Delayed multiorgan non-neoplastic damage after exposure to radiotherapy in infancy.
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
C Russo
Publications and source records attributed to C Russo.
Enhancement of glycine release from human brain cortex synaptosomes by acetylcholine acting at M4 muscarinic receptors.
Synaptosomes prepared from fresh specimens of human cerebral cortex were labeled with [3H]glycine ([3H]Gly) and distributed in parallel superfusion chambers. Exposure to 15 mM KCl evoked a tritium overflow which was largely prevented by 10 mM Mg++, suggesting a consistent component of Ca(++)-dependent [3H]Gly release. Acetylcholine (ACh; 1-100 microM), added during K(+)-depolarization, increased the release of tritium in a concentration-dependent manner (maximal effect, 60%; EC50 = 7 microM). Oxotremorine (1-100 microM) mimicked ACh. The effect of 10 microM ACh was insensitive to the nicotinic antagonist mecamylamine (100 microM), but it was blocked by the muscarinic antagonist atropine (0.1 microM). Three muscarinic receptor antagonists, pirenzepine, AF-DX 116 (11-[12-[diethylamino-methyl]-1-piperidinyl]acetyl-5-11-dihydro -6H-pyrido-[2-3-b][1,4]benzodiazepine-6-one) and himbacine, endowed with relative selectivity for various muscarinic receptor subtypes, prevented with differential affinities the effect of 10 microM ACh. Himbacine was the most potent antagonist of ACh, its pA2 (8.34) being 20- or 50-fold higher than that of pirenzepine (7.27) or AF-DX 116 (6.65). It is concluded that: 1) ACh can increase the release of Gly in human cerebral cortex; 2) the interaction occurs through muscarinic receptors which resemble most the M4 subtype; and 3) considering that Gly is required to activate the N-methyl-D-aspartate glutamate receptor, the ACh-evoked Gly release may represent a linkage between cholinergic and glutamatergic transmission, two systems strongly implicated in cognitive processes.
Acetylcholine↗
Altered major histocompatibility complex-restricted antigen recognition by T cells from elderly humans.
Positive selection of T cells within the thymus gland leads to major histocompatibility complex (MHC)-restricted recognition of antigen by T lymphocytes. As the thymus gland involutes with age, altered MHC-restricted antigen recognition by T cells from elderly humans would be expected. We have tested this hypothesis by comparing the proliferative response of T cells and T cell clones from aged and young subjects to influenza determinants presented by autologous or allogeneic antigen-presenting cells (APC). Under conditions in which the allogeneic mixed lymphocyte reaction was minimal, T cells from six of seven aged donors but only one of seven young donors were stimulated by influenza vaccine presented by allogeneic APC. More importantly, one-half of the influenza-specific T cell clones derived from aged donors, but none of the clones derived from young donors, were activated by influenza vaccine presented by allogeneic APC. While 80% of the MHC-nonrestricted influenza-specific T cell clones expressed the gamma/delta T cell receptor, 20% of these clones expressed the alpha/beta T cell receptor. Thus, changes in MHC-restricted antigen recognition by T cells and in altered distribution of alpha/beta versus the gamma/delta T cell receptor bearing antigen-specific T cell clones occur with aging.
Adult↗
Evaluation and treatment of secondary tricuspid insufficiency.
