Examining the impact of a leisure time intervention on participation in organized out-of-school activities among adolescents: a quasi-experimental study in Franklin County, KY, USA.

Guided by the Icelandic Prevention Model, a community-led coalition in Franklin County, KY, aimed to subsidize costs for participation in supervised organized leisure time programs among its youth via adaptation of the Reykjavik City Leisure Card program, locally known as the 'YES Card' voucher program. This study examined whether the proportion of students participating in supervised out-of-school activities and sports was higher in the YES Card intervention group compared to a similar group of youth who did not receive the voucher across two time points. Two waves of survey data were collected in one intervention middle school and two geographically and demographically similar comparison schools in 2020 (n for intervention = 112, n for comparison = 723) and 2021 (n for intervention = 134, n for comparison = 873). The expected age of students ranged between 12 and 15 years. Analyses were conducted using logistic regression. The YES Card receivers were two-and-a-half times more likely to participate in nonsport organized recreational activities [odds ratio, OR, 2.43 (95% confidence interval, CI, 1.07-5.52)] and almost twice as likely to participate in sports [OR: 1.91 (95%CI: 1.08-3.38)] over the 1-year study period, compared to non-YES Card youth. We conclude that Franklin County in KY in the USA has successfully adapted the Reykjavik City Leisure time voucher program.

HIV nucleoside reverse transcriptase inhibitors efavirenz and tenofovir change the growth and differentiation of primary gingival epithelium.

OBJECTIVES: An increasing number of HIV-infected patients are combating HIV infection through the use of antiretroviral drugs, including reverse transcriptase inhibitors. Oral complications associated with these drugs are becoming a mounting cause for concern. In our previous studies, both protease inhibitors and reverse transcriptase inhibitors have been shown to change the proliferation and differentiation state of oral tissues. This study examined the effect of a nonnucleoside and a nucleoside reverse transcriptase inhibitor on the growth and differentiation of gingival epithelium. METHODS: Organotypic (raft) cultures of gingival keratinocytes were treated with a range of efavirenz and tenofovir concentrations. Raft cultures were immunohistochemically analysed to determine the effect of these drugs on the expression of key differentiation and proliferation markers, including cytokeratins and proliferating cell nuclear antigen (PCNA). RESULTS: These drugs dramatically changed the proliferation and differentiation state of gingival tissues when they were present throughout the growth period of the raft tissue as well as when drugs were added to established tissue on day 8. Treatment with the drugs increased the expression of cytokeratin 10 and PCNA and, conversely, decreased expression of cytokeratin 5, involucrin and cytokeratin 6. Gingival tissue exhibited increased proliferation in the suprabasal layers, increased fragility, and an inability to heal itself. CONCLUSIONS: Our results suggest that efavirenz and tenofovir treatments, even when applied in low concentrations for short periods of time, deregulated the cell cycle/proliferation and differentiation pathways, resulting in abnormal epithelial repair and proliferation. Our system could be developed as a potential model for studying the effects of HIV and highly active antiretroviral therapy (HAART) in vitro.

Tibetan sound meditation for cognitive dysfunction: results of a randomized controlled pilot trial.

OBJECTIVE: Although chemotherapy-induced cognitive impairment is common among breast cancer patients, evidence for effective interventions addressing cognitive deficits is limited. This randomized controlled trial examined the feasibility and preliminary efficacy of a Tibetan Sound Meditation (TSM) program to improve cognitive function and quality of life in breast cancer patients. METHODS: Forty-seven breast cancer patients (mean age 56.3 years), who were staged I-III at diagnosis, 6-60 months post-chemotherapy, and reported cognitive impairment at study entry were recruited. Participants were randomized to either two weekly TSM sessions for 6 weeks or a wait list control group. Neuropsychological assessments were completed at baseline and 1 month post-treatment. Self-report measures of cognitive function (Functional Assessment of Cancer Therapy (FACT)-Cog), quality of life (SF-36), depressive symptoms (Center for Epidemiologic Studies Depression Scale), sleep disturbance (Pittsburgh Sleep Quality Index), fatigue (Brief Fatigue Inventory), and spirituality (FACT-Sp) were completed at baseline, the end of treatment, and 1 month later. RESULTS: Relative to the control group, women in the TSM group performed better on the verbal memory test (Rey Auditory Verbal Learning Test trial 1) (p = 0.06) and the short-term memory and processing speed task (Digit Symbol) (p = 0.09) and reported improved cognitive function (p = 0.06), cognitive abilities (p = 0.08), mental health (p = 0.04), and spirituality (p = 0.05) at the end of treatment but not 1 month later. CONCLUSIONS: This randomized controlled trial revealed that TSM program appears to be a feasible and acceptable intervention and may be associated with short-term improvements in objective and subjective cognitive function as well as mental health and spirituality in breast cancer patients.

