUSIONS: The low rate of somatic APC and K-ras mutations in duodenal adenomas may indicate another neoplastic pathway than in FAP adenomas of the large bowel, or that a modifier gene is cosegregating with the disease.

Adenoma↗
PubMed1999

Mitochondrial DNA point mutations detected in four cases of sudden infant death syndrome.

The aim of this study was to investigate the tRNA(Leu(UUR)) gene and the first part of the ND1 gene in mitochondrial DNA (mtDNA) in cases of sudden infant death syndrome (SIDS). A total of 158 cases of SIDS and 97 controls were included in the study, and the base pairs in the range 3230-3330 were investigated using polymerase chain reaction (PCR) and temporal temperature gradient electrophoresis (TTGE). If a band shift was detected by TTGE, the area investigated and the D-loop was sequenced. Three different point mutations (T3290C, T3308C and T3308G) were detected in four of the SIDS cases, while none of the controls were mutated. We also found a high D-loop substitution rate in these four cases. The findings indicate that mtDNA mutations may play a role in some cases of SIDS.

DNA, Mitochondrial↗
PubMed1999

Villous, hypermucinous mucosa in long standing ulcerative colitis shows high frequency of K-ras mutations.

BACKGROUND: K-ras mutation is one of the first genetic alterations in classical colorectal carcinogenesis. AIMS: To investigate the role of K-ras mutations in carcinogenesis, in long standing ulcerative colitis. METHODS: A total of 161 microdissected and 100 DNA samples from 13 patients were analysed for K-ras codons 12 and 13 mutations by means of a combination of enriched polymerase chain reaction amplification and temporal temperature gradient electrophoresis. RESULTS: K-ras mutations were found in 21/161 (13%) microdissected samples in 7/13 large bowels (16 and five in codons 12 and 13, respectively), and in 10/100 (10%) mucosal DNA samples (six and four, respectively). One of four patients with six adenocarcinomas had a K-ras mutation in a carcinoma, as well as one of two patients with large dysplasia associated lesion or mass (DALM). Eight of 13 (61%) areas with villous architecture and large, distended goblet cells, had a K-ras mutation, which was significantly more frequent than in low grade dysplasia (one of 23, 4%) but did not reach significance versus high grade dysplasia (four of 14, 28.5%). K-ras mutations were found in one of 20 (5%) flat lesions indefinite for dysplasia, two of 14 (14%) in non-villous, hypermucinous mucosa, and in one of 57 flat areas negative for dysplasia. CONCLUSION: The highest K-ras mutation frequency was found in villous, hypermucinous mucosa. We suggest that this entity should be investigated further as a potential risk lesion for cancer development. It may represent a pathway directly from non-classical dysplasia to cancer, not previously described.

Adenocarcinoma↗
PubMed1999

IL-6 cerebrospinal fluid levels are related to laryngeal IgA and epithelial HLA-DR response in sudden infant death syndrome.

The objective was to investigate whether there is any correlation between signs of central and peripheral immune stimulation in victims of sudden infant death syndrome (SIDS), the former expressed by IL-6 in cerebrospinal fluid (CSF), the latter by IgA, IgG, and IgM immunocytes, T lymphocytes, and HLA-DR expression in laryngeal mucosa. Seventeen SIDS cases with low CSF IL-6 levels (< or =5 pg/mL) and 20 cases with high CSF IL-6 levels (> or =30 pg/mL) were subjected to immunohistochemical quantitation of IgA, IgG, and IgM immunocytes; semiquantitative scoring of T lymphocytes in the mucosa of epiglottis and larynx, and semiquantitative evaluation of HLA-DR expression. SIDS cases with IL-6 levels > or =30 pg/mL had a significantly higher number of IgA immunocytes in laryngeal mucosa (p = 0.007) and in epiglottis (p = 0.03) than cases with IL-6 levels < or =5 pg/mL. Furthermore, laryngeal HLA-DR expression was significantly more extensive in SIDS cases with IL-6 levels > or =30 pg/mL than in those with levels < or =5 pg/mL (p = 0.05). No differences were found for IgG and IgM immunocytes or for T cells. In addition, babies found prone more often had symptoms of slight infection before death and had a higher number of IgA immunocytes in the larynx (p = 0.02) than babies sleeping on their side or back. Because IL-6 levels > or =30 pg/mL correspond to the levels found in infants who die from infectious diseases such as meningitis/septicemia and pneumonia, the findings favor the hypothesis that many SIDS cases may be caused by an "overreaction" of the immune system to an otherwise harmless infection.

Epithelium↗
PubMed1998

The APC gene I1307K variant is rare in Norwegian patients with familial and sporadic colorectal or breast cancer.

Recently, a T-to-A transversion creating an 8-base mononucleotide tract in the APC gene, resulting in substitution of lysine for isoleucine at codon 1307 (I1307K), was found in a subset of Ashkenazi Jews. This sequence variant was most frequent in colorectal cancer patients with a positive family history of colorectal cancer. To determine whether the I1307K variant plays a role in colorectal or breast cancer predisposition in the Norwegian population, we have analyzed blood samples from 210 colorectal cancer patients and 183 breast cancer patients by PCR and direct sequencing. Thirty-seven of the colorectal cancer patients had a positive family history of cancer. Among the breast cancer patients, 24 had a family history of colorectal cancer and 75 a family history of breast and/or ovarian cancer. Only one colorectal cancer patient who belonged to a Jewish family was found to carry the A variant. Our data show that the I1307K variant is rare in the Norwegian population and should not be viewed as a candidate for susceptibility testing for colorectal cancer.

Alleles↗
PubMed1998

SIDS--changes in the epidemiological pattern in eastern Norway 1984-1996.

The objective was to analyse differences in the epidemiological pattern of sudden death in infancy during two time periods--the Sudden Infant Death Syndrome (SIDS) 'epidemic': 1984-1989, and the period of rapid decline in the SIDS rate 1990-1996. Sex distribution, age, sleeping position, signs of infection, day of the week and place of death were registered and compared for the two time periods studied in all SIDS cases autopsied at the Institute of Forensic Medicine, Oslo. There were significantly more deaths in the age group under four months in the period 1984-89 than in the second period. Prone sleeping position, signs of infection, death outdoors and during the winter were more frequent during the first period than in the second. These features also were more frequent in the age group under four months than in the older babies during the first period. The shift in the epidemiological pattern after 1990, when the risk factor campaign was launched, indicates that prone sleeping position, cold climate, sleeping outdoors and infections seem to be risk factors that are particularly harmful to the youngest infants.

Humans↗