Botulism associated with vacuum-packed smoked whitefish in Finland, June-July 2006.
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Aged↗
Biomedical subjects
M Lindstrom
Publications and source records attributed to M Lindstrom.
Childhood misery and disease in later life: the effects on mortality in old age of hazards experienced in early life, southern Sweden, 1760-1894.
This paper assesses the importance of early-life conditions relative to the prevailing conditions for mortality by cause of death in later life using historical data for four rural parishes in southern Sweden for which both demographic and economic data are very good. Longitudinal demographic data for individuals are combined with household socio-economic data and community data on food costs and the disease load using a Cox regression framework. We find strong support for the hypothesis that the disease load experienced during the first year of life has a strong impact on mortality in later life, in particular on the outcome of airborne infectious diseases. Hypotheses about the effects of the disease load on mothers during pregnancy and access to nutrition during the first years of life are not supported. Contemporary short-term economic stress on the elderly was generally of limited importance although mortality varied by socio-economic group.
Aged↗
Distinct clinical and laboratory activity of two recombinant interleukin-2 preparations.
Interleukin-2 (IL-2) is a potent lymphokine that activates natural killer cells, T cells, and other cells of the immune system. Several distinct recombinant human IL-2 preparations have shown antitumor activity, particularly for renal cell cancer and melanoma. Somewhat distinct immune and clinical effects have been noted when different IL-2 preparations have been tested clinically; however, the regimens and doses used were not identical. To compare these more directly, we have evaluated two clinical recombinant IL-2 preparations in vitro and in vivo using similar regimens and similar IUs of IL-2. We used the Food and Drug Administration-approved, commercially available Chiron IL-2 and the Hoffmann LaRoche (HLR) IL-2 supplied by the National Cancer Institute. Using equivalent IUs of IL-2, we noted quantitative differences in vitro and in vivo in the IL-2 activity of these two preparations. In patients receiving comparable IUs of the two preparations, HLR IL-2 induced the release of more soluble IL-2 receptor alpha into the serum than Chiron IL-2. In addition, more toxicities were noted in patients receiving 1.5 x 10(6) IU of HLR IL-2 than were seen in patients treated with 1.5 x 10(6) or even 4.5 x 10(6) IU of Chiron IL-2. These toxicities included fever, nausea and vomiting, and hepatic toxicity. In vitro proliferative assays using IL-2-dependent human and murine cell lines indicated that the IU of HLR IL-2 was more effective than Chiron IL-2 at inducing tritiated thymidine incorporation. Using flow cytometry, we also found quantitative differences in the ability of these two preparations to bind to IL-2 receptors. These findings indicate that approximately 3-6 IU of Chiron IL-2 are required to induce the same biological effect as 1 IU of HLR IL-2.
Animals↗
Accretion rates of meteorites and cosmic dust in the Early Ordovician.
Abundant fossil meteorites in marine, condensed Lower Ordovician limestones from Kinnekulle, Sweden, indicate that accretion rates of meteorites were one to two orders of magnitude higher during an interval of the Early Ordovician than at present. Osmium isotope and iridium analyses of whole-rock limestone indicate a coeval enhancement of one order of magnitude in the influx rate of cosmic dust. Enhanced accretion of cosmic matter may be related to the disruption of the L chondrite parent body around 500 million years ago.
Calcium Carbonate↗
Effects of cytokines on the pituitary-adrenal axis in cancer patients.
Cytokines, which include interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), are immunoregulatory proteins produced by lymphocytes and inflammatory cells. Several cytokines, most noteworthy IFNs and ILs, stimulate glucocorticoid secretion. In this study, the effects of variable doses and repetitive administration of IFNs and TNF on secretion of pituitary hormones and cortisol were measured. Patients were given for a period of 15 days on alternating days injections of IFN-beta (IFN-beta ser), 90 or 450 x 10(6) IU, IFN-gamma, 0.1-100 x 10(6) IU, or TNF 125-275 micrograms/m2. Sixty to 120 min after IFN-beta ser injection median levels of cortisol, adrenocorticotropin (ACTH), prolactin (PRL), and growth hormone (GH) rose two-fold. Urinary free cortisol excretion increased significantly during the day following IFN-beta ser administration. IFN-gamma > or = 30 x 10(6) IU caused a comparable rise in plasma cortisol. TNF induced two- to four-fold increases in ACTH and cortisol. The fact that increased cortisol secretion was associated with a rise in the level of ACTH as well as PRL and GH suggests that the cytokines increased cortisol by stimulating the anterior pituitary. The hormonal response induced by cytokines was unrelated to their pyrogenic effect, undiminished with repetitive treatment, and not dose-dependent above a threshold level. These observations reinforce the concept of a physiologic link between the immune system and the hypothalamic-pituitary-adrenal (HPA) axis.
Adrenocorticotropic Hormone↗
Tumorigenic transformation and neoplastic progression of human uroepithelial cells after exposure in vitro to 4-aminobiphenyl or its metabolites.