To define the role of functional tricuspid insufficiency and right ventricular (RV) failure in patients with mitral disease, the data of 121 patients with secondary tricuspid insufficiency that underwent mitral valve replacement (MVR) from January 1982 to December 1987 were analyzed. The mitral hemodynamic lesion was: stenosis in 41 patients (33.9%); insufficiency in 11 (9.1%) and mixed stenosis and insufficiency in 69 (57.0%). NYHA functional class was: II in 4 patients (3.3%), III in 78 (64.5%) and IV in 39 (32.2%). In 100 cases (group 1) with tricuspid insufficiency defined as moderate or severe, a De Vega annuloplasty was performed while in 21 (group 2) with mild tricuspid insufficiency, no tricuspid surgical procedure was performed. Hospital deaths occurred in 17 of 121 patients [14% (CL 10.8-17.0)]. There was no significant difference in hospital mortality between group 1 and group 2 (15% vs 9.5%; P = 0.75). Incremental risk factors for hospital mortality as determined by multivariate analysis, include: cardiothoracic ratio (P = 0.0016), total aortic cross-clamp time (P = 0.006), associated cardiac disease (P = 0.0209) and emergency operations (P = 0.0318). Mean follow-up of surviving patients was 50.1 +/- 28.1 months. Late deaths occurred in 16 patients [15.4% (CL 11.7-18.7)]. The actuarial survival rate was 85.6% and 73.8% at 5 and 9 years, respectively. Nine patients [8.6% (CL 5.9-11.3)] required reoperation. There was no significant difference between group 1 and group 2 in the rate of late cardiac related deaths (5.9% vs 5.3%, P = 0.66) and of tricuspid reoperations (4.7% vs 5.3%, P = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Repeat myocardial revascularization].
Eighty-two consecutive patients undergoing reoperation for coronary revascularization from January 1980 to November 1990 were reviewed to determine early and late results and predictors of survival. Seventy patients were male and 12 female; age ranged from 36 to 75 years (mean 56.4 +/- 8.1). All were symptomatic for angina. The mean interval between first and second operation was 62.8 +/- 47.8 months (range 1 to 220 months). Angiographic indications for reoperation were: graft failure (34.1%), progression of atherosclerosis in the native coronary circulation (6.1%) and combination of the two (59.8%). Mean ejection fraction was 45.9 +/- 10.2 (range 11 to 67). Surgical indication was elective in 79.3%, urgent in 14.6% and emergent in 6.1%; 199 grafts were performed (2.4 +/- 1 grafts/patient). Hospital mortality was 6.1% (5 cases). Late mortality was 5.2% (4 cases). Actuarial survival rate (including hospital mortality) was 87.9% at 3, 5 and 10 years. Multivariate analysis identified left main stenosis (p = 0.00001), family history of coronary disease (p = 0.003), urgent/emergency operation (p = 0.015) as predictors of increased in-hospital mortality; postoperative myocardial infarction (p = 0.002) and preoperative heart failure (p = 0.01) as predictors of increased late mortality. Follow-up of in-hospital survivors (mean interval 42.7 +/- 25.8 months, range 3 to 120 months) documented 27 cardiac major events (other than death) in 24 patients (32.9%). Actuarial rates of freedom from major cardiac events were 70%, 52.9% and 48.1% at 3, 5 and 10 years respectively. Multivariate analysis identified preoperative ejection fraction (p = 0.01) as predictor of recurrence of angina and preoperative heart failure (p = 0.02) as predictor of occurrence of cardiac major events.
Adult↗
[Surgical revascularization in acute myocardial infarct].
To determine the potential role of emergency surgical revascularization as treatment of acute myocardial infarction (AMI), results in 79 patients undergoing operation for myocardial revascularization during AMI from January 1986 to January 1991 were reviewed. Clinical characteristics for inclusion in the study were: 1) emergency operation; 2) persistent angina not controlled by medical therapy; 3) fixed ST segment elevation until surgical procedure, independently from magnitude of enzymatic levels. The 79 patients were divided in 2 groups: 27 with AMI or evolving AMI (Group 1); 52 with AMI due to complications during PTCA (Group 2). Twenty-eight patients had extremely severe clinical conditions. Mean interval between the beginning of AMI and operation was 4.2 +/- 6.7 hours, with a statistically significant difference between Group 1 (8.7 +/- 10.0) and Group 2 (1.9 +/- 1.0). One hundred ninety-two grafts were performed (2.4 +/- 1.1 grafts/patient). Overall hospital mortality was 10.1% (CL 6.7-13.3) (8 deaths) with a difference between Group 1 [18.5% (CL 10.7-25.3)] and Group 2 [5.8% (CL 4.7-6.6)] (p = 0.074). The incidence of perioperative myocardial infarction was 30.4% (CL 24.9-35.1) for that one in the area of ischemic muscle and 2.6% (CL 0.8-4.1) for infarction in remote muscle. Multivariate analysis for the entire series (79 patients) identified as independent predictors of increased in-hospital mortality: preoperative cardiogenic shock (p = 1.000E-4) and hyperlipidemia (p = 0.008). In Group 1 multivariate analysis identified as independent predictors of increased in-hospital mortality: the attempt of revascularization by PTCA and hyperlipidemia; in Group 2: preoperative need of mechanical ventilatory support.(ABSTRACT TRUNCATED AT 250 WORDS)
Chi-Square Distribution↗
T helper cell-dependent, microbial superantigen-induced murine B cell activation: polyclonal and antigen-specific antibody responses.
