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Biomedical subjects

J Gudmundsson

Publications and source records attributed to J Gudmundsson.

At least 19 recordsLinked to original sources

Symbiotic and saprophytic survival of three unmarked Rhizobium leguminosarum biovar trifolii strains introduced into the field.

The symbiotic and saprophytic persistence of three unmarked Rhizobium leguminosarum biovar trifolii (Rlt) strains introduced into a field site in Iceland were followed. This site was free of clover cultivation and initially devoid of clover-nodulating rhizobia as tested by nodulation studies. Nodule occupancy by strains was identified based on their distinct ERIC-polymerase chain reaction (PCR) DNA fingerprint patterns. The survival and persistence of the individual strains in soil were monitored by the quantitative real-time PCR (qRT-PCR) assay, targeting the host-specific nodE gene. The most dominant strain in the nodule population, Rlt 20-15, showed relatively less saprophytic survival ability and maintained high numbers only in the presence of the appropriate host plant. Conversely, the minor nodule occupant, Rlt 32-28, persisted in soil at a relatively higher abundance both in the presence of its host legumes and in the presence of a non-host grass. The qRT-PCR assay was successfully applied to quantify rhizobial strains directly in soil without culturing or nodulation. However, the assay demonstrated less sensitivity compared with the plant infection most-probable-number (MPN) method for estimating the population size of rhizobia in soil. The quantitative detection limit of our qRT-PCR assays was 1 x 10(3) cells per gram of soil, as opposed to the MPN test which has a detection limit of 10 cells per gram of soil.

Acyltransferases↗

Respiration as the main determinant of carbon balance in European forests.

Carbon exchange between the terrestrial biosphere and the atmosphere is one of the key processes that need to be assessed in the context of the Kyoto Protocol. Several studies suggest that the terrestrial biosphere is gaining carbon, but these estimates are obtained primarily by indirect methods, and the factors that control terrestrial carbon exchange, its magnitude and primary locations, are under debate. Here we present data of net ecosystem carbon exchange, collected between 1996 and 1998 from 15 European forests, which confirm that many European forest ecosystems act as carbon sinks. The annual carbon balances range from an uptake of 6.6 tonnes of carbon per hectare per year to a release of nearly 1 t C ha(-1) yr(-1), with a large variability between forests. The data show a significant increase of carbon uptake with decreasing latitude, whereas the gross primary production seems to be largely independent of latitude. Our observations indicate that, in general, ecosystem respiration determines net ecosystem carbon exchange. Also, for an accurate assessment of the carbon balance in a particular forest ecosystem, remote sensing of the normalized difference vegetation index or estimates based on forest inventories may not be sufficient.

Atmosphere↗

European multicenter study on LOH of APOC3 at 11q23 in 766 breast cancer patients: relation to clinical variables. Breast Cancer Somatic Genetics Consortium.

High frequencies of loss of heterozygosity (LOH) in chromosome 11q22-qter have been observed in various malignancies, including breast cancer. Previous studies on breast carcinomas by Winqvist et al (Cancer Res 55: 2660-2664) have indicated that a survival factor gene is located in band 11q23, and that the highly informative microsatellite polymorphism at the APOC3 locus would be a suitable tool to perform more extensive LOH studies. In this European multicentre study, we have examined the occurrence of APOC3 LOH and evaluated the effect of LOH of this chromosomal subregion on the clinical behaviour of the disease in a cohort of 766 breast cancer patients in more detail. LOH for APOC3 was found in 42% of the studied tumours, but it was not found to be significantly associated with any of the studied clinical variables, including cancer-specific survival time or survival time after recurrent/metastatic disease. According to the present findings, the putative survival factor gene on 11q23 is not located close enough to the APOC3 gene, but apparently at a more proximal location.

Adult↗

High incidence of loss of heterozygosity in breast tumors from carriers of the BRCA2 999del5 mutation.

