Biomedical subjects

K L Erickson

Publications and source records attributed to K L Erickson.

At least 73 records · Page 4Linked to original sources

PubMed1993

Knee flexor-extensor strength in children.

Isokinetic measurements of knee flexion extension in children and adolescents are a useful means of quantifying strength. In the routine clinical situation with a unilateral problem, evaluation of the affected extremity is usually based on comparisons with the unaffected side. To interpret these results, there must be an appreciation for normal side-to-side differences. Twenty-one normal, healthy children (ages 6-16 years) were evaluated using a Cybex II isokinetic dynamometer at 90 and 240 degrees/sec. In children who were able to generate peak torque values greater than 50 ft-lbs, the side-to-side differences in peak torque averaged 11 +/- 12% (mean +/- SD). A similar amount of variability has been reported with adults. For children with whom peak torque values were less than 50 ft-lbs, the side-to-side differences were much greater (mean = 22 +/- 19%). The stronger leg was equally likely to be on the nondominant side as the dominant side. Side-to-side variability was slightly decreased if the mean of several repetitions was used for comparisons rather than comparing just the single highest peak torque values.

Adolescent↗

PubMed1993

Regulation of murine macrophage function by IL-4: IL-4 and IFN-gamma differentially regulate macrophage tumoricidal activation.

To understand the differential role of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in the process of macrophage tumoricidal activation, we investigated the production of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide in activated murine macrophages and the effects of those lymphokines on prostaglandin E2 (PGE2)-mediated down-regulation. IFN-gamma and IL-4 increased lipopolysaccharide (LPS)-induced TNF-alpha production by different mechanisms because IL-4, unlike IFN-gamma, failed to overcome the LPS-hyporesponsiveness in C3H/HeJ mice. Moreover, only IFN-gamma synergized with LPS to induce nitric oxide production and blocked eicosanoid-mediated down-regulation. These differential effects of IFN-gamma and IL-4 on the select efferent cytolytic activities may be the result of an altered or different signal transduction pathway. Because potentiation of protein kinase C (PKC) activity by IFN-gamma has been previously documented, we next studied the role of IFN-gamma and IL-4 in alteration of enzymatic activity of PKC. Two lymphokines caused translocation of PKC from cytosol to membrane with different levels, providing a biochemical basis for explaining how two lymphokines lead to different phenotypic responses. Although treatment of macrophages with IFN-gamma and IL-4 gave rise to a similar enhancing effect on macrophage TNF-alpha production, these two lymphokines appeared to differentially regulate the overall functional state of macrophages for tumour cell killing capability. Additionally, this differential regulation seems to be accomplished in part by different biochemical events.

Animals↗

PubMed1992

Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation.

A 25-kDa homodimeric protein was purified from demineralized bovine bone extract and identified as activin A. The bovine bone activin enhanced formation of ectopic bone in rat subcutis when implanted in combination with partially purified bovine bone morphogenetic protein (BMP-2, BMP-3) in collagen/ceramic carrier. The implants, removed at 14 days, contained markedly elevated levels of alkaline phosphatase activity. Histological examination revealed an extensive formation of woven bone with very little cartilage. In contrast, a combination of transforming growth factor-beta 2 and BMP promoted formation of bone with an abundance of cartilage. The implants with BMP alone exhibited some osteoinductive activity, while the implants with activin alone showed no activity. These results demonstrate that bone is a rich source of activin and that activin plays an important role in modulating bone formation.

Activins↗

PubMed1991

Effect of dietary fish oil on development and selected functions of murine inflammatory macrophages.

