Biomedical subjects

K Kline

Publications and source records attributed to K Kline.

At least 37 records · Page 2Linked to original sources

PubMed1995

Nutrition, immunology and cancer: an overview.

There is epidemiological, laboratory and some clinical evidence that certain dietary factors play a role in either promoting or inhibiting cancer development. An understanding of the mechanisms whereby specific nutrients are having effects in the promotion or prevention of cancer is beginning to take shape. Research into nutrient effects on the expression of specific genes, especially cytokine and cytokine receptor expression, will help increase our basic knowledge of cancer biology. Since cytokines can either enhance or suppress both immune defense and cancer growth, increased understanding of nutrient effects on the cytokine network will be beneficial. The regulation of specific gene expression by specific nutrients, indeed, identifies a major frontier for present and future nutritional biologists.

Allergy and Immunology↗

PubMed1995

Vitamin E succinate induction of HL-60 cell adhesion: a role for fibronectin and a 72-kDa fibronectin-binding molecule.

HL-60 cells, growing as single cells in suspension, exhibit marked cell-cell adhesion when treated for 24 hours with 10 micrograms/ml RRR-alpha-tocopheryl succinate, also called vitamin E succinate (VES). VES-induced cell-cell adhesion is dependent on divalent cations and a functional cytoskeleton and is protein mediated. Cell adhesion molecules CD11a/CD18, CD11b/CD18, CD29, and CD54 do not appear to be mediating VES-induced cell adhesion. HL-60 cells treated with VES adhere to fibronectin-coated plastic and secrete elevated levels of fibronectin. A 72-kDa fibronectin-binding membrane molecule was detected on VES-treated HL-60 cells, and antibodies to fibronectin were shown to inhibit VES-induced cell aggregation. VES induction of HL-60 cell-cell adhesion is proposed to result from increased amounts of extracellular fibronectin binding to VES-induced cell surface fibronectin-binding molecules.

Antibodies↗

PubMed1995

RRR-alpha-tocopheryl succinate inhibits the proliferation of human prostatic tumor cells with defective cell cycle/differentiation pathways.

The RRR-alpha-tocopheryl succinate derivative of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of three metastatic human prostatic cancer cell lines, LNCaP, PC-3, and DU-145. LNCaP is a lymph node-derived androgen-sensitive prostate cell line; these cells are defective for response to transforming growth factor-beta (TGF-beta) but are normal for cell cycle-related tumor suppressor genes: p53 and retinoblastoma (Rb). PC-3 is a bone marrow-derived androgen-insensitive prostate cell line; these cells are defective for both p53 alleles but normal for both Rb alleles. DU-145 is a brain-derived androgen-insensitive prostate cell line; these cells are defective for both p53 and both Rb alleles. VES at 5, 10, and 20 micrograms/ml inhibited DNA synthesis in the three cell lines in a dose-dependent manner. Purified TGF-beta 1 at 1 ng/ml inhibited DNA synthesis of PC-3 cells within 24-72 hours and DU-145 cells at 72 hours but did not inhibit DNA synthesis of LNCaP cells. Previous studies in our laboratory showed that VES growth-inhibited tumor cells secrete biologically active antiproliferative factor TGF-beta s, suggesting that VES's mechanism of growth inhibition may involve the TGF-beta system of growth control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1995

RRR-alpha-tocopheryl succinate inhibits DNA synthesis and enhances the production and secretion of biologically active transforming growth factor-beta by avian retrovirus-transformed lymphoid cells.

The RRR-alpha-tocopheryl succinate form of vitamin E, referred to as vitamin E succinate (VES), inhibits the proliferation of avian reticuloendotheliosis virus-transformed RECC-UTC4-1 (C4-1) lymphoblastoid cells in a dose-dependent manner in vitro. Analyses of conditioned medium (CM) from VES growth-inhibited cells revealed a potent antiproliferative activity. Characterization of the antiproliferative activity as transforming growth factor-beta (TGF-beta) was established by 1) growth inhibition of TGF-beta-responsive Mv1Lu mink lung and murine CTLL-2 cell lines, 2) a combination of physical characteristics including heat stability, acid stability, and Bio-Gel P-60 column chromatography elution profile, 3) neutralization of the antiproliferative activity by antibodies specific for TGF-beta, and 4) immunoprecipitation of metabolically labeled TGF-beta in CM from VES-treated C4-1 cells by use of TGF-beta-specific antibodies. Northern blot analyses of total cellular RNA revealed that VES does not alter the levels of constitutively expressed TGF-beta isoform-specific mRNAs; namely, VES does not alter the levels of the 3.9- and 4.1-kb TGF-beta 2 mRNAs, the 3.0-kb TGF-beta 3 mRNA, or the 2.5-, 2.7-, and 1.7-kb TGF-beta 4 mRNAs. The data show that VES inhibits C4-1 cell proliferation and induces the cells to produce and secrete active forms of TGF-beta, suggesting that one mechanism whereby VES inhibits C4-1 cell proliferation may be via the TGF-beta pathway for cellular growth control.

Animals↗

PubMed1993

RRR-alpha-tocopheryl succinate inhibits proliferation and enhances secretion of transforming growth factor-beta (TGF-beta) by human breast cancer cells.

The RRR-alpha-tocopheryl succinate form of vitamin E inhibits the proliferation of estrogen receptor-positive and estrogen receptor-negative human breast cancer cell lines in a dose-dependent manner in vitro. Analyses of cell-conditioned medium from RRR-alpha-tocopheryl succinate growth-inhibited cells revealed the presence of a potent antiproliferative activity. Characterization of the antiproliferative activity as transforming growth factor-beta (TGF-beta) was established by 1) growth inhibition of the TGF-beta-responsive Mv1Lu-CCL-64 mink lung and murine CTLL-2 cell lines, 2) combination of physical characteristics including heat stability, acid stability, and Bio-Gel P-60 column chromatography elution profile, and 3) neutralization of the antiproliferative activity in the conditioned media by antibodies specific for TGF-beta.

Antioxidants↗

PubMed1993

RRR-alpha-tocopheryl succinate inhibition of lectin-induced T cell proliferation.

The effect of RRR-alpha-tocopheryl succinate (VES) on lectin-induced chicken T cell proliferation was investigated. The T cell mitogens concanavalin A and phytohemagglutinin induce chicken thymic and splenic T cell proliferation. Addition of VES to the in vitro cultures inhibited T cell proliferation in a dose-dependent manner. Addition of VES to spleen cell cultures at different times after mitogen stimulation also suppressed T cell mitogenesis, suggesting that VES is not mediating its antiproliferative effects by interfering with ligand (mitogen)-receptor binding or early ligand-bound receptor-signaling events. Three lines of evidence suggest that the growth-inhibitory properties of VES are unique and may not involve antioxidant properties. 1) Three other forms of vitamin E, dl-alpha-tocopherol, d-alpha-tocopherol, and d-alpha-tocopherol acetate, do not inhibit the proliferation of mitogen-stimulated chicken spleen cells. 2) Spleen cells were treated with an inhibitor of nonspecific esterases to prevent the conversion of VES, which does not exhibit antioxidant properties to d-alpha-tocopherol, a lipid-soluble antioxidant. Treatment of spleen cells with the inhibitor did not affect VES's growth-inhibitory properties. 3) Trolox, a water-soluble vitamin E analogue with potent antioxidant properties and two lipid-soluble antioxidants, butylated hydroxyanisole and butylated hydroxytoluene, did not inhibit mitogen-induced T cell proliferation. Attempts to reverse VES's antiproliferative effects by addition of exogenous interleukin-2 or addition of sodium selenite, an enhancer of interleukin-2 receptors, failed. Acetylsalicylic acid had no effect on VES's inhibition of mitogen-activated T cell proliferation. These studies support the role of VES as a growth inhibitor of lectin-activated normal T cells in chickens.

Animals↗

PubMed1993

Effects of RRR-alpha-tocopheryl succinate on IL-1 and PGE2 production by macrophages.

