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M Valentine

Publications and source records attributed to M Valentine.

At least 55 records · Page 3Linked to original sources
PubMed1990

A second nonrandom translocation, der(16)t(1;16)(q21;q13), in Ewing sarcoma and peripheral neuroectodermal tumor.

The majority of Ewing sarcomas and peripheral neuroectodermal tumors (PNET) that have been karyotyped contain a specific translocation, t(11;22)(q23;q11). We report here a second nonrandom translocation, der(16)t(1;16)(q21;q13), in 2 of 20 cases of Ewing sarcoma (seven previously unreported) and 2 of 7 cases of PNET (all previously unreported). All cases with this translocation also contained the t(11;22). Comparison of C-banding patterns in tumor and peripheral lymphocyte karyotypes in one case indicated that the likely breakpoints were 1q21 and 16q13. The presence of this translocation in cell lines will enable further investigation of the molecular events important in the pathogenesis of Ewing sarcoma and PNET.

Adolescent↗
PubMed1989

Molecular analysis of chromosome 1 abnormalities in neuroblastoma.

Tumor cells from 70% of neuroblastoma patients contain a deletion of part of the short arm of chromosome 1, indicating that this chromosomal region includes a gene involved in tumor formation. To more precisely evaluate the boundaries and mechanisms involved in generating these deletions, we have examined four neuroblastoma cell lines using a combination of somatic cell hybridization, isozyme analysis, and nucleic acid hybridization employing both standard and restriction fragment length polymorphic probes. The data suggest that the truncation of chromosome 1 in these neuroblastomas was most likely due to a complex translocation and deletion mechanism rather than a simple unbalanced translocation or terminal or interstitial deletion. This conclusion is supported by the frequent removal of MYCL from the altered chromosome 1 to another chromosome. Furthermore, the data suggest that the frequency of breakpoints previously assigned by karyotypic analysis to bands other than 1p32 in neuroblastomas may be overestimated. Finally, this study identified a breakpoint at 1p32 that was localized between the genes JUN and MYCL for one neuroblastoma thus establishing the order of these genes as centromere, JUN, MYCL, telomere. We conclude that the observed breakpoints within chromosome 1p in human neuroblastoma are not as variable as previously described and suggest the results of this study provide evidence for the involvement of specific DNA sequences within 1p32 in the generation of neuroblastoma.

Animals↗
PubMed1989

Closely linked loci on the long arm of chromosome 13 flank a specific 2;13 translocation breakpoint in childhood rhabdomyosarcoma.

A specific chromosomal translocation, t(2;13)(q35;q14), is present in tumor cells from about one-half of children with alveolar rhabdomyosarcoma, who generally have widely disseminated disease at diagnosis. Using a series of six DNA probes from five loci previously assigned to bands 13q12----q14, we have localized the translocation breakpoint on chromosome 13 by in situ hybridization. Each probe was used to examine metaphase spreads from two or more rhabdomyosarcoma cell lines that have the t(2;13), as well as from control lymphoblastoid cell metaphases. All six probes bound to chromosome 13q12----q14 in the control cell line, but showed no appreciable hybridization to other sites. With rhabdomyosarcoma metaphases, cDNA clones of the retinoblastoma susceptibility gene (RB1) and the esterase D gene (ESD), as well as the arbitrary genomic fragment 7D2 (D13S10), showed specific hybridization to the normal chromosome 13 and the der(2) marker, but not to the der(13). By contrast, the genomic fragments HU10 (D13S6) and 7F12 (D13S1) hybridized specifically to the normal chromosome 13 and the der(13), but not to the der(2). Thus, the breakpoint of this translocation lies distal to D13S6 and D13S1 and proximal to ESD, RB1, and D13S10. Our data indicate that the locus affected by the translocation breakpoint on chromosome 13, which we have termed RMS, is physically distinct from the RB1 locus and is, in fact, proximal to ESD, which others have placed at least 10(6) bp proximal to RB1. The consistent presence of the der(2) marker chromosome, coupled with occasional loss of the der(13), suggests that the RMS gene, or at least a critical component, moves to chromosome 2 in tumors with this translocation.