Inflammatory macrophages from mice fed diets containing menhaden fish oil (MFO) have a reduced capacity for cytotoxicity of mastocytoma cells upon activation with interferon-gamma (IFN gamma) and lipopolysaccharide due to an altered responsiveness to IFN gamma. In an effort to elucidate further how dietary MFO effects macrophage function, we have studied the maturation of inflammatory macrophages from mice fed MFO compared with mice fed safflower oil (SFO) using several processes that serve as markers of the activational state. No significant differences in the recruitment or percentage of peritoneal exudate cells as macrophages after thioglycollate injection and no differences in spreading, binding, or phagocytosis of sheep erythrocytes or phagocytosis of yeast by inflammatory macrophages were observed when the dietary groups were compared. However, MFO macrophages had an altered capacity for peroxide release when stimulated with unopsonized zymosan (10-200 micrograms/ml). Furthermore, to elucidate how MFO feeding could alter IFN gamma-induced responses of inflammatory macrophages, we assessed phorbol-12-myristate-13-acetate-induced hydrogen peroxide production and expression of class II MHC determinants (Ia). There were no differences between macrophages from mice fed the two diets with respect to the production of peroxide when they were preincubated with 0.1-10 U/ml of IFN gamma. However, MFO macrophages had greater peroxide production after enhancement with 100 U/ml of IFN gamma. With respect to Ia induction, the percentage of macrophages responding to IFN gamma was not altered by diet, and there were no differences in expression of Ia induced by 24 hr exposure to IFN gamma. Thus the differential effect of MFO compared with SFO is probably mediated not by an alteration in the maturation of inflammatory macrophages but rather through the alteration of IFN gamma-induced functions such as peroxide production.

Administration, Oral↗

PubMed1991

Role of dietary oleic acid in linoleic acid-enhanced metastasis of a mouse mammary tumor.

We have previously shown that a high fat diet (20% w/w) containing 12% linoleic acid (18:2) can significantly increase the metastasis of mammary tumor cells when compared with high fat diets that contain 8% or less 18:2 with a constant level of oleic acid (18:1). This effect may have been due to an alteration of eicosanoid metabolism because the cyclooxygenase inhibitor, indomethacin, abolished the increase. Because 18:1 may interfere with the metabolism of 18:2 to 20:4, we have now tested whether the 18:1 that supplements the 18:2 diet can have an effect on spontaneous or experimental metastasis of the line 4526 murine mammary tumor. For this, six 20% fat diets were formulated with 1%, 6%, and 12% 18:2 and either high or low levels of 18:1. Our results indicate that the amount of select fatty acids other than 18:2 at 12% has no significant effect on mouse growth, tumor growth, or tumor latency. When spontaneous metastatic burden was calculated, no significant differences between mice fed diets containing 1% and 6% 18:2 were observed. However, 4 to 5 times more of a metastatic burden was observed in mice fed diets containing 12% 18:2. No significant differences were observed between high and low 18:1 diets when the 18:2 content was 1 or 12%. However, at 6% 18:2, 18:1 significantly decreased metastatic burden. When experimental metastasis was assessed, relatively low levels of surface lung nodules were observed at 1% and 6% 18:2, but significantly higher levels were observed at 12% 18:2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Relationship of the uptake and beta-oxidation of 18-carbon fatty acids with stimulation of murine mammary tumor cell growth.

The effects of stearic (18:0), oleic (18:1) and linoleic (18:2) acid on the in vitro growth of murine mammary tumor cell line 4526 were compared to 4526 uptake and beta-oxidation of those fatty acids. Both 18:1 and 18:2 stimulated, while 18:0 inhibited growth. Likewise, uptake and oxidation rates were much lower for 18:0 than for 18:1 and 18:2. The influence of glucose, insulin and fatty acid-depletion on 4526 fatty acid incorporation and oxidation was also determined. The correlation between effects on in vitro growth and ability to assimilate 18:0, 18:1 and 18:2 may partially explain the stimulation by unsaturated and inhibition by saturated fatty acids of in vivo 4526 tumorigenesis.

Animals↗

PubMed1991

Eicosanoids and linoleate-enhanced growth of mouse mammary tumor cells.

Metastatic mouse mammary tumor cell line 4526 was used to determine whether linoleate (LN)-derived cyclooxygenase metabolites were involved in the mechanism of LN-enhanced 4526 tumor growth. Unstimulated line 4526 cells converted LN to both PGE1 and PGE2 in serum free medium (SFM). However, neither prostaglandin (PG) influenced growth, while db-cGMP, but not db-cAMP, stimulated growth to the same extent as LN. Cyclooxygenase inhibitors stimulated growth while suppressing PG synthesis. Lipoxygenase inhibitors decreased growth in a dose dependent manner. Supplemental LN had no effect on cyclooxygenase inhibition while the IC50s for lipoxygenase inhibition were increased several fold. These results indicate that lipoxygenase products rather than cyclooxygenase metabolites play a major role in LN-stimulated growth of line 4526 cells.

