In search of realistic optimism. Meaning, knowledge, and warm fuzziness.

Is it better to be realistic or optimistic? A realistic outlook improves chances to negotiate the environment successfully, whereas an optimistic outlook places priority on feeling good. But are realistic and optimistic outlooks necessarily in conflict? The author suggests that the fuzzy nature of accuracy typically places only loose boundaries on what it means to be realistic. As a result, there are many forms of optimism that do not, in principle, yield unrealistic assessments. Nevertheless, there remain numerous "optimistic biases" that do involve self-deception, or convincing oneself of desired beliefs without appropriate reality checks. The author describes several ways that realistic and unrealistic optimism can be differentiated and explores the impact of this distinction for current views of optimism. This critique reveals how positive psychology may benefit from a focus on personal meaning and knowledge as they relate to making the most of life.

Role of transforming growth factor-beta1 in the suppressed allostimulatory function of AIDS patients.

BACKGROUND: The T-cell stimulatory function of accessory cells isolated from peripheral blood lymphocytes of AIDS patients has been reported to be suppressed. These patients also have elevated levels of the immunosuppressive factor transforming growth factor (TGF)-beta1 in their serum and plasma. OBJECTIVE: To explore the role of TGF-beta1 in the loss of accessory cell function of peripheral blood lymphocytes from AIDS patients. METHODS: Fluorescent labeled anti-TGF-beta1 and confocal microscopy were used to detect the presence of TGF-beta1 on the cell membrane of dendritic cells. To assess the role of TGF-beta1 in the inhibition of accessory cell function in AIDS, antibodies against TGF-beta1 or the TGF-beta1 type III receptor, beta-glycan, were added to a mixed lymphocyte reaction. RESULTS: TGF-beta1 was detected on the cell membrane of dendritic cells isolated from AIDS patients. The addition of blocking antibodies against either TGF-beta1 or beta-glycan restored the T-cell stimulatory function to accessory cells from these patients. CONCLUSIONS: T-cell stimulatory function was not irreversibly lost in AIDS patients. Our data suggested that beta-glycan-TGF-beta1 immunosuppressive complexes may contribute to the suppression of accessory cell function in these patients.

Moving health care education into the community.

The A+ Asthma Club, an educational program developed for elementary school children in inner-city schools, is offered through a series of six sessions during school hours with an additional three booster sessions. This article describes how the program was designed, its theoretical basis, the curriculum and its staffing.

Differential regulation of TGF-beta 2 by hormones in rat uterus and mammary gland.

Previous work from this laboratory has shown that transforming growth factor beta 2 (TGF-beta 2) mRNA is abundant in the pregnant uterus. In the present study, we examined the synthesis and secretion of TGF-beta 1,2 and 3 in the rat uterus and mammary gland and show differential secretion and expression of TGF-beta 2 in a tissue specific manner. Elevated levels of TGF-beta 2 were detected in late pregnant maternal plasmas (> 100 pM), and in the milk (> 500 pM) during early lactation. High concentrations of TGF-beta 2 (> 200 pM) were also detected in uterine fluids collected from ovariectomized adult rats after high dose estrogen treatment. TGF-beta 2 mRNA levels were elevated in lobuloalveolar epithelial cells isolated from pregnant mammary gland. Three major transcripts of 3.5, 4.0, and 4.7 kb were seen, of which the 4.7 kb, dominates. Mammary glands of estrogen treated ovariectomized rats showed a similar pattern of TGF-beta 2 transcripts. In contrast, four major TGF-beta 2 mRNA transcripts of 5.7, 4.7, 4.0, and 3.5 kb, with the dominant species of 4.0 and 5.7 kb, were observed in uteri from the estrogen treated animals up to 48 h after the last estrogen injection. This suggests that TGF-beta 2 is regulated in a tissue specific manner. We conclude that the secretion of TGF-beta 2 is tightly regulated by hormones and that estrogen and prolactin are critical factors in the tissue-specific regulation of the local production of TGF-beta 2 in the mammary gland and female reproductive tract.

Training wh-question production in agrammatic aphasia: analysis of argument and adjunct movement.

