Motivation and context of concurrent stimulant and opioid use among persons who use drugs in the rural United States: a multi-site qualitative inquiry.

BACKGROUND: In recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings. METHODS: We conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use. RESULTS: We interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment. CONCLUSION: In a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.

Geographic distribution of risk ("Hotspots") for HIV, HCV, and drug overdose among persons who use drugs in New York City: the importance of local history.

AIMS: To identify geographic "hotspots" for potential transmission of HIV and HCV and for drug overdose among persons who use heroin and cocaine in New York City and to examine historical continuities in problem drug use hotspots in the city. METHODS: A total of 2714 study participants were recruited among persons entering Beth Israel substance use treatment programs. A structured questionnaire was administered and blood samples for HIV and HCV testing were collected. Hotspots for potential virus transmission were defined as ZIP codes with 10+ participants, 2+ persons infected with the virus and engaging in transmission behavior, and 2+ persons not infected and engaging in acquisition behavior. ZIP codes with 3+ persons with previous overdoses were considered potential hotspots for future overdoses. RESULTS: Participants resided in 166/178 (93%) of the ZIP codes in New York City. Injecting drug use was reported in 150/178 (84%) of the ZIP codes. No zip codes were identified for injecting-related HIV transmission, 5 zip codes were identified for sexual HIV transmission, 3 for HCV transmission, and 8 for drug overdose. Many of the ZIP code potential hotspots were in neighborhoods long associated with drug use: Lower Eastside and Harlem in Manhattan, the South Bronx, and Central Brooklyn. DISCUSSION: Heroin and cocaine use requiring treatment were reported from almost all ZIP codes in New York City, indicating needs for widely dispersed harm reduction services. Identified hotspots should be targeted for reducing sexual transmission of HIV, transmission of HCV, and drug overdoses. Some of the hotspots have persisted as problem drug use areas for 40 to over 100 years. Monitoring of drug use patterns in historical hotspot neighborhoods may permit early identification of and response to emerging drug use-related health problems. Persistent historical hotspots for problem drug use present a complex problem for implementing harm reduction services that deserve additional research.

Combined HIV prevention, the New York City condom distribution program, and the evolution of safer sex behavior among persons who inject drugs in New York City.

Examine long term sexual risk behaviors among persons who inject drugs (PWID) in New York City following implementation of "combined" prevention programming, including condom social marketing. Quantitative interviews and human immunodeficiency virus (HIV) testing were conducted among PWID entering Beth Israel Medical Center drug treatment programs 1990-2012. Data were analyzed by four time periods corresponding to the cumulative implementation of HIV prevention interventions. 7,132 subjects were recruited from 1990 to 2012; little change in sexual behavior occurred among HIV seronegative subjects, while HIV seropositive subjects reported significant decreases in being sexually active and significant increases in consistent condom use. HIV transmission risk (being HIV positive and engaging in unprotected sex) declined from 14 % in 1990-1995 to 2 % in 2007-2012 for primary sexual partners and from 6 to 1 % for casual partners. Cumulative implementation of combined prevention programming for PWID was associated with substantial decreases in sexual risk behavior among HIV seropositives.

Presence of the HLA-A*3101 allele in a familial case of drug reaction with eosinophilia and systemic symptoms, secondary to carbamazepine.

Anticonvulsants such as carbamazepine and phenytoin are associated with adverse skin reactions ranging from maculopapular exanthems to more severe reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome and toxic epidermal necrolysis. In addition to their antiepileptic role, anticonvulsants are also used to treat pain syndromes including trigeminal neuralgia. Until recently, the associated skin reactions were thought to be unpredictable; however, the current literature suggests a genetic predisposition involving the human leucocyte antigen (HLA) in cutaneous reactions associated with carbamazepine usage. We present two familial cases of DRESS secondary to carbamazepine, in which an underlying genetic predisposition and allelic association were identified.

A qualitative analysis of rural syringe service program fidelity in Appalachian Kentucky: Staff and participant perspectives.

