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Biomedical subjects

S Braun

Publications and source records attributed to S Braun.

At least 91 records · Page 5Linked to original sources

The WeeFIM instrument: its utility in detecting change in children with developmental disabilities.

OBJECTIVE: To examine the utility of the WeeFIM instrument ("WeeFIM") in detecting changes in the functional status of children with disability. DESIGN: Prospective longitudinal design with correlation and responsiveness analysis. SETTING: Three facilities providing services to children with developmental disabilities in western New York State. PARTICIPANTS: Two hundred five children (72 girls, 133 boys) with identified medical disabilities receiving special services were administered the WeeFIM. Subjects ranged in age from 11 to 87 months and came from diverse socioeconomic and ethnic backgrounds. Scores for 174 children were available for 3 administrations performed over a 1-year period. MAIN OUTCOME MEASURES: The responsiveness of the WeeFIM instrument was examined using 5 statistical procedures: Reliability Change Index, Proportional Change Index, effect size, standardized response means, and paired t tests. RESULTS: All 5 indexes of responsiveness indicated statistically significant (p < .05) or reliable changes over time. The transfer subscale of the WeeFIM showed a skewed distribution that affected the results for some responsiveness indexes. The advantage, limitations, and assumptions of the responsiveness indexes are described and graphic examples of change over time are presented to validate the responsiveness of the WeeFIM instrument. CONCLUSION: The WeeFIM instrument showed the ability to document change in functional abilities over a 1-year period in children with chronic disabilities.

Activities of Daily Living↗

Uncontrolled reoxygenation by initiating cardiopulmonary bypass is associated with higher protein S100 in cyanotic versus acyanotic patients.

BACKGROUND: The systemic reoxygenation injury produced by initiating cardiopulmonary bypass (CPB) in infants with cyanotic heart disease may be associated with cerebral dysfunction and injury. Increased protein S100 (S100) serum levels may indicate cerebral and blood brain barrier damage as well as inflammatory changes, therefore serving to quantify these changes. The present clinical study assessed S100 in cyanotic patients undergoing CPB with normoxic versus hyperoxic paO2 in acyanotic cases and in controls without CPB. METHODS: 43 patients with congenital heart disease aged 5 days to 15 years (mean 4.4 years) were enrolled consecutively and divided in four groups: (1) Cyanotic infants undergoing controlled normoxic reoxygenation on CPB (n = 12), (2) cyanotic infants undergoing uncontrolled hyperoxic reoxygenation on CPB (n = 9), (3) acyanotic infants operated with CPB (n = 16) and (4) patients operated without CPB (n = 6). Blood samples were collected after induction of anesthesia (A), up to 4 hours after surgery (B) and at postoperative day one (C). RESULTS: Preoperative S100 serum levels [microg/l] in all groups were below clinical relevance. S100 increased markedly after surgery in groups 1 and 2. Differences in postoperative S100 levels were significant between groups 1 (0.45 +/- 0.13) and 3 (0.35 +/- 0.09; p = 0.018), between groups 2 (1.41 +/- 0.47) and 3 (p = 0.01), and between groups 2 and 4 (0.29 +/- 0.09; p = 0.045). There were no significant differences in postoperative S100 levels (B) between groups 1 and 2 (p = 0.05), groups 1 and 4 (p = 0.05), or groups 3 and 4 (p = 0.93). CONCLUSION: Uncontrolled hyperoxic reoxygenation on CPB for surgical correction of congenital heart defects is associated with higher S100 levels in cyanotic infants as compared to acyanotic patients undergoing comparable operations.

Adolescent↗

A European study on the genetics of mite sensitization.

