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At least 1,315 records · Page 73Linked to original sources
PubMed1991

Natural antibody recognition of v-H-ras-induced 10T1/2 transformation.

An increasing body of evidence supports a role for natural antitumor antibodies acting against tumors in vivo. However, a role for natural antibodies (NAb) in tumor surveillance would imply that sensitivity to NAb should increase following events associated with cellular transformation. To test this prediction we examined by flow cytometry the effect on serum NAb binding of v-H-ras expression and integration in 10T1/2. The co-introduction of v-H-ras and the neomycin resistance (neor) gene into 10T1/2 followed by G418 selection resulted in a marked and heterogeneous increase in NAb binding. Clonal analysis of this population demonstrated that the increased NAb binding was associated with tumorigenic conversion and ras-p21 expression. The results provide the first evidence for a NAb-susceptible phase of ras-induced transformation.

Animals↗
PubMedDate not supplied

Clonal structure and variation in virulence of Salmonella enteritidis isolated from mice, chickens, and humans.

The clonal analysis of a diverse collection of Salmonella Enteritidis indicates that most strains belong to a single multilocus genotype (i.e., ET-3) regardless of phage type, geographic origin, or time of isolation that spanned over 2 decades (1978 to 2004). Attachment and invasion assays, however, indicate that, among ET-3 isolates, there is a distinct invasive bacterial subpopulation that is more readily recovered from eggs and clinical cases in humans than from chicken cecal samples. These observations support the hypothesis that the specialized ability of S. Enteritidis to infect the avian reproductive tract and contaminate eggs has been critical in its emergence as a frequent cause of human illness.

Alleles↗
PubMed2006

[Two patients with hypereosinophilic syndrome].

Persistent eosinophilia was diagnosed in a 19-year-old woman with general malaise, dyspnoea attacks, coughing and episodes of angioedema and associated swallowing problems, and in a 21-year-old man with visual problems, dyspnoea, fatigue, reduced appetite, weight loss and gastrointestinal problems. Both had hypereosinophilic syndrome (a rare disease) with organ damage. In both patients, fluorescence-in-situ-hybridisation (FISH) was negative for the fusion gene FIP1L1-PDGFRA (FIPI-like-1-platelet-derived growth factor receptor alpha). The female patient's disease did not respond to either oral corticosteroids or imatinib, but did respond to hydroxycarbamide. The male patient successively received prednisone, interferon alpha and hydroxycarbamide. His eosinophilia progressed nonetheless, but responded partially to imatinib. In addition, the patient underwent an allogenic non-myeloblative stem cell transplantation from his HLA-identical sister. In patients with persistent eosinophilia accompanied by organ damage or organ dysfunction, hypereosinophilic syndrome can be diagnosed providing all secondary causes of the eosinophilia have been ruled out. Complementary investigations should include cytogenetic and clonal analysis to rule out haemopoietic malignancy. Prednisone, hydroxycarbamide, interferon alpha and the promising imatinib are all treatment options.

Adult↗
PubMed1990

Critical factors in the biology of human cancer metastasis: twenty-eighth G.H.A. Clowes memorial award lecture.

The process of metastasis is not random. Rather, it consists of a series of linked, sequential steps that must be completed by tumor cells if a metastasis is to develop. Although some of the steps in this process contain stochastic elements, as a whole, metastasis favors the survival and growth of a few subpopulations of cells that preexist within the parent neoplasm. Moreover, metastases can have a clonal origin, and different metastases can originate from the proliferation of single cells. The outcome of metastasis depends on the interaction of metastatic cells with different organ environments. Organ-specific metastases have been demonstrated in a variety of experimental tumor systems. Moreover, we have found tumor growth that is specific to a particular site within one organ. Whether the same conclusions can be reached for human cancers remained unanswered until very recently. Studies from our laboratory and from others have shown that the implantation of human cancer cells derived from surgical specimens into correct anatomical sites of nude mice can provide a suitable model of metastasis of human tumors. Clonal analysis of a human renal carcinoma, colon carcinomas, and melanomas has revealed that these tumors are indeed heterogeneous for metastatic properties, an observation made only after orthotopic implantation. Thus, growth in the environment of specific organs can be selective and the environment per se influences this process. While it is clear that vascularity and local immunity can facilitate or retard tumor growth, we have concentrated on understanding how damage to an organ and the subsequent repair process can facilitate tumor cell proliferation. Accelerated growth of human colon cancer cells was found in hepatectomized nude mice, whereas accelerated growth of human renal cancer cells was found in nephrectomized nude mice. These data suggest that systemic physiological signals can be recognized by neoplastic cells presumably by mechanisms similar to those shared by their normal cell counterparts. In summary, the critical factors that regulate metastasis are the intrinsic properties of metastatic cells and host factors involved in homeostasis. The recent increase in our understanding of metastasis should provide important leads for developing more effective approaches to the treatment of disseminated cancer.