PURPOSE: As drug-related epidemics have expanded from cities to rural areas, syringe service programs (SSPs) and other harm reduction programs have been slow to follow. The recent implementation of SSPs in rural areas demands attention to program fidelity based on core components of SSP success. METHODS: Semistructured interviews conducted with clients and staff at 5 SSPs in 5 counties within 2 Central Appalachian health districts. Interviews covered fidelity of SSP implementation to 6 core components: (1) meet needs for harm reduction supplies; (2) education and counseling for sexual, injection, and overdose risks; (3) cooperation between SSPs and local law enforcement; (4) provide other health and social services; (5) ensure low threshold access to services; and (6) promote dignity, the impact of poor fidelity on vulnerability to drug-related harms, and the risk environment's influence on program fidelity. We applied thematic methods to analyze the data. FINDINGS: Rural SSPs were mostly faithful to the 6 core components. Deviations from core components can be attributed to certain characteristics of the local rural risk environment outlined in the risk environment model, including geographic remoteness, lack of resources and underdeveloped infrastructure, and stigma against people who inject drugs (PWID) CONCLUSIONS: As drug-related epidemics continue to expand outside cities, scaling up SSPs to serve rural PWID is essential. Future research should explore whether the risk environment features identified also influence SSP fidelity in other rural areas and develop and test strategies to strengthen core components in these vulnerable areas.

Treatment outcomes of patients with Atopic Dermatitis (AD) treated with dupilumab through the Early Access to Medicines Scheme (EAMS) in the UK.

BACKGROUND: Dupilumab, a monoclonal antibody against interleukin (IL)-4 receptor alpha that inhibits IL-4/IL-13 signalling is indicated in dermatology for the treatment of moderate-to-severe atopic dermatitis (AD) in adult and adolescent patients 12 years and older and severe AD in children 6-11 years, who are candidates for systemic therapy. Dupilumab received Early Access to Medicines Scheme (EAMS) approval for adults in March 2017. OBJECTIVES: The purpose of this study was to assess the efficacy outcomes of treatment with dupilumab in EAMS. METHODS: A retrospective analysis of adult patients enrolled in the dupilumab EAMS in the UK. Scores were assessed at baseline and follow up, including the Eczema Area and Severity Index (EASI), Investigator's Global Assessment Score (IGA) and Dermatology Life Quality Index (DLQI). RESULTS: Data were available for 57 adult patients treated with dupilumab for at least 12 weeks; 73.6% of patients had received prior treatment with 3 or 4 immunosuppressants. Baseline scores for the EASI and DLQI were 27.93 (standard deviation, SD 13.09) and 18.26 (SD 6.18) respectively. AD severity scores showed statistically significant improvement at week 16±4 weeks (p <0.001 for all). The mean change in EASI was 14.13 points with 66.7% and 36.7% achieving a 50% (EASI-50) and 75% (EASI-75) improvement in EASI, respectively at 16+/- 4 weeks. IGA scores improved by at least two categories for 75% patients. DLQI scores decreased by a mean of 9.0 points, with 80% patients demonstrating a MCID 4-point improvement. For 85% patients, clinicians rated the treatment response as being either 'better' (19%) or 'much better' (65%). CONCLUSIONS: Dupilumab is associated with a significant and clinically relevant improvements in AD as measured by patient- and physician-reported outcome measures. Importantly, the clinical efficacy, despite the refractory disease of this EAMS cohort, is comparable to that previously reported in clinical trials.

Studies on human peripheral blood lymphocytes in vitro. II. Morphological and biochemical studies on the transformation of lymphocytes by pokeweed mitogen.

A study of the kinetics of RNA and DNA synthesis in PWM-stimulated lymphocytes revealed that RNA synthesis preceded the onset of DNA synthesis by approximately 24 hr and that DNA synthesis and transformation was maximal between 66 to 78 hr. Histochemical and radioautographic studies on PWM stimulated cultures indicated that at 72 hr 50 to 60% of the cell population had been transformed by PWM, and that a distinct cell type bearing cytologic resemblance to the early plasma cell had emerged. The RNA sedimentation profile for newly synthesized RNA in PWM-stimulated cells showed that a large peak of 45 to 50 S material was formed after 24 and 40 hr. PWM thus produces a distinctive transformation of human peripheral blood lymphocytes.