BACKGROUND: Sensitization to mite allergens represents a prominent feature of atopy and an important predictor of bronchial asthma. OBJECTIVE: It was the intention of this study to define genetic loci linked to mite sensitization because these could represent the genetic basis of the important atopic component of asthma. METHODS: We studied a multiethnic white population of 99 families, including 224 sib pairs sensitized to Dermatophagoides pteronyssinus. A genome-wide candidate-region search was performed that covered potential asthma and atopy regions. RESULTS: As for nonparametric linkage (NPL) analysis, 14 of the candidate regions showed evidence for linkage (NPL > 2.0), and 4 of them showed prominent linkage (NPL > 3.0). However, there were substantial ethnic differences. Maximizing the LOD score analysis identified candidate regions with suspected dominant and recessive mode of inheritance. Furthermore, genetic imprinting models provided significant evidence for linkage in the 8p23 region and revealed potential maternal imprinting. The regions found are distinct to those in asthma searches that have been found to be linked to asthma, as well to other inflammatory diseases. In addition, we could not find linkage to the HLA region. By different cutoff points of the phenotype definition, the IL cluster showed evidence of being linked to the degree of sensitization rather than to sensitization per se. CONCLUSION: The results indicate that the genetic basis of the atopic component of asthma is different from that of the inflammatory component. Furthermore, it seems reasonable to assume that specific sensitizations are influenced by distinct genetic variants leading to their initiation versus those leading to their enhancement.

Allergens↗

The relationship of arch length to alterations in dental arch width.

An accurate method is presented for forecasting alterations in arch length related to various width increases in each dental arch. It is based on combined beta and hyperbolic cosine functions which express the expanded dental arches with correlation coefficients of r = 0.98, between measured data and representations of the dental arch. When the midpalatal suture is expanded, canine width and molar width alterations are not equal because the line of action of the expanding force is anterior to the center of resistance of the dentomaxillary complex. Therefore, canine to molar width ratio alterations of 1:1, 1.25:1, and 1.5:1 are examined, and simple linear functions are presented for purposes of predicting changes in arch length.

Cephalometry↗

The biomechanics of rapid maxillary sutural expansion.

Micro-displacements (fringe patterns) in the bones of the craniofacial complex as seen through laser holography during midpalatal sutural expansion with the Hyrax appliance are used to define the centers of rotation of the maxillary halves in both the frontal and occlusal views. Biomechanical analyses of the maxillary expansion force system are concomitant with the holographic findings and strongly suggest that the stainless steel wires joining the teeth to any expansion device be of the largest diameter possible. In addition, in the case of the Hyrax expansion device, it is recommended that the manufacturer increase the diameter of the activating screw as well as those of the 2 adjacent wire guides. And, importantly, the use of acrylic as a structural member to join the teeth to a sutural expansion device should be avoided if tipping of the maxillary halves is to be minimized, as the acrylic lacks sufficient rigidity.

Acrylic Resins↗

The relationship of the glenoid fossa to the functional occlusal plane.

The geometric relationship of the functional occlusal plane to the center of the glenoid fossa, as seen in the sagittal view, is described for males and females from age 7 through 25 years. This relationship is fully described by the distance from the geometric center of the glenoid fossa perpendicular to the functional occlusal plane (L, in millimeters) and its angulation (theta, in degrees) relative to a constructed Frankfort horizontal (SN-7 degrees ). Regression formulas with 95% confidence levels are described for L and theta for both genders combined. The differences between genders were found to be statistically insignificant. No correlation was found between these dimensions relative to the presence of temporomandibular joint dysfunction symptoms. A statistically significant difference in both L and theta was found in males who exhibited a Class III relationship compared with males exhibiting a Class II relationship.

Adolescent↗

Glutathione and a UV light-induced glutathione S-transferase are involved in signaling to chalcone synthase in cell cultures.

UV irradiation stimulates expression of the gene encoding the key enzyme chalcone synthase (CHS), which leads to the generation of protective flavonoids in parsley cell cultures. CHS transcripts increase after 3 to 4 hr, and early genes are involved in the signal transduction to the CHS promoter. By using the fluorescent differential display technique in a large-scale screening, several early UV light-induced genes were isolated. Of these, a novel glutathione S-transferase (PcGST1) is induced within 2 hr and precedes CHS expression. Overexpression of PcGST1 in transformed cell lines containing a CHS promoter/luciferase reporter (CHS-LUC) affected the onset of LUC transcription. Supplementing these cell lines with glutathione immediately stimulated CHS-LUC expression within 2 hr in dark-incubated cells and resulted in a biphasic induction profile in UV-irradiated cells. Our data indicate the involvement of glutathione and PcGST1 in early events of a UV light-dependent signal transduction pathway to CHS. In this context, the oxidative status of a cell acts as a central regulating element.

Acyltransferases↗

Gene rearrangements in bone marrow cells of patients with acute myelogenous leukemia.

