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Biomedical subjects

I Nordenson

Publications and source records attributed to I Nordenson.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Clastogenic effects in human lymphocytes of power frequency electric fields: in vivo and in vitro studies.

In vivo and in vitro studies of the clastogenic effects of power frequency electric fields and transient electric currents have been performed. For the in vivo investigation peripheral lymphocytes from twenty switchyard workers were screened for chromosome anomalies. The rates of chromatid and chromosome breaks were found to be significantly increased compared to the rates in 17 controls. Exposure of human peripheral lymphocytes, in vitro, to a 50-Hz current with 1 mA/cm2 current density did not induce any chromosome damage. Exposure to ten 3 mus-long spark discharge pulses with a peak field strength in the samples of 3.5 kV/cm, however, resulted in chromosome breaks at a frequency similar to that induced in lymphocytes in vitro by ionizing radiation at 0.75 Gy. The biological significance of chromosomal damage induced in somatic cells is discussed.

Adult↗

Chromosomal aberrations and cancer risk.

Chromosomal aberrations in lymphocytes were studied in patients with untreated cancers of the lung and skin (basal cell carcinoma) and in controls matched for sex, age, and smoking habits. Patients with skin cancer were found to have a significantly increased rate of chromosome type aberrations. Among the patients with lung cancer, there was a tendency towards an increased rate of aberrations which, however, did not reach statistical significance. The results suggest that an increased rate of chromosomal aberrations in cultured lymphocytes is an indicator of genetic damage which may increase the cancer risk.

Adult↗

Chromosomal aberrations in lymphocytes of workers exposed to low levels of styrene.

Chromosomal aberrations were studied in lymphocytes of 15 workers exposed to styrene and 13 controls. The average styrene concentration in the work room air was 24 ppm, and the levels of urinary mandelic acid were below 2 mmol/l. No significant increase in the rates of gaps and breaks was found. However, the rate of micronuclei was significantly increased, which indicates that the mitotic spindle mechanism may be more sensitive to styrene and its metabolites than DNA.

Adult↗

Somatic chromosomal aberrations and male infertility.

A significant correlation was found between the frequency of chromosomally aberrant peripheral lymphocytes and a low frequency of morphologically normal spermatozoa in men. No correlation was found between increased chromosomal breakage, other sperm parameters and density, motility or agglutination of spermatozoa. Smokers had significantly more cells with aberrations than nonsmokers. The significance of induced lesions in peripheral lymphocytes and their relationship to reproduction was discussed.

Adult↗

Patient with B-cell neoplasia (immunoblastic sarcoma) and the Philadelphia chromosome.

Philadelphia chromosome-positive cells with a standard translocation (9;22) were found in bone marrow and peripheral blood samples from a patient with non-Hodgkin's lymphoma (immunoblastic sarcoma) in the final leukemic phase. The neoplastic clone was of monoclonal B-cell character with surface Ig (mu, kappa) and mouse red blood cell receptors. This is the first case with surface Ig and t(9;22) cells reported without evidence of chronic myeloid leukemia. Also, additional consistent chromosome aberrations were found.

B-Lymphocytes↗

Fragile X syndrome in mildly mentally retarded children in a northern Swedish county. A prevalence study.

In an extensive etiological study of an unselected series of mildly mentally retarded children (MMR) (IQ 50-70) born 1959-1970 in a northern Swedish county, 5 of 110 boys (4.5%) and none of 61 girls had a fragile site on the distal end of the X-chromosome (Fra Xq 28). Consequently fragile X was seen in 2.9% of the total series of 171 children. In a combined series of severe and mild mental retardation, the incidence of the fragile X syndrome was calculated to be 1:3000 in the county of Västerbotten. Next to trisomy 21 the fragile X syndrome was the most common single identified cause of MMR in boys. A cytogenetic investigation using special cultural conditions and banding techniques should be performed in cases of mental retardation of unclear etiology and in possible female carriers.

Adolescent↗