Effect of the HIV nucleoside reverse transcriptase inhibitor zidovudine on the growth and differentiation of primary gingival epithelium.

OBJECTIVES: Oral complications associated with HIV infection and with the antiretroviral drugs used to treat it are of increasing concern in HIV-infected patients. Protease inhibitors have been shown to change the proliferation and differentiation state of oral tissues but the effect of nucleoside reverse transcriptase inhibitors is currently unknown. This study examined the effect of zidovudine on the growth and differentiation of the gingival epithelium. METHODS: Gingival keratinocyte organotypic (raft) cultures were established. The raft cultures were treated with a range of zidovudine concentrations. Haematoxylin and eosin staining was performed to examine the effect of zidovudine on gingival epithelium growth and stratification. Raft cultures were immunohistochemically analysed to determine the effect of this drug on the expression of key differentiation and proliferation markers, including cytokeratins and proliferating cell nuclear antigen (PCNA). RESULTS: Zidovudine dramatically changed the proliferation and differentiation state of gingival tissues both when it was present throughout the growth period of the tissue and when it was added to established tissue at day 8. Zidovudine treatment increased the expression of cytokeratin 10, PCNA and cyclin A. Conversely, cytokeratin 5, involucrin and cytokeratin 6 expression was decreased. The tissue exhibited characteristics of increased proliferation in the suprabasal layers as well as an increased fragility and an inability to heal itself. CONCLUSIONS: Zidovudine treatment, even when applied at low concentrations for short periods of time, deregulated the cell cycle/proliferation and differentiation pathways, resulting in abnormal epithelial repair and proliferation. Our system could potentially be developed as a model for studying the effects of HIV and highly active antiretroviral therapy in vitro.

A randomized trial on the efficacy of methylphenidate and modafinil for improving cognitive functioning and symptoms in patients with a primary brain tumor.

Limited research is available regarding the efficacy of psychostimulants in treating cognitive function in primary brain tumor patients. An open-label, randomized, pilot trial examined both the general and differential efficacy of 4 weeks of methylphenidate (MPH) and modafinil (MOD) in 24 brain tumor patients. Participants completed cognitive tests and self-report measures of fatigue, sleep disturbance, mood and quality of life at baseline and after 4 weeks.Following stimulant treatment, there was evidence of a beneficial effect on test performance in speed of processing and executive function requiring divided attention. Patients with the greatest deficit in executive function at baseline appeared to derive the greatest benefit following stimulant therapy. Inconsistent, differential effects were found on a measure of attention in favor of MPH and on a measure of processing speed in favor of MOD. There was also evidence of a general beneficial effect on patient-reported measures of fatigue, mood, and quality of life, with no statistically significant differences between treatment arms in these measures over time. The results from this small pilot study should be interpreted with caution, but appear to warrant additional research, in larger study samples, targeting fatigue, processing speed and executive function, and exploring different doses of stimulants. Future studies may also wish to explore the specific patient factors that may be associated with responsiveness to psychostimulant treatment.

The HIV protease inhibitor lopinavir/ritonavir (Kaletra) alters the growth, differentiation and proliferation of primary gingival epithelium.

OBJECTIVE: This study was designed to evaluate the effects of the HIV protease inhibitor lopinavir/ritonavir on gingival epithelium growth, integrity and differentiation. METHODS: Organotypic (raft) cultures of gingival keratinocytes were established and treated with a range of lopinavir/ritonavir concentrations. To examine the effect of lopinavir/ritonavir on gingival epithelium growth and stratification, haematoxylin and eosin staining was performed. To investigate the effect of this drug on tissue integrity, transmission electron microscopy (TEM) was performed on untreated and drug-treated tissues. Further, immunohistochemical analysis of raft cultures was performed to assess the effect of lopinavir/ritonavir on the expression of key differentiation and proliferation markers including cytokeratins, proliferating cell nuclear antigen (PCNA) and cyclin A. RESULTS: Lopinavir/ritonavir treatments drastically inhibited the growth of gingival epithelium when the drug was present throughout the growth period of the tissue. When the drug was added on day 8 of tissue growth, lopinavir/ritonavir treatments compromised tissue integrity over time and altered the proliferation and differentiation of gingival keratinocytes. Expression of cytokeratins 5, 14, 10 and 6, PCNA and cyclin A was induced, and their expression patterns were also altered over time in treated rafts. CONCLUSIONS: The findings of our studies suggest that lopinavir/ritonavir treatments compromised tissue integrity over time and deregulated the cell cycle/proliferation and differentiation pathways, resulting in abnormal epithelial repair and proliferation. Our study provides a model of potential utility in studying the effects of antiretroviral drugs in vitro.

