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Biomedical subjects

R Kibler

Publications and source records attributed to R Kibler.

At least 19 recordsLinked to original sources
PubMed1998

[Alimentary intake of selected pollutants and nitrate--results of a duplicate study in Bavarian homes for youth and seniors].

In a duplicate study during 1987-1991, 478 24-h duplicate samples from 14 homes for elderly people and 10 homes for youth were investigated for their contents of selected harmful substances. The analyses covered 45 active substances of pesticides, 17 PCB-congeners as well as lead, cadmium, and nitrate contents. Pesticides could be detected only in 15% of the investigated samples. The pesticide contents reached max. 8% of the respective FAO/WHO-limits. As the mean intake of the three most important PCB-congeners (sum of the congeners 138, 153, and 180) values of 0.9 and 1.1 micrograms per day and ration or person, respectively, were found. Also in the worst case the daily PCB intake was below the recommended ADI value of the FDA of 1 microgram/kg of body weight. The daily nutritional intake of lead and cadmium via the investigated daily rations reached about 5.6% and 20% of the Provisionally Tolerably Weekly Intake values of the FAO/WHO. The mean nitrate content of the duplicate portions was 101 mg per day and person (median: 79 mg per day and person). Referred to the median value the WHO limit (3.65 mg/kg body weight and day) was exhausted to about 36%.

Adolescent↗
PubMed1994

Automated enumeration of CD34+ cells in peripheral blood and bone marrow.

We have developed a rapid and accurate method to enumerate the number of CD34+ cells in peripheral blood, bone marrow, and leukopheresis samples. The method consists of a two-tube assay and a dedicated software program for data acquisition and analysis. The first reagent combination consists of (a) a nucleic acid dye to identify nucleated cells, (b) a CD45 monoclonal antibody labeled with PE/CY5 to discriminate progenitor cells from mature lymphoid, neutrophil, erythroid, and monocytic cells, (c) an IgG1 control antibody labeled with PE to establish the boundary between specific and nonspecific staining, and (d) a known number of fluorescent beads to determine an absolute count of cells. In the second reagent combination the IgG1 control antibody is replaced by a CD34 antibody labeled with PE that is used to identify the CD34+ cells in the location established by the control reagent combination. The software program uses the fluorescent beads to adjust the forward light scatter, orthogonal light scatter, and three fluorescence detectors of the flow cytometer. The expected location of the CD34+ cells is then established with the control reagent combination followed by the enumeration of the CD34+ cells per microliter of sample with the reagent combination containing the CD34 antibody. This method is sensitive enough to detect CD34+ cells in peripheral blood of normal donors and can reliably determine an increase in CD34+ cells in the peripheral blood of patients treated with chemotherapy and/or growth factors. The method alleviates some of the difficulties encountered when small numbers of CD34+ cells are enumerated. The system allows for more precise evaluations of the grafts used for bone marrow transplantation.

Antigens, CD↗
PubMed1993

Characterization of cross-reactive anti-DNA autoantibodies in murine lupus.

The role of crossreactive anti-DNA autoantibodies in the pathogenesis of Systemic Lupus Erythematosus (SLE) and its counterpart in the mouse (murine lupus) remains undefined. Five murine monoclonal anti-DNA autoantibodies tested in ELISA and immunofluorescence assays were found to cross-react with a variety of both nucleic acid and non-nucleic acid antigens. These included double stranded DNA (dsDNA), single stranded DNA (ssDNA), transfer RNA (tRNA), and the murine thymoma cell lines WEHI-22, WEHI-7, and EL-4. The majority of the autoantibodies reacted with all antigens tested; none of the autoantibodies reacted with only one antigen. To determine if the multiple reactivities demonstrated by these hybridoma-derived monoclonal anti-DNA autoantibodies accurately reflects the in vivo, autoimmune environment, the same assays were used to measure the reactivities of autoantibodies secreted directly from unfused autoimmune spleen cells cultured in vitro. These spleen cell-derived autoantibodies were found to display reactivities very similar to those demonstrated by the monoclonal anti-DNA autoantibodies indicating that the hybridoma process itself does not appear to select and amplify reactivities which are not present in vivo. Initial molecular characterization of F11, a monoclonal anti-DNA autoantibody crossreactive with both dsDNA and ssDNA, revealed that it utilizes the same VH gene segment as an anti-DNA autoantibody specific for ssDNA. F11 was also found to utilize similar VH, D, and JH gene segments as an antibody directed against the hapten polymer (Glutamic acid60, Alanine30, Tyrosine10)n (GAT). Thus, the same Ig gene segments used to encode crossreactive anti-DNA autoantibodies can also be utilized by anti-DNA autoantibodies displaying strict antigen specificity as well as by antibodies directed against exogenous antigens.