Microbial superantigens (SA), bound to human B cell surface MHC class II molecules, have been shown to promote direct, "cognate" interaction with SA-reactive autologous Th cells, resulting in polyclonal Ig production. To investigate the potential for microbial SA to support Th cell-dependent, Ag-specific antibody responses, we have extended our studies to the murine system. BALB/c Th cell lines (TCL), specific for either the Mycoplasma arthritis-derived SA or the Staphylococcus aureus-derived toxic shock syndrome toxin-1) were generated. These TCL cells are SA-specific, functionally noncross-reactive, and utilize distinct TCR V beta gene families. Coculture of SA-reactive TCL cells and syngeneic B cells bearing the relevant SA results in B cell proliferation and polyclonal IgM and IgG production. In contrast, Ag-specific (SRBC-specific) antibody-forming cells are only generated in cultures that also contain SRBC. Thus, microbial SA-mediated Th-B cell interactions induce both polyclonal B cell activation and provide selective help for the proliferation and/or differentiation of B cells that have encountered specific Ag. In additional studies, we determined that the in vivo administration of toxic shock syndrome toxin-1 to young, athymic (nude) BALB/c mice results in SA binding to splenic B cells, rendering these B cells effective stimulators of and targets for SA-reactive helper TCL cells. Taken together, these results demonstrate that microbial SA mediate productive Th-B cell interactions analogous to those that occur during allospecific Th-B cell interactions in vitro and GVHD in vivo. These findings are consistent with the hypothesis that microbial SA represent environmental factors that may trigger autoimmune disease in the genetically susceptible host.
Animals↗
Philadelphia chromosome and monosomy 7 in childhood acute lymphoblastic leukemia: a Pediatric Oncology Group study.
During an 8-year period, 3,638 children from institutions of the Pediatric Oncology Group (POG) were diagnosed with acute lymphoblastic leukemia (ALL). Fifty-seven patients had Philadelphia chromosome-positive (Ph1) ALL. Blast cells obtained at diagnosis from 13 of these 57 cases (23%) were also found to have partial or complete monosomy 7 (-7). This subgroup of children with Ph1/-7 ALL was comprised primarily of older males with early B-lineage ALL. Bone marrow specimens from six Ph1/-7 patients were studied further using the polymerase chain reaction and primers that flank the ALL, and chronic myelogenous leukemia breakpoints to determine the molecular characteristic of the 9;22 translocation. Rearrangements were detected in RNA from bone marrow and/or peripheral blood cells of six patients, although four were in hematologic remission at the time of the analysis. Five cases showed the ALL breakpoint, while one child with Ph1/-7 showed the chronic myelogenous leukemia breakpoint. The induction failure rate was much higher in this subgroup (31%) as compared with Ph1-negative cases, and the projected duration of event-free survival reflected the aggressive nature of this subgroup because no children are projected to remain in remission at 2 years. ALL with both the 9;22 translocation and -7 appears to represent a unique and previously undescribed subgroup of childhood ALL associated with a particularly adverse outcome. Leukemic transformation in such patients may involve the interaction of a dominant oncogene (Ph1) and a tumor suppressor gene (-7).
Adolescent↗
T lymphocytes can mediate lysis of autologous melanoma cells by multiple mechanisms: evidence with a single T cell clone.
