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C Russo

Publications and source records attributed to C Russo.

At least 19 recordsLinked to original sources
PubMed1995

Hospital morbidity and mortality after myocardial revascularisation surgery: current changes in risk factors.

To identify the operating risks for mortality and morbidity in patients undergoing aortocoronary bypass surgery, the data of 514 myocardial revascularisation procedures performed consecutively between January 1991 and December 1992 were analysed; 73.2% of the patients had associated diseases and 59.3% had suffered one or more previous myocardial infarctions. The mean ejection fraction of the population as a whole was 52.2 +/- 13. In 10.5% of the cases there was severe left ventricular (LV) function impairment with a mean ejection fraction (EF) of 30.2 +/- 4.4 (range 20-35). A major preoperative complication occurred in 8.2% of the entire population and 68.8% of the patients undergoing emergency surgery. Surgery was elective in 72.7% of the cases, urgent in 15.4% and emergency in 11.9%. Hospital mortality was 4.1% (CL 3.2-4.9). In the group of electively operated patients, mortality was 2.7% (CL 1.8-3.5), with no statistically significant difference (P = 0.943) from the mortality observed in the patients undergoing urgent surgery [2.5% (CL 0.8-4.1)]. The mortality in both groups was statistically different (P = 0.0001 and P = 0.008) from that of the patients undergoing emergency surgery [14.7% (CL 10.1-18.9)]. Perioperative acute myocardial infarction occurred in 5.4% of the patients (CL 4.4-6.4), in three cases resulting in death [10.7% (CL 4.8-15.8)]. Fourteen of the acute myocardial infarctions (AMI) occurred in the 42 patients undergoing emergency surgery for acute coronary occlusion (33.3%). A percentage of 18.7% of the 493 surviving patients suffered a postoperative complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1995

Time to peak serum antibody response to influenza vaccine.

The time to the appearance of a peak serum antibody response to influenza virus vaccine is not clearly defined. We compared the most commonly used time intervals described in the literature--4 and 6 weeks after vaccination. We studied 118 elderly patients from three different geographic sites. The 1992 to 1993 trivalent inactivated influenza virus vaccine containing influenza virus A/Beijing/353/89 (H3N2), influenza virus A/Texas/36/91 (H1N1), and influenza virus B/Panama/45/90 was used. No statistically significant differences were found at the 4- and 6-week intervals after vaccination.

Aged↗
PubMed1995

Oxytocin receptor gene expression in the rat uterus during pregnancy and the estrous cycle and in response to gonadal steroid treatment.

It is well established that uterine oxytocin receptors (OTRs) are strongly up-regulated immediately before parturition as well as in response to estrogen (E2) administration. Progesterone (P4), on the other hand, induces a rapid down-regulation. We recently cloned the rat OTR gene and characterized its expression in the rat uterus. In this study, we examined the regulation of OTR messenger RNA (mRNA) levels in rat uterus during pregnancy, the estrous cycle, and in response to gonadal steroid treatment. OTR mRNA levels increased more than 25-fold during gestation: 4.5-fold during the first 21 days and 6-fold within 24 h between day 21 and the onset of parturition. Uterine OTR mRNA levels fell rapidly by 85% within 24 h following parturition. By in situ hybridization, OTR mRNA was localized specifically to the longitudinal and circular layers of the myometrium but was not detected in the endometrium. During the estrous cycle, OTR mRNA levels increased 2-fold between metestrus and proestrus, whereas oxytocin (OT) binding rose more than 10-fold within this same interval. Treatment of ovariectomized rats with E2 lead to a significant increase in both OTR mRNA levels (4.4-fold) and OT binding (< 6-fold). Cotreatment with P4 strongly reduced OT binding by 75% (P < 0.01) but did not significantly affect the E2-induced rise in OTR mRNA (11% decrease, P > 0.1). Our data suggest that the increased expression of OT binding sites observed at the onset of labor and at proestrus is mediated, at least in part, by an E2-induced up-regulation of OTR gene expression. However, it also appears that OTR mRNA levels are not the sole determinants of uterine OT binding. Specifically, P4-mediated OTR down-regulation cannot be explained by an effect on OTR mRNA accumulation and may involve novel mechanisms acting at translational or posttranslational levels.

Animals↗
PubMed1995

[The multiple-organ failure syndrome in acute pancreatitis. Its pathogenesis and treatment].

Multiple organ system failure (MOSF) is a severe clinical process that causes progressive renal and liver failure. Acute pancreatitis (AP) can cause MOSF. Several series document high mortality rate from necrotizing forms is associated with MOSF. The authors observed 199 cases of acute necrotizing pancreatitis in 10 years, with a mortality rate of 14.1%. MOSF occurred in 14 cases, resulting in death in 100% of affected patients. In AP, MOSF follows hemodynamic abnormalities suspected to be secondary to activation of kinins system and other vasoactive peptides that are responsible for pathogenetic mechanism of disease. Similar hemodynamic abnormalities can be observed in septic shock. Then many authors suppose causes of MOSF in AP are local (abscess, infection of pancreatic necrosis) and systemic septic complications or translocation of enteric bacteria or their endotoxins from the gut lumen. So it is important to provide prophylactic use of antibiotics that are effective against expected bacteria and also achieve a therapeutic concentration in pancreatic tissue and juice. Fluid replacement, nutritional support and other therapeutic strategies must be employed to prevent MOSF. When the MOSF is clearly developed, medical and surgical measures are unuseful and the mortality rate is very high also in an intensive care unit.

Acute Disease↗
PubMed1994

Vaccine immune response and side effects with the use of acetaminophen with influenza vaccine.

The purpose of this study was to determine whether acetaminophen impairs the immune response to influenza vaccine. Influenza vaccine is an under-utilized preventive measure, partly because of the unfounded perception that fever and myalgias frequently follow vaccination. While acetaminophen may decrease these infrequent side effects, it may also alter the immune response to vaccination. We compare the effect of acetaminophen with placebo on the humoral immune response to the 1991-1992 commercially available influenza vaccine. We studied 60 healthy, elderly subjects from a geriatric clinic and 20 infirm, elderly subjects from a nursing home. The subjects were randomly assigned to receive placebo or acetaminophen (1,000 mg every 6 h) for 2 days. Acetaminophen did not depress or enhance the immune development of serum hemagglutination inhibition antibody to the three vaccine antigens. The systemic side effects of fever and myalgia were uncommon in both groups. The healthy elderly subjects mounted a significantly better immune response to the influenza virus A/Taiwan/1/86 (H1N1) vaccine strain than did the infirm elderly subjects (geometric mean titer, 115 versus 51; P = 0.003). The functional activity score obtained by using the chronic healthy evaluation component of the Acute Physiology and Chronic Health Evaluation system could be used to distinguish the healthy from the infirm elderly (scores of 1.27 versus 3.75, P < 0.001). Acetaminophen neither depressed nor enhanced the serum antibody response to the vaccine in the healthy and infirm elderly subjects studied.

Acetaminophen↗
PubMed1993

Effect of age on the expressed B cell repertoire: role of B cell subsets.

Aged humans and experimental animals are impaired in their responses to most foreign antigens although they produce greater amounts of autoantibodies. We have examined the effect of age on the production of antibodies to a prototypic foreign antigen, sheep erythrocytes (SRBC), and to a prototypic autoantigen, bromelain-treated mouse erythrocytes (BrMRBC), in young and old mice before and after immunization with SRBC. Old mice express more anti-BrMRBC plaque-forming cell (PFC) antibodies before and an even greater number after immunization with SRBC than young mice. Conversely, old mice produce far fewer anti-SRBC PFC than young mice following immunization with SRBC. We hypothesized that the differences in the responses of old mice to BrMRBC and SRBC reflects differences in the activity of CD5+ and CD5- B cells. To test this hypothesis we immunized young and old mice with foreign antigens reported (and confirmed in our studies) to stimulate CD5+ B cells [TNP-ficoll and phosphorylcholine-keyhole limpet hemocyanin (KLH)] or CD5- B cells (SRBC and TNP-KLH). We found that the PFC response of old mice to antigens mediated by CD5+ B cells was equal to or greater than that of young mice. In contrast the PFC response of old mice induced by antigens mediated by CD5- B cells was only 10% that of young mice. Thus it appears that the immune response of old mice is well maintained for antigens which elicit a CD5+ B cell response but not for those which elicit a CD5- B cell response.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Posterior annuloplasty in the surgical treatment of mitral insufficiency.

One hundred and twenty-nine patients underwent posterior mitral annuloplasty with a Gore-Tex tube for mitral regurgitation between January 1982 and June 1991. The hospital mortality was 1.5% (CL = 0.5%-2.5%). The overall survival of hospital survivors was 96.5% +/- 2.7% at five and 86.2% +/- 7.6% at nine years, freedom from cardiac death was 99.1% +/- 0.9% and 95.2% +/- 3.9%, respectively. The actuarial freedom from embolism was 96.1% +/- 2.3% at five and 88.5% +/- 5.5% at nine years. The freedom from endocarditis (one patient) was 100% and 92.6 +/- 7.1%, respectively. Reoperation was necessary in six cases between one and 72 months after the operation (mean 38.5 +/- 30.5 months). The etiology of the valvular insufficiency was rheumatic in all reoperated cases. The freedom from reoperation was 94.1% +/- 3.2% at five and 87.2% +/- 5.6% at nine years. There was no mortality at reoperation. Of the 117 patients alive at the end of follow up and not requiring reintervention, 113 (96.6%) showed good functional improvement and were in NYHA functional class I or II. We conclude that both the immediate and long-term results of reconstructive surgery using the technique of inserting a half-ring on the posterior mitral annulus compare favorably with those obtained using other annuloplasty methods.

Actuarial Analysis↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

[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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