Cell Line↗
PubMed1987

A specific chromosomal abnormality in rhabdomyosarcoma.

A specific chromosomal abnormality, t(2;13)(q35;q14), was discovered in five cases of advanced rhabdomyosarcoma. It was identified directly in cells that had metastasized from bone marrow in one patient and in xenografts derived from the tumors of four other patients. The translocation was not restricted by histologic subtype, but was found in cases classified as alveolar, undifferentiated, or embryonal. Cytogenetic hallmarks of gene amplification (double minute chromosomes and homogeneously staining regions) were apparent in three cases. Other frequent abnormalities included rearrangements of chromosomes lp and trisomy of chromosome 8. The absence of the t(2;13) in more than 100 cases of other pediatric solid tumors investigated in our laboratory indicates its specificity for rhabdomyosarcoma. These cytogenetic findings suggest directions for further investigation of the molecular events underlying the genesis of this tumor.

Adolescent↗
PubMed1986

Tetraheme cytochrome c-554 from Nitrosomonas europaea. Heme-heme interactions and ligand binding.

Cytochrome c-554 functions in the ammonia oxidizing system of Nitrosomonas europaea. We have investigated its molecular and ligand binding properties and studied the protein with optical, EPR, and Mössbauer spectroscopies in the pH range from 2 to 13. Amino acid, heme, and metal analyses show that the protein has Mr = 25,000 and that it contains four c-type hemes per molecule. Optical spectra reveal that the heme ligand structures are sensitive to the pH of the medium and that the hemes can bind small molecules such as CN-, CO, and NO under certain conditions. According to the Mössbauer and EPR studies of the ferric protein, the hemes are predominantly (75%) high spin at pH 2 and low spin (approximately equal to 100%) above pH 10. At neutral pH, Mössbauer data show that 75% of the heme is low spin and that the remainder is high spin. The EPR data, however, do not reveal any signals attributable to typical high spin or low spin species. Rather, a very complex and unusual spectrum with a main feature at g = 3.3 is observed at X-band, this feature shifts to approximately g = 3 at S-band. The EPR and Mössbauer data show clearly that the hemes are magnetically interacting, by dipolar and exchange interactions. At pH 2, the EPR spectra reveal resonances at g = 6 and 2. The Mössbauer spectra prove that all hemes are magnetically coupled at this pH. Coupling is also borne out by the observation of a half-field EPR resonance near g = 12.

Amino Acids↗
PubMed1986

Lymphoblastoid B cell lines produce an interleukin-1-like activity that can be serologically distinct from macrophage interleukin-1.

Antigen presentation by macrophages is accompanied by the production of interleukin-1 (IL-1) for successful T cell triggering. We have described EBV infected B cell lines that served as antigen presenting cells (APC) and now report the ability of these cells and their supernates, as well as EBV negative B cell lines, to support IL-2 production by a T cell line JM in the presence of the monoclonal antibody that recognizes the CD3 complex. Both EBV-transformed B cell lines and EBV-negative lines, and their supernates, exhibited IL-1-like activity in two different IL-1 dependent assays. These IL-1-like molecules were released constitutively from five of six EBV positive lines and three of five non-infected B cell lines. The activity from both, one virally infected and one non-infected B cell line, eluted from Sephadex G-75 in two peaks at 15-18K and 30-35K and could not be neutralized by antibody specific for macrophage IL-1. Supernates having IL-1-like molecules also contained a higher molecular weight inhibitor of proliferation. These data indicate that: both EBV-positive and EBV-negative B cell lines are capable of elaborating the IL-1-like activity; and the IL-1-like activity from these cells can be serologically distinct from macrophage IL-1. This suggests the presence of a family of molecules with IL-1 activity that derive from different cell types.

Animals↗
PubMed1986

t(11;22) and other chromosomal rearrangements in Ewing's sarcoma.

