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Biomedical subjects

I Nordenson

Publications and source records attributed to I Nordenson.

At least 19 recordsLinked to original sources
PubMed1992

Idiopathic hemochromatosis and chromosomal damage.

Spontaneous and radiation-induced chromosome damage in cultured lymphocytes was examined in a pilot study of 11 patients with idiopathic hemochromatosis and matched controls. Increased frequencies of chromosome breaks were found in the patients, both spontaneously and after exposure to ionizing radiation, but the differences between patients and controls were not statistically significant (p greater than 0.05) when individual data were analyzed. When pooled (group) data for patients and controls were compared, significant increases in spontaneous and radiation-induced chromosome breaks were found among the patients. The results suggest that iron overload may lead to chromosome damage in idiopathic hemochromatosis.

Cells, Cultured↗
PubMed1991

Multiple DNA rearrangements in the BCL2 region in a patient with follicular lymphoma.

A 39-year-old male with follicular non-Hodgkin's lymphoma was repeatedly studied with respect to DNA rearrangements with the two probes pFL-1 and pFL-2, representing two segments of chromosome 18. The oncogene BCL2, detected by pFL-1, was as expected translocated to the J region of the immunoglobulin locus. The standard BCL2 translocation was found in three samples, one obtained at diagnosis, one ten months later, and one after 5 years. Another translocation was found with the probe pFL-2 hybridizing with a region located about 20 kb 3' from BCL2. This latter rearrangement was found only in the first biopsy, which was obtained at the time of diagnosis, but not in the two later samples, when the morphology of the lymphoma was unchanged. No cytotoxic therapy had been given in the interval from diagnosis to disappearance of the latter rearrangement. Thus, one of the observed translocations (pFL-2) was detected only in the first biopsy, while the other (pFL-1) was a clonal marker in all three biopsies. The finding suggests that clonal evolution does not necessarily mean clinical progression.

Adult↗
PubMed1991

Is the genotoxic effect of arsenic mediated by oxygen free radicals?

Previous investigations have shown that trivalent arsenic is inducing chromosomal aberrations and sister chromatid exchanges (SCEs). In a search for the genotoxic mechanism we have studied the effects of the oxygen-radical-scavenging enzymes superoxide dismutase (SOD) and catalase (CAT) on arsenic-induced SCEs in cultured human lymphocytes. The results indicate that SOD and possibly also CAT have a protective effect against arsenic-induced DNA damage. Arsenic, which is emitted in environmental pollutions e.g. from smelters and coal-fired power plants, appears to be underestimated as environmental mutagen and potential synergist to ionizing radiation.

Arsenic↗
PubMed1991

Cytogenetic and flow cytometric DNA analysis in renal cell carcinoma.

Cytogenetic and flow cytometric DNA analyses were performed on 37 tumor samples from 16 patients with renal cell carcinoma. 36 cultures were chromosomally abnormal and 1 was normal. The most frequent abnormality was trisomy or tetrasomy of chromosome 7 (13 of 16 tumors), suggesting that this abnormality might be a primary change in renal cell carcinoma. Abnormalities of chromosome 3 were seen in 9 of 16 tumors (56%). Eight of 11 tumors (73%) with cytogenetic results from multiple tumor samples showed intratumor cytogenetic heterogeneity. Twelve of the 16 patients had aneuploid tumors, and 4 had homogeneously diploid tumors. DNA index correlated with chromosome number. No association was found between cytogenetic results and clinical stage.

Aneuploidy↗
PubMed1990

Cytogenetic abnormalities and leukemic transformation in hydroxyurea-treated patients with Philadelphia chromosome negative chronic myeloproliferative disease.

Eighty-one consecutive hydroxyurea-treated patients with Philadelphia (Ph) chromosome negative chronic myeloproliferative disease were followed prospectively from 1981 to 1989; 35 of them had polycythemia vera, 32 had essential thrombocythemia, 12 had myelofibrosis, and 2 had myeloproliferative syndromes. The 81 patients were treated with hydroxyurea for a total of 3,804 months during the observation time. Only three patients had been treated with alkylating agents or 32P before start of hydroxyurea treatment. Four patients transformed into acute myeloid leukemia or myelodysplastic syndromes; three of these patients had essential thrombocythemia, and one had a myeloproliferative syndrome. Two patients died of solid cancers. Five out of 53 evaluable patients (9%) had pretreatment clonal cytogenetic abnormalities involving chromosomes 1, 9, 20, and 21. At follow-up, during or after hydroxyurea treatment, 15% had cytogenetic abnormalities, an unexpectedly low frequency compared to the previously reported frequency in patients with polycythemia vera treated with alkylating agents. None of our patients who developed cytogenetic clonal changes during hydroxyurea therapy had polycythemia vera. However, follow-up is too short to draw any conclusions about the mutagenic potential of hydroxyurea compared to alkylating agents.

Adult↗
PubMed1990

An inter-Nordic prospective study on cytogenetic endpoints and cancer risk. Nordic Study Group on the Health Risk of Chromosome Damage.