Vitamin E is thought to enhance immunity by increasing interleukin-1 (IL-1) production and by downregulating prostaglandin E2 (PGE2) synthesis. In an effort to understand the mechanism(s) whereby the form of vitamin E known as RRR-alpha-tocopheryl succinate [also called vitamin E succinate (VES)] ameliorates retrovirus-induced immune dysfunctions, peritoneal exudate cells (PECs) derived from normal chickens and avian and murine macrophage cell lines were used as in vitro model systems to test the effects of VES treatments on PGE2 and IL-1 production. Supernatants from PECs that were exposed to avian erythroblastosis virus (AEV) for 45 minutes exhibited a 256% increase in PGE2 levels compared with supernatants from replica cultures of PECs not exposed to AEV. Pretreatment of PECs with VES before exposure to AEV maintained PGE2 levels at normal control levels. VES treatment enhanced IL-1 production by avian (HD11) and murine (P388D1) macrophage cells, respectively. Supernatants from VES-treated HD11- and P388D1-stimulated cells contained IL-1 activity 196% and 385%, respectively, greater than that observed with supernatants from untreated control cells. On the basis of these studies, downregulation of retrovirus-induced PGE2 production and/or upregulation of IL-1 production by VES are potential mechanisms for VES amelioration of retrovirus-induced immune suppression.

Animals↗

PubMed1993

RRR-alpha-tocopheryl succinate induced interleukin-2 production by avian splenic T lymphocytes and murine EL-4 thymic lymphoma cells.

RRR-alpha-tocopheryl succinate (vitamin E succinate) was studied for its effects on interleukin-2 (IL-2) production by chicken splenic derived T lymphocytes and murine EL-4 thymic lymphoma cells. Supernatants from 0.1 microgram/mL vitamin E succinate-supplemented chicken splenic T cell cultures exhibited 42-72% enhanced IL-2 production over vehicle controls when tested in a chicken T cell blast bioassay. Supplementation of chicken splenic T lymphocyte cultures with butylated hydroxyanisole (BHT) and butylated hydroxytoluene (BHA) also induced elevated levels of IL-2, suggesting a role for antioxidants in IL-2 production by avian splenic T lymphocytes. Supernatants from vitamin E succinate-supplemented murine EL-4 cells (0.1 microgram/mL vitamin E succinate) induced 52-75% increased levels of IL-2 when compared to supernatants from vehicle controls when tested using a murine, IL-2-dependent CTLL-2 bioassay. IL-2 production by EL-4 cells was not enhanced by treatments with BHT, BHA, or Trolox, suggesting that vitamin E succinate-induced IL-2 production by EL-4 cells may involve a mechanism other than antioxidant effects. Vitamin E succinate plus suboptimal levels of the protein kinase C (PKC) activator phorbol myristate acetate (PMA) induced the highest levels of IL-2 by EL-4 cells. The studies provide evidence that vitamin E succinate can directly potentiate either the production or release of IL-2 from avian splenocytes and murine EL-4 cells.

Animals↗

PubMed1992

RRR-alpha-tocopheryl succinate modulation of human promyelocytic leukemia (HL-60) cell proliferation and differentiation.

HL-60 human promyelocytic leukemia cells can be induced to differentiate to granulocytes by retinoic acid and dimethyl sulfoxide or monocyte-macrophages by phorbol esters and 1,25-dihydroxyvitamin D3. These studies show that RRR-alpha-tocopheryl succinate (TS) inhibits HL-60 cell proliferation and induces the HL-60 cells to differentiate toward a functionally deficient macrophage-like cell. TS at (15 micrograms/ml) was found to suppress HL-60 cell proliferation by 63% and 89% at 24 and 48 hours, respectively. This suppression of proliferation, however, is not permanent and requires the presence of TS. HL-60 cells treated for 48 hours with TS (15 micrograms/ml) were found to be blocked in the G2/M phase of the cell cycle. HL-60 cells blocked in the G2/M cell cycle phase by TS expressed normal levels of the transferrin receptor. TS-treated HL-60 cells exhibited binucleated morphological appearance; however, the cells did not exhibit chemotaxis, phagocytosis, or changes in the expression of the cell surface markers, CD11a and CD18. However, HL-60 cells treated for 48 hours with TS (15 micrograms/ml) could be stimulated to produce superoxide radicals and exhibited nonspecific esterase activity, two characteristics of macrophages. These results suggest a role for TS as an antitumor proliferative agent and as a modifier of human leukemia cell differentiation.

Antigens, CD↗

PubMed1991

RRR-alpha-tocopheryl succinate enhances T cell mitogen-induced proliferation and reduces suppressor activity in spleen cells derived from AEV-infected chickens.

RRR-alpha-tocopheryl succinate was demonstrated to be a potent in vitro modulator of retrovirus-induced immune abnormalities. Spleen cells from avian erythroblastosis virus (AEV)-infected chickens exhibit suppressed T cell mitogen-induced proliferative responses and elevated levels of suppressor T cell activity. In vitro addition of RRR-alpha-tocopheryl succinate resulted in amelioration of these abnormalities. Antioxidants including Trolox (a water-soluble analogue of RRR-alpha-tocopherol with antioxidant properties) and a combination of butylated hydroxyanisole and butylated hydroxytoluene were able to restore immune functions to levels similar to those achieved with RRR-alpha-tocopheryl succinate treatment. Aspirin, an irreversible inhibitor of cyclooxygenase activity, was capable of ameliorating some of the AEV-induced immune dysfunctions. These studies suggest a role for the antioxidant functions of RRR-alpha-tocopheryl succinate in modulation of retrovirus-induced immune abnormalities.

Alpharetrovirus↗

PubMed1991

Apparent role of adenosine diphosphoribosyl transferase in the development of Mytilus edulis and the inhibition of differentiation by ligands of the enzyme protein.

The poly(ADP-ribose) polymerase or transferase (ADPRT) activity of developing embryos of Mytilus edulis increases with the progression of larval growth. ADPRT protein was partially purified from 2-hr-old embryos and identified by gel electrophoresis and immunotransblot, demonstrating cross-reactivity with anti-ADPRT IgG produced against the calf thymus enzyme. Two inhibitors of ADPRT, benzamide, competing with NAD at the nicotinamide binding site, and 6-amino-1,2-benzopyrone, which competes with DNA at the DNA binding site(s), both selectively arrest differentiation at the prodissoconch stage. The DNA site-oriented inhibitor, 6-amino-1,2-benzopyrone, has a much larger differentiation arresting effect than benzamide. The arrest of differentiation by 6-amino-1,2-benzopyrone is reversible. A probable ecotoxicity of ADPRT ligands on mussel differentiation is proposed.

Animals↗

PubMed1990

Immune abnormalities in avian erythroblastosis virus-infected chickens.

Infection of animals with retroviruses frequently leads to immunosuppressed states. The immune status of chickens injected with the replication-defective avian erythroblastosis virus (AEV), with its naturally occurring subgroup B helper virus (avian erythroblastosis-associated virus; AEAV), was evaluated daily and compared to the immune status of age-matched uninfected control chickens. Spleen cells from AEV-infected chickens gave depressed responses to concanavalin A, phytohemagglutinin, and pokeweed mitogen beginning 3 days after injection of the virus and continuing until death. Spleen cells from AEV-infected chickens suppressed the T-cell mitogen-induced blastogenic responses of spleen cells from uninfected chickens. The ability of spleen cells from infected chickens to suppress mitogen-induced blastogenic responses of spleen cells from normal chickens in coculture was transient beginning 4 days following viral inoculation, reaching peak levels of suppression on day 7 and disappearing by day 12. Cytolysis of splenic cells from AEV-infected chickens with polyclonal anti-T-cell-serum removed the suppressor activity. Addition of conditioned medium rich in T-cell growth factor resulted in a partial restoration of the blastogenic responsiveness of splenic cells from 6-day post-AEV-infected chickens. Addition of exogenous T-cell growth factor had no effect on the suppressed blastogenic responsiveness of spleen cells from 12-day post-AEV-infected chickens, and it had no effect on coculture suppression. In addition to suppressed T-cell responses to polyclonal mitogen-induced proliferation in vitro and transiently expressed T-suppressor cells, thymic atrophy and structural disruption was observed in AEV-infected chickens.

Alpharetrovirus↗

PubMed1990

Characterization and developmental expression of the chicken B-G heterodimer.

Monoclonal antibody R7-3 recognized an erythroid specific cell surface molecule with a m.w. of approximately 98 kilodaltons (Kd) under nonreducing conditions and molecules of 40 and 44 Kd under reducing conditions on both embryonic- and adult-derived peripheral RBC. Immunochemical characterization, including limited peptide map analyses of these molecules, provided evidence that mAb R7-3 was recognizing the MHC coded B-G heterodimer. This is the first report of a monoclonal antibody that recognizes the B-G heterodimer. Affinity binding studies suggested that mAb R7-3 preferentially recognized the 44 Kd molecule. Immune depletion analyses demonstrated the presence of a single population of B-G heterodimers. Endoglycosidase-F and neuraminidase digestions suggested that the 44 and 40 Kd molecules contained very little, if any, carbohydrate. B-G heterodimer expression was examined on primitive and definitive RBC during embryonic development. B-G heterodimer expression was not detected on RBC of other avians.

Animals↗

PubMed1990

Growth-inhibitory effects of vitamin E succinate on retrovirus-transformed tumor cells in vitro.

Vitamin E succinate inhibited proliferation of C4#1 cells, an established avian retrovirus [reticuloendotheliosis virus (REV)]-transformed immature lymphoid tumor cell line, in a dose-dependent manner. The cytostatic effects of vitamin E succinate were reversible in that treated cells regained their ability to divide after vitamin E succinate removal. Possible mechanism(s) for the antiproliferative actions of vitamin E succinate were investigated. Analyses of C4#1 cell surface membrane antigen profiles and morphology indicated that vitamin E succinate was not inducing differentiation of the tumor cells to a more mature, differentiated, nonproliferative state. Five antioxidants, including a synthetic analogue of vitamin E, Trolox, as well as the active vitamin form, DL-alpha-tocopherol, were incapable of inhibiting C4#1 tumor cell growth, indicating that a mechanism of action other than or in addition to functions as an antioxidant may be operating. Cell cycle analyses suggested that C4#1 tumor cells treated with vitamin E succinate were blocked in the G0G1/early S phases of the cell cycle. Tumor growth arrested by vitamin E succinate did not affect the expression of the REV-encoded oncogene, v-rel, at either the RNA or protein level. These studies demonstrated that vitamin E, in the form of vitamin E succinate, inhibited the growth of retrovirus-transformed tumor cells in vitro and suggested that the antiproliferative effects of vitamin E succinate did not involve antioxidant properties but rather, as yet, unidentified mechanisms leading to cell cycle blockage.

Antioxidants↗

PubMed1990

Teacher characteristics and competencies related to substance abuse prevention.

Teacher characteristics and competencies perceived as beneficial for preventing substance use among students were identified through a literature search, review of existing prevention curricula, and consultation with state and local experts. These qualities were integrated into a questionnaire and administered to acknowledge professionals in the substance use and abuse arena who were affiliated with universities, public schools, and prevention/intervention agencies. A factor analysis yielded six constructs which were then scaled, examined for psychometric appropriateness, and subsequently employed to quantify perceptions of importance. Teacher-Student Relations emerged as the most important aspect of teacher comportment, followed by knowledge associated with Human Behavior, Substances, User Recognition and Referral, Prevention Curricula, and Legal Issues. These findings are encouraging in that the characteristics and skills perceived as important to prevention can be developed in both pre- and in-service teacher training.

Adult↗

PubMed1990

Effect of sodium bicarbonate on racing Standardbreds.

Twenty-two Standardbred horses in race training were used in a crossover experiment to determine the effect of oral sodium bicarbonate (NaHCO3) administration on performance and metabolic responses to a 1.6-km (1-mile) race. Horses were paired and one horse in each pair was treated with either NaHCO3 (300 mg/kg BW) or a placebo, 2.5 h before they raced against each other. Each horse was scheduled to compete in two races, approximately 1 wk apart, one on each treatment. Horses always raced in the same pairs. Fourteen horses successfully completed both races. Jugular blood samples were obtained 1.5 h after treatment (rest), immediately before racing, 5 min post-race and 15 min post-race. In six horses, blood samples also were obtained 30 min post-race. Race times averaged 1.1 s faster after NaHCO3 treatment (P less than .1). Sodium bicarbonate treatment also elevated blood pH (P less than .05). In the horses sampled 15 and 30 min post-race, blood lactate disappearance was faster with the NaHCO3 treatment (P less than .05). The NaHCO3 may delay the fatigue precipitated by i.m. acidosis. Because other factors may limit performance (musculoskeletal soundness, cardiovascular and respiratory ability), NaHCO3 would not be expected to enhance the performance of all horses. However, the effect of NaHCO3 on lactate clearance may have implications for all intensively worked horses; because lactate and the associated hydrogen ions are believed to cause muscle damage and soreness, any mechanism to increase their removal rate could benefit the equine athlete.

Acid-Base Equilibrium↗

PubMed1989

Chicken transferrin receptor expression during erythroid differentiation and by retrovirus transformed cells.

Antiserum prepared against sucrose gradient purified reticuloendotheliosis virus (REV) recognized the chicken transferrin receptor. Molecules immunoprecipitated from red blood cells (RBC) obtained from embryonic chickens with either the anti-REV reagent or a chicken transferrin immunomatrix were demonstrated to be identical by co-migration in both reducing and nonreducing SDS-polyacrylamide gels and in two-dimensional isoelectric focusing analyses, reciprocal immunodepletion analyses and by peptide mapping. The chicken transferrin receptor was shown to be a 190,000 dalton cell surface membrane molecule consisting of two similar disulfide-bonded subunits of approximately 95,000 daltons. The chicken transferrin receptor was expressed on erythroid cell surface membranes as 95,000 dalton monomers as well as 190,000 dalton dimers. The chicken transferrin receptor was expressed on all differentiation/maturation stages, including mature RBC, of both the primitive and definitive type I erythroid cell series. In adult chickens, the transferrin receptor was expressed by immature erythroid cells in the bone marrow, but not by mature circulating RBC. REV-transformed immature lymphoid cells and avian erythroblastosis virus (AEV)-transformed erythroid cells expressed dimers composed of 95,000 and 110,000 dalton subunits. Comparisons among V8 protease derived peptides from 95,000 dalton transferrin receptors obtained from RBC and REV-transformed lymphoid cells revealed a high degree of homology; however, the 95,000 dalton molecules isolated from REV-transformed lymphoid cells exhibited a 56,000 dalton peptide that was unique. Cloned AEV-transformed erythroleukemia cells induced to differentiate by supplementation of the media with 1 mM butyric acid expressed elevated transferrin receptor levels. Both serological and peptide mapping studies demonstrated the human transferrin receptor on K562 cells and the chicken transferrin receptor to be distinct. However, chicken transferrin was shown to be capable of reacting with the human transferrin receptors on K562 cells.

Animals↗

PubMed1987

Impact of commercial eating on nutrient adequacy.

The purpose of this study was to investigate the impact of eating away from home (at commercial establishments) on nutrient adequacy by examining frequency of eating away from home, the nutritional value of foods eaten both away and at home, and the nutritional adequacy of the daily diets of individuals. Data from 3,500 individuals, 15 years of age or older, interviewed in the fall quarter of the 1977-78 Nationwide Food Consumption Survey were used. Results indicate that although the nutrient density of food eaten away from home was lower than that of food eaten at home, the persons studied did not eat out frequently enough to influence the adequacy of their diets significantly. The low nutrient density of food eaten away from home does suggest, however, that individuals could be putting themselves at risk of some nutrient inadequacies (particularly of calcium and vitamins A, B-6, and C) or of caloric excess if they substantially increase their frequency of eating away from home. Teenagers and senior citizens seem most vulnerable to potential nutritional inadequacies.

Adolescent↗