Ethanol and isopropanol inactivation of human coronavirus on hard surfaces.

BACKGROUND: The coronavirus disease 2019 pandemic has greatly increased the frequency of disinfecting surfaces in public places, causing a strain on the ability to obtain disinfectant solutions. An alternative is to use plain alcohols (EtOH and IPA) or sodium hypochlorite (SH). AIM: To determine the efficacy of various concentrations of EtOH, IPA and SH on a human coronavirus (HCoV) dried on to surfaces using short contact times. METHODS: High concentrations of infectious HCoV were dried on to porcelain and ceramic tiles, then treated with various concentrations of the alcohols for contact times of 15 s, 30 s and 1 min. Three concentrations of SH were also tested. Reductions in titres were measured using the tissue culture infectious dose 50 assay. FINDINGS: Concentrations of EtOH and IPA from 62% to 80% were very efficient at inactivating high concentrations of HCoV dried on to tile surfaces, even with a 15-s contact time. Concentrations of 95% dehydrated the virus, allowing infectious virus to survive. The dilutions of SH recommended by the Centers for Disease Control and Prevention (1/10 and 1/50) were efficient at inactivating high concentrations of HCoV dried on to tile surfaces, whereas a 1/100 dilution had substantially lower activity. CONCLUSIONS: Multiple concentrations of EtOH, IPA and SH efficiently inactivated infectious HCoV on hard surfaces, typical of those found in public places. Often no remaining infectious HCoV could be detected.

Two phase II trials of temozolomide with interferon-alpha2b (pegylated and non-pegylated) in patients with recurrent glioblastoma multiforme.

BACKGROUND: Because of the poor outcomes for patients with recurrent glioblastoma multiforme (GBM), and some laboratory and clinical evidence of efficacy using interferon in GBM, we assessed the toxicity and efficacy of temozolomide (TMZ) combined with either short-acting (IFN) or long-acting (pegylated) interferon alpha2b (PEG) in two single-arm phase II studies, and compared the results to 6-month progression-free survival (PFS-6) data from historical controls. METHODS: Two single-arm phase II studies were carried out in adults with GBM. Patients were treated with the standard regimen of TMZ (150-200 mg m(-2) per day x 5 days every month) combined with either 4 million units per m(2) subcutaneously (SQ) three times weekly of IFN or 0.5 microg kg(-1) SQ weekly of PEG. Physical exams and imaging evaluations were carried out every 8 weeks. RESULTS: On the IFN study, 34 adults (74% men) were enrolled, and 29 adults (55% men) on the PEG study; median Karnofsky performance status was 80 and 90 for the IFN and PEG studies, respectively. Grade 3 or 4 toxicities were common, leucopoenia and thrombocytopoenia occurring in 35-38% and 18-21% of patients, respectively. Grade 3 or 4 fatigue occurred in 18% of patients on both studies. Lymphopoenia was infrequent. PFS-6 was 31% for 29 evaluable patients in the IFN study and 38% for 26 evaluable patients in the PEG study. CONCLUSION: In recurrent GBM patients, both studies of standard dose TMZ with either IFN or PEG showed improved efficacy when compared to historical controls, or reports using TMZ alone. Even though the TMZ+PEG study met criteria for further study, the results of both of these studies must be considered in light of the standard of care (TMZ plus radiotherapy) for newly diagnosed GBM, which has evolved since the inception of these studies. Despite the results of the current studies being eclipsed by the new GBM standard of care, these results can still inform the development of newer approaches for GBM, either in an earlier, upfront setting, or by extrapolation of the results and consideration of the use of PEG or IFN in conjunction with other antiglioma strategies.

Fish: serologic evidence of infection with human pathogens.