The present research utilized aspects of the Principles and Parameters Approach (P&PA; Chomsky, 1991, 1993) in linguistic theory as well as findings from the psycholinguistic literature as a basis for examining sentence production in aphasic individuals. We examined the production of particular wh-movement constructions--wh-questions requiring movement of an argument noun phrase (i.e., who and what questions) and those which require adjunct movement (i.e., when and where questions). Using a single-subject experimental treatment paradigm, subjects were sequentially trained to produce these wh-questions and, throughout training, generalization to untrained wh-questions relying on similar wh-movement processes was tested. As well, the influence of training on aspects of narrative and conversational discourse was examined. Seven agrammatic aphasic subjects who evinced difficulty producing (and comprehending) "complex" sentences (e.g., passives, object relative clauses, wh-questions)--sentences that involve movement of noun phrases (NPs) out of their canonical positions, leaving behind a "trace" of that movement or "gap"--participated in the study. Subjects were trained to produce wh-questions by taking them through a series of steps emphasizing the lexical and syntactic properties (e.g., thematic role assignment, movement processes, and proper selection of wh-morpheme) of declarative sentence counterparts of target sentences. Results revealed improved sentence production abilities in all subjects under study in both constrained sentence production and, importantly, in discourse tasks. The argument/adjunct distinction was observed in the sentence production recovery patterns noted in six of the seven subjects. Three of the subjects evinced correct argument movement across trained and untrained question structures when wh-questions relying on argument movement were trained; similarly, for these subjects, training structures relying of adjunct movement resulted in improved adjunct movement. Three of the remaining four subjects who required additional treatment to alleviate their wh-morpheme selection deficits, too showed covariance between argument and adjunct movement structures with each type of movement emerging across structures in temporal sequence. We discuss these data in terms of the operations necessary to produce wh-questions, the importance of considering linguistic and psycholinguistic data when designing treatment programs for language disordered patients, and the contribution that detailed recovery data can make both to understanding the nature of sentence production deficits and to issues regarding normal sentence production.

Comparative virulence of periodontopathogens in a mouse abscess model.

OBJECTIVE(S): This report compares the virulence of selected strains of P. gingivalis, A. actinomycetemcomitans, C. rectus, F. nucleatum and T. denticola in a murine model as a measure of pathogenic potential of these oral microorganisms. The characteristics of the tissue destruction associated with these monoinfections were then related to a potential model for bacterial synergism in progressing periodontitis. DESIGN AND METHODS: All bacterial strains were grown to mid-logarithmic to early stationary growth phase, harvested and used at various doses to challenge BALB/c normal and BALB/c dexamethasone (DEX) treated mice to mimic a neutrophil dysfunction. The characteristics of tissue destruction, and overt tissue destructive capacity of these species were examined as a function of challenge dose and time. OUTCOME MEASURES: The mice were examined for an interval of approximately 15 days post-challenge and the presence/absence of lesions, localized or generalized nature of the lesion (including size in mm2), and lethality of the infection were assessed. RESULTS: Comparison of the virulence of the various P. gingivalis strains related to lethality and lesion size associated with destruction of the connective tissue, indicated a virulence capacity of P. gingivalis strains 53977>W50 = T22>3079>33277>381. C. rectus elicited localized necrotic lesions which were limited to the epithelial layers of the skin. The size of the lesions also indicated a graded difference in virulence, such that C. rectus strains 234>576>>33238. A. actinomycetemcomitans caused the formation of classic localized abscesses with a PMN infiltrate and inflammatory exudates. Although each of the A. actinomycetemcomitans strains exhibited a similar virulence pattern in this murine model, A. actinomycetemcomitans serotype b representative strains were potentially more pathogenic with a virulence capacity of 3113D-N = 3975A>JP2 > or = Y4>29523>33384. Both C. rectus and A. actinomycetemcomitans strains showed clear evidence that recent clinical isolates were more virulent than laboratory strains. Challenge with F. nucleatum resulted in tissue destructive responses which were different from those observed with the other strains used in this study. A rapid onset of dose-dependent lesion development, related to the formation of either closed abscesses or open lesions, was observed with F. nucleatum. Tissue involvement was also greater at lower F. nucleatum doses when compared to the other bacteria. F. nucleatum challenge of DEX-treated mice resulted in a shift to open lesions. T. denticola appeared to be more tissue invasive than the other species examined in this study. Challenge of mice with T. denticola resulted in involvement of multiple tissues, including epithelial and connective tissues, as well as appearing to invade muscle layers and deeper tissues. In addition to invading deeper tissues, the resulting lesions took considerably longer to resolve. In the DEX-treated mice (neutrophil depleted), P. gingivalis, C. rectus, and A. actinomycetemcomitans were significantly more virulent. In contrast, while DEX treatment altered the characteristics of lesions caused by F. nucleatum, the extent of lesions produced by F. nucleatum and T. denticola was not substantially enhanced. CONCLUSIONS: The results obtained from this study suggest that different microorganisms have the ability to provide individual pathologies which may act in an additive/synergistic fashion contributing to the tissue destruction noted in periodontitis.