A guide to anticoagulation and endocarditis prophylaxis during cutaneous surgery.

Management of perioperative antiplatelet/anticoagulation drugs and appropriate antibiotic prophylaxis for endocarditis are two controversial issues in the safe practice of cutaneous surgery. This article highlights the current best practice based on a literature review on these topics. Antiplatelet agents should be continued perioperatively whenever clinically possible, and discontinued only after consultation with the patient's cardiologist. The exception to this is primary cardiovascular disease, when antiplatelet drugs should be stopped for 1 week before surgery. Warfarin can be continued perioperatively when the international normalised ratio is controlled at < 3. The use of antibiotics in patients at risk of endocarditis has been recently reviewed by the National Institute of Health and Clinical Excellence (NICE), the American Heart Association, and the European Society of Cardiology. The advice has changed significantly over the past few years, and the routine use of antibiotics perioperatively should occur only when there is evidence of infection perioperatively at the site of surgery.

Scombrotoxin poisoning: an important differential diagnosis for anaphylaxis.

We report a case of scombrotoxin poisoning, an acute illness that develops within minutes to hours of eating poorly processed oily fish, such as tuna or mackerel. It presents with symptoms that can mimic an anaphylactic reaction. It is presumed to arise due to ingestion of histamine that is formed by contaminating bacteria that have flourished during periods of suboptimal refrigeration, following capture. Knowledge of this underdiagnosed malady as a potential differential diagnosis for patients presenting with symptoms suggestive of histamine release is important. It is a notifiable condition. The alternative diagnosis of anaphylaxis may have significant lifestyle implications for the patient. This article reports on one such presentation and the way that the diagnosis was explored.

Synthesis of nonribosomal RNA by lymphocytes: a response to phytohemagglutinin treatment.

When lymphocytes are stimulated to enlarge and divide by treatment with phytohemagglutinin, most of the rapidly synthesized RNA is nonribosomal. The phenomenon is a response by lymphocytes to stimulation by phytohemagglutinin, rather than a general concomitant of lymphocyte growth.

Aryl hydrocarbon (benzopyrene) hydroxylase is stimulated in human lymphocytes by mitogens and benz(a)anthracene.

A mixed-function oxidase that requires reduced nicotinamide adenine dinucleotide phosphate, is carbon monoxide sensitive, and is drug-metabolizing is present in human lymphocytes and is increased to different levels by treatment with phytohemagglutinin, pokeweed mitogen, and a polycyclic hydrocarbon.

Potential geographic "hotspots" for drug-injection related transmission of HIV and HCV and for initiation into injecting drug use in New York City, 2011-2015, with implications for the current opioid epidemic in the US.

OBJECTIVE: We identified potential geographic "hotspots" for drug-injecting transmission of HIV and hepatitis C virus (HCV) among persons who inject drugs (PWID) in New York City. The HIV epidemic among PWID is currently in an "end of the epidemic" stage, while HCV is in a continuing, high prevalence (> 50%) stage. METHODS: We recruited 910 PWID entering Mount Sinai Beth Israel substance use treatment programs from 2011-2015. Structured interviews and HIV/ HCV testing were conducted. Residential ZIP codes were used as geographic units of analysis. Potential "hotspots" for HIV and HCV transmission were defined as 1) having relatively large numbers of PWID 2) having 2 or more HIV (or HCV) seropositive PWID reporting transmission risk-passing on used syringes to others, and 3) having 2 or more HIV (or HCV) seronegative PWID reporting acquisition risk-injecting with previously used needles/syringes. Hotspots for injecting drug use initiation were defined as ZIP codes with 5 or more persons who began injecting within the previous 6 years. RESULTS: Among PWID, 96% injected heroin, 81% male, 34% White, 15% African-American, 47% Latinx, mean age 40 (SD = 10), 7% HIV seropositive, 62% HCV seropositive. Participants resided in 234 ZIP codes. No ZIP codes were identified as potential hotspots due to small numbers of HIV seropositive PWID reporting transmission risk. Four ZIP codes were identified as potential hotspots for HCV transmission. 12 ZIP codes identified as hotspots for injecting drug use initiation. DISCUSSION: For HIV, the lack of potential hotspots is further validation of widespread effectiveness of efforts to reduce injecting-related HIV transmission. Injecting-related HIV transmission is likely to be a rare, random event. HCV prevention efforts should include focus on potential hotspots for transmission and on hotspots for initiation into injecting drug use. We consider application of methods for the current opioid epidemic in the US.