Specific antibodies to several bacteria pathogenic to humans were detected in the serums of white perch from surface waters adjacent to heavily populated areas on Chesapeake Bay. White perch from surface waters adjacent to sparsely populated areas were free of such antibodies. We suggest that fish may become actively infected with human pathogens by exposure to contaminated water and may constitute a hazard to public health.

Biosynthesis of human papillomavirus from a continuous cell line upon epithelial differentiation.

The study of the human pathogen papillomaviruses (HPVs) has been hampered by the inability to propagate the virus in tissue culture. The addition of 12-O-tetradecanoyl phorbol-13-acetate to the media of organotypic (raft) cultures increased expression of physiological markers of keratinocyte differentiation and concomitantly induced production of virions. Capsid production was detected in differentiated suprabasal cells. Virions approximately 54 nanometers in size were observed by electron microscopy in raft tissue cross sections in the suprabasal layers. Virions purified through isopycnic gradients were found to contain type 31b DNA and exhibited an icosahedral shape similar to that of papillomaviruses found in clinical samples.

Production and characterization of a novel HPV anti-L2 monoclonal antibody panel.

The major capsid protein of HPV, L1, assembles into pentamers that form a T = 7 icosahedral particle, but the location of the co-assembled minor capsid protein, L2, remains controversial. Several researchers have developed useful monoclonal antibodies targeting L2, but most react with linear epitopes toward the N-terminus. As a means to better define the virus capsid and better assess the localization and exposure of L2 epitopes in the context of assembled HPV, we have developed a panel of 30 monoclonal antibodies (mAbs) which target the N-terminus of L2 amino acids 11-200, previously defined as a broadly protective immunogen. Select mAbs were processed with enzymes and anti-L2 Fabs were generated. These new mAb/Fab probes will be beneficial in future studies to unravel the placement of L2 and to help better define the role of L2 in the HPV lifecycle and the nature of the broadly protective epitopes.

Effector mechanisms in organ-specific autoimmunity. I. Characterization of a CD8+ T cell line that mediates murine interstitial nephritis.

To further investigate mechanisms of cell-mediated tissue destruction in an organ-specific autoimmune disease, we have established and characterized a nephritogenic CD8+ T cell line. This target antigen-specific effector T cell line, M52, was derived from bulk populations of CD8+ T cells isolated from susceptible animals immunized to produce anti-tubular basement membrane (alpha TBM) disease. Our studies show that M52 retains the phenotypic and functional characteristics of nephritogenic T cells induced in vivo. M52 mediates antigen-specific delayed-type hypersensitivity (DTH) responses to the target antigen 3M-1, it is cytotoxic to 3M-1-expressing renal tubular epithelial cells in vitro, and it adoptively transfers interstitial nephritis to naive syngeneic recipients. Clonal analysis of these nephritogenic CD8+ T cells reveals distinct functional phenotypes within the M52 cell line. We have isolated a cytotoxic CD8+ clone, M52.26, which is not DTH-reactive to 3M-1, and multiple DTH-reactive clones which mediate less efficient cytotoxicity to 3M-1-expressing target cells. Cytofluorographic analysis of four randomly selected clones reveals alpha beta T cell receptor expression. Further characterization of these functionally distinct CD8+ T cell clones will help to define their respective roles in mediating tubular epithelial cell injury and the inflammatory lesion of autoimmune interstitial nephritis.

Inhibition of murine nephritogenic effector T cells by a clone-specific suppressor factor.

We have used a murine model of organ-specific autoimmunity to characterize therapeutic modalities capable of down-regulating the cellular limb of the autoimmune response. Murine interstitial nephritis is an autoimmune disease mediated by tubular antigen-specific CD8+ nephritogenic effector T cells which are delayed-type hypersensitivity (DTH) reactive and cytotoxic to renal epithelial cells. Previous studies have demonstrated that disease can be suppressed with experimentally induced populations of T cells (Ts1 and Ts2 cells) obtained after injection of tubular antigen-coupled splenocytes into syngeneic mice. As the target of Ts2 is the CD8+ effector T cell, we have evaluated its effects on nephritogenic effector T cell clones isolated from diseased animals. Our studies demonstrate that soluble proteins expressed by Ts2 cells (TsF2) specifically abrogate the DTH, cytotoxic, and nephritogenic potential of M52 cells, although T cell receptor and IL-2 receptor expression are unchanged in these unresponsive M52 clones. TsF2-induced inhibition is dependent on new mRNA and protein synthesis. In a cytotoxic clone, M52.26, exposure to TsF2 induces expression of TGF-beta 1 which is, in turn, required for inhibition of cytotoxicity and nephritogenicity. Our studies are consistent with TGF-beta 1 behaving, at least in some T cells, as a nonspecific final effector of clone-specific suppression.