Abnormal karyotypes from 13 human cases of Ewing's sarcoma are reported in this paper. The t(11;22) was seen in 9 cases, with 2 additional cases containing only a del(22). Other abnormalities included trisomy of 1q, translocations to 19p13, deletions of 3p and 6q, and homogeneously staining regions.

Adolescent↗
PubMed1985

The role of the T3 molecular complex on human T lymphocyte-mediated cytotoxicity.

The above overview of the experimental data clearly indicates that the T3 molecular complex is intimately involved in T cell activation. The precise role of the T3 complex in the activation process, however, is not clearly understood. The surface association of the T3 complex with the antigen receptor, along with the ability of antibodies to these molecules to render T cells receptive to IL2, reveal a possible mechanism by which specific antigen initiates T cell activation and growth. However, it would be difficult to reconcile this specific effect of anti-T3 antibodies with their effect on CTL function. Since the T3 complex is not a specific marker of any particular effector T cell population, but it is found on all T lymphocytes, we favor the hypothesis that the complex is involved in a more fundamental step of T cell activation, and we believe that triggering of the 'lethal hit', expression of IL2 receptors, and secretion of IL2 are mere manifestations of this basic process. The natural ligand of the antigen receptor is obviously the specific antigen. However, the natural ligand of the T3 complex is unknown. Possibly, its natural ligand is the antigen receptor itself after it has interacted with antigen. A simple scenario, then of the early events of T cell activation would include antigen recognition and binding, followed by an interaction between the antigen receptor and the T3 complex which then activates or allows expression of specific pathways depending on the particular effector population involved. Thus, the inhibition of CTL function by anti-T3 antibodies could be explained by interference with the antigen receptor-T3 complex interaction following target cell recognition. This interaction may be the event that signals the initiation of the 'lethal hit' process.

Antibodies, Monoclonal↗
PubMed1985

Activation of resting T lymphocytes by anti-CD3 (T3) antibodies in the absence of monocytes.

The antigen receptor molecules on human T lymphocytes are noncovalently associated on the cell surface with the CD3 (T3) molecular complex. Perturbation of this complex with anti-CD3 monoclonal antibodies induces T cell activation. Previous studies have demonstrated that this process requires the participation of monocytes. In the present report, we demonstrate that purified, resting (G0 phase) T cells incubated with monoclonal anti-CD3 antibodies proliferate in response to purified interleukin 2 (IL 2), in a lymphokine dose-dependent fashion. Anti-CD3 antibody or IL 2 alone did not trigger cell division. The effect was specific for anti-CD3 antibodies because monoclonal antibodies reactive with other surface molecules (OKT4, OKT8, L368) were inactive. Furthermore, the same phenomenon was observed when anti-CD3 antibody Leu-4 (IgG1) was incubated with cells of individuals whose monocytes cannot process antibodies of the IgG1 subclass (Leu-4 nonresponders). In addition, both F(ab')2 and Fab fragments of anti-CD3 antibody OKT3 were also capable of rendering T cells receptive to the IL 2 growth signal. These data indicate that neither monocytes nor CD3 receptor cross-linking are required absolutely for resting T cell activation, provided that IL 2 is supplied exogenously. T lymphocytes treated with anti-CD3 antibodies proliferated in response to both purified mitogen-induced and recombinant IL 2. Antibodies to the IL 2 receptor (anti-Tac) inhibited the proliferation. Thus, the most likely mechanism for anti-CD3 antibody-mediated triggering is induction of IL 2 receptors.

Antibodies, Monoclonal↗
PubMed1984

Chloroperoxidase compound I: Electron paramagnetic resonance and Mössbauer studies.