The specificity analysis of a CD3+, WT31+, CD8+ cytotoxic T lymphocyte (CTL) clone (CTL 49), isolated from peripheral blood lymphocytes of a melanoma patient (no. 665) after mixed lymphocyte culture with an HLA-A2+ allogeneic lymphoblastoid cell line (VSKB-LCL), revealed that CTL 49 could lyse, in addition to HLA-A2+ lines, autologous HLA-A2- melanoma (Me665/2) and K562 targets. Killing of VSKB-LCL, but not of Me665/2, could be inhibited by anti-CD3 and by anti-HLA-A2 antibodies or by modulation of the CD3 complex. Cold-target competition studies showed that K562, but not VSKB-LCL, could compete with Me665/2 for lysis by CTL 49. However, unlike K562, Me665/2 could be lysed by CTL 49 in a Ca2(+)-independent fashion in 4 h and 18 h assays. CTL 49 expressed mRNA specific for tumor necrosis factor (TNF alpha) and, to a lesser extent, for lymphotoxin (TNF beta). Exposure of the clone to anti-CD3 antibodies induced the expression of interferon(IFN)-gamma-specific mRNA. Antibodies to TNF alpha, TNF beta and IFN reduced the lysis of Me665/2, but not of K562, by CTL 49 in 18-h cytotoxic assays. Antibodies to TNF alpha and to IFN gamma almost completely inhibited the lysis seen on Me665/2 (but not on K562), in 96-h assays, by supernatants isolated from VSKB-LCL- or anti-CD3-stimulated CTL 49 cells. Taken together, these data indicate that major-histocompatibility-complex-independent lysis of autologous tumor cells and of natural killer reference targets by the same alloreactive T cell clone are activities related at the level of target recognition but distinct at the level of the lytic hit. Thus, efficient lysis of autologous tumor cells results from a complex mechanism based upon direct effector-target interaction as well as on cytokine-mediated cytolytic effects.
Calcium↗
An improved method for production of intravenous contrast during echocardiography.
Explore the source record for details and available documents.
Adult↗
Immunological studies of aging. Normal B-cell repertoire in aged mice: studies at a clonal level.
As previously reported, old mice produce lower avidity plaque-forming cells (PFC) after immunization with 2,4,6-trinitrophenyl-Ficoll (TNP-F) than do young mice. However, if spleen cells from TNP-F-immunized old mice are incubated with hapten to elute auto-anti-idiotype antibody then high avidity PFC, comparable to those in young mice, are detected. To further evaluate the effect of age on the B-cell repertoire anti-2,4,6-trinitrophenyl-bovine gamma globulin (TNP-BGG) hybridomas were prepared from young (6 to 8 weeks old) and old (18 to 24 months old) mice which had been primed and boosted with TNP-BGG. The monoclonal antibodies (MoAb's) were TNP-specific. Spleens from old and young mice were comparable with respect to the incidence of immunoglobulin-secreting hybridomas obtained, the incidence of TNP-BGG-specific hybridomas obtained, and the isotype distribution of the anti-TNP-BGG hybridomas. The avidities for TNP-BGG of the IgG1 anti-TNP-BGG MoAb's obtained from old and young donors were also comparable. The overall results thus suggest that old and young mice have similar B-cell repertoires and that differences in the antibodies produced are due to regulatory influences.
Aging↗
Selective changes in expression of HLA class I polymorphic determinants in human solid tumors.