Nicotinic acid induces secretion of prostaglandin D2 in human macrophages: an in vitro model of the niacin flush.

Nicotinic acid is a safe, broad-spectrum lipid agent shown to prevent cardiovascular disease, yet its widespread use is limited by the prostaglandin D2 (PGD2) mediated niacin flush. Previous research suggests that nicotinic acid-induced PGD2 secretion is mediated by the skin, but the exact cell type remains unclear. We hypothesized that macrophages are a source of nicotinic acid-induced PGD2 secretion and performed a series of experiments to confirm this. Nicotinic acid (0.1-3 mM) induced PGD2 secretion in cultured human macrophages, but not monocytes or endothelial cells. The PGD2 secretion was dependent on the concentration of nicotinic acid and the time of exposure. Nicotinuric acid, but not nicotinamide, also induced PGD2 secretion. Pre-incubation of the cells with aspirin (100 microM) entirely prevented the nicotinic acid effects on PGD2 secretion. The PGD2 secreting effects of nicotinic acid were additive to the effects of the calcium ionophore A23187 (6 microM), but were independent of extra cellular calcium. These findings, combined with recent in vivo work, provide evidence that macrophages play a significant role in mediating the niacin flush and may lead to better strategies to eliminate this limiting side effect.

The alpha7 nicotinic receptor agonist 4OH-GTS-21 protects axotomized septohippocampal cholinergic neurons in wild type but not amyloid-overexpressing transgenic mice.

While activation of alpha7 nicotinic receptors protects neurons from a variety of apoptotic insults in vitro, little is known about this neuroprotective action in vivo, especially under amyloidogenic conditions that mimic Alzheimer's disease. We therefore investigated the effects of 4OH-GTS-21, a selective partial agonist for these receptors, on septohippocampal cholinergic and GABAergic neuron survival following fimbria fornix (FFX) lesions in three strains of mice: C57BL/6J wild type mice; human presenilin-1 mutant M146L (PS1) transgenic mice; and mice expressing both mutant PS1 and Swedish mutant K670N/M671L amyloid precursor protein (APP). Initial studies to demonstrated that 4OH-GTS-21 is likely brain permeant based on its ability to improve passive avoidance and Morris water task behaviors in nucleus basalis-lesioned rats. In FFX-lesioned mice, twice per day i.p. injections of 1 mg/kg of 4OH-GTS-21 for 2 weeks promoted the survival and prevented the atrophy of septal cholinergic neurons. Septal parvalbumin-staining GABAergic neurons were not protected by this treatment, although they also express alpha7 nicotinic receptors, suggesting an indirect, nerve growth factor (NGF)-mediated mechanism. No protection of cholinergic neurons was observed in similarly treated PS1 or APP/PS1 transgenic mice. 4OH-GTS-21 treatment actually reduced cholinergic neuronal size in APP/PS1 mice. Hippocampal amyloid deposition was not affected by FFX lesions or treatment with this alpha7 nicotinic receptor agonist in APP/PS1 mice under these conditions. These results indicate that brain alpha7 nicotinic receptors are potential targets for protecting at-risk brain neurons in Alzheimer's disease, perhaps via their effects on NGF receptors; however, this protection may be sensitive under some conditions to environmental factors such as inhibitory amyloid-peptides.

Disruption of Myc-tubulin interaction by hyperphosphorylation of c-Myc during mitosis or by constitutive hyperphosphorylation of mutant c-Myc in Burkitt's lymphoma.

Somatic mutations at Thr-58 of c-Myc have been detected in Burkitt's lymphoma (BL) tumors and have been shown to affect the transforming potential of the Myc oncoprotein. In addition, the N-terminal domain of c-Myc has been shown to interact with microtubules in vivo, and the binding of c-Myc to alpha-tubulin was localized to amino acids 48 to 135 within the c-Myc protein. We demonstrate that c-Myc proteins harboring a naturally occurring mutation at Thr-58 from BL cell lines have increased stability and are constitutively hyperphosphorylated, which disrupts the in vivo interaction of c-Myc with alpha-tubulin. In addition, we show that wild-type c-Myc-alpha-tubulin interactions are also disrupted during a transient mitosis-specific hyperphosphorylation of c-Myc, which resembles the constitutive hyperphosphorylation pattern of Thr-58 in BL cells.

