bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mechanism of action of the C3b inactivator (conglutinogen- activating factor) on its naturally occurring substrate, the major fragment of the third component of complement (C3b)
Authors: Gitlin JD , Rosen FS , Lachmann PJ 
Published: June 2004

The fixation of the third component of complement (C3) results in many important biological phenomenon, among which are (a) immune adherence (1), (b) enhancement of phagocytosis (2,3), (c) the release of an anaphylatoxin which is a potent releaser of histamine (4), and (d) the feedback activation of the alternative pathway (5,6). The physiological mechanisms involving C3 fixation require the generation of a C3 convertase which may occur by two separate pathways. C3 convertase can be generated, in the form of C42, by the so-called classical pathway of activation or in the form C3b,B by the alternative or properdin pathway (7). In both cases, C3 is converted to C3b by cleavage of a small peptide, C3a. Normal human serum contains an inactivator of activated C3b. This C2b inactivator or conglutinogen-activating factor (KAF) has been shown to inhibit both immune hemolysis and the immune adherence properties of C3b and to cause cleavage of C3b in the fixed and fluid- phase stages (8-11).
Although it is known that the C3b inactivator is not depleted during its reaction with C3b and that C3b treated with the C3b inactivator becomes extremely sensitive to proteolytic digestion by trypsin and trypsin-like enzymes (9), the exact molecular nature of the action of the C3b inactivator on C3b has not been studied. In an effort to delineate the products of this interaction, purified C3b and C3b inactivator were allowed to react for various specific lengths of time and the products of these reactions were then analyzed.
Terminal deoxynucleotidyl transferase is found in prothymocytes
Authors: Silverstone AE , Cantor H , Goldstein G , Baltimore D 
Published: June 2004

Terminal deoxynucleotidyl transferase is an enzyme which has the unique property of polymerizing polydeoxynucleotides onto a primer in the absence of a template (1,2). This enzyme is found both in the thymus and the bone marrow of birds, rodents, and humans (3-7). Whether the marrow cells that contain terminal transferase are related to thymocytes, or are on a separate pathway of differentiation, is not yet known (7,8).
To determine the lineage of the murine bone marrow cells that have terminal transferase, we have investigated whether these cells have the antigen Thy-1 induced on the cells by treatment with thymopoietin (9). Thymopoietin is known to induce a set of characteristic T-cell markers including the Thy-1 alloantigen on the surface of a subpopulation of bone marrow cells committed to T-cell differentiation (prothymocytes) (10). Destruction of Thy- 1-positive cells after exposure to thymopoietin allows elimination of a substantial fraction of those bone marrow cells that can repopulate an irradiated thymus (11). We find that such an elimination after induction with the thymic polypeptide removes a substantial amount of terminal transferase from the bone marrow cell population, suggesting that at least one-half of the marrow cells bearing this enzyme are related to those found in the thymus.
Effect of sodium butyrate on lymphocyte activation
Authors: Kyner D , Zabos P , Christman J , Acs G 
Published: June 2004

Butyrate, in relatively low concentrations, has been shown to induce synthesis of enzymes, cause changes in cell morphology, and inhibit growth of a variety of mammalian cells in tissue culture (reviewed in [1]).
In this communication, we report our observations on the effect of butyrate on lymphocyte activation. Butyrate completely and reversibly inhibits mitogen-induced blast formation. We present evidence that it does not interfere with the binding of mitogens, that it does not inhibit a number of the early reactions involved in activation, and that it does not affect ongoing DNA synthesis for an extended period of time. However, butyrate rapidly inhibits any increase in the rate of DNA synthesis.
Regulation of cholesterol synthesis by low density lipoprotein in isolated human lymphocytes
Authors: Ho YK , JR Faust , Bilheimer DW , Brown MS , Goldstein JL 
Published: June 2004