At diagnosis, clonal gene rearrangement probes [retinoic acid receptor (RAR)-alpha, major breakpoint cluster region (M-bcr), immunoglobulin (Ig)-JH, T cell receptor (TcR)-beta, myeloid lymphoid leukemia (MLL) or cytokine genes (GM-CSF, G-CSF, IL-3)] were detected in bone marrow samples from 71 of 153 patients with acute myelogenous leukemia (AML) (46%): in 41 patients with primary AML (pAML) (58%) and in 30 patients with secondary AML (42%). In all cases with promyelocytic leukemia (AML-M3) RAR-alpha gene rearrangements were detected (n = 9). Gene rearrangements in the Ig-JH or the TcR-beta or GM-CSF or IL-3 or MLL gene were detected in 12, 10, 16 and 12% of the cases, respectively, whereas only few cases showed gene rearrangements in the M-bcr (6%) or G-CSF gene (3%). Survival of pAML patients with TcR-beta gene rearrangements was longer and survival of pAML patients with IL-3 or GM-CSF gene rearrangement was shorter than in patients without those rearrangements. No worse survival outcome was seen in patients with rearrangements in the MLL, Ig-JH or M-bcr gene. In remission of AML (CR), clonal gene rearrangements were detected in 23 of 48 cases (48%) if samples were taken once in CR, in 23 of 26 cases (88%) if samples were taken twice in CR and in 23 of 23 cases (100%) if samples were studied three times in CR. All cases with gene rearrangements at diagnosis showed the same kind of rearrangement at relapse of the disease (n = 12). Our data show that (1) populations with clonal gene rearrangements can be regularly detected at diagnosis, in CR and at relapse of AML. (2) Certain gene rearrangements that are detectable at diagnosis have a prognostic significance for the patients' outcome. Our results point out the significance of gene rearrangement analyses at diagnosis of AML in order to identify 'poor risk' patients - independently of the karyotype. Moreover, the persistence of clonal cells in the further course of AML can be studied by gene rearrangement analysis.

Acute Disease↗

Lymphokine-activated killer (LAK) cells and cytokines synergize to kill clonal cells in acute myeloid leukemia (AML) in vitro.

We studied the influence of autologous lymphokine-activated-killer (LAK) cells on the survival of clonal and CD34-positive bone marrow (BM) cells from patients with acute myeloid leukemia (AML) in a coculture assay in vitro. (1) LAK cells were grown in the presence of IL-2, in some cases additionally with IL-6. (2) These cytotoxic cells were cocultured with (untreated or cytokine pretreated) AML-BM cells obtained at different stages of the disease. Therefore BM cells were (a) either frozen in liquid nitrogen or (b) precultured for 14 days with cytokines: IL-1beta, IL-3, IL-6, erythropoietin (EPO), stem cell factor (SCF) with ('Cytok1') or without granulocyte macrophage colony stimulating factor (GM-CSF) ('Cytok2') or with no added cytokines ('ISC/FCS') as a control. (3) Southern blot analysis was used to detect clonal BM cells. At diagnosis, 76 of 151 cases (50%) studied showed clonal gene rearrangements in marker genes. (4) Southern blot analysis and flow cytometry were used to compare the amount of clonal and CD34 positive BM cells before and after coculture procedures. Coculture experiments with untreated BM and autologous LAK cells led to a reduction of clonal cells in 2 of 5 cases at diagnosis, in 11 of 17 BM samples in complete remission but not in the one case studied at relapse. Similar results were found if precultured AML cells (with or without cytokines) were cocultivated with LAK cells. However the cytotoxic effect of LAK cells was more pronounced if cytokines (especially GM-CSF and SCF) were comprised. Our data indicate, that (1) clonality in AML can be demonstrated by Southern blot analysis; (2) CD34 positive cells in AML are clonal, gene rearranged cells; (3) clonal cell populations persist in BM during complete remission and relapse in most of the patients; (4) incubation of AML-BM cells with LAK cells lead to a reduction of clonal, rearranged cells in 11 of 17 AML cases in complete remission, but only in 2 of 6 cases at diagnosis or relapse; (5) AML cells can be sensitized to theLAK cell treatment by preincubation of AML-BM cells with cytokines (IL-1beta, IL-3, IL-6, SCF, EPO and GM-CSF) or by adding SCF to the coculture conditions. Southern blot analysis and flow cytometry are appropriate methods to detect and quantify leukemic disease. Cytokines and LAK cells synergize to kill AML blasts in vitro. This is a feasible approach to immunotherapy of AML and merits further investigations.