Germ-line mutation in the BRCA2 gene confers an increased risk of breast cancer. An elevation of additional genetic defects in tumors of patients with germ-line mutation in the BRCA2 gene compared with sporadic breast tumors has been reported. To evaluate the nature of the difference, we did detailed mapping of chromosomes 1p, 3p, 6q, 11, 13q, 16q, 17, and 20q, using microsatellite markers. We found that the frequency of loss of heterozygosity was similar at some chromosomal regions in the BRCA2 999del5 and sporadic tumors but significantly different at others. These others include chromosomal arms 3p, 6q, 11p, 11q, 13q, and 17p. Loss of heterozygosity mapping suggests that the same chromosome regions are involved in both tumor groups but at elevated frequencies in BRCA2 999del5 tumors. This higher frequency of genetic aberrations could pinpoint genes that selectively promote tumor progression in individuals predisposed to breast cancer due to the BRCA2 999del5 germ-line mutation. Accumulation of somatic genetic changes during tumor progression may follow a specific and more aggressive pathway of chromosome damage in these individuals.

BRCA2 Protein↗

Mapping loss of heterozygosity at chromosome 13q: loss at 13q12-q13 is associated with breast tumour progression and poor prognosis.

Several chromosome regions exhibit loss of heterozygosity (LOH) in human breast carcinoma and are thought to harbour tumour suppressor genes (TSG). At chromosome 13q, two TSGs have been identified, RB1 at 13q14 and BRCA2 at 13q12-q13. In this study, 139 sporadic breast tumours were analysed with 18 polymorphic microsatellite markers for detailed mapping of LOH at chromosome 13q and evaluation of an association with known progression factors. LOH with at least one marker was observed in 71 (51%) of the tumours analysed. The deletion mapping indicated three LOH target regions, 13q12-q13, 13q14 and 13q31-q34. LOH at chromosome 13q12-q13 was associated with low progesterone receptor content, a high S phase fraction and aneuploidy. Multivariate analysis adjusting for lymph node involvement and S phase fraction showed that patients with tumours exhibiting LOH at 13q12-q13 have a 3-4-fold increased risk of recurrence and death compared with other patients. Our results suggest there are at least three separate LOH target regions at chromosome 13q and inactivation of one or more genes at chromosome 13q12-q13 results in poor prognosis for breast cancer patients.

Aneuploidy↗

High prevalence of the 999del5 mutation in icelandic breast and ovarian cancer patients.

Studies on Icelandic breast cancer families have shown that most of them segregate a 999del5 BRCA2 mutation. Here, we report the frequency of the 999del5 BRCA2 mutation in an Icelandic control population and four different groups of cancer patients diagnosed with (a) breast cancer; (b) ovarian cancer; (c) prostate cancer (patients younger than 65 years); and (d) other cancer types. The proportions of individuals carrying the mutation were 0.4% in the control population and in the patient groups 8.5%, 7.9%, 2.7%, and 1.0%, respectively. Our results indicate that BRCA2 confers a very high risk of breast cancer and is responsible for a substantial fraction of breast and ovarian cancer in Iceland, but only a small proportion of other cancers.

Adult↗

Frequent occurrence of BRCA2 linkage in Icelandic breast cancer families and segregation of a common BRCA2 haplotype.

Cloning of a breast cancer-predisposing gene (BRCA2) on chromosome 13Q12-14 has been reported recently. We analyzed seven large Icelandic breast cancer families with markers from the BRCA2 region. Five families showed strong evidence of linkage. The maximum two-point LOD scores for the five BRCA2-linked families ranged from 1.06 to 3.19. Haplotype analyses revealed a region with identical allele sizes between the families, suggesting that they have inherited the mutation from a common ancestor. Cancer types other than breast cancer occur in individuals, segregating the affected haplotype within these families. This suggests that mutations in the gene may also confer some risk of other malignancies in both males and females.

Aged↗

Loss of heterozygosity on chromosome 9 in human breast cancer: association with clinical variables and genetic changes at other chromosome regions.

Primary breast tumors were tested for loss of heterozygosity (LOH), on chromosome 9p with microsatellite markers restricted to a 28 cM region including the MTS1 gene. LOH was found with at least 1 marker in 38% of the 201 cases analyzed. A high frequency of deletions was detected at the 9p23-p21 region, indicating a tumor suppressor gene(s) important for breast cancer tumorigenesis. Tumors with and without LOH on 9p were compared with respect to clinico-pathological factors using chi 2 analysis. Tumors with 9p LOH were significantly associated with high S-phase status and aneuploidy, but not with type, node status, estrogen and progesterone receptor content or age of the patients at diagnosis. Survival analysis showed that LOH at 9p did not significantly affect the survival rate of breast cancer patients. Our results indicate that the aberrations on 9p detected in this study are not of independent prognostic value. A significant association was found between LOH at 9p and LOH at chromosomal arms 3p and 6q, which is an additional contribution toward understanding the genetic events in breast tumor pathogenesis.

Alleles↗

Different tumor types from BRCA2 carriers show wild-type chromosome deletions on 13q12-q13.

In this study we examined loss of heterozygosity (LOH) on chromosome 13q12-13 in 50 tumors from BRCA2 carriers in five families showing strong evidence of linkage to BRCA2. In addition to high frequency of LOH in female breast cancer, LOH was observed in tumors of the prostate, ovary, cervix, colon, male breast, and ureter. All detected losses involved the wild-type chromosome. These results suggest that BRCA2 is a tumor suppressor gene and may be involved in the tumorigenesis of several cancer types in addition to breast cancer.

BRCA2 Protein↗

Loss of heterozygosity at chromosome 11 in breast cancer: association of prognostic factors with genetic alterations.

We examined DNA from 116 female and four male breast cancer patients for loss of heterozygosity (LOH). DNA was analysed by polymerase chain reaction using ten microsatellite markers on chromosome 11. Three distinct regions of LOH were identified: 11p15.5, 11q13 and 11q22-qter with a LOH frequency of 19, 23 and 37-43% respectively. The marker D11S969 showing the highest frequency of LOH (43%) is located at the 11q24.1-q25 region. No previous molecular genetic studies have shown frequent LOH at the region telomeric to q23 on chromosome 11. Southern analysis revealed that LOH at 11q13 was due to amplification, whereas LOH at 11q22qter was due to deletion. LOH at 11p15.5 was associated with paucity of hormone receptor proteins, high S-phase and positive node status. An association was found between LOH at 11q13 and positive node status. LOH at the 11q22-qter region correlated with a high S-phase fraction. A significant association was found between LOH at 11p15 and chromosome regions 17q21 (the BRCA1 region) and 3p.

Blotting, Southern↗

Identification of a breast tumor with microsatellite instability in a potential carrier of the hereditary non-polyposis colon cancer trait.

Allelic expansion at microsatellite loci in colorectal tumor DNA indicates a genomic instability caused by defects in DNA mismatch repair. This is observed in a high proportion of tumors from individuals affected by hereditary non-polyposis colorectal carcinoma, but to a lesser extent in sporadic colorectal tumors. In this study we screened 46 colorectal tumors for replication errors (RER). Tumors from six patients were found to be RER positive, two of which had a marked family history of colon cancer. In both cases the RER + phenotype was detected in colon tumors from other family members, suggesting a germline mutation in mismatch repair genes. Additionally, RER + phenotype, distinct from that of the colon and sporadic breast tumors, was found in malignant breast tissue from the mother of one proband.

Adult↗

Chromosome 17q-linkage seems to be infrequent in Icelandic families at risk of breast cancer.

Eight Icelandic families with multiple cases of breast cancer, and 17 pairs of sisters diagnosed by the age of 50 were analysed for linkage to markers around BRCA1 on chromosome 17q. The sister-pairs are thought to represent a wider population as compared to the larger high-risk families. Tumours were also analysed for LOH involving BRCA1. In accordance with a proposed tumour-suppressive function of BRCA1, and high prevalence of LOH in 'linked' tumours, the paired sisters' tumours were assayed for double LOH events with common alleles retained. No such pair was observed, and LOH events were seemingly randomly distributed at a 38% frequency. This indicates that most or all pairs are due to other genes than BRCA1 or sporadic involvement. Of the eight high-risk families, only one showed convincing evidence of 17q-linkage. Therefore, BRCA1 mutations seem to be a minor explanation of familial risk of breast cancer in Iceland.