TGF-beta 2 gene and protein expression in maternal and fetal tissues at various stages of murine development.

The transforming growth factor beta family of peptides have diverse actions on the reproductive tracts of primates and rodents. In this study we report the expression of high levels of mRNA of one member of this superfamily, TGF-beta 2, in the pregnant mouse uterus. Using Northern blot analysis and in situ hybridization techniques, we have examined the pattern of expression of TGF-beta 1, TGF-beta 2 and colony-stimulating factor (CSF-1) in mouse maternal and fetal tissue at specific days of gestation. We report here that TGF-beta 2 is synthesized primarily in maternal decidual and uterine epithelial tissues. We observed a shift in the major site of synthesis from decidua to uterus between days 8.5 and 10.5 of gestation. These data demonstrate that the expression of TGF-beta 2 is differentially regulated in the decidua and uterine epithelial cells at various times during gestation. Small amounts of TGF-beta 2 mRNAs were detected in the fetus, and none was detected in placenta, yolk sac, or amniotic membrane. The uterus is likely the major site of synthesis of the TGF-beta 2 found in mouse amniotic fluid. TGF-beta 1 mRNAs are expressed in the uterus at markedly lower levels when compared to TGF-beta 2 mRNAs in both the decidua and uterus. Our results suggest that there is a unique regulation of TGF-beta 2 during pregnancy which may depend on pregnancy hormone(s) and differentiates it from the other mammalian isoforms of the TGF-beta s. TGF-beta 2 may play an important, albeit unknown, role at the maternal/fetal interface.

Do we know what we've learned from listening to the news?

This study investigates the relationship between knowledge acquisition and an awareness of that knowledge within the context of listening to the news. Subjects listened to a recording of a radio news program consisting of regular news items as well as editorials, manipulated to be of high or low personal relevance. They then completed a surprise memory test and rated their confidence in their answers. In contrast to many studies, the results indicated a strong positive confidence-accuracy relationship. Confidence ratings were generally a better predictor of an individual's performance than were predictions based on item difficulty. Whereas subjects reported strong and accurate feelings of knowing, they apparently lacked complementary feelings of not knowing. The implications of these findings and others are discussed.

Framing and conflict: aspiration level contingency, the status quo, and current theories of risky choice.

The effect of positive versus negative frames on risky choice was examined for a variety of scenarios and risks. Preferences in the positive domain were strong and mainly risk averse, with notable exceptions. Preferences in the negative domain, however, were marked by their inconsistency, shown both by an overwhelming lack of significant majority preferences and a surprisingly strong tendency of individual subjects to vacillate in their negatively framed choices across presentations. This finding is accounted for by a proposed aspiration level contingency in which aspiration levels are systematically set to be more difficult to achieve in the face of a perceived loss than a gain. The implications of the results, and the aspiration level contingency, are explored with respect to current theories of risky choice, including Kahneman and Tversky's (1979) prospect theory and Lopes's (1987, 1990) security-potential/aspiration theory.

A transforming growth factor beta 2 (TGF-beta 2)-like immunosuppressive factor in amniotic fluid and localization of TGF-beta 2 mRNA in the pregnant uterus.

This report describes a murine amniotic fluid (MAF) immunosuppressive factor that has properties similar to transforming growth factor beta (TGF-beta). The MAF factor exhibits TGF-beta-like activity in stimulating soft agar colony formation by AKR-2B cells and inhibiting thymidine uptake by Mv1Lu cells. We demonstrate that both the immunosuppressive and TGF-beta-like activities of the MAF factor are completely neutralized by anti-TGF-beta 2-specific antibodies and not by anti-TGF-beta 1-specific antisera. The immunosuppressive factor in MAF is novel in that it appears to be identical or very closely related to TGF-beta 2 and is active in its native state. This active and anti-TGF-beta 2-neutralizable factor chromatographs at approximately 70 kD on Sephadex at neutral pH and appears to be able to complex with alpha-fetoprotein in native amniotic fluid. Chromatography of native MAF under acidic conditions demonstrates a lower molecular mass protein that chromatographs on BioGel in the same position as the mature 25-kD TGF-beta. This protein has the biological properties of TGF-beta and is immunosuppressive. Both of these activities are neutralizable with anti-TGF-beta 2 but not with anti-TGF-beta 1 or other antisera. By Northern analysis, we find high levels of TGF-beta 2 mRNA (with little or no TGF-beta 1) in the pregnant uterus that peak around day 15 of gestation and then fall rapidly by day 19 as birth approaches. The TGF-beta 2-like factor could possibly play a role in maternal immunity, in the retention of the fetal allograft, as well as in regulating fetal and neonatal immunological competence.