Acute Disease↗

Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients.

PURPOSE: There is an urgent need for markers that can predict the efficacy of adjuvant chemotherapy in patients with solid tumors. This study was designed to evaluate whether monitoring of micrometastases in bone marrow can predict the response to systemic chemotherapy in breast cancer. PATIENTS AND METHODS: Bone marrow aspirates of 59 newly diagnosed breast cancer patients with either inflammatory (n = 23) or advanced (> four nodes involved) disease (n = 36) were examined immunocytochemically with the monoclonal anticytokeratin (CK) antibody A45-B/B3 (murine immunoglobulin G(1); Micromet, Munich, Germany) before and after chemotherapy with taxanes and anthracyclines. RESULTS: Of 59 patients, 29 (49.2%) and 26 (44.1%) presented with CK-positive tumor cells in bone marrow before and after chemotherapy, respectively. After chemotherapy, less than half of the previously CK-positive patients (14 of 29 patients; 48.3%) had a CK-negative bone marrow finding, and 11 (36. 7%) of 30 previously CK-negative patients were CK-positive. At a median follow-up of 19 months (range, 6 to 39 months), Kaplan-Meier analysis of 55 assessable patients revealed a significantly reduced overall survival (P =.011; log-rank test) if CK-positive cells were detected after chemotherapy. In multivariate analysis, the presence of CK-positive tumor cells in bone marrow after chemotherapy was an independent predictor for reduced overall survival (relative risk = 5.0; P =.016). CONCLUSION: The cytotoxic agents currently used for chemotherapy in high-risk breast cancer patients do not completely eliminate CK-positive tumor cells in bone marrow. The presence of these tumor cells after chemotherapy is associated with poor prognosis. Thus, bone marrow monitoring might help predict the response to systemic chemotherapy.

Analysis of Variance↗

Clinical relevance of occult metastatic cells in the bone marrow of patients with different stages of breast cancer.

Data are emerging about the prognostic relevance of occult metastatic cells in the bone marrow of patients with various solid tumors. Discrepancies among different studies on the prognostic relevance of isolated tumor cells may be caused by tumor cell heterogeneity and the use of different immunoassays. There is increasing evidence that validated anticytokeratin antibodies (e.g., A45-B/B3) represent the present standard for the detection of isolated tumor cells. This immunocytochemical assay allows the identification of patients with occult tumor cell dissemination that cannot be identified by conventional screening methods in tumor staging. According to recent studies, these patients are at higher risk for subsequent development of distant metastases and might therefore benefit from early systemic therapy. At advanced stages of the disease, the micrometastatic tumor load after adjuvant therapy, or at the time of emerging recurrences, appears to reflect the tumor's ability to progress. Therapeutic monitoring and cell-cycle independent antibody-based therapy are among possible implications of this new, promising diagnostic tool. The present review also focuses on state of the art, reliable detection methods of occult metastatic cells in the bone marrow of breast cancer patients and on the prognostic relevance of these cells at different stages of the disease.

Antigens, Neoplasm↗

The effect of vanadium-contaminated commercially available albumin solutions on renal tubular function.

We report our findings in a patient with coronary heart disease who received an intravenous albumin solution that contained a significant level of vanadium on the first day after elective primary coronary revascularization. Six patients who underwent similar surgical procedures without albumin infusion were taken as a control group. After administration of the V-contaminated albumin solution, the urinary excretion rates of alpha-glutathione S-transferase, a marker of proximal tubular damage, showed a several-fold elevation above the reference value, and the mean excretion rate was significantly different from that of the control group (p < 0.05). pi-Glutathione S-transferase, a marker of distal tubular damage, only marginally exceeded the upper reference limit in two urine samples from this patient. In all urine samples from the control group the excretion rates of pi-GST were below the detection limit. No significant differences in the excretion rates of alpha1-microglobulin and N-acetyl-beta-D-glucosaminidase were found between the patient treated with the albumin infusion and the patients of the control group. The biological half-life of intravenously administered V was approximately 125 h. All commercially available albumin solutions contain traces of vanadium with the concentration varying between 1.1 and 677 microg/l. The free V fraction in the albumin solutions increased with total V concentration, the highest concentration of free V found being 299 microg/l. The data suggest that the use of albumin solutions containing high levels of vanadium can lead to renal injuries, especially in patients with existing impaired renal function, as is the case with extracorporal circulation. The contamination is believed to be a result of the commercial isolation process.