To investigate whether high rates of chromosomal aberrations (CAs), sister chromatid exchange (SCE), or micronuclei(MN) in peripheral lymphocytes indicate an increased risk for subsequent cancer, a prospective cohort study of 2,969 subjects cytogenetically examined between 1970 and 1988 in four Swedish, two Finnish, and two Norwegian laboratories was initiated. To standardize for the interlaboratory variation, the results of the three cytogenetic endpoints were trichotomized for each laboratory into "low" (1st to 33rd percentile), "medium" (34th to 66th percentile), and "high" (67th to 100th percentile]. Thirty-four cancers had been diagnosed in the cohort during the observation period (1970 to 1985). The point-estimates of the standardized morbidity ratio (SMR) in the three CA strata were 90, 92, and 180, respectively. This trend for a positive association was not statistically significant (p = 0.06). There was no significant trend between SMR and the trichotomized rates of SCE. In the subcohort examined for MN only two cases of cancer had been diagnosed until now. If subjects with "high" frequencies of CA or SCE have a two-fold (or greater) risk of developing cancer as compared with individuals who have "medium" or "low" frequencies, we estimate that there is a likelihood of 80% and 70%, respectively, that this will be detectable as significant (p less than or equal to 0.05) differences after a further follow-up period of 5 years. Weaker associations between cancer risk and the cytogenetic endpoints would not be possible to evaluate until even later follow-ups.

Chromosome Aberrations↗
PubMed1989

Philadelphia chromosome negative acute lymphoblastic leukemia preceding Philadelphia positive chronic myelogenous leukemia.

A patient with Philadelphia chromosome (Ph) negative acute lymphoblastic leukemia (ALL, FAB type L1) developed Ph-positive chronic myelogenous leukemia (CML) after more than 2 years in complete remission. Subsequently, Ph-positive lymphoblastic transformation occurred, which was again successfully treated. Thereafter, the CML state was interrupted twice more by blast crisis. The additional chromosomal abnormalities were atypical for Ph-positive CML. The course is interpreted as a possible example of the multistep development of CML. Blastic transformation occurring prior to the Ph chromosome has been reported in only two cases previously.

Adult↗
PubMed1989

The effect of CPH 82 on the growth of human lymphocytes in vitro. Definition of cytobiological action.

A drug composed of two semisynthetic podophylline derivatives, CPH 82, has recently been launched for the treatment of severe rheumatoid arthritis. The present in vitro study of PHA-stimulated human T-lymphocytes showed that CPH 82 arrested cell division in a metaphase-like configuration. The cell cycle effects of CPH 82 were indistinguishable from the cell cycle effects of the classical microtubule depolymerizers, Colcemid (a colchicine derivative) and podophyllotoxin. A CPH 82 concentration of 1 microgram/ml, which is close to therapeutic serum concentrations, had an almost maximal effect on cell division. It is suggested that at least part of the anti-inflammatory effect of CPH 82 is due to a colchicine-like activity on, for example, proliferating lymphocytes.

Glycosides↗
PubMed1988

Chromosomal effects in lymphocytes of 400 kV-substation workers.

In a previous study we found an increased rate of chromosomal aberrations in substation workers. To follow up this finding we in this study present data from 38 employees of electric power companies; 19 of the subjects worked with the repair and maintenance of circuit breakers and disconnectors in 400 kV-substations. The other 19 served as controls and were only exposed to normal environmental electromagnetic fields. Coded blood samples were sent to a laboratory for determination of the rate of chromosomal aberrations (CA), sister chromatid exchanges (SCE), and cells with micronuclei (MN). Compared to the control group the exposed men displayed a statistically significant increase in CA and cells with MN. No increase was found in the frequency of SCE. Since "in vitro" studies of lymphocytes exposed to transient electric currents (spark discharges) produced similar results the increase in chromosomal damage in substation workers may be associated with exposure to transient electric currents during work.

Adult↗
PubMed1988

Chromosomes in renal carcinoma with reference to intratumor heterogeneity.

Cytogenetic studies of renal tumors from seven patients were performed (six renal cell carcinomas, one transitional cell carcinoma). Multiple samples were obtained from each tumor as well as one sample from normal tissue. Cultures were established after collagenase disaggregation. From five tumors, two or more cultures were available for chromosome analysis. All tumors were chromosomally abnormal, although some cultures had a normal chromosome complement. Aberrations involving chromosome 3 were seen in four tumors. Two patients had an identical marker chromosome del(3)(p14), suggesting that the breakpoint may be of significance for the development of tumors of the kidney. An extra chromosome 7 was found in four patients. In all four tumors from which two or more tumor cultures were studied, the chromosome constitution showed, besides a primary cytogenetic change, additional clonal abnormalities illustrating intratumoral heterogeneity.