Animals↗
PubMed1992

A distinct type of GD3+, flat astrocyte in rat CNS cultures.

We have identified what is apparently a distinct type of astrocyte in primary cultures from several regions of the neonatal rat CNS. These cells express GD3 ganglioside for long periods in vitro, and are GFAP+, but do not express the oligodendrocyte antigens O4 or galactocerebroside (GC). The majority, but not all, are A2B5+. The cells grow in a flat, highly spread morphology with many thin cytoplasmic processes. Gene transfer with a replication-deficient retrovirus combined with immunostaining for astro- and oligodendroglial markers (antibodies to GFAP, GD3 ganglioside, GC, and the A2B5 and O4 antibodies) demonstrated that in the neonatal rat CNS cultures these cells are clonally separate from oligodendrocytes and from the majority of (GD3-) astrocytes. The clonal analysis suggests a distinct progenitor cell and a distinct developmental sequence for these astrocytes.

Animals↗
PubMedDate not supplied

Monoclonal autoantibody to thyroglobulin as a possible vector in immunodiagnosis and immunotherapy of differentiated thyroid cancer.

Differentiated thyroid carcinoma synthetize and secrete thyroglobulin. During its biosynthesis this antigen becomes expressed in the microvilli-bearing surface of carcinoma cells. Attempts have been carried out to target, with specific antithyroglobulin antibodies, the membrane bound absorption thyroglobulin in cancer cells for in vivo diagnosis and therapy. In the serum of patients with autoimmune thyroid diseases a high concentration of antithyroglobulin antibodies is frequently found (1-3 mg/ml). Their purification by immunoabsorption and dissociation is hampered by a low recovery and partial denaturation. It has been recently reported that about 1% of sera from Hashimoto's thyroiditis bear in their electrophoretogram a "myeloma-like protein". In the present report we describe in the serum of a Hashimoto patient a myeloma-like IgG which is an antithyroglobulin autoantibody with restricted functional and structural properties. The serum concentration of this myeloma-like IgG was found to be 40 mg/ml with a capacity of 6.5 nM of human thyroglobulin/mg IgG. The light chain composition was determined to be mostly of the lambda type. The clonal analysis of this myeloma IgG carried out by isoelectrofocusing, immunoblotting and autoradiography resulted in the recognition of several distinct clones, two of which were prominent at pH 8.7 and 7.8. By this technique and in view of the high serum concentration of this myeloma-like IgG, single clones of antithyroglobulin autoantibody can be easily obtained in high yields and without denaturation from human serum. This reagent could offer an ideal immunovector to target membrane-bound thyroglobulin of cancer cells.

Antibodies, Monoclonal↗
PubMed1985

A synthetic decapeptide of influenza virus hemagglutinin elicits helper T cells with the same fine recognition specificities as occur in response to whole virus.

The immunogenicity of an isolated murine helper T cell determinant was studied. Mice were immunized with a synthetic peptide corresponding to amino acid residues 111-120 of the influenza PR8 hemagglutinin (HA) heavy chain, a region previously identified as a major target of the helper T cell response to the HA molecule in virus-primed BALB/c mice. Lymph node T cells from these mice were fused with BW 5147 cells to produce T hybrids for clonal analysis of their recognition specificities. Three T cell hybridoma clones, obtained from two different mice, responded to the immunizing peptide when presented by syngeneic antigen-presenting cells. All of these clones responded also to antigen provided as intact wild-type PR8 virus. The fine specificity of the peptide-induced T cell hybridomas, in response to a panel of mutant and variant influenza viruses, was indistinguishable from the fine specificities of T cells to the corresponding region of the HA1 chain of the HA molecule which had been generated by priming of mice with intact wild-type virus. These results suggest that an immunogenic determinant is contained within the 111-120 sequence that is able to elicit anti-influenza virus T cells with a similar repertoire to those elicited by immunization with whole virus.

Amino Acid Sequence↗
PubMedDate not supplied

[Mutant Bac. subtilis A2 with an enhanced capacity to induce an adaptive response].

Mutant A2 with increased ability to induce adaptive response was isolated in Bac. subtilis and its properties studied. Mutant A2 was shown to be more resistant to mutagenic action of MNNG, EMS, UV light. It was also discovered that A2 was more sensitive to the lethal action of MNNG and UV light than parent strain 103. It was shown by clonal analysis of mutant colonies, formed by mutant cells A2 and 103 that A2 strain had increased ability to form complete mutants. Properties of A2 mutant suggest that in the process adaptive response induction were is expression of both adaptive response enzymes and some other which are necessary for reparation of premutagenic UV lesions.

Adaptation, Physiological↗
PubMed1989

Selection against lethal alleles in females heterozygous for incontinentia pigmenti.

Studies of five heterozygous females from three kindreds segregating incontinentia pigmenti indicate that cells expressing the mutation have been eliminated from skin fibroblast cultures and in varying degrees from hematopoietic tissues. Clonal analysis was carried out using G6PD variants and methylation patterns at the HPRT locus. Our results confirm X linkage in these families and suggest that selection against cells expressing mutations that are lethal to males in utero may help ameliorate the deleterious phenotype in carrier females.

Adolescent↗
PubMed1989

In vitro lymphocyte response to autologous melanoma: clues in designing new adoptive immunotherapy protocols.

Recent studies indicate that different types of antitumour lymphocytes (T and non-T) can be generated in vitro and in vivo after exposure to recombinant interleukin-2 (rIL-2). In vitro it is possible to selectively expand the CD3 cells by using anti-CD3 monoclonal antibody and rIL-2. Adherence can select a minor subpopulation of lymphokine-activated killer (LAK) cells (A-LAK) endowed with a higher lytic activity. We have investigated whether melanoma-specific T-lymphocytes can be obtained to be used for therapy or endogenously expanded in vivo by the appropriate use of limited amounts of rIL-2. Clonal analysis of lymphocytes obtained either from tumour lesions or from blood indicated the existence of melanoma-restricted T-lymphocytes, both with cytotoxic or helper function. Though a minority, these cells can be generated and expanded with low amounts of rIL-2 (3-30 Cetus U/ml) in the presence of autologous melanoma and B-cells. The use of rIL-1 and rIL-4, together with rIL-2 at certain phases of T-lymphocyte growth, can help in expanding more selectively the melanoma-specific cells. These T-cells are major histocompatibility complex-restricted in their killing but they also need to see adhesion molecules (ICAM-1) on the target cells. New clinical protocols can thus be conceived on the basis of some of these results.

Humans↗
PubMed1987

Evidence for the interleukin-2 dependent expansion of leukemic cells in adult T cell leukemia.

Interleukin 2 (IL-2) receptor/Tac antigen is abnormally expressed on cells of patients with adult T cell leukemia (ATL) caused by infection with human T lymphotropic virus type I (HTLV-I). Twenty-five patients with ATL were examined to determine whether their leukemic cells continued to show IL-2-dependent proliferation. In 21 patients, the in vitro proliferation of HTLV-I-infected nonleukemic T cell clones was found to be dependent on IL-2. However, clonality analysis based on T cell receptor gene rearrangement profiles and the site of HTLV-I provirus integration revealed IL-2-dependent growth in leukemic cells in four patients with ATL. These results provide evidence for the IL-2-dependent proliferation of leukemic cells in some ATL patients.

Antigens, Surface↗
PubMed1978

Interspecies interactions of arboviruses. III. Competition for virus envelope antigens in mixed Getah and Sindbis virus populations.

Interactions of Getah and Sindbis virus populations in mixed infections of 5 tissue systems were competitive or neutral. The type of interaction is regulated by the host cell and virus population density. On reproduction in mouse brains and SPEV cell cultures the mixed population exhibited antigenic markers of Getah virus; in Syrian hamster kidney and chick embryo cell cultures those of Sindbis virus; and in Chinese hamster kidney cell cultures the antigenic markers of both viruses. Mixed populations with monospecific antigenic characteristics contained genomes of both viruses detectable by the TC marker (dual spetrum of cytopathogenicity). Clonal analysis of such populations confirmed the occurrence of genome masking and demonstrated the formation of genotypically mixed particles. Possible mechanisms of the antigenic dominance of one virus and selective blocking of functions of the other virus are discussed.

Antigens, Viral↗
PubMed1988

Loss of CD45R (Lp220) represents a post-thymic T cell differentiation event.

CD45R+ and CDw29+ CD4+ T cells are widely regarded as separate functionally defined T cell lineages. The work described here indicates that they represent maturation stages within the same differentiation pathway. Purified populations of CD4+ or CD8+ T cells, after stimulation with PHA, lose cell surface expression of CD45R (Lp220) and gain an increased surface density of CDw29 (4B4). Clonal analysis demonstrated that individual CD4+ CD45R+ T cells lost CD45R and acquired CDw29 with time in culture. This effect was selective for the high Mr 220-kDa form of the T200 (CD45) complex because the density of CD45, detected by an antibody to common determinants, did not decrease. This strongly indicates that CD45R+ cells are an immature stage in a lineage that culminates in CDw29 expression. To further define the expression of CD45R and CDw29, we analyzed infant thymus cells. Thymocytes include only 4 to 6% CD45R+ cells, but 95% express CDw29 in moderate density. The CD45R+ set appears to include mainly single CD4+ or CD8+, CD3 "bright" medullary cells, although only 15 to 25% of thymocytes with medullary phenotype express CD45R. In vitro culture of thymocytes with Con A and T cell growth factor induces expression of CD45R but these cells differ from the peripheral CD45R+ set by virtue of their co-expression of a high density of CDw29 (4B4) Ag. We postulate that post-thymically CD45R (Lp200) and CDw29 (4B4) comprise a functional assembly on the surface of T cells that changes in composition after stimulation with Ag or mitogen. This may result in enhanced ability of an Ag-experienced T cell to respond effectively to Ag due perhaps to a more efficient signaling complex.

Antigens, Differentiation↗
PubMed1987

Activation of help and contrasuppression as essential prerequisites for immune response.

The network theory proposes the immune system as a self-centered defense mechanism, which continuously maintains a steady state of activity via idiotypic-anti-idiotypic interactions. In line with this hypothesis, the steady state of the immune system has been described to represent a status of suppressed activity, response being manifested by release from suppression. There is evidence that release from suppression is initiated by activation of contrasuppressor cells (TCS), which either transfer a state of resistance towards suppression on helper T-cells (TH) or interact directly with suppressor T-cells (TS). In the latter case, it was postulated that the nominal antigen of contrasuppressor T-cells are antibodies and that TS and TCS interact one with the other via idiotypic-anti-idiotypic structures. The present report examined the role of TCS in initiation of response and proved that the responding state requires activation of TH as well as TCS. While antigenic stimulation (TNP) resulted in concomitant activation of TH and TCS, it was possible to dissect these two prerequisites for response by application of a monoclonal anti-TNP antibody (AB) carrying a recurrent idiotype (Sp6) followed by application of a subimmunogenic dose of the nominal antigen. Clonal analysis of regulatory cells via limiting dilution (LD) cultures revealed that a subimmunogenic dose of antigen led to activation of help but failed to activate TCS. On the other hand application of AB, which did not initiate response, resulted in activation of TCS, but not in activation of TH, i.e., these were not released from suppression. However, consecutive activation of TCS via AB and of help via a subimmunogenic dose of antigen moved the immune system into the responding state. Activation of TCS via AB was found to be independent from the mode of application, i.e., free AB, AB coupled to syngeneic cells, or AB coupled to the nominal antigen, although most straightforward results were obtained with free AB, since syngeneic cells exerted an additional suppressive effect, and AB-antigen (TNP) conjugates activated TNP-specific TH as well as TCS. Furthermore, AB-induced activation of TCS was independent of the recipient's age. Yet, the effect was most pronounced when AB were applied neonatally, i.e., after a hyporesponsive stage, animals were hyperreactive towards the nominal antigen, and this hyperreactivity was initiated by expansion of TCS. This extends the notion of high idiotypic connectivity in the neonatal period to the level of regulatory T-cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

[Differentiation of the neural crest. Influence of growth factors].