Continuous postoperative epidural analgesia for gynecologic oncology patients.

The efficacy of continuous postoperative epidural analgesia (CPEA) was assessed in 193 patients who collectively underwent 254 gynecologic oncology procedures. Seventy-five patients elected to receive CPEA; 118 did not. The CPEA patients received an epidural catheter the morning of surgery. Postoperatively, a bolus of meperidine was placed in each catheter. An IVAC pump continued to deliver meperidine at the rate of 14 to 20 mg per hour. The 193 patients also received a total of 655 postoperative intramuscular narcotic injections. CPEA patients were three times less likely to request injections, and those who did required an average of 6.58 compared with 12.42 for non-CPEA patients. The presence or absence of CPEA was the only significant variable. The use of CPEA led to no secondary complications, and it greatly enhanced mood and ability to participate in postoperative care. We conclude that CPEA provides excellent postoperative analgesia for such high-risk patients.

Isolation and characterization of an adriamycin-resistant breast tumor cell line.

An adriamycin-resistant human breast tumor cell line MDA-A1R was generated by step-wise selection in increasing concentrations of drug from the parent cell line MDA-MB-231. MDA-A1R cells grow as loosely attached cell aggregates with a doubling time of 28-32 h; the MDA-MB-231 parent cell line grows as a standard monolayer culture with a 20-h doubling time. The MDA-A1R cell line is highly resistant to adriamycin compared to the parent cell line, and is cross-resistant to velban and colchicine suggestive of a multidrug resistance (MDR) phenotype. MDA-A1R cells exhibit reduced net adriamycin content as compared to the parent cell line. The MDR-associated P-glycoprotein gene is amplified approximately 10- to 30-fold in MDA-A1R cells. P-glycoprotein sequences are overexpressed in the resistant cells and are stable for up to 13 wk after drug removal. Moreover, MDA-A1R cells show the presence of very high levels of P-glycoprotein. MDA-A1R is thus an in vitro model system to study the mechanism of MDR in human breast cancer.

Prostate. III--A structural feature characteristic of the rat prostate 5 alpha-reductase active site.

To aid in the design of new inhibitors of steroidal 5 alpha-reductase for treatment of prostate cancer, we have studied the topography of the 5 alpha-reductase active site (5 alpha-R) and of the related androgen (RA) and progesterone (RP) receptors in the region complementary to C.6 of progesterone. To this end we have determined the total structures of 17 alpha-acetoxy-6-methylene-4-pregnene-3,20-dione (VII; R = H) and of 17 beta-hydroxy-6,6-ethylene-4-androsten-3-one (VIa) by X-ray crystal structure analysis and, using these data, have developed Newman projections of the 6 alpha-Me, 6 beta-Me, 6-methylene and 6,6-ethylene derivatives of progesterone. From them we have developed a Newman projection of a composite model formed from steroids (V), (VI), (VIIIa) and (VIIIb). This is shown in Fig. 4 and illustrates the relative conformations of these substituents around C.6. From there we proceeded to receptor-binding studies. Our results led to the conclusion that androgen receptor, (RA), takes up preferred but different conformations when bound to testosterone (T) and to 17 beta-hydroxy-5 alpha-androstan-3-one (5 alpha-dihydrotestosterone, DHT), respectively, and that the resulting steroid-receptor complexes bind preferentially to different chromatin acceptor sites. We have therefore used the convention RT and RDHT in place of RA as appropriate. Working on the assumption that binding affinities reflect spatial contours, we have developed comparative silhouettes for the 5 alpha-R, RP and RDHT protein binding sites complementary to C.6 of the steroidal ligand. These data show that the 5 alpha-reductase active site is characterized by a hydrophobic pocket which specifically accommodates a 6-methylenic moiety and partially accommodates a 6 beta-methyl group. RDHT, in contrast, shows much less specificity and largely accommodates all the above substituents. Progesterone receptor differs in failing to accommodate 6,6-ethylene and 6 beta-methyl, with minimal accommodation of 6-methylene. It possesses a hydrophobic pocket skewed towards the alpha-face of the steroid, thereby allowing optimal binding of the 6 alpha-methyl substituent to the receptor. 6-Methylene-4-pregnene-3,20-dione (V) fails to bind significantly to androgen and progesterone receptors thereby supporting the postulate that its antiprostatic activity stems primarily from 5 alpha-reductase inhibition.