The rate of cholesterol synthesis from [14C]acetate was low in circulating blood lymphocytes freshly isolated from 17 normal subjects and 4 subjects with homozygous FH. On the other hand, the rate of cholesterol synthesis was two to fourfold above normal in freshly isolated lymphocytes from two subjects with abetalipoproteinemia. When the lymphocytes from subjects with all three genotypes were incubated for 48-72 h in the absence of lipoproteins, the rate of cholesterol synthesis increased by 5-15-fold. The subsequent addition of plasma LDL, but not HDL, rapidly suppressed cholesterol synthesis in the lymphocytes from normal subjects. In contrast, lymphocytes from the FH homozygotes, which have been shown previously to be deficient in cell surface LDL receptors, were resistant to LDL-mediated suppression of cholesterol synthesis.
In addition to its ability to suppress cholesterol synthesis after it had been elevated by incubation of the cells in the absence of lipoproteins, LDL was able to suppress the induction of the enhanced rate of sterol synthesis when added to normal lymphocytes immediately after their isolation from the bloodstream. In contrast to the former action of LDL, the latter action of LDL-i.e., the suppression of induction of sterol synthesis-also occurred to a limited extent in lymphocytes from FH homozygotes. However, the FH lymphocytes, but not the normal cells, could be made resistant to this action of LDL by inclusion in the incubation medium of lipoprotein-deficient serum (30 percent, vol/vol) plus HDL (1 mg protein/ml). Considered together with previous data demonstrating a deficiency of LDL receptors in freshly isolated lymphocytes from FH homozygotes, the current studies provide evidence in support of the hypothesis that the interaction of plasma LDL with its cell surface receptor serves to regulate cholesterol synthesis in human lymphocytes.
Pathogenesis of shigella diarrhea. VII. Evidence for a cell membrane toxin receptor involving β1 {arrow} 4-linked N-acetyl-D-glucosamine oligomers
Authors: Keusch GT , Jacewicz M 
Published: June 2004

The binding of ShigeUa dysenteriae 1 cytotoxin to HeLa cells in culture and to isolated rat liver cell membranes was studied by means of an indirect consumption assay of toxicity from the medium, or by determination of cytotoxicity to the HeLa cell monolayer. Both liver cell membranes and HeLa cells removed toxicity from the medium during incubation, in contrast to WI-38 and Y-1 mouse adrenal tumor cells, both of which neither bound nor were affected by the toxin. Uptake of toxin was directly related to concentration of membranes added, time,and temperature, and indirectly related to the ionic strength of the buffer used.
The chemical nature of the membrane receptor was characterized by using three principal approaches: (a) enzymatic sensitivity; (b) competitive inhibition and (c) receptor blockade studies. The receptor was destroyed by proteolytic enzymes, phospholipases (which markedly altered the gross appearance of the membrane preparation) and by lysozyme, but not by a variety of other enzymes. Of 28 carbohydrate and glycoprotein haptens studied, including cholera toxin and ganglioside, only the chitin oligosaccharide lysozyme substrates, per N-acetylated chitotriose, chitotetraose, and chitopentaose were effective competitive inhibitors. Greatest inhibition was found with the trimer, N, N', N" triacetyl chitotriose. Of three lectins studied as possible receptor blockers, including phytohemagglutinin, concanavalin A, and wheat germ agglutinin, only the latter, which is known to possess specific binding affinity for N, N', N" triacetyl chitotriose, was able to block toxin uptake.
Evidence from all three approaches indicate, therefore, existence of a glycoprotein toxin receptor on mammalian cells, with involvement of oligomeric β1{arrow}4-1inked N-acetyl glucosamine in the receptor. This receptor is clearly distinct from the G(M1) ganglioside thought to be involved in the binding of cholera toxin to the cell membrane of a variety of cell types susceptible to its action.
Enzymes of heme metabolism is the kidney. Regulation by trace metals which do not form heme complexes
Authors: Maines MD , Kappas A 
Published: June 2004