Biopsy↗
PubMed1988

Homozygosity for the transthyretin-met30-gene in two Swedish sibs with familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder. Recent biochemical studies have revealed that amyloid protein in FAP of Japanese, Swedish and Portuguese origin mainly consists of a variant transthyretin (TTR) (formerly called prealbumin) with one amino acid substitution of methionine for valine at position 30. In a 56-year-old man with typical polyneuropathy, gastrointestinal problems and vitreous amyloid, we diagnosed homozygosity for the TTR-met30-gene using RFLP analysis. In a family study, a sister presented the same homozygous RFLP pattern; however, in a careful clinical investigation we were not able to demonstrate any of the typical symptoms of FAP, nor could we demonstrate amyloid deposits in a biopsy skin specimen. This is the first report of homozygosity for the TTR-met30-gene, and it shows that the mutation of the protein involved in amyloid formation may be necessary but is clearly not sufficient for the clinical symptoms.

Adult↗
PubMed1988

Diagnosis of familial amyloidotic polyneuropathy in Sweden by RFLP analysis.

Genomic DNA from 17 Swedish patients with familial amyloidotic polyneuropathy (FAP), and 50 healthy controls were tested with a cDNA transthyretin probe. In seven of the patients, FAP was not reported in either of their parents. All 50 controls showed restriction fragments of 6.6 kb and 3.2 kb after cleavage with Nsil, while the 17 FAP patients showed RFLP markers of 5.1 and 1.5 kb. These observations indicate the same methionine for valine substitution at position 30 in Swedish patients with FAP as seen in patients with FAP from Japan, Portugal and FAP-patients of Swedish descent from USA. However, the mean onset of FAP symptoms for the 17 Swedish patients was found to be significantly later than for the patients from Japan, Portugal and USA.

Adult↗
PubMed1988

Transferrin C2 and radiation-induced chromosomal damage.

Radiation-induced chromosomal damage (after exposure to 1 Gy) in lymphocytes was studied in relation to transferrin C subtype (C1 vs. C2). In 72-hour lymphocyte cultures a significantly increased frequency of cells with radiation induced aberrations was observed in individuals with the transferrin type C2. Thus the results lend some support to the hypothesis that transferrin C2 may act as an enhancer of chromosomal damage.

Chromosomes↗
PubMed1988

Near-haploidy in childhood leukemia: a high-risk component.

We present a 4-year-old girl with acute lymphocytic leukemia (ALL) and only 25 chromosomes at cytogenetic examination of her bone marrow. Severe hypodiploidy is extremely rare in childhood leukemia and is almost exclusively associated with ALL. To our knowledge only six cases with banded metaphases have been published. The chromosome number in the present case is the lowest ever reported. Our patient as well as other reported cases have disomy for chromosome 21. The prognosis for ALL with hypodiploidy is poor with a reported mean survival of 9 months. All published patients are females.

Bone Marrow↗
PubMed1988

Cluster formation in PHA-stimulated mononuclear cells from peripheral blood: effects of colcemid and taxol.

Mononuclear cells from peripheral blood were incubated with phytohemagglutinin (PHA) for 24-72 hours. The cells formed dense cell clusters with firm cell-to-cell attachment and signs of cell communication, proliferation and differentiation. At the end of a 72-hour period of incubation, the test preparations were treated for 90 minutes with the classical microtubule antagonist Colcemid and the new microtubule antagonist taxol. Taxol produced approximately twice as many mitoses as Colcemid. Chromosomes in taxol-blocked mitoses appeared to be more contracted than chromosomes in Colcemid-blocked mitoses. It is suggested that one beneficial side effect of Colcemid preparation of chromosomes is stretching due to microtubule disassembly.

Alkaloids↗
PubMed1986

Chronic monocytic leukemia terminating in blastic transformation.

Chronic monocytic leukemia (CMoL) is a rare disorder, closely related to malignant histiocytosis, but a separate entity. The clinical course of the patient described in this case report was characterized by persistent monocytosis without response to cytotoxic therapy, and a large number of infections. On two occasions a clone of cells containing an extra chromosome 20 was observed. The disease terminated in a phase with rapidly increasing numbers of immature monocytoid cells, corresponding to blastic transformation.

Cell Transformation, Neoplastic↗
PubMed1986

Interaction between some common genotoxic agents.

The clastogenic effects of arsenic, lead and sulphur dioxide and the protective effect of selenium were studied in short-term lymphocyte cultures. The three agents selected are the major toxic substances in emissions from copper smelters. Cells from non-smoking, healthy individuals were exposed to individual agents and combinations of the four agents (sodium arsenite, lead acetate, sodium sulphite and sodium selenite) and the cells were analysed for chromosome aberrations and sister chromatide exchanges. Selenium showed an antagonistic (protective) effect against the other agents. No synergistic effects were found, and the interactions between arsenic, lead and sulphur dioxide were mainly antagonistic. These rather unexpected findings indicate that mixed exposure from copper smelters, and other mixed exposures where arsenic, lead and sulphur dioxide are involved, may cause less genetic damage than expected and that an adequate dietary supplement of selenium may reduce the genotoxic effects of these agents.

Arsenic↗