Analysis of surgical biopsies with monoclonal antibodies (mAbs) to framework determinants of major histocompatibility complex class I antigens has shown that malignant transformation is frequently associated with a marked loss of these cell surface molecules. The present study sought to determine whether more selective losses of major histocompatibility complex class I expression occur. Multiple specimens from 13 different types of primary and metastatic tumors were tested utilizing mAb BB7.2, which recognizes a polymorphic HLA-A2 epitope. In each case, expression of HLA-A,B,C molecules was determined by testing with mAb W6/32 directed to a framework HLA class I determinant. We have found that in HLA-A2-positive patients (identified by reactivity of their normal tissues with mAb BB7.2), HLA-A2 products are not detectable or are reduced in their expression in 70-80% of endometrial, colorectal, mammary, and renal tumors; in 40-60% of soft-tissue, skin, ovary, urinary bladder, prostate, and stomach tumors; and in 25-30% of melanomas and lung carcinomas tested. All tumors expressed the framework HLA-A,B,C determinant. The HLA-A2 epitope recognized by mAb BB7.2 is located in a portion of the HLA-A2 molecule postulated to react with the T-cell receptor. Immune surveillance to tumors is thought to depend on cytotoxic T cells, which require corecognition of polymorphic HLA class I epitopes, and on natural killer cells, which are, on the contrary, activated by the absence of HLA class I antigens. The selective loss of an HLA class I polymorphic epitope shown in this study may explain the mechanism by which tumor cells escape both T-cell recognition and natural killer cell surveillance.
Antibodies, Monoclonal↗
Peripheral T cells select the B-cell repertoire in old mice.
These studies have shown that the alterations in the repertoire of antibody produced by old mice is not due to an intrinsic defect in the bone marrow or in the B-lymphocyte population arising from the bone marrow but rather to a selective downregulation by auto-anti-idiotypic antibody and idiotype-anti-idiotype interactions, shifting the idiotype distribution in the peripheral B-cell population. Thus, the clonal distributions of B cells generated by bone marrow of old and young mice are very comparable. The age-related differences in antibodies expressed by young and old mice are, to a great extent, determined by the activity of a peripheral regulatory immune network. This immune cellular network operates prior to exposure to antigen, presumably on the basis of an idiotype-anti-idiotype network between T and B lymphocytes. After exposure to antigen, a network of idiotype-anti-idiotype antibody interactions also contributes to differences in the immune responses of old and young mice to foreign antigens. If the expressed repertoire of antibody reflects down-regulation of auto-anti-idiotypic antibody, comparable repertoires of B-cell clones would be expected to be recovered from old and young mice if B cells from old mice were rescued from selective peripheral downregulatory influences active in old mice. Support for this hypothesis has been obtained by generating B-cell hybridomas from young and old mice immunized with TNP bovine gamme globulin (Marcenario et al. 1989). The same number of anti-TNP hybridomas and a comparable number of IgG and high-affinity antibody-producing clones were recovered from the spleens of young and old mice. Thus, the actual B-cell clonal repertoires of young and old mice appear to be similar although the expressed repertoires of antibody-producing lymphocytes from old and young mice are very different. This conclusion has considerable impact on strategies that could be employed to reverse the senescence of humoral immunity. Strategies to counter downregulatory influences which constrain the expression of the B-cell population should be more effective than attempts to reconstitute the repertoire of B lymphocytes in aged individuals. Finally, the mechanisms underlying these age-associated shifts in the expressed humoral antibody response can be attributed to life-long interactions with self and foreign antigens. The overall shift may be described as a decreased reactivity to foreign antigens and a complementary increase in reactivity with self antigens.(ABSTRACT TRUNCATED AT 400 WORDS)
Aging↗
Lymphocyte transformation induced by autologous cells. XVI: Distinctive role of discrete regions of class I MHC antigens in the autologous mixed leucocyte reaction.
The role of Class I major histocompatibility complex (MHC) molecules in the autologous (AMLR) and allogeneic mixed lymphocyte reactions was investigated by using monoclonal antibodies (MoAb) directed to polymorphic MHC determinants. The AMLR from subjects with the HLA-A2 phenotype was consistently inhibited by the anti-HLA-A2 MoAb, CR11-351, and the inhibition was dose-dependent and complete even at low antibody concentrations. The allogeneic MLR was inhibited by CR11-351 less than 30% when HLA-A2-bearing cells were used either as stimulator or responder cells. Addition of interleukins 1 and/or 2 to the AMLR in the presence of the inhibiting MoAbs did not restore the proliferative response. These studies suggest that Class I MHC polymorphic determinants, or closely related structures, participate in the induction of the AMLR.