The in vivo regulation by metal ions of the enzymes of heme metabolism in kidney-particularly of ALAS, the rate-limiting enzyme in heine formation- was investigated. Ni(2+) and Pt(4+), metals which do not enzymatically form metalloporphyrins, were found to regulate ALAS in kidney as they do in liver. The pattern of this regulation was generally similar to that observed with heme and metal ions in liver, i.e., a late increase in enzyme activity after an early period in which ALAS activity was unaltered or inhibited. The metals did not interact with the enzyme in vitro to alter its activity. In this study no direct reciprocal relationship between ALAS activity and total cellular heine content was demonstrated. The metal ions, particularly Pt(4+), also altered the activity of other enzymes of heme biosynthesis in kidney. Pt(4+) severely inhibited the activity of ALAD and UROS. Ni(2+) and Pt(4+) were potent inducers of heme oxygenase, the initial and rate-limiting enzyme in heine degradation.
It is proposed that the physiological regulation of ALAS is mediated through the action of metal ions, rather than by the cellular content of heine, and that the regulation of ALAS by heine reflects the action of the central metal ion of heme rather than that of the entire metalloporphyrin complex. In this proposed mechanism for metal ion regulation of ALAS, the tetrapyrrole moiety of heine is considered to function principally as an efficient carrier of metal to the regulatory site for ALAS production, inasmuch as the tetrapyrrole ring itself has been shown in earlier studies not to have any effect on ALAS activity. The production of heine oxygenase is believed to be similarly regulated.
The role of H-2-linked genes in helper T-cell function. I. In vitro expression in B cells of immune response genes controlling helper T-cell activity
Authors: Kappler JW , Marrack P 
Published: June 2004

The ability of murine helper T cells primed to the antigen, sheep erythrocytes (SRBC) to cross-react with burro erythrocytes (BRBC) in the in vitro anti-trinitrophenol (TNP) response to TNP-RBC was shown to be under genetic control. Although non-H-2 genes were shown to influence the absolute level of helper activity assayed after SRBC priming, the extent of cross-reaction of SRBC-primed helpers with BRBC was shown to be controlled by an H-2-1inked Ir gene(s). H-2 haplotypes were identified which determined high, intermediate, or low response to the cross- reacting determinants and the gene(s) controlling the cross-reaction tentatively mapped to the K through I-E end of the H-2 complex.
Helpers primed in F(1) mice of high x intermediate or high x low responder parents were tested for cross-reaction using B cells and macrophages (Mφ) of parental haplotypes. In each case the extent of cross-reaction was predicted by the H-2 haplotype of the B cells and Mφ, establishing the expression of the Ir gene(s) in B cells and/or Mφ a t least, but not ruling out its expression in T cells as well. The low cross-reaction seen when T cells from F(1) mice of high × low responder parents were tested on low responder B cells and Mφ was not increased by the presence of high responder Mφ, indicating the Ir gene(s) is expressed in the B cell a t least although it may be expressed in Mφ as well. These and our previously reported experiments are consistent with the hypothesis that helper T cells recognize antigen bound to the surface of B cells and Mφ in association with the product(s) of Ir gene(s) expressed on the B cell and Mφ.
Cytotoxic cells induced during lymphocytic choriomeningitis virus infection of mice. I. Characterization of natural killer cell induction
Authors: Welsh Jr. RM 
Published: June 2004

Lymphocytic choriomeningitis virus (LCMV) infection of C3H/St, nude (BALB/c background), and other mice induced high levels of natural killer (NK) cell activity in the spleen and peritoneum. L-929 cells were used as targetsand were not lysed by spleen or peritoneal cells from uninfected mice. The cytotoxic cells were characterized as NK cells because they were nonadherent, nonphagocytic lymphocytes lacking θ and immunoglobulin antigens on their plasma membranes. Their activity was sensitive to 6 mM EDTA and to heating for 5 h at 37 degrees C, but resisted treatment with 0.5 percent trypsin. No role for antibody could be demonstrated in these assays. Relative to cytotoxic T-cell activity, the induction of NK cell activity was resistant to X-irradiation of mice with 1,000 rads but was sensitive if mice were first treated with Strontium-89, a bone-seeking isotope.
NK cells were induced by LCMV in all tested strains of mice. In C3H/St mice NK cell activity was detected as early as 1 day and peaked at 3 days postinfection. Maximum activity in C3H/St mice was observed in mice 5-10 wk of age, but significant NK activity was also induced in newborns, which subsequently carried virus in their tissues for the duration of their lives. Older LCMV-carriers did not have detectable spleen NK cell activity. No memory oranamnestic response could be demonstrated for NK cell induction. NK cell activity was not induced by LCMV challenge of LCMV-immune mice, but was induced in those mice by infection with Pichinde virus, a closely related virus. The advent of NK cell activity correlated with the synthesis of interferon in LCMV-infected mice. Culture fluids lacking virus infectivity but containing interferon induced cytotoxic cell activity in nude and C3H/St mice. These experiments suggest that LCMV induced NK cells via an interferon-dependent mechanism. When studied in several strains of mice, the continued expression of NK cell activity did not seem to directly correlate with spleen interferon levels, suggesting that additional factors may play a role as well in maintaining the activity of the NK cell in vivo.
The detection of a spleen focus-forming virus neoantigen by lymphocyte- mediated cytolysis
Authors: Gillis S , Gillis AE , Smith KA 
Published: June 2004