Hepatitis C virus prevalence and estimated incidence among new injectors during the opioid epidemic in New York City, 2000-2017: Protective effects of non-injecting drug use.

OBJECTIVE: Assess hepatitis C virus (HCV) prevalence and incidence among person who began injecting drugs during the opioid epidemic in New York City (NYC) and identify possible new directions for reducing HCV infection among persons who inject drugs. METHODS: 846 persons who began injecting drugs between 2000 and 2017 were recruited from persons entering Mount Sinai Beth Israel substance use treatment programs. A structured interview was administered and HCV antibody testing conducted. Protective effects of non-injecting drug use were examined among persons who "reversed transitioned" to non-injecting drug use and persons who used non-injected heroin in addition to injecting. RESULTS: Participants were 79% male, 41% White, 15% African-American, 40% Latinx, with a mean age of 35. Of those who began injecting in 2000 or later, 97 persons (11%) "reverse transitioned" back to non-injecting drug use. Reverse transitioning was strongly associated with lower HCV seroprevalence (30% versus 47% among those who continued injecting, p < 0.005). Among those who continued injecting, HCV seropositivity was inversely associated with current non-injecting heroin use (AOR = 0.72, 95%CI 0.52-0.99). HCV incidence among persons continuing to inject was estimated as 13/100 person-years. HCV seropositive persons currently injecting cocaine were particularly likely to report behavior likely to transmit HCV. CONCLUSIONS: Similar to other locations in the US, NYC is experiencing high rates of HCV infection among persons who have begun injecting since 2000. New interventions that facilitate substitution of non-injecting for injecting drug use and that reduce transmission behavior among HCV seropositives may provide additional methods for reducing HCV transmission.

Suppression of tropomyosin synthesis, a common biochemical feature of oncogenesis by structurally diverse retroviral oncogenes.

To identify proteins whose production may be altered as a common event in the expression of structurally diverse oncogenes, we compared two-dimensional electropherograms of newly synthesized proteins from NIH/3T3 cell lines transformed by a variety of retroviral oncogenes, from cellular revertant lines, and from a line (433.3) which expresses the v-ras oncogene in response to corticosteroids. Most alterations in the synthesis of specific proteins detected by this approach appeared to be the result of selection during prolonged cultivation and were probably unrelated to the transformation process. However, we detected seven proteins whose synthesis was strongly suppressed in cell lines transformed by each of the six retroviral oncogenes we studied and whose production was fully or partially restored in two cellular revertant lines. Suppression of two of these proteins was also correlated with the initial appearance of morphological alteration during corticosteroid-induced oncogene expression in 433.3 cells. These proteins (p37/4.78 and p41/4.75) were identified as tropomyosins, a group of at least five cytoskeletal proteins. Transformation by the papovaviruses simian virus 40 and polyomavirus caused no suppression of synthesis of these tropomyosins. This indicates that suppression of tropomyosin synthesis is not a nonspecific response by cells to being forced to grow with the transformed phenotype but is specifically associated with oncogenesis by diverse retroviral oncogenes. The results are consistent with the hypothesis that the different biochemical processes initiated by expression of structurally diverse retroviral oncogenes may converge on a limited number of common targets, one of which is the mechanism which regulates the synthesis of tropomyosins.

Cell-free system studies on the phosphorylation of the 17,000-20,000 dalton protein induced by phorbol ester in human leukemic cells and evidence for a similar event in virally transformed murine fibroblasts.