A multistep in vitro/in vivo transformation system was used to test the transforming effect(s) of the human bladder procarcinogen 4-amino-biphenyl (ABP) and two putative proximate carcinogenic metabolites, N-hydroxy-4-aminobiphenyl (N-OH-ABP) and N-hydroxy-4-acetylamino-biphenyl (N-OH-AABP), on a clonally derived nontumorigenic SV40-immortalized human uroepithelial cell line, SV-HUC. SV-HUC were exposed in vitro to concentrations of ABP, N-OH-ABP, or N-OH-AABP that caused a range of cytotoxicity from 5 to 76%. Tumorigenic transformation of SV-HUC, as assessed by the ability of the exposed cells to form carcinomas when inoculated s.c. into athymic nude mice, was achieved after a single exposure to ABP, N-OH-ABP, or N-OH-AABP. In the tumorigenic transformation experiments, 28 of 45 mice representing all 15 carcinogen-exposed observation groups formed carcinomas, whereas none of 9 mice from control groups formed carcinomas (P = 0.001). Neoplastic progression of a low grade regressive squamous cell carcinoma, MC-T11, was also achieved in this system after in vitro exposure to ABP, N-OH-ABP, or N-OH-AABP. In these progression experiments, 11 of 33 mice representing 7 of 12 carcinogen-exposed observation groups formed persistent, high grade nongressing tumors, while only 1 of 19 untreated MC-T11 controls spontaneously progressed on reinoculation (P = 0.022). Forty independent carcinomas generated in athymic nude mice recapitulated diverse cancer phenotypes (including different growth kinetics and histopathological subtypes and grades) represented in clinical bladder cancers. These results demonstrate for the first time the transforming effects of the potent human carcinogen ABP and two of its proximate N-hydroxy metabolites on a prime human target cell type, HUC.
Aminobiphenyl Compounds↗
Induction of thioguanine-resistant mutations in human uroepithelial cells by 4-aminobiphenyl and its N-hydroxy derivatives.
The mutagenic potentials of the human bladder carcinogen 4-amino-biphenyl (ABP) and three of its proximate carcinogenic metabolites, N-hydroxy-4-aminobiphenyl (N-OH-ABP), N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and N-acetoxy-4-acetylaminobiphenyl (N-OAc-AABP) were tested on a prime human target cell type for carcinogenesis, human uroepithelial cells (HUC). SV-HUC (PC), a near diploid, clonally derived, nontumorigenic SV40-immortalized human uroepithelial cell line that is transformable to tumorigenicity after exposure to ABP and its metabolites, was used for quantitative mutation assays. The end point used was the induction of mutations in the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus, selected using 6-thioguanine resistance (TGr). A single, 24-h exposure of SV-HUC to ABP, N-OH-ABP, N-OH-AABP, or N-OAc-AABP caused a statistically significant, dose-dependent increase in mutation frequency resulting in a 2-30-fold increase in the number of TGr mutants in carcinogen-exposed groups compared to untreated controls. These chemicals were similarly mutagenic towards MC-T11, an SV-HUC-derived low grade tumor cell line that was also shown to be responsive to transformation (in a separate study) by ABP, N-OH-ABP, or N-OH-AABP as judged by the generation of higher grade tumors. In contrast, the mutagenic potencies of ABP and N-OH-ABP were lower when tested on a subclone of SV-HUC (BC) that is refractory to transformation by these chemicals. Thus, these data support a model of transformation in which ABP as well as its metabolites contribute to tumorigenic transformation and neoplastic progression of HUC by inducing mutations in susceptible target cell genes.
Aminobiphenyl Compounds↗
Immunological effects of levamisole in vitro.
Levamisole, an anthelminthic drug with immunological properties, has recently been reported to have antitumor activity when administered with 5-fluorouracil in patients with Duke's C colorectal carcinoma. The mechanism of this antitumor effect is unknown, but has been postulated to be related to levamisole's immunomodulatory properties. To define further the immunomodulatory activities of levamisole, we studied the in vitro effects of levamisole on monocyte and lymphocyte cytotoxicity, activation, and proliferation; induction of cytokine-induced proteins; and expression of tumor-associated antigens. Experiments utilized peripheral blood mononuclear cells from normal donors incubated in the presence of increasing concentrations of levamisole (0.1 to 100 micrograms/ml). Levamisole had no consistent effect on induction of 2',5'-oligoadenylate synthetase activity or indoleamine-2,3-dioxygenase activity, or production of tumor necrosis factor. Levamisole had no effect on monocyte cytotoxicity or expression of HLA-DR, HLA-DQ, HLA-DP, and the Fc receptor. Similarly, levamisole had no significant effect on NK or LAK cytotoxicity or the immunological activation of T-lymphocytes, assessed by expression of CD3, CD4, CD8, CD16, CD25, and CD56. Proliferation of lymphocytes from normal donors, patients with benign polyps, and patients with malignancies, with or without IL-2 or irradiated LS174T cells, was not significantly increased overall. No significant enhancement in the expression of three tumor-associated antigens (880364, NRCO-4, and ING-1) and the intercellular adhesion molecule-1 (ICAM-1) antigen on four human cancer cell lines was observed following in vitro exposure to levamisole. We conclude that levamisole is not a potent modulator of the immune parameters we examined, and that the mechanism behind the unique clinical interaction between levamisole and 5-fluorouracil in colorectal carcinoma remains to be identified.
2',5'-Oligoadenylate Synthetase↗
Holistic nursing: a basis for curriculum.
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Curriculum↗