The existence of a nonvirion tumor-associated cell surface antigen (TASA) on cells transformed with Friend (FLV) on Rauscher (RLV) leukemia virus has been difficult to demonstrate. Antisera raised against classically defined Friend- Moloney-Rauscher antigenic determinants have been shown to react with virus structural proteins coded for by genetic information contained in the lymphatic leukemia or helper (LLV) virus genome. The recent development of nontrans-formed fibroblast cell lines which contain the replication-defective spleen focus-forming virus (SFFV) genome, free of replicating LLV, has allowed investigation of an SFFV-specific antigen. We have applied the techniques of mixed tumor-lymphocyte culture stimulation followed by lymphocyte-mediated cytolysis assays to search for the cell surface expression of an antigen coded expressly by SFFV genetic information.
SFFV nonproducer-immune, in vitro activated spleen cells were capable of effecting the lysis of SFFV-containing BALB/c 3T3 and Fischer rat epithelial, cloned cell lines. Normal BALB/c 3T3 and BALB/c 3T3 cells infected with three types of ecotropic LLV were unaffected. Syngeneic FLV and RLV-induced murine leukemia cells were also killed by SFFV nonproducer-immune lymphocytes. In addition, Kirsten sarcoma virus-transformed, replication-defective and replication-rescued BALB/c 3T3 fibroblasts were not susceptible to SFFV antigen-directed cytolysis. Antibody-dependent complement-mediated cytolysis assays using monospecific goat antisera confirmed that SFFV nonproducers lacked cell surface expression of virion structural proteins.
These observations suggest that the antigen detected in LMC experiments was not coded for by genetic information contained in the helper component of FLV, and that it represents a true SFFV-specific cell surface antigen. Based upon the recent molecular evaluation of the SFFV genome as consisting of both xenotropic and ecotropic virus sequences, it appears reasonable that xenotropic genetic information may be responsible for expression of the SFFV- specific antigen. Since the replication-defective SFFV genome is also responsible for the malignant transformation associated with FLV-induced erythroleukemia, one might postulate that gene sequences capable of programming transformation may also code for the TASA detected in these studies.
A dichotomy between the expression of IgD on B cells and its requirement for triggering such cells with two T-independent antigens
Authors: Buck LB , Yuan D , Vitetta ES 
Published: June 2004