We have shown previously that a prominent early signal in the phorbol-12-myristate-13-acetate (PMA) effect on leukemic cells as well as on other malignant cells is a rapid and dramatic increase in the turnover of phosphate in a Mr 17,000 to 20,000 cytosolic protein and a moderate increase in turnover of phosphate in a Mr 27,000 protein, as detected in the intact cells by 2-dimensional gel electrophoresis. To further elucidate the mechanism of this phosphorylation event, we have examined the protein kinases which can reconstitute this event in a cell-free system. Activation of the endogenous Ca2+-activated phospholipid-dependent protein kinase (Ca-PL-PK) as well as addition of purified Ca-PL-PK to the cytosol of HL-60 leukemic cells resulted in enhanced phosphorylation of phosphoprotein Mr 27,000 (PP27) but did not affect the phosphorylation of phosphoprotein Mr 17,000 to 20,000 (PP17-20). In contrast, PP17-20 was heavily phosphorylated under cell-free conditions by the catalytic subunit of cAMP-dependent protein kinase (cAMP-PK). Exposure of intact cells to dibutyryl-cAMP resulted in increased phosphorylation of PP17-20. These conditions also enhanced the phosphorylation of PP27, showing that PP27 can act as a substrate for both Ca-PL-PK and cAMP-PK under cell-free conditions. Tryptic digest analysis of PP17-20 showed that one of four phosphopeptides is preferentially phosphorylated in PMA-induced PP17-20. An additional phosphopeptide was phosphorylated in cAMP-PK-catalyzed PP17-20. Thus, cAMP-PK alone mimics the effect of PMA on phosphorylation of PP17-20, but it introduces additional modifications. The precise role of this kinase in PMA-induced phosphorylation of PP17-20 remains to be clarified. We found further that enhanced phosphorylation of PP17-20 is also associated with malignant transformation of NIH/3T3 cells transformed by V-rasKi oncogene of Kirsten sarcoma virus. The tryptic phosphopeptide map of PP17-20 (phosphorylated in vivo) in the transformed cells was similar to that of PP17-20 in PMA-treated HL-60 cells but not to that induced by cAMP-PK, suggesting that the process activated by PMA which leads to phosphorylation of PP17-20 resembles an intrinsic cellular process which is enhanced in certain malignant cells.

Purification and composition of the human tumor-associated glycoprotein (TAG-72) defined by monoclonal antibodies CC49 and B72.3.

Human mammary and other carcinoma cells secrete and express on their cell surfaces complex, mucin-like glycoproteins (Mr greater than 10(6] that are recognized as tumor-associated antigens by a variety of monoclonal antibodies (MAbs). One such MAb, B72.3, has been extensively studied as to range of reactivity for a variety of carcinomas versus normal tissues. The B72.3-reactive antigen, designated tumor-associated glycoprotein (TAG)-72, which is a high-molecular-weight mucin, was partially purified and used as immunogen to produce second generation anti-TAG-72 MAbs. One of these second generation MAbs, CC49, was chosen to be used to develop a procedure to yield preparative amounts of purified antigen suitable for analyzing amino acid sequence. One of the reasons for the selection of CC49 for these studies is that it demonstrated a higher Ka for TAG-72 compared with B72.3. Xenografts of LS174T cells (a human colon carcinoma cell line) grown in nude mice were solubilized, extracted with several chaotropic agents and treated with perchloric acid. The acid soluble antigen was subjected to MAb CC49 affinity chromatography, gel filtration, and ion-exchange chromatography using fast protein liquid chromatography and high-performance liquid chromatography methodologies. A double-determinant liquid competition radioimmunoassay for TAG-72 showed greater than a 1000-fold purification. Radiolabeled protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated an apparently homogeneous high molecular weight mucin and a small amount of an additional protein with an apparent Mr of 63,000. Chemical deglycosylation using trifluoromethanesulfonic acid yielded low molecular weight proteins, which could be analyzed for amino acid sequence, and also became susceptible to tryptic digestion. The amino acid composition of the purified TAG-72 mucin was similar to that of other purified mucins.

Effect of epidermal growth factor and 12-O-tetradecanoylphorbol-13-acetate on the phosphorylