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Biomedical subjects

H Olsson

Publications and source records attributed to H Olsson.

At least 235 records · Page 13Linked to original sources

Relation between occupational exposure to organic solvents and chromosome aberrations in non-Hodgkin's lymphoma.

Chromosome analysis of lymphoma cells was performed in 54 untreated patients with non-Hodgkin's lymphoma (NHL). 10 patients had a history of daily occupational handling of organic solvents for at least 1 year (exposed group) and 44 patients had never (or only for shorter periods) worked with solvents (unexposed group). There were no differences between exposed and unexposed patients regarding age, clinical stage or histologic malignancy grade. The patients were assigned to three categories: Patients with 0-4, 5-9, or greater than or equal to 10 cytogenetic events producing clonal aberrations of the lymphoma cells. The proportions of exposed patients in these categories were 2/26 (8%), 5/20 (25%) and 3/8 (38%); respectively, i.e. with increasing numbers of events there was an increasing probability of previous exposure to solvents (p = 0.035, trend analysis). 5 of 7 exposed patients (71%) with intermediate or high-grade lymphomas displayed translocations involving the band 14q32. Such 14q+ markers were found in only 5 out of 28 unexposed patients (18%) with lymphomas of comparable malignancy grade (p = 0.01). Among unexposed patients with intermediate or high-grade lymphoma the most common clonal aberration was 6q- which occurred in 10 out of 28 patients (36%). This abnormality was not observed in the exposed patients with lymphomas of corresponding malignancy grades (p = 0.08). It thus appears that the number of clonal chromosome aberrations is especially large in NHL patients with a history of occupational exposure to organic solvents. Moreover, such exposure may be associated with characteristic cytogenetic changes in the lymphoma cells.

Adult↗

No abnormal C-band polymorphism in lung cancer patients.

The C-band heterochromatin polymorphism of chromosomes 1, 9, and 16 was studied in lymphocytes from 52 lung cancer patients and 183 control persons. No significant differences between the controls and patients were found regarding heterochromatin block size, the frequency of partial and total inversions, or the symmetry/asymmetry pattern.

Chromosome Banding↗

Oral contraceptives and breast cancer. A review.

Case-control and cohort studies published between 1977 and 1988 were reviewed with the purpose to evaluate the relationship between use of oral contraceptives (OC-use) and breast cancer risk, tumour biology and tumour prognosis with special emphasis on early OC-use. The risk of breast cancer was assessed in 30 case-referent studies and 5 cohort studies, and the prognosis of breast cancer had been studied in 9 reports. Definition of OC-use, prevalence of OC-use, latency time between start of OC-use and tumour diagnosis, case identification and choice of referents, study size, study quality were assessed. The outcome of the studies is presented. From the results of the analyses the author concludes that there is no overall risk for breast cancer among OC-users. However, with the emphasis on early OC-use, consistent results seem to emerge showing an increased risk of premenopausal breast cancer, when the possible bias of different latency times is taken into account. Also results on breast cancer incidence in early exposed age groups, tumour biology and prognosis in early OC-users with breast cancer support a genuine risk relationship. The effects of different OC-brands and dose, and the risk of peri- and postmenopausal breast cancer after early OC-use can at present not be assessed.

Adolescent↗

Cancer incidence after cholecystectomy--a cohort study with 30 years follow-up.

Cholecystectomy has been connected with an increase in colorectal, breast and reproductive system cancers. On 472 patients, 398 women and 74 men, cholecystectomized during the years 1951 to 1955, cancer incidence was investigated. Our results show an elevated risk of breast cancer in the female group (P = 0.016), but no significant increased risk in colorectal or gynaecologic cancer. The risk for breast cancer increased with time after operation. In our small group of men an elevated SMR was noted for colon cancer without reaching statistical significance. Possible aetiological factors for the association between cholecystectomy and breast cancer are discussed.

Adolescent↗

Head trauma and exposure to prolactin-elevating drugs as risk factors for male breast cancer.

On the basis of information obtained from a population-based cancer registry in Sweden, male patients with breast cancer (n = 95) were found to have experienced significantly more brain concussions and skull fractures than male patients with lung cancer (n = 383) or malignant lymphoma (n = 69). Other risk factors significantly associated with breast cancer among men were drug treatment associated with prolactin elevations, radiation treatment, family history of breast cancer among first-degree relatives, a history of gynecomastia, gonadal injury, and treatment for inguinal hernias. The results confirm some previously described risk factors for male breast cancer and suggest that events elevating plasma prolactin (e.g., drugs, brain concussions, and skull fractures) and events predisposing for inguinal hernias may be new risk factors for the disease. Using hospital charts is likely to underestimate exposure for different risk factors; therefore, the results need to be confirmed in studies that directly retrieve information. However, such studies are difficult or impossible to undertake in most countries because the disease is so rare.

Adult↗

Phosphorylation and dephosphorylation of hormone-sensitive lipase. Interactions between the regulatory and basal phosphorylation sites.

Phosphorylation of the basal site with glycogen synthase kinase-4 enhanced the rate of phosphorylation of the regulatory site by cyclic AMP-dependent protein kinase 1.7-fold. In contrast, the phosphorylation state of the regulatory site did not affect the rate of phosphorylation of the basal site with glycogen synthase kinase-4. The rate of dephosphorylation of either the regulatory or the basal phosphorylation site by protein phosphatase-1, 2A or 2C was independent of the phosphorylation state of the other site. These results suggest that the basal phosphorylation site could play an indirect role in the control of the hormone-sensitive lipase activity in the adipocyte by functioning as a recognition site for the cyclic AMP-dependent protein kinase in the phosphorylation of the activity-controlling regulatory phosphorylation site in response to lipolytic hormones.

Animals↗

Trisomy 5 and t(5;14)(q11;q32) as the sole abnormalities in two different clones from a centroblastic non-Hodgkin's lymphoma.

A 62-year-old previously healthy woman presented with a centroblastic non-Hodgkin's lymphoma in the thyroid. Chromosome analysis revealed two unrelated clones, 47,XX,+5 and 46,XX,-14,+der(14)t(5;14)(q11;q32). The two clones may reflect a polyclonal origin, or they may be the descendants of the same neoplastically rearranged cell. In the latter case, the clonal aberrations are either secondary to an event detectable only at the molecular level, or one of them is a primary cytogenetic event while the other arose through clonal evolution with loss of the primary aberration. The best candidate for the primary change would be trisomy 5. Trisomy 5 has previously been associated with lymphomas with diffuse, large, noncleaved morphology, a group within the Working Formulation largely equivalent to centroblastic lymphomas in the Kiel classification. Our findings thus support the notion that trisomy 5 may be associated with centroblastic/diffuse, large, noncleaved lymphomas.

Chromosome Banding↗

Risk of non-Hodgkin's lymphoma among men occupationally exposed to organic solvents.

An occupational history of exposure to organic solvents, defined as daily occupational exposure for at least one year, was more common among 167 men with newly diagnosed non-Hodgkin's lymphoma than among 130 healthy referents from the general population (38 versus 14%). Categorization in five-year age groups gave 3.3 as a Mantel-Haenszel estimate of the odds ratio (95% CI 1.9-5.8). The odds ratio was 6.5 (95% CI 3.2-13.3) for localized supradiaphragmatic tumors and 2.3 (95% CI 1.3-4.3) for other lymphoma presentations. In a logistic model including age and organic solvent, phenoxy acid, and chlorophenol exposure, it could be shown that solvent exposure was an independent risk factor and that no important interaction occurred between the risk factors. With increasing duration of exposure there was a significantly increased risk of lymphoma, a finding implying a dose-response relationship. There was no significant difference in tumor histology between the exposed and unexposed patients. These findings support the concept that occupational exposure to organic solvents is a risk factor for non-Hodgkin's lymphoma. The results also confirm a strong association between such exposure and an initial supradiaphragmatic location of the lymphomas.

Adult↗

The regulatory and basal phosphorylation sites of hormone-sensitive lipase are dephosphorylated by protein phosphatase-1, 2A and 2C but not by protein phosphatase-2B.

The activity of hormone-sensitive lipase, the rate-limiting enzyme in adipose tissue lipolysis, is controlled by cAMP-mediated phosphorylation at a specific regulatory phosphorylation site. The lipase is also phosphorylated at a site, termed basal, without any effects on its activity [Strålfors et al. (1984) Proc. Natl Acad. Sci. USA 81, 3317-3321]. The capacity of protein phosphatase-1, 2A, 2B and 2C to dephosphorylate the lipase, selectively phosphorylated by glycogen synthase kinase-4 and cAMP-dependent protein kinase at the basal and regulatory phosphorylation sites, was compared with that towards glycogen phosphorylase and phosphorylase kinase (alpha subunit). Protein phosphatase-1, 2A and 2C were found to dephosphorylate both phosphorylation sites of hormone-sensitive lipase, while protein phosphatase-2B had no measureable activity towards any of the sites. When the activities of protein phosphatase-1, 2A and 2C were normalized with respect to the reference substrates, they were found to dephosphorylate the lipase regulatory site in the approximate relations of 1:4:3 and the basal site in the approximate relations of 1:6:4. Protein phosphatase-1 showed 20% higher and protein phosphatase-2A and 2C 80% higher activity towards the basal site compared to the regulatory site. The two phosphorylation sites of the lipase were comparable to good substrates for protein phosphatase-2A and 2C, but relatively poor substrates for protein phosphatase-1. Protein phosphatase-2C activity towards the lipase was completely dependent on Mg2+ with a half-maximal effect at 3 mM. Protamine increased the lipase dephosphorylation by protein phosphatase-1 3-5-fold with half-maximal effect at 0.6 microgram/ml, and by protein phosphatase-2A about 2-fold with half-maximal effect at 3-5 micrograms/ml, thus illustrating the potential for control of these lipase phosphatase activities.

Adipose Tissue↗

Use of protein G for preparation and characterization of rabbit antibodies against rat adipose tissue hormone-sensitive lipase.