Adenocarcinoma↗

PubMed1990

5-series peptido-leukotriene synthesis in mouse peritoneal macrophages: modulation by dietary n-3 fatty acids.

This study was undertaken to elucidate the metabolic fate of dietary eicosapentaenoic acid (20:5n-3), a major n-3 polyunsaturated fatty acid constituent of fish oil, in the mouse peritoneal macrophage. Mice were fed diets containing menhaden fish oil (FO) or safflower oil (SO). After 3 weeks, resident or responsive peritoneal macrophages were isolated and stimulated with zymosan and A23187, respectively. We demonstrate the novel synthesis of leukotriene C5 (LTC5), derived from 20:5n-3, in addition to LTC4 in both resident and responsive macrophages from FO fed mice. The structures of these peptido-leukotrienes were characterized by their retention times on reverse phase high pressure liquid chromatography, by their u.v. absorbance spectra, and by cross-reactivity with peptido-leukotriene antibody. These results demonstrate for the first time that macrophages are capable of metabolizing dietary 20:5n-3 to LTC5, a pentaene peptido-leukotriene.

Animals↗

PubMed1990

Modulation of mouse mammary tumor growth and linoleate enhanced metastasis by oleate.

This study examines whether oleate may influence the linoleate enhanced metastasis of line 4526 murine mammary tumors. In addition, the in vitro proliferative response of line 4526 to oleate and other selected fatty acids was assessed. Initially, the tumor cells were grown in a defined medium supplemented with palmitate, stearate, oleate, linoleate, linolenate or arachidonate. The unsaturated fatty acids stimulated and the saturated fatty acids inhibited proliferation compared to fatty acid-free medium. Next, we examined the effect of oleate on the linoleate enhanced metastasis of 4526 tumors by substituting oleate for saturated fat in isoenergetic diets containing high or low levels of linoleate. Oleate had no effect on metastasis in mice fed the high linoleate diets but it significantly increased metastasis in mice fed the low linoleate diets. Finally, the fatty acid compositions of tumors and mammary fat pads were compared to diet fatty acid compositions and metastatic frequency. Metastasis corresponded more closely to total unsaturated fatty acids than to total polyunsaturated fatty acids or to any individual fatty acid. These studies suggest that both mono- and polyunsaturated fatty acids may stimulate mammary tumor metastasis. However, the influence of dietary oleate probably depends on the level of linoleate and total unsaturated fatty acids in the diet.

Animals↗

PubMed1990

Dietary fat and tumor metastasis.

Evidence from several types of studies indicates a relationship between fat intake and occurrence of malignant tumors at specific sites. When rodents are fed high-fat diets, the incidence of mammary tumors sharply increases and latency of tumor appearance is greatly diminished, as compared with the same parameters in animals fed low levels of fat. Despite advances in surgical technique and the development of aggressive therapies for the treatment of primary cancers, most deaths in humans with cancer are caused by metastasis. Accordingly, we have reviewed the process of metastasis and have focused on the question of whether dietary fat can play a role. Metastasis is a complex, multistep, progressive process, and dietary fats may affect specific events such as implantation, survival, and proliferation of tumors. Finally, we discuss possible mechanisms by which dietary fat can modulate metastasis. Available data lead us to stress the importance of assessment of metastasis in studies of the effects of dietary fat on tumorigenesis.

Dietary Fats↗

PubMed1989

Alteration of in vitro murine peritoneal macrophage function by dietary enrichment with eicosapentaenoic and docosahexaenoic acids in menhaden fish oil.