Perceptual learning of spatiotemporal events: evidence from an unfamiliar modality.

Perceptual learning was examined in two experiments in which subjects, originally unfamiliar with vibrotactile stimulation, were required to identify dynamic vibrotactile patterns with static visual patterns of the same two-dimensional shapes. In Experiment 1 we examined changes in performance with practice under a variety of vibrotactile spatial and temporal conditions. In Experiment 2 we investigated transfer of learning from one set of vibrotactile patterns to another different set. In neither experiment were subjects supplied with knowledge of results. Substantial perceptual learning (improvement in identification with practice) was observed in Experiment 1, although a minority of subjects did not exhibit improvement. Experiment 2 confirmed the general findings of Experiment 1 and also provided evidence of substantial positive transfer. In both experiments, multidimensional scaling of pattern confusion data revealed that practice (and improvement in identification) did not qualitatively change the relative confusability of patterns, suggesting that the (informative) structure of the patterns, irrespective of familiarity with a specific set of patterns, determined confusability. The findings are interpreted in terms of learning constructs offered by E. J. and J. J. Gibson. We conclude by considering the prospects that a connectionist mechanism can account for the observed perceptual learning.

Human breast tumor imaging using 111In labeled monoclonal antibody: athymic mouse model.

The monoclonal antibody (MoAb) 323/A3, an IgG1, was raised against the human breast tumor cell line MCF-7 and recognized a 43 Kd membrane associated glycoprotein. Histochemical studies with the antibody detected 75% of metastatic lymph nodes, 59% of primary breast tumors, and showed some staining in 20% of benign breast lesions. For radionuclide imaging, the MoAb 323/A3 was labeled with both 125I and 111In, via covalently coupled diethylenetriaminepentaacetic acid (DTPA) by the mixed anhydride method. The antibody activity of the DTPA modified 323/A3 was assessed by an immunoassay using viable and fixed MCF-7 target cells. Male athymic nude mice bearing BT-20 human mammary tumors were injected with dual 125I/111In labeled DTPA 323/A3 via the tail veins. The animals were imaged with a gamma camera equipped with a pinhole collimator at 1-3 h, 1, 2, 3, 4 and 5 days after the tracer administration. On day 5 or 6, the animals were killed, and the biodistribution of the radiotracers was determined for the blood, thyroid, heart, lungs, liver, spleen, kidneys, gastrointestinal tract and tumor. Target to blood ratio at 6 days for the 111In tracer was 24:1 in the group with a mean tumor weight of 0.492 g, and 13:1 in another group with a mean tumor weight of 0.1906 g (day 5). However, the 125I activity showed only 3.6:1 and 5.4:1 target to blood ratios in the corresponding groups. The larger tumors localized less 111In tracer (27.13% +/- 7.57% injected dose/g, Mean +/- SD) than the smaller tumors (52.75% +/- 22.25% ID/g).(ABSTRACT TRUNCATED AT 250 WORDS)

P-glycoprotein expression in human breast cancer cells.

Multidrug resistance in Chinese hamster ovary cells is associated with the Mr 170,000 surface glycoprotein. Using our monoclonal antibody to this protein, we have isolated a complementary DNA clone from an expression vector library. This complementary DNA recognizes a 4.5-kilobase mRNA in drug-resistant but not-sensitive Chinese hamster ovary cells; it also recognizes a 5.0-kilobase mRNA in our Adriamycin-resistant subline of the MDA-231 human breast cancer cell line which is not expressed in the drug-sensitive parent line. Southern blot analysis shows that the P-glycoprotein sequences are greatly amplified in resistant Chinese hamster ovary cells but not in the resistant human breast cancer cells, indicating that amplification and expression of the Mr 170,000 P-glycoprotein gene are not necessarily coordinate events. Amplification of this gene may not be required for multidrug resistance in human cells.

Differential expression of neural isozymes by human medulloblastomas and gliomas and neuroectodermal cell lines.