Amino Acid Sequence↗
PubMed1990

[Intake of polychlorinated biphenyls (PCB) in the total diet].

The content of six selected indicator polychlorobiphenyl (PCB) congeners (nos 28, 52, 101, 138, 153, and 180) in 159 samples of total diet obtained from 20 different people has been determined by capillary gas chromatography. The congeners most frequently found were nos 138 and 153. The mean daily intake of the sum of the three congeners 138, 153, and 180 was 2.3 micrograms/person. This value compares favourable with a value calculated from PCB content of selected foods and consumption data.

Chromatography, Gas↗
PubMed1987

Prolactin-dependent mitogenesis in Nb 2 node lymphoma cells: effects of immunosuppressive cyclopeptides.

Prolactin (PRL)-stimulated ornithine decarboxylase (ODC) activity and subsequent proliferation are inhibited by the cyclopeptides cyclosporine (CsA) and didemnin B (DB) in Nb 2 node lymphoma cells. Similar concentrations of these agents also inhibit 125I-PRL binding, suggesting that their inhibitory effects on these PRL-dependent physiologic responses are mediated at least in part at the level of PRL receptor interactions. The phorbol ester TPA stimulated ODC activity and [3H]thymidine incorporation to 54% and 31% that of a near-optimal mitogenic concentration of PRL (10 ng/ml), suggesting that mitogenesis in these cells is coupled to some degree to the activation of protein kinase C (PKC). The calcium ionophore A23187 increased ODC activity only slightly and actually decreased [3H]thymidine incorporation to a value below the "cells only" controls. The addition of TPA plus A23187 did not further enhance the effects of TPA to elevate ODC activity and [3H]thymidine incorporation. However, A23187 significantly elevated PRL-stimulated ODC activity with a subsequent inhibition of [3H]thymidine incorporation, suggesting a block of entry into S phase. Both cyclopeptides decreased the elevation of ODC activity in G1 phase of cell cycle in response to PRL, suggestive of a site of action for these agents in early G1, a conclusion compatible with their ability to inhibit PRL binding to these cells. Addition of CsA or DB 2 hr after PRL had no effect on PRL-stimulated ODC activity detectable at 6 hr, but addition of either as late as 6 hr still affected the extent of mitogenesis. This is in line with the requirement for PRL to be present in the culture medium for a minimum of 3 to 6 hr to invoke a maximal effect on mitogenesis. Addition of either cyclopeptide after the cells were in S phase had no effect on the extent of [3H]thymidine incorporation. An inhibitor of the cyclooxygenase pathway (indomethacin) enhanced both PRL-stimulated ODC activity and proliferation, whereas inhibition of the lipoxygenase pathway by NDGA attenuated only proliferation, suggesting that in Nb 2 cells, products of the lipoxygenase pathway may contribute to the mechanism of PRL-stimulated mitogenesis. Because Nb 2 lymphoma cells were derived from estrogenized rats, estrogen was tested as a mitogen. By itself it was not mitogenic, but in conjunction with PRL, estradiol-17 beta elevated the ODC response and inhibited proliferation. Inhibitors of PKC known to have minimal effects on RNA synthesis, quercetin and gossypol, totally inhibited both the elevations of ODC activity and [3H]thymidine incorporation in response to PRL in Nb 2 lymphoma cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Ultrastructural morphometric analysis of nuclear contour irregularity in normal cord and adult blood: correlation with distinct lymphocyte subpopulations.

Cord blood lymphocytes obtained from ten healthy newborns and peripheral blood obtained from ten healthy adults were compared by using ultrastructural morphometric methods. Cord blood lymphocytes could be distinguished from adult lymphocytes on the basis of nuclear contour irregularity (form factor) and perimeter (P less than .001). The mean nuclear form factor (FF) value of the cord lymphocytes, as a group, was 0.603 +/- 0.034; the mean nuclear FF value of adult lymphocytes was 0.755 +/- 0.032. Lymphocyte subpopulations were quantitated by flow cytometric and immunofluorescence techniques and correlated with nuclear contour irregularity (mean FF values) by using linear regression analysis. Overall, the correlations between nuclear contour irregularity and the proportions of distinct lymphocyte subpopulations were opposite for cord and adult blood. Increased nuclear contour irregularity was associated with increased proportions of immature lymphocytes (non-T, non-B lymphocyte population) in the neonate and with increased proportions of T cells in the adult. Of the T cells, increased nuclear contour irregularity showed a better correlation with increased proportions of T helper cells compared with T suppressor cells. A plot of the distribution of FF values indicated two populations of lymphocytes having convoluted and nonconvoluted nuclei, respectively. No true Sézary cells could be identified in cord blood with ultrastructural morphometric criteria, despite the abundance of cerebriform mononuclear cells identified by visual inspection. The lymphocyte with the most irregular nuclear contour was found in an adult and had an FF value of 0.132 (13% of a circle). The contribution of this study to the diagnosis of cutaneous T cell lymphomas and the Sézary syndrome is discussed.

Adult↗
PubMed1986

Prolactin stimulation of ornithine decarboxylase and mitogenesis in Nb2 node lymphoma cells: the role of protein kinase C and calcium mobilization.

The tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) in combination with calcium ionophores has been shown to bypass the requisite antigen- or lectin-induced signal for lymphocyte mitogenesis. This suggests that protein kinase C activation and calcium mobilization may be early events required for lymphocyte proliferation. Therefore, the relationship(s) of protein kinase C activation and calcium mobilization to ornithine decarboxylase induction and cellular proliferation were examined in a rat node lymphoma cell line (Nb2) which is dependent upon prolactin (PRL) for mitogenesis. TPA enhanced PRL-stimulated Nb2 node lymphoma cell ornithine decarboxylase induction and [3H]thymidine incorporation. Addition of a calcium ionophore (A23187) to cultures containing TPA plus PRL increased ornithine decarboxylase above PRL alone or PRL plus TPA but inhibited proliferation compared to the PRL plus TPA regimen. Exposure of cells to TPA or TPA plus A23187 increased [3H]thymidine incorporation in a similar manner to that demonstrated for low-dose PRL. However, optimal concentrations were only 20-25% as effective as mitogens as was optimal PRL. Protein kinase C and calmodulin antagonists inhibited PRL-stimulated ornithine decarboxylase induction and proliferation. Ca2+ chelation or cation channel antagonism inhibited both PRL-stimulated responses. The cyclic AMP analogue, 8Br-cAMP, inhibited PRL-stimulated ornithine decarboxylase activity as well as cellular proliferation processes assessed by [3H]thymidine incorporation. Finally, tumor-promoting phorbol esters inhibited 125I-rPRL binding. These data strongly suggest that protein kinase C activation and calcium mobilization are requisite events for PRL-stimulated ornithine decarboxylase induction and cellular proliferation in Nb2 node lymphoma cells. An additional component that is linked to alterations in K+ channeling is also implicated. These data support a role for protein kinase C in PRL-coupled mitogenesis. However, other critical Ca2+ and/or ion-induced events are also required.

Animals↗
PubMed1986

A comparative analysis of cord blood and adult lymphocytes: interleukin-2 and interferon production, natural killer cell activity, and lymphocyte populations.

A comprehensive comparative analysis of lymphocyte populations, natural killer cell activity, and interleukin-2 (IL-2) and interferon production was performed on cord blood and adult peripheral blood mononuclear cell populations. Analysis of the cell types present demonstrated significantly lower percentages of T3+, T8+, and Leu 11+ cells for the cord blood samples compared to the adult samples. Also, both natural killer cell activity and gamma interferon production were significantly lower in the cord blood group. These findings may correlate with the increased susceptibility of young infants to infection. Differences between the two groups were not evident for the percentages of T4+ cells, B cells, and large granular lymphocytes. IL-2 production by cells stimulated with concanavalin A and a phorbol ester was higher in cord blood. Individually, half of the cord blood samples contained more IL-2 than any of the adult samples. This result could be caused either by greater production of IL-2 by the cord blood samples or by greater utilization of IL-2 by the adult samples.

Antigens, Surface↗
PubMed1985

Immune function in chronic active Epstein-Barr virus infection.

The spectrum of illness attributed to Epstein-Barr virus (EBV) includes patients with symptoms persisting for more than 1 year without any other obvious underlying disease. High titers of antibodies to EBV, either IgG antiviral capsid antigen or anti-early antigen, can be demonstrated. In this study, 13 patients diagnosed as having chronic active EBV infection were examined to determine aspects of their immunologic status. Morphological examination and fluorescent antibody analysis revealed no abnormalities in the phenotypes of peripheral blood white cells present in these patients. Compared to those from healthy control individuals, mononuclear cells from the patients showed a markedly depressed ability to produce both interleukin-2 and interferon after stimulation with mitogen and a phorbol ester. Studies of natural killer (NK) cell activity revealed that unfractionated mononuclear cells from patients with chronic active EBV infection were significantly lower in killing activity compared to the control group. Fractionation procedures to enrich for large granular lymphocytes resulted in an increase in NK activity for all individuals, but killing activity still remained slightly lower in the patients than in the control group. The dysfunctions which were found in patients with chronic active EBV infection may reflect a primary defect in natural immune functions of the patients predisposing them to a chronic or intermittent clinical disease rather than a self-limiting illness. Alternatively, the abnormalities detected in these experiments may be a result of the viral infection itself.

Adolescent↗
PubMed1985

Surface features of human natural killer cells and antibody-dependent cytotoxic cells.

The purpose of the present study was to examine the surface features of purified large granular lymphocytes (LGLs) (natural killer (NK) cells, antibody-dependent cytotoxic lymphoid (ADCL) cells, K-cells, Fc gamma (+) third population (non-T, non-B) lymphoid cells, T gamma cells) by scanning electron microscopy (SEM) and to compare their surface features with granulocytes, monocytes and Fc gamma (-) lymphoid cells that were all fixed for SEM under identical conditions. We have determined that 72-80% of LGLs enriched by rosette formation with sensitized erythrocytes or using Percoll gradients, have a complex microvillous surface (CMS) pattern identical to that of lymphocytes. The LGL fraction appears by SEM to represent a morphologically homogeneous population of cells. Monocytes prepared for SEM under identical conditions had distinct surface folds and granulocytes displayed numerous broad-based ridge-like profiles. The majority of lymphoid cells in an unfractioned population have a CMS pattern when incubated at room temperature (25 degrees C) before fixation, and a sparse microvillous surface (SMS) pattern when incubated at body temperature (37 degrees C). Ficoll-Hypaque (FH) also had a direct effect on the cell surface pattern. Over half of the unfractionated lymphoid cells displayed a CMS pattern after cells were washed free of FH and incubated at 37 degrees C before fixation. The CMS pattern is therefore not unique to LGLs but can be produced by the surface alteration of non-LGLs found in unfractionated buffy coat and mononuclear fractions. The interactions between LGLs and sensitized erythrocytes in an antibody-dependent cytotoxic assay system, and LGLs and K562 target cells in an NK assay system, were also examined. This is the first report that describes the surface features of human LGLs interacting with K562 target cells in an NK assay system. The LGL populations studied by SEM were determined to have a high percentage of Leu-11(+) and Leu-7(+) cells. These same population were also shown to have high antibody-dependent cytotoxicity and NK activity using the 51Cr release assay.

Cell Fractionation↗
PubMed1985

Evidence for active Epstein-Barr virus infection in patients with persistent, unexplained illnesses: elevated anti-early antigen antibodies.

Forty-four patients, including 26 adults and 18 children under 15 years of age, were referred for evaluation of recurrent or persistent illnesses, with symptoms including pharyngitis, lymphadenopathy, fever, headaches, arthralgia, fatigue, depression, dyslogia, and myalgia. Thirty-nine patients were positive for Epstein-Barr virus antibody with antibody levels compatible with active infection for at least 1 year. Antiviral capsid antigen and anti-early antigen titers of patients were significantly greater (p less than 0.001) than age-group-matched controls. The frequency, number, duration, and patterns of symptoms, as well as patient sex, were compared by age in study patients seropositive and seronegative for Epstein-Barr virus. Illness patterns were not associated with changes in specific antibody titers or clinical findings. Lymphocyte phenotype and function analyses were done in 11 of the 39 patients positive for Epstein-Barr virus antibody; no consistent differences from normal were found. Only 1 of 32 patients had circulating interferon, in contrast to 7 of 7 patients with acute infectious mononucleosis. There were many adverse consequences of the illness. Epstein-Barr virus infection may not be self-limiting, and the virus may be associated with clinically recognizable illness other than infectious mononucleosis in children as well as in adults.

Adolescent↗
PubMed1985

Prolactin receptors on human T and B lymphocytes: antagonism of prolactin binding by cyclosporine.

Prolactin (PRL) receptors have been identified recently on human peripheral blood mononuclear cells (MNC) and may be involved in the regulation of cell-mediated immunity. Cyclosporine (CsA), an immunosuppressive cyclic endecapeptide utilized to prolong graft survival in human organ transplant patients, affects PRL binding to MNC. At concentrations of CsA from 10(-10) through 10(-8) M, the amount of PRL bound to MNC markedly increased to ca. 400% of controls, whereas CsA concentrations of 10(-6) and 10(-5) M totally inhibited PRL binding to lymphocytes. The ability of low concentrations of CsA to enhance PRL binding was temperature-dependent and did not occur when binding assays were conducted at 4 degrees C. PRL displaced [3H]CsA from lymphocytes with ca. 50% displacement at 10(-9) M PRL and total displacement at concentrations of 10(-7), 10(-6), and 10(-5) M. Growth hormone did not displace [3H]CsA in similar experiments. CsA also did not alter the binding of a beta-receptor antagonist to MNC, again suggesting that CsA was specific in its antagonism of PRL binding. A CsA analog with no immunosuppressive action, cyclosporin H, did not alter PRL binding to MNC. Furthermore, PRL receptors were demonstrated on four cell lines of human and mouse origin. Finally, PRL receptors were identified on purified populations of T and B lymphocytes isolated from human spleens, and CsA again inhibited PRL binding at concentrations of 10(-7) and 10(-6) M. The presence of PRL receptors on T and B lymphocytes suggests that PRL may be involved in the regulation of humoral and cell-mediated immunity, and that one effect of CsA on immune function may be its ability to inhibit the effects of PRL action on these lymphocytes.

Animals↗
PubMed1984

Prolactin receptors on human lymphocytes and their modulation by cyclosporine.

Prolactin receptors have been identified for the first time on human peripheral blood lymphocytes. These receptors are present on T- and B-cells as well as monocytes. The specific binding of [125I]prolactin to these cells can be selectively enhanced at certain concentrations and blocked by higher concentrations of cyclosporine , a known immunosuppressive agent which inhibits the mitogenesis of T-cells. Prolactin also induces ornithine decarboxylase, a key growth regulatory enzyme, in lymphocytes. Therefore, we suggest that the lymphocyte prolactin receptor may be involved in regulating lymphocyte function, and that one of the actions of cyclosporine is to block this rather ubiquitously occurring receptor.

B-Lymphocytes↗
PubMed1980

Investigations on ploidy levels of haploid and diploid callus and cell suspension cultures of Datura innoxia Mill.

Using haploid and diploid Datura innoxia Mill, callus cultures and cell suspensions it was shown that meristematic material usually attains the lowest possible C-value of a given ploidy level. Parenchyma material of callus cultures, however, indicates a broad scattering of C-values up to 16 C, which is paralleled by C-value distribution of the free cell fraction in actively dividing cell suspensions. In these suspensions, cell division activity seems to be restricted to small meristem-like clusters.

Cell Cycle↗
PubMed1978

Cell-mediated cytotoxicity: comparison of primary and secondary immune reactions after parainfluenza type 1 virus inoculation.

H-2 antigen compatibility of effector spleen cells and target cells was necessary for cell-mediated cytotoxicity (CMC) after both 1 and 2 intraperitoneal inoculation of 6/94 virus into mice. T cells were responsible for both primary and secondary CMS reactions. Neither reaction was influenced by the presence of virus-specific antibody added to the test system. Secondary CMC peaked earlier than the primary response and declined more rapidly. In vitro stimulation of primed spleen cells could also be used to detect the secondary CMC response.

Animals↗
PubMed1975

Transfer factor therapy in patients with subacute sclerosing panencephalitis.

Thirteen patients with subacute sclerosing panencephalitis (S.S.P.E.) at different stages of the disease were admitted for transfer factor treatment. The transfer factor was prepared from non-selected blood bank donors. The activity of the transfer factor was tested in patients with diseases other than S.S.P.E. and was found to be either clinically or immunologically active. Regardless of the number of transfer factor units applied a significant influence on the course of the disease was not apparant. The observed intermittant improvement of 3 patients was considered as spontaneous remission which is known to occur occasionally in S.S.P.E. The humoral and cellular immune response before and after transfer factor therapy did not reveal significant changes which could be correlated with transfer factor therapy.

Adolescent↗
PubMed1975

Antibody-mediated cytotoxicity after measles virus infection.

Antibody cytotoxicity in the presence of complement to measles virus-infected cells was determined in sera of individuals at various stages of measles virus infection. A measles virus carrier cell line, which possessed viral antigens on the cell membrane, was employed as target cells. The cytotoxic effect was measured by 51-Cr release from the measles virus-infected cells. A microtiter method was used to determine the titer of antibody cytotoxicity. Cytotoxic antibodies could be detected in serum specimens from individuals after natural measles virus infection and vaccination. Sera from subacute sclerosing panencephalitis (SSPE) patients had only slightly higher titers than were found in sera obtained from individuals 1 week to 3 months after measles virus infection. Sera from children inoculated with measles virus vaccine lost their ability to react in hemagglutination inhibition, neutralization (NT) and cytotoxicity (CT) tests after absorption with the hemagglutinin from measles virus. SSPE sera treated in a similar manner retained their activity in NT and CT tests. Cytotoxic antibody was, therefore, shown to be directed against the hemagglutinin and some other antigen of measles virus.

Animals↗