The effects of diets containing menhaden fish oil (MFO), compared with those of diets containing safflower oil (SAF) or an essential fatty acid deficient hydrogenated coconut oil (HCO), on in vitro activation of tumoricidal capacity by murine macrophages were assessed. Mice fed the experimental diets for 4 weeks were injected intraperitoneally with sterile thioglycollate broth 3 days before use. There was no difference between any of the groups with respect to total peritoneal exudate cells or the percentage of macrophages, although the fatty acid profile of purified adherent macrophages closely paralleled that of the diets. Macrophages from mice fed MFO killed fewer P815 mastocytoma cells upon activation with recombinant interferon gamma (IFN gamma) and lipopolysaccharide. Macrophages from all diets were equally competent for tumoricidal capacity when activated pharmacologically with calcium ionophore, phorbol 12-myristate 13-acetate, and lipopolysaccharide (LPS), suggesting that MFO diet macrophages were hyporesponsive to IFN gamma. Priming with higher concentrations of IFN gamma restored the partial defect in activation of MFO macrophages. When activated for 24 hr with high levels of LPS, macrophages from mice fed SAF displayed little cytolytic capacity; addition of indomethacin. (1 microM) resulted in enhanced levels of P815 kill. In contrast, MFO and HCO diet macrophages were highly cytolytic with similar LPS treatment with or without indomethacin. Macrophages from mice fed SAF produced threefold more prostaglandin E in response to LPS than did MFO and HCO diet macrophages. These results suggest that dietary manipulation of fatty acids can alter activation of tumoricidal capacity of macrophages, possibly both dependent and independent of changes in eicosanoid synthesis.

Animals↗

PubMed1989

Linoleic acid metabolism in metastatic and nonmetastatic murine mammary tumor cells.

The mechanism(s) by which dietary linoleic acid (18:2n-6) enhances mammary tumor growth and metastasis is not known. Since arachidonic acid (20:4n-6)-derived prostaglandins (PG) may play a role in the metastatic dissemination of tumor cells, the ability of two murine mammary tumor cell lines, 4526 (metastasis positive) and line 168 (spontaneous metastasis negative), to convert 18:2n-6 into prostaglandins was examined. Cells were initially incubated with [14C]18:2n-6 and after 8-24 h the [14C]fatty acids were quantitated by high-performance liquid chromatography following transesterification. [14C]18:2n-6 was metabolized primarily to [14C]dihomogammalinolenic acid (20:3n-6) in line 4526 cells and [14C]20:4n-6 in line 168 cells. Examination of cellular fatty acid levels revealed a 20:3n-6/20:4n-6 ratio of 1.79 +/- 0.36 and 0.20 +/- 0.02 in line 4526 and 168 cells, respectively. These data are consistent with an inherently lower delta 5 desaturase activity in line 4526 relative to 168. To assess the metabolism of 18:2n-6 into eicosanoid products, the cell lines were prelabeled with [14C]18:2n-6 or 0-40 microM nonradiolabeled 18:2n-6 overnight and subsequently stimulated with calcium ionophore A23187 for 1 h. Total PGE production, as determined by radioimmunoassay, was greater in 168 relative to 4526 cells at all 18:2n-6 concentrations. 14C-prostaglandins detected by high-performance liquid chromatography and argentation thin-layer chromatography were: PGF1 alpha and PGE1 (derived from 20:3n-6) and PGF2 alpha and PGE 2 (derived from 20:4n-6) from line 4526; PGE1 and PGE2 from line 168. PGE1/PGE2 ratios were 1.43 +/- 0.07 and 0.23 +/- 0.03 for 4526 and 168 lines, respectively. Neither cell line synthesized lipoxygenase products following [14C]18:2n-6 or [3H]-20:4n-6 incubations under the conditions employed. Additional studies are warranted in order to define the biological properties of 1- and 2-series cyclooxygenase products as they relate to tumor cell metastasis.

Animals↗

PubMed1989

Regulation of murine macrophage function by IL-4. I. Activation of macrophages by a T-T cell hybridoma is due to IL-4.