The peripheral nervous system (PNS) is derived from a transitory embryonic structure, the neural crest with an additional contribution of the cephalic ectodermal placodes to the sensory ganglia of certain cranial nerves. In vivo grafting experiments, taking advantage of the quail/chick marker system, allowed the fate map of the neural crest to be constructed and the precise level of origin along the neuraxis of the component cells of PNS ganglia to be defined. It appeared that the neural crest is regionalized in different areas from which a limited number of phenotypes arise. However, if the position of neural crest fragments is experimentally changed prior to the onset of migration, it turns out that virtually all the cell types represented in PNS ganglia can arise from any level of the neural crest, provided it is transplanted into the appropriate level of the neuraxis. This means that the microenvironment into which the neural crest cells migrate plays a critical role in directing their differentiation. Further in vivo studies along with in vitro clonal analysis of neural crest developmental potencies revealed that, during the migratory phase, the crest cells are already highly heterogeneous in their state of commitment. When they reach the sites of gangliogenesis, they exhibit different requirements for growth and differentiation. Our current studies are aimed at identifying the factors that, in spinal and sympathetic ganglia respectively, trigger the differentiation of sensory and adrenergic sympathetic neurons. The brain-derived neurotrophic factor (BDNF) and insulin (and/or IGF1) have been shown to play a role in these processes.

Animals↗
PubMed1977

[Single-stranded conjugation in Escherichia coli K-12: characteristics of the formation of a heterogenous progeny].

During a single-stranded conjugation donor DNA, being a single-stranded form, takes part in the process of recombination. That is why a heteroduplex DNA must be an intermediate product of the recombination. The heteroduplex can be partially corrected as it was supposed for genetic transformation. The division of such a corrected heteroduplex gives the heterogenous progeny of exoconjugants. And this "correctional" heterogeneity must possess two following properties: 1) the mixed progeny must consist of only two recombinational genotypes; 2) the heterogeneity must be marker-specific. The experimental support to both predictions was obtained by the method of clonal analysis of conjugational merozygotes.

Conjugation, Genetic↗
PubMed1986

Dosage of the Sts gene in the mouse.

In this study we compared steroid sulfatase levels in XO, XX, and XY mice and carried out a clonal analysis in fibroblast cell cultures from mice heterozygous for the steroid sulfatase deficiency gene and heterozygous at the X-linked electrophoretic phosphoglycerate kinase locus. The combined results indicate that the murine steroid sulfatase locus is not dosage compensated and is not subject to X-inactivation. With respect to X-inactivation, it behaves in a somewhat different way from the closely linked sex-reversed gene and the human steroid sulfatase locus.

Alleles↗
PubMed1986

Non-random spatial arrangement of clone sizes in chimaeric retinal pigment epithelium.

Clonal analysis of whole-mount preparations of entire retinal pigment epithelium (RPE), using SWR in equilibrium C57BL/6JLac and DDK in equilibrium C3H/Bi mouse aggregation chimaeras in which one of the two parental components predominated, revealed a markedly non-random spatial arrangement of patch (clone) sizes. Single-cell and small patches predominated in an area around the optic nerve head while large patches occurred most frequently near the periphery. Mechanisms are discussed which may explain these results. Patch size frequency distributions were concave and skewed. Singletons were the most frequent size class, but a wide range of sizes and a smaller number of much larger patches were also always found. The results preclude the use of statistical methods previously employed to calculate clone sizes from the geometric means of observed patch sizes. Instead, the median and interquartile range may provide the best summary of the observed patch size frequency distributions. Our findings support a stochastic model of tissue growth.

Animals↗