The majority of adult B lymphocytes in the mouse bear two immunoglobulin isotypes, IgM and IgD (μ(+)δ(+) cells) (1). A small population of IgM-bearing cells lacks, or expresses very low levels of IgD (μ- predominant [μp] cells) (1). These cells are believed to constitute a less mature subset of B cells analogous to neonatal B cells (2). Based on the time during ontogeny when responses to T-independent (TI) and T-dependent (TD) antigens appear (3, 4) and the ability to block in vitro responses with anti- μ or anti-δ (5, 6, D. Mosier, personal communication), it has been suggested that the precursors of two TI-1 responses, trinitrophenyl (TNP)- Brucella (TNP-BA) and TNP-lipopolysaccharide (TNP-LPS) are μp cells (5, 6), whereas the precursor for a TD response, TNP-sheep erythrocytes (TNP-SRBC), bears both IgM and IgD (6). However, the possibility cannot be excluded that IgD is present on some or all of the TI precursors, but that it is not obligatory for triggering.
In the present experiments we have examined the phenotypes of TI and TD precursors by treating cells with C' and either anti-μ or anti-δ before stimulation with antigen. Our results suggest that the majority of B cells that respond to TNP-BA, TNP-LPS, and TNP-SRBC bear IgD, even though in the case of the two TI antigens, IgD is not required for triggering.
Direct evidence that natural killer cells in nonimmune spleen cell populations prevent tumor growth in vivo
Authors: Kasai M , Leclerc JC , McVay-Boudreau L , Shen FW , Cantor H 
Published: June 2004

Relatively large numbers of nonimmune spleen cells do not protect against the local growth of two lymphomas. However, this heterogeneous population of splenic lymphocytes contains a subset of cells that efficiently protects against in vivo tumor growth. This cell population (cell-surface phenotype Thyl.2(-)Ig(-)Ly5.1(+)) represents less than 5 percent of the spleen cell population and is responsible for in vitro NK-mediated lysis.
Although these studies clearly and directly demonstrate that Ly5(+) NK cells selected from a heterogeneous lymphoid population from nonimmune mice can protect syngeneic mice against local in vivo growth of two different types of tumor cells (in contrast to other lymphocyte sets within the spleen), they do not directly bear upon the role of NK cells in immunosurveillance. They do indicate that highly enriched Ig(-)Thyl(-)Ly5(+) cells, which account for virtually all in vitro NK activity, can retard tumor growth in vivo.
It is difficult to ascribe all anti-tumor surveillance activity to NK cells, because they probably do not recirculate freely throughout the various organ systems of the body. Perhaps NK ceils may play a role in prevention of neoplastic growth within discrete anatomic compartments where there is rapid differentiation of stem cells to mature progeny (e.g., bone marrow, spleen, and portions of the gastrointestinal tract)and may normally act to regulate the growth and differentiation of non-neoplastic stem cells. Long-term observation of chimeric mice repopulated with bone marrow from congenic or mutant donors expressing very low or very high NK activity may help to answer these questions.
B-cell influences on the induction of allotype suppressor T cells
Authors: Black SJ , Herzenberg LA 
Published: June 2004

Allotype suppressor T-cell (Ts) populations that persist for the life of the animal arise in (BALB/c × SJL)F(1) hybrids exposed perinatally to antibody to the paternal (Ig-1b) allotype on IgG(2a)-isotype immunoglobulin H chains. These Ts suppress Ig-lb production by depleting the supply of allotype- specific helper T cells (Th) required, in addition to carrier-specific Th, for the latter stages of Ig-1b memory B-cell differentiation.
In this publication, we show that specific Ig-1 allotype Ts are induced by perinatal exposure to antisera which interfere with normal B-cell maturation, i.e., by antibodies reactive with surface IgM on immature precursors of IgG(2a), memory cells. Antibodies to IgM (Ig-6) allotypes carried on precursors induce specific suppression for the IgG2, allotype produced by progeny of the target precursor. Anti-Ig-6a and anti-Ig-6b induce Ts that specifically suppress Ig-1a and Ig-1b, respectively. Heterologous (goat) anti-IgM induces suppression for both IgG(2a) immunoglobulins (Ig-1a and Ig-1b). Ts activity in these antiprecursor-Ig-suppressed mice is expressed in adoptive transfer assays and, as with anti-Ig-1b-induced Ts, is rendered ineffective by cotransfer of adequate numbers of T cells but not B cells from nonsuppressed mice. The Ts induction, in contrast with Ts expression, is reversed by the introduction of appropriate adult B-cell populations from nonsuppressed donors.
Taken together, these data suggest that the development of mature B cells plays a central role in the early establishment of the balance between helper cells and suppressor cells that determines whether Ts or Th will dominate in regulating Ig-1b production in adult animals.