A T-cell hybridoma produced by fusion of concanavalin A-stimulated murine splenocytes produced a factor (MAFH) capable of activating tumoricidal capacity by responsive murine peritoneal macrophages. Macrophages treated with the MAFH required an additional trigger signal of bacterial lipopolysaccharide (LPS) for maximal activity. In contrast to interferon-gamma (IFN gamma), which induced tumoricidal activity against all tumor cells tested, MAFH only induced macrophage-mediated kill of the BI6P51 and 168 lines, and not of the P815 or B16BL6 lines. An identical pattern of tumoricidal activity was obtained by treating macrophages with recombinant interleukin-4 (IL-4). The active moiety of MAFH appeared to be IL-4 as (i) monoclonal antibody against IL-4 blocked MAFH, but not IFN gamma, activity, and (ii) the T-cell hybridoma contained large amounts of mRNA for IL-4 and no detectable mRNA for IFN gamma (as determined by Northern dot analysis). The pattern of tumoricidal activity observed may be due to an IL-4 mediated enhancement of tumor necrosis factor production by LPS-triggered macrophages.

Animals↗

PubMed1989

Effect of dietary linoleic acid level on lodgement, proliferation and survival of mammary tumor metastases.

High levels of dietary linoleic acid (18:2) have been shown to increase the spontaneous metastasis of line 4526 mouse mammary tumors. In this report, the influence of 18:2 on specific events of tumor metastasis, namely, lodgement, proliferation and survival, were studied using spontaneous and experimental metastasis assays with line 4526 cells. A significantly greater number of radiolabeled tumor cells lodged in the lungs of mice fed 4, 8 and 12% 18:2 when compared with mice fed lower levels of 18:2. The effect of dietary 18:2 appeared to be on the host tissue (lungs) and not the tumor cells. Lodgement of tumor cells first cultured in serum of mice fed 18:2 then injected into mice fed 1% 18:2 was not affected. There were no significant differences in the percentage of [3H]thymidine labeled metastatic cells from lungs of mice fed different levels of 18:2. However, the number of surface lung nodules that appeared in mice 21 days after injection of unlabeled line 4526 cells increased in mice fed 8 and 12% 18:2 compared with those fed lower levels of 18:2. Thus, dietary 18:2 may increase metastasis by influencing the lodgement, implantation and survival but not proliferation of line 4526 mouse mammary tumor cells.

Animals↗

PubMed1989

Lack of an influence of dietary fat on murine natural killer cell activity.

The influence of the degree of saturation and the concentration of dietary fat on murine natural killer (NK) cell activity was investigated using C3H/HeN and C57BL/6N mice. Mice were fed purified diets containing either 0% fat (fat free), 5 or 20% safflower oil or 5 or 20% palm oil. Safflower oil and palm oil were used because they are comparable in carbon chain length but vary in the amount of linoleic acid [18:2(n-6)]. Cytotoxicity of splenic NK cells from mice stimulated or unstimulated by the interferon inducer poly I:C was measured against either the YAC-1 lymphoma or line 168 mammary tumor targets. The number of asialo GM1+ cells was not influenced by concentration or degree of saturation of dietary fat. Generally, dietary fat had no consistent influence on NK cell cytotoxicity of spleen cells from either the high responder C3H/HeN mice or the moderate responder C57BL/6N mice against either tumor target. The level of 18:2(n-6) in NK cell-enriched splenic lymphocytes increased with greater levels of dietary safflower oil. Nevertheless, there appeared to be no correlation between lymphocyte fatty acid composition and NK cell cytotoxic capabilities. Therefore, the concentration of dietary safflower or palm oil, and thus 18:2 (n-6), did not appear to effect the number or activity of murine NK cells.

Animals↗

PubMed1988

Inhibition of growth and linoleate-enhanced metastasis of a transplantable mouse mammary tumor by indomethacin.