Albumins↗

[Infective endocarditis: short and long-term results in 261 cases managed by a multidisciplinary approach].

BACKGROUND: Early diagnosis, an effective treatment and prompt recognition of complications are essential to improve the prognosis of infective endocarditis (IE). AIM: To report the results of a multidisciplinary approach to diagnosis and management of patients with IE at the Universidad Católica de Chile Hospital. PATIENTS AND METHODS: The clinical history, diagnosis, treatment and outcome of 261 episodes (Duke criteria) of IE admitted between January 1980 and January 1999 were analyzed. These included 185 episodes of native, 73 of prosthetic valve and 3 of nonvalvular IE. RESULTS: Sixty nine percent of patients were men and the mean age was 49 +/- 16 years. Seventy five percent had a definite diagnosis of IE (Duke). S. viridans, staphylococci and enterococci together constituted 85% of the isolated bacterial strains. Twenty seven had culture-negative IE, related to a high incidence of antibiotic therapy prior to diagnosis. Transesophageal echocardiography was performed in 102 cases and it detected vegetations in 91% of aortic and 96% of mitral IE, rupture or prosthesis dehiscence in 67% of aortic and 52% of mitral IE and abscesses in 51% of aortic and 15% of mitral IE. Fifty one percent developed heart failure and 34% had embolic events. S. aureus IE was associated to a higher incidence of embolic events, complications which contraindicated surgery and increased mortality rate (27%). Of all patients, 40% were treated exclusively with antibiotics, 52% were operated on and 8% had surgical indication but were nonoperable because of serious complications. The overall mortality was 16.3%: 13% in the medical, 9% in the surgical and 81% in the non-operable groups. The type of treatment and mortality rates did not differ between IE of native valves and prosthetic valves. Long term follow up showed survival rates of 73% at 5 years and 66% at 10 years. CONCLUSION: A multidisciplinary approach may be very helpful to improve the prognosis of IE.

Adolescent↗

[Thoracic splenosis with symptoms of coronary heart disease].

HISTORY AND REASON FOR ADMISSION: A 53-year-old man, who had undergone a splenectomy for a traumatic splenic tear 20 years previously, was admitted because an acute myocardial infarction was suspected. 20 years ago, a splenectomy had been performed because of traumatic rupture. INVESTIGATIONS: Laboratory values were normal except for a microcytic anaemia, thrombocytopenia (109,000/microliter) and a raised ferritin level (547 ng/ml). Coronary heart disease as well as other cardiac and upper gastrointestinal abnormalities were excluded. Computed tomography revealed a space-occupying mass in the left lower lobe of the lung near the heart. This filled with contrast medium on coelangiography at the same time as the liver and a subphrenic mass thought to be an accessory spleen. TREATMENT AND COURSE: At thoracotomy numerous splenic masses, maximally 7 cm in diameter, were removed from near the heart, the costal pleura and the lung margin. There were haematological changes similar to those after splenectomy: leucocytosis (32,400/microliter) and thrombocytosis (637,000/microliter) on the 11th postoperative day and Howell-Jolly bodies noted on the 16th day. CONCLUSION: In splenosis the disseminated pieces of splenic tissue can partly substitute for the normal spleen's functions. Splenosis tissue should, therefore, not be removed in every case, especially, if it does not cause symptoms.

Diagnosis, Differential↗

In vitro and in vivo effects of glucocorticoids on gene transfer to skeletal muscle.

As a pharmacological approach to potentially improve gene transfer efficiency into skeletal muscle cells, glucocorticoids were shown here to allow efficient transfection of cultured and mouse human myoblasts, human pulmonary A549 cells, but not dog myoblasts, independently of the transfection protocol, the reporter gene and the transcription promoter employed. Transduction with adenovirus was also increased by dexamethasone. Pretreatment of cells 48 h prior to transfection was most effective and was shown to be concentration-dependent. This effect is mediated by binding to the glucocorticoid receptor, but not by glucocorticoid responsive elements present in the vectors. The acute dexamethasone effect could be due to increased plasmid entry into the cells as suggested by Southern blot, whereas the sustained increase of luciferase activity in dexamethasone-treated cultures may be related to intracellular mechanisms following cell entry. In mice in vivo, a similar increase of luciferase activity upon glucocorticoid treatment was found.