Antibodies, Monoclonal↗
Biochemical and immunological similarity of soluble angiotensin II-binding proteins in different organs.
Binding of angiotensin II has been detected in soluble extracts of rabbit liver, adrenal gland, aorta, brain, kidney and uterus. In each case, binding required p-chloromercuriphenylsulfonic acid and bound angiotensin II was released by treatment with dithiothreitol. These properties resemble those of the 75 kDa binding protein purified from liver. Immobilized guinea pig antiserum developed against the isolated hepatic protein removed binding activities from the different extracts in an immune-specific, quantitatively comparable manner. In addition, the activities were removed by a mouse monoclonal antibody which specifically recognized a protein of 75 kDa in the various preparations. An immunologically homologous angiotensin II-binding protein with similar characteristics was also identified in the soluble fraction of rat liver.
Adrenal Glands↗
Long-term growth of human T cell lines and clones on anti-CD3 antibody-treated tissue culture plates.
Long-term growth of antigen-specific human T cells requires, in addition to IL-2, periodic exposure to antigen and accessory cells. In certain cases, accessory cells are not available or their presence in culture is undesired. We have developed a method of growing and sustaining human T cell lines and clones in long-term tissue culture in the absence of specific antigen or accessory cells. The requirement for antigen and/or accessory cells could be replaced by a monoclonal antibody to the CD3 determinant of human T cells (OKT3) bound to the surface of plastic tissue culture wells. Autoreactive, alloreactive, and antigen-reactive T cell lines and clones were maintained in culture for 8-12 weeks without antigen or accessory cells. The antigen specificity of these T cells was maintained.
Antigens, Differentiation, T-Lymphocyte↗
Peripheral but not thymic T cells participate in an autoreactive T cell network.
Splenic T cells proliferate in response to the anti-I-Ab reactive T cell hybridoma T1.203 in an H-2-restricted but MHC antigen-independent manner. We propose that this anti-idiotypic response is mediated by "Type 2 autoreactive" T cells that are induced in peripheral lymphoid tissues following interaction with the particular idiotype expressed by the anti-self-I-A T cells. Thus, we define this phenomenon as an idiotype-restricted MHC-related cell interaction. To study the ontogeny of this response, we examined the distribution of Type 2 autoreactive cells. Spleen and lymph node but not thymic C57BL/6 T cells vigorously proliferate to T1.203. Mature (PNA-) as well as immature (PNA+) thymic T cells respond poorly. The frequency of cells responding to T1.203 is far greater in the spleen than in the thymus. The responding T cells were of both Lyt 1+ and Lyt 2+ T phenotype. The results suggest that Type 2 autoreactive cells are induced in peripheral lymphoid tissues following interaction with anti-I-A autoreactive T cells which escape from the thymus or develop in the periphery.
Age Factors↗
CD3 pathway of T-cell activation. II. Role of HLA-class I molecules in early events.
The role of distinct regions of HLA class I molecules in regulating T-cell activation via the CD3-antigen receptor complex was investigated. Monoclonal antibodies (MoAbs) which recognize monomorphic and polymorphic epitopes on HLA Class I molecules were shown to inhibit T-cell proliferation to OKT3. These MoAbs have differential effects on the synthesis of interleukin-2 (IL-2) and IL-2 receptor expression. Cell cycle analysis demonstrated that these MoAbs function both in inhibiting cell cycle entry (G0-G1 shift) and in blocking cell cycle progression (G1-S shift) of activated T cells. Furthermore, these MoAbs have regulatory effects on the alternate pathway of T-cell activation via the CD2 molecule, T-cell activation induced by PHA, and activation induced by the phorbol ester PMA in conjunction with the calcium ionophore Ionomycin. Thus these MoAbs have different effects depending upon the pathway of T-cell activation. The results indicate that HLA class I molecules are selectively involved in the sequence of intracellular events leading to T-cell activation and proliferation.
Antibodies, Monoclonal↗