For the determination of their possible utility as tumors markers, 2 neural-associated isozymes, neuron-specific enolase [(NSE) EC 4.2.1.11] and creatine kinase BB [(CK-BB) EC 2.7.3.2], were quantitated by radioimmunoassay in human neuroectodermal-derived cell lines, primary brain tumors, and sera and cerebrospinal fluid (CSF) from brain tumor patients. The NSE content of neuroblastoma cell lines was more than sixfold that of the glioma and medulloblastoma lines; the CK-BB content of neuroblastoma and medulloblastoma lines was fourfold to nineteen-fold that of the glioma and other lines. Expression of NSE in neuroblastoma cell lines was not related to time in culture and was cell line specific. NSE in ex vivo medulloblastomas was raised six to ten times that in astrocytomas and gliomas, although no significant differences were noted for the CK-BB content. Serum and CSF NSE levels were markedly raised above control values in 10 of 29 and 6 of 10 cases of astrocytoma, respectively. Raised CK-BB levels in serum (greater than 10 ng/ml) and CSF (greater than 12 ng/ml) were found in 9 of 18 and 2 of 10 patients, respectively. These data suggest that NSE is preferentially expressed by neuroblastoma lines and medulloblastomas and that NSE and CK-BB may have clinical utility as markers for prognosis, diagnosis, and monitoring of response to therapy.

Serum neuron-specific enolase in children with neuroblastoma. Relationship to stage and disease course.

Serum neuron-specific enolase (NSE) was measured in 61 children at diagnosis with all stages of neuroblastoma. The median serum values for Stages I, II, III, IV, and IV-S were 13, 23, 40, 214, and 40 ng/ml, respectively. Mean serum levels were different between groups I versus IV, (P = 0.0004) II versus IV (P = 0.0001) and IV-S versus IV (P = 0.004). The prognostic value of serum NSE for disease-free survival was determined in 54 patients at risk for relapse 2 or more years after diagnosis. The disease-free survival rate of all patients with levels of less than 100 ng/ml was 27/34 (79%), whereas it was 2/20 (10%) for those with higher levels. In 28 patients with lower stage disease and a good prognosis (Stages I, II, and IV-S) NSE levels were not predictive of relapse. Only 1 of these 28 patients had a raised level (greater than 100 ng/ml) and survived without relapse, whereas 4 patients who relapsed had serum NSE less than 100 ng/ml at diagnosis. In patients with Stages III and IV disease, a raised serum NSE level was associated with poor outcome: only 1/19 (5%) survived with NSE levels greater than 100 ng/ml, whereas survival was 5/8 (63%) with values below 100 ng/ml. Serial samples were analyzed on 17 patients; all 8 patients with initial NSE levels greater than 100 ng/ml achieved near normal levels during remission (median, 21 ng/ml). However, in only 4/10 patients studied at time of relapse, did the levels rise coincident with relapse. The sera of 47 patients with other forms of cancer and 19 siblings of cancer patients were at or near the normal limits (0-15 ng/ml), with three exceptions: acute lymphoblastic leukemia (286 ng/ml), hepatoblastoma (176 ng/ml), and primitive neuroectodermal tumor (105 ng/ml). Serum NSE is a useful marker for patients with advanced neuroblastoma in whom elevated levels were associated with a poor outcome; the raised NSE levels returned to near normal after therapy. In patients with Stage IV-S disease serum NSE levels were significantly lower than those in Stage IV despite their extensive tumor burden. Serum NSE estimation may confirm Stage IV-S status and suggest a more benign clinical course.

Cloning of pediatric malignancies for drug sensitivity testing in the human tumor cloning assay.

In a 4-year period 168 tumor specimens received from 119 pediatric patients were plated in a soft agar cloning system. Overall, 47 or 28% of the tumor specimens had growth adequate enough for drug sensitivity testing. Drug sensitivity testing was performed using a variety of standards as well as investigational anticancer agents. Overall, 129 evaluable in vitro drug sensitivity tests were performed with 33 (26%) of the tests showing sensitivity to an agent. The most active drugs in vitro included the standard agents doxorubicin and cis-platinum as well as the investigational agents mitoxantrone and m-AMSA. From these data it is clear the cloning assay can be used to study pediatric malignancies. However, before the cloning assay can be applied to clinical pediatric oncology practice, the assay must be improved in terms of tumor growth and validated with prospective clinical trials.