The newly described immunoglobulin G-binding streptococcal surface protein, protein G, was used to prepare and characterize rabbit antibodies. The antibodies were directed against rat hormone-sensitive lipase, the rate-limiting enzyme in the hydrolysis of the triacylglycerols stored in adipose tissue. Antiserum was obtained after two injections with 20 micrograms enzyme protein, and the immunoglobulin fraction was obtained using a protein G-based solid-phase radioimmunoassay. The hydrolysis of acylglycerols by the enzyme was inhibited by the antibodies, and the enzyme could be efficiently removed from a solution using the antibodies and heat-killed streptococci expressing surface protein G. By Western blot and detection with 125I-protein G, the antibodies were found to selectively bind to hormone-sensitive lipase and to a smaller extent to two minor contaminants, possibly proteolytic fragments of the lipase. The amount of 125I-labelled protein G bound to the lipase on the blot was quantitatively related to the amount of enzyme protein down to the detection limit 10 ng.

Adipose Tissue↗

Prognostic implication of cytogenetic findings in 106 patients with non-Hodgkin lymphoma.

The cytogenetic findings in samples from 106 patients with non-Hodgkin lymphomas (NHL), histopathologically classified according to the Kiel classification, have been correlated with survival time. Clonal chromosomal abnormalities were found in 60 patients, and only normal karyotypes in ten. The chromosome analysis of the remaining samples failed. The failures did not differ in survival compared with the cytogenetically successful cases, indicating that this group is not a prognostic entity within NHL. The cytogenetic findings were classified in six ways in order to evaluate the prognostic value of the cytogenetic pattern. Multivariate analysis demonstrated that presence of clonal chromosome abnormalities and the number of aberrations both were important prognostic factors independent of histopathology, whereas, the modal chromosome number, presence of translocations, or unidentified marker chromosomes were not. Some characteristic chromosome abnormalities were correlated with survival time: Patients with a 1p+ marker or +7 had a significantly shorter survival time than patients with normal karyotypes only (NN). Patients with +3, +12, 6q-, i(17q), and t(14;18)(q32;q21) did not differ significantly from the NN group.

Chromosome Aberrations↗

Mitotic activity in non-Hodgkin's lymphoma. Relation to the Kiel classification and to prognosis.

At histopathological diagnosis of non-Hodgkin's lymphoma (NHL) the mean number of mitoses in 10 high power fields (X 40) was determined in thin sections (2 micron) and designated 'mitotic index' (MI). In 38 patients the thymidine labelling index (LI) of the lymphoma cells was also determined. There was a close correlation between MIs and LIs (r = 0.81, P less than 0.001) indicating that MI reflects the proliferative activity in NHL. Among 101 patients with NHL classified according to the Kiel nomenclature MIs were generally lower in lymphomas of low grade malignant type than in the high grade malignant lymphomas. The variation of MIs within morphological subgroups was especially pronounced in high grade lymphomas. Only 18 of 49 patients (37%) with MI greater than or equal to 2 have survived for 2 years in contrast to 37 of 52 patients (77%) with MI less than 2 (P = 0.001). For patients with histologically low grade lymphomas and MI greater than or equal to 2.0 the median survival was 23 months and for those with MI less than 2.0 58 months (P = 0.09). Patients with high grade lymphomas and MI greater than or equal to 2.0 had a median survival of 15 months compared to 57 months for those with MI less than 2.0 (P = 0.04). In a multivariate analysis of 50 patients with centroblastic-centrocytic (CB-CC) or centroblastic (CB) lymphomas the importance of different prognostic factors was analysed. Among the variables age, MI, growth pattern (follicular vs. diffuse), cell type (CB-CC vs. CB), clinical stage (I vs. II-IV), initial chemotherapy (active vs. less active) only age and MI gave significant prognostic information. It is concluded that the assessment of mitoses in NHL gives prognostic information in addition to histopathologic classification. The method is simple and the proliferative activity and histopathological diagnosis can be ascertained routinely on the same occasion.

Adult↗

Survival following combination chemotherapy in advanced high grade non-Hodgkin's lymphomas: relation to proliferative activity of the lymphoma cells.

In 18 untreated adult patients (median age 62.5 yr) with advanced non-Hodgkin's lymphoma of unfavourable histology, thymidine labelling indices (LIs) of the lymphoma cells were assessed. The patients were treated with combination chemotherapy and have been followed for 29-60 (median 52) months or until death. The survival curve had a steep fall during the first 2 yr. Between 2-5 yr after treatment there was a flattening of the curve and survival seemed to be similar to the survival expected for a Swedish population matched for age and sex. 11 patients died with 2 yr and 7 patients have survived for a longer period. Age, histopathologic classification and clinical stages were comparable in short-term and long-term survivors and treatment was not more aggressive for the long-term survivors. The LIs were significantly higher (median 8.2) in short-term survivors than in the long-term survivors (median 1.4). Long-term survival following combination chemotherapy of advanced NHL of unfavourable histology seems to be achieved mainly in patients with a low proliferative activity of the lymphoma cells. It is suggested that in NHL a high proliferative activity may facilitate the generation of new mutants and that some of these are spontaneously resistant to various chemotherapeutic drugs.

Adult↗