The influence of the cyclo-oxygenase inhibitor, indomethacin (IM), on the metastasis, development and prostaglandin E (PGE) levels of line 4526 mammary tumors grown in mice fed high fat (HF, 20%, w/w) diets containing various levels of linoleic acid (18:2) was investigated. Control mice that grew primary tumors and were fed HF diets containing 12% 18:2 (w/w) had 2-3 times the number of lung metastases than mice fed 1%, 4%, or 8% 18:2. Chronic treatment of mice with 10 micrograms/ml IM in drinking water reduced metastasis in 1% and 4% 18:2-fed mice compared to controls and completely inhibited the increased metastasis of mice fed the 12% 18:2 diet. Treatment with IM also increased the latency and decreased the growth rates of primary 4526 tumors of all dietary groups. Treatment of mice with a higher dosage of IM (20 micrograms/ml), decreased tumor metastasis even further compared to controls, but did not decrease tumor growth rate compared to the lower dosage of IM (10 micrograms/ml). Tumor PGE levels, measured by radioimmunoassay (RIA), were decreased by IM treatment. These data provide evidence that arachidonic acid metabolites such as PGE may be involved in the metastasis of 4526 mammary tumors.

Animals↗

PubMed1988

Ability of 15-hydroxyeicosatrienoic acid (15-OH-20:3) to modulate macrophage arachidonic acid metabolism.

Mouse peritoneal macrophages metabolize dihomogammalinolenic acid (20:3n-6) primarily to 15-hydroxy-8,11,13-eicosatrienoic acid (15-OH-20:3). Since the biological properties of this novel trienoic eicosanoid remain poorly defined, the effects of increasing concentrations of 15-OH-20:3 and its arachidonic acid (20:4n-6) derived analogue. 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE), on mouse macrophage 20:4n-6 metabolism were investigated. Resident peritoneal macrophages were prelabeled with [3H]-20:4n-6 and subsequently stimulated with zymosan in the presence of either 15-OH-20:3 or 15-HETE (1-30 microM). After 1 hr, the radiolabeled soluble metabolites were analyzed by reverse phase high performance liquid chromatography. 15-OH-20:3 inhibited zymosan-induced leukotriene C4 (IC50 = 2.4 microM) and 5-HETE (IC50 = 3.1 microM) synthesis. In contrast to the inhibition of macrophage 5-lipoxygenase, 15-OH-20:3 enhanced 12-HETE synthesis (5-30 microM) and had no measurable effect on cyclooxygenase metabolism (1-10 microM) i.e., 6-keto-prostaglandin F1 alpha and prostaglandin E2 synthesis. Addition of exogenous 15-HETE produced similar effects. These results suggest that the manipulation of macrophage 15-OH-20:3n-6 levels may provide a measure of cellular control over 20:4n-6 metabolism, specifically, leukotriene production.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1988

Utilization of dihomo-gamma-linolenic acid (8,11,14-eicosatrienoic acid) by murine peritoneal macrophages.

This study examined the metabolism of dihomo-gamma-linolenic acid (20:3(n-6] in casein-elicited murine peritoneal macrophages. Cells were incubated with [14C]20:3(n-6) in the presence of 1% fetal bovine serum (FBS) or 0.025% bovine serum albumin (BSA), and the distribution and identity of membrane-bound and soluble products were determined. Approx. 70-80% of the [14C]20:3(n-6) was recovered in membrane phospholipids. The distribution of radiolabel in individual cellular phospholipids revealed a time-dependent (6 vs. 16 h) increase in the percentage of radiolabel esterified to phosphatidylethanolamine (PE). Analysis of cellular total lipids following transmethylation indicated that approx. 4, 2 and 9% of the incorporated 20:3(n-6), respectively, had been desaturated and elongated into 20:4(n-6), 22:4(n-6) and 22:3(n-6). When cells prelabeled for 16 h were incubated in the presence of the divalent cation ionophore, A23187, or zymosan for 30-60 min, two radiolabeled metabolites were isolated in the incubation supernatant. These metabolites were identified as 12-hydroxy-8,10,14- and 15-hydroxy-8,11,13-eicosatrienoic acids, as determined by reverse-phase and normal-phase high-performance liquid chromatography. The generation of monohydroxy fatty acids was notably absent in prelabeled quiescent cells and A23187-stimulated cells incubated with BW755C, a dual cyclooxygenase and lipoxygenase inhibitor. We conclude that casein-elicited murine peritoneal macrophages can extensively metabolize 20:3(n-6) through delta 5-desaturase, elongase and oxygenation reactions.

8,11,14-Eicosatrienoic Acid↗