In vivo confocal fluorescence imaging of skin surface cellular morphology: a pilot study of its potential as a clinical tool in skin research.

The cellular morphology of the stratum corneum was studied in vivo using a novel imaging technique that uses confocal fluorescence microscopy in combination with topical application of a fluorescent contrast agent. Images obtained with this method show a strong variation in skin surface cellular morphology among healthy subjects. The results of several clinical studies suggest that cellular morphology is affected by the efficiency of the process of desquamation. As such, cellular morphology shows strong potential to serve as an indicator of skin health that yields mechanistic insight into the origins of skin ailments, such as xerosis, and the effectiveness of their treatments.

Tetrasomy is induced by human papillomavirus type 18 E7 gene expression in keratinocyte raft cultures.

We have demonstrated previously that oncogenic human papillomaviruses (HPVs) induce basal cell tetrasomy in low-grade squamous intraepithelial lesions of the cervix. To identify HPV genes and growth conditions involved in this process, we analyzed: (a) organotypic raft cultures of primary human keratinocytes transfected with whole HPV-18 genomes; and (b) organotypic raft cultures acutely infected with recombinant retroviruses expressing the HPV-18 E6, E7, or E6/E7 genes from the differentiation-dependent HPV-18 enhancer-promoter. Cultures were examined for HPV DNA by in situ hybridization and for karyotype by interphase cytogenetics. Tetrasomy occurred in the suprabasal strata of raft cultures expressing E7 and E6/E7 but not in those expressing E6 alone or in a control culture. These data indicate that suprabasal tetrasomy occurs in association with expression of the E7 gene alone. Basal cell tetrasomy was additionally observed in the raft culture transfected with whole HPV-18 genomes, consistent with observations in low-grade squamous intraepithelial lesions. The distribution of tetrasomic cells in these raft cultures may reflect the involvement of additional viral genes or possibly differences in the pattern of viral oncogene and host gene expression.

Investigation of hormone-receptor interactions by means of fluorescence labeling.

Fluorescent-labeled hormones can be used to study hormone-receptor interactions by means of fluorescence polarization, visualization by fluorescence microscopy, or separation methods, e.g., dextran-coated charcoal. Subcellular fragments, single cells, and tissue preparations are amenable to study; in this work rat uterine cytosol was used unless otherwise noted. Estrone labeled with fluorescein at position 17 gives 50% inhibition in the radiometric dextran-coated charcoal assay at 8.3 X 10(-7) M as compared to 3.4 and 3.5 X 10(-8) M for diethylstilbestrol and estradiol, respectively. Scatchard plots from fluorescence polarization are hyperbolic and consistent with two classes of binding sites having association constants 5.6 X 10(10) and 6.4 X 10(7) M-1. Binding by high-affinity sites, which were present at about 3 times the concentraion of "specific" sites (radiometric dextran-coated charcoal assay), was abrogated by estradiol or diethylstilbestrol. Kinetic measurements showed that binding sites that can be blocked by excess estradiol or diethylstilbestrol are those that are both slowly associating and slowly dissociating. Staining of tissues by estrone labeled with fluorescein at position 17 as seen in the fluorescence microscope showed specificity. In normal rat uterus only epithelial cells were stained. In one human infiltrating ductal carcinoma only the malignant ductoid elements stained, while in another there was essentially no staining.

Synergistic interaction of two classes of transforming growth factors from murine sarcoma cells.

Transforming growth factors (TGFs) isolated from murine sarcoma virus-transformed 3T3 cells have been separated by high-pressure liquid chromatography into two subsets. One subset, called TGF alpha, competes with epidermal growth factor (EGF) for receptor sites, whereas the other, called TGF beta, does not. TGB beta, purified by high-pressure liquid chromatography, will not induce formation of large colonies of cells in soft agar in the absence of TGF alpha or EGF. However, the combined action of either TGF alpha or EGF (which by themselves are relatively ineffective in promoting growth of cells in soft agar) together with TGF beta results in a potent synergistic effect, with formation of large colonies. Chemically modified analogs of EGF also potentiate TGF beta activity to the extent that they bind to the EGF receptor. It is suggested that TGF beta may be an important mediator of the known effects of both TGF alpha and EGF on neoplastic transformation.