The green primary compound of chloroperoxidase was prepared by freeze-quenching the enzyme after rapid mixing with a 5-fold excess of peracetic acid. The electron paramagnetic resonance (EPR) spectra of these preparations consisted of at least three distinct signals that could be assigned to native enzyme, a free radical, and the green compound I as reported earlier. The absorption spectrum of compound I was obtained through subtraction of EPR signals measured under passage conditions. The signal is well approximated by an effective spin Seff = 1/2 model with g = 1.64, 1.73, 2.00 and a highly anisotropic line width. Mössbauer difference spectra of compound I samples minus native enzyme showed well-resolved magnetic splitting at 4.2 K, an isomer shift delta Fe = 0.15 mm/s, and quadrupole splitting delta EQ = 1.02 mm/s. All data are consistent with the model of an exchange-coupled spin S = 1 ferryl iron and a spin S' = 1/2 porphyrin radical. As a result of the large zero field splitting, D, of the ferryl iron and of intermediate antiferromagnetic exchange, S.J.S'.J approximately 1.02 D, the system consists of three Kramers doublets that are widely separated in energy. The model relates the EPR and Mössbauer spectra of the ground doublet to the intrinsic parameters of the ferryl iron, D/k = 52 K, E/D congruent to 0.035, and A perpendicular (gn beta n) = 20 T, and the porphyrin radical.(ABSTRACT TRUNCATED AT 250 WORDS)

Chloride Peroxidase↗
PubMed1983

Chemical nature of the porphyrin pi cation radical in horseradish peroxidase compound I.

The electron paramagnetic resonance (EPR) and Mössbauer properties of native horseradish peroxidase have been compared with those of a synthetic derivative of the enzyme in which a mesohemin residue replaces the natural iron protoporphyrin IX heme prosthetic group. The oxyferryl pi cation radical intermediate, compound I, has been formed from both the native and synthetic enzyme, and the magnetic properties of both intermediates have been examined. The optical absorption characteristics of compound I prepared from mesoheme-substituted horseradish peroxidase are different from those of the compound I prepared from native enzyme [DiNello, R. K., & Dolphin, D. (1981) J. Biol. Chem. 256, 6903-6912]. By analogy to model-compound studies, it has been suggested that these optical absorption differences are due to the formation of an A2u and an A1u pi cation radical species, respectively. However, the EPR and Mössbauer properties of the native and synthetic enzyme and of their oxidized intermediates are quite similar, if not identical, and the data favor an A2u radical for both compounds I.

Cations↗
PubMed1976

Allergy to insect stings. II. Phospholipase A: the major allergen in honeybee venom.

In order to determine the proteins of major allergenic importance in honeybee venom (Apis mellifera) it was chromatographed on G-50 Sephadex. The four major protein peaks eluted were identified as hyaluronidase, phospholipase, melittin, and apamin. Testing these preparations on the leukocytes of 6 honeybee-sensitive patients, with the in vitro method of histamine release, revealed that all individuals were most sensitive to phospholipase A. IgE antibodies against phospholipase A (RAST) were found in the sera of honeybee-sensitive patients and IgG antibodies to this venom component were found in the sera from beekeepers and venom-treated patients. Melittin appeared to be allergenic in several patients, but the results were variable and were possibly due to contamination with phospholipase. All patients were insensitive to the hyaluronidase and apamin preparations. We conclude that phospholipase A is the major allergen of honeybee venom and, since this protein is readily available, it should be useful for diagnostic and therapeutic studies as well as for the standardization of materials used in the management of honeybee-sensitive patients.

Allergens↗
PubMed1976

A profile for trimipramine.

A series of sixty-one patients with depressive symptoms were treated with trimipramine in single nightly dosages. Analysis of the data indicated that a favourable outcome was likely to be associated with the following features: absence of gastro-intestinal complaints; absence of hypochondriasis; a level of anxiety not more than the average for psychiatric patients; absence of situational palpitation; possession of a stable work record; and possession of a family history positive for psychiatric disorder. These features are not claimed to be specific to treatment with trimipramine. Age, sex, out-patient/in-patient status and the over-all degree of depression were not found to be relevant. Trimipramine was associated with a favourable outcome in 64% of all cases treated, and in 73% of primarily depressive conditions.

Adult↗