Adult↗

Production of Rhizobium Inoculants for Lupinus nootkatensis on Nutrient-Supplemented Pumice.

The use of the legume Lupinus nootkatensis as a pioneer plant to fight soil erosion and to reclaim eroded soils in Iceland has been under development for a few years. Production of a robust, low-cost bacterial inoculant was therefore a prerequisite for the extended use of this plant. Volcanic pumice is a naturally expanded mineral which is available in vast amounts in Iceland. It was tested as a carrier for solid fermentation of Rhizobium lupini. Nutrient-supplemented pumice containing a small percentage of peat and diatomaceous earth and kept in sterile plastic bags promoted good growth of the bacteria. Viable-colony counts remained stable at 10 to 10/g for at least 35 weeks when the carrier was stored at 22 degrees C. The pumice-based inoculant had good storage and handling properties and could be mixed directly with the seeds during the sowing process. When seeds of L. nootkatensis were sown manually into nutrient-poor eroded sandy soils, about 56% of the first-year plants were successfully nodulated.

Journal Article↗

Screening as a prognostic factor in cervical cancer: analysis of survival and prognostic factors based on Icelandic population data, 1964-1988.

Survival rates were computed for 376 women diagnosed with carcinoma of the uterine cervix between 1964 and 1988. The 5-year survival rate for the entire group was 63%. The effect of age at diagnosis, clinical stage, histopathology, year of diagnosis, and screening program attendance was studied by univariate analysis and simultaneously with a multivariate analysis, the Cox proportional hazards model. All these parameters had a significant effect on survival, with clinical stage as the strongest parameter followed by histology, year of diagnosis, age at diagnosis, and attendance at screening. Women who had attended the cervical screening program fared significantly better than those who had never attended. Patients treated in the late years of the study period had a significantly better survival rate, possibly indicating improved treatment. Young women had a significantly better prognosis than older women. Women with adenocarcinoma and anaplastic tumors had a significantly worse prognosis than women with squamous and adenosquamous carcinoma. The prognostic effect of screening was mainly attributed to the more favorable distribution of early stages and younger age at diagnosis among the screened women. After all the analyzed parameters had been adjusted for the nonattenders still had poorer prognosis.

Adult↗

Luteinization to oocyte retrieval delay in women in whom multiple follicular growth was induced as part of an in vitro fertilization/gamete intrafallopian transfer program.

Different luteinization-to-oocyte-retrieval delays were examined in 64 IVF/GIFT patients. Multiple follicular stimulation was induced with combined therapy of hMG and GnRH-a to create continuous pituitary suppression and thus eliminate endogenous gonadotropin fluctuations. The results demonstrated that with this induction regime, the time interval can be extended to 39 hours without preoperative ovulation and with improved oocyte maturity.

Buserelin↗

Rapid detection of Chlamydia trachomatis by an enzyme immunoassay method.

Chlamydia trachomatis has been shown to be a major cause of sexually transmitted diseases in the United States. An enzyme immunoassay (Abbot Laboratories) has been developed that detects chlamydial antigen directly in the urogenital specimens of patients. We have evaluated specimens from 1,074 patients belonging to one of three risk groups. Three swabs were collected from each patient--one each for Neisseria gonorrhoeae, chlamydia cell culture, and enzyme immunoassay. When compared with cell culture, the sensitivity and specificity of the enzyme immunoassay for symptomatic males and females attending a sexually transmitted disease clinic was 82% and 100%, and 91.3% and 95.0%, respectively. A moderate risk group, consisting of female patients seen at either urology or gynecology clinics for genitourinary symptoms was also evaluated. The sensitivity and specificity of the test on this group was 96% and 96.7%. A population of females at low risk were also screened for chlamydial infection. In this group, the sensitivity and specificity of the enzyme immunoassay was 89.3% and 93.2%, respectively. This rapid test is a highly specific and sensitive procedure for the detection of chlamydial antigen in genital specimens from high risk female patients as well as symptomatic males.

Antigens, Bacterial↗