Adenoviridae↗

Lipoprotein(a) and coronary thrombosis and restenosis after stent placement.

OBJECTIVES: The objective of this prospective study was to evaluate the relation between high lipoprotein(a) levels and thrombotic and restenotic events after coronary stent implantation. BACKGROUND: Lipoprotein(a) may promote atherogenesis, coronary thrombosis and restenosis after balloon angioplasty, but the clinical significance remains unclear. METHODS: The study included 2,223 consecutive patients with successful coronary stent placement. According to the serum level of lipoprotein(a), patients were divided in two groups: 457 patients of the highest quintile formed the high lipoprotein(a) group, and 1,766 patients of the lower four quintiles formed the low lipoprotein(a) group. Primary end points were the incidence of angiographic restenosis at six months and the event-free survival at one year. Secondary end point was the incidence of angiographic stent occlusion. RESULTS: Early stent occlusion occurred in four of the 457 patients (0.9%) with high and 37 of the 1,766 patients (2.1%) with low lipoprotein(a) levels, odds ratio of 0.41 (95% confidence interval, 0.15 to 1.16). Angiographic restenosis occurred in 173 of the 523 lesions (33.2%) in the high lipoprotein(a) group and 636 of the 1,943 lesions (32.7%) in the low lipoprotein(a) group, odds ratio of 1.02 (0.83 to 1.25). The probability of event-free survival was 73.0% in the high lipoprotein(a) group and 74.8% in the low lipoprotein(a) group (p = 0.45). On the basis of the findings in the low lipoprotein(a) group, the power of this study to detect a 25% increase in the incidence of restenosis and adverse events in the group with elevated lipoprotein(a) was 90% and 75%, respectively. CONCLUSIONS: Elevated lipoprotein(a) levels did not influence the one-year clinical and angiographic outcome after stent placement. Thrombotic events and measures of restenosis were not adversely affected by the presence of high lipoprotein(a) levels.

Aged↗

Tumor-antigen heterogeneity of disseminated breast cancer cells: implications for immunotherapy of minimal residual disease.

Single micrometastatic tumor cells encased in mesenchymal tissues, such as bone marrow (BM), are regarded as suitable targets for adjuvant immunotherapy since they are easily accessible for both immunoglobulins and immune effector cells. However, the antigen profile of such cells, to which antibody therapy might be targeted, cannot be deduced from the antigen pattern of the primary tumor. To evaluate the antigen profile of disseminated cells found in BM aspirates from 20 breast cancer patients, we applied a quantitative immuno-cytochemical double-marker assay and typed for 4 common tumor-associated cell-surface antigens (c-erbB-2, CO17-1A, MUC-1, LewisY). Individual breast cancer cells were identified by F(ab) fragments of the pan-cytokeratin (CK) monoclonal antibody (MAb) A45-B/B3, directly conjugated with alkaline phosphatase, which identified cancer cells as sensitively as the standard APAAP procedure (r = 0.998; p < 0.0001). CK+ cells co-expressed c-erbB-2, CO17-1A, MUC-1 and LewisY in 87%, 78%, 79% and 79% of patients, respectively; however, the frequency of double-positive cells per sample varied considerably. The mean percentage of double-positive cells per total number of CK+ cells was 41% for c-erbB-2 (range 0-92%), 47% for CO17-1A (range 0-75%), 49% for MUC-1 (range 0-67%) and 32% for LewisY (range 0-59%). In 14 of these patients, we used an antibody cocktail to type CK+ cells for the combined expression of all 4 antigens. The antibody cocktail labeled significantly more CK+ cells than each of the single MAbs alone, resulting in a mean of 71% double-positive tumor cells (34-100%). We conclude that expression of tumor-associated cell-surface antigens on micrometastatic cancer cells in BM is heterogeneous, which may limit the efficacy of monovalent immunotherapeutic strategies directed against only one particular antigen. Thus, defining target antigens expressed by the actual target cells emerges as a crucial first step in selecting appropriate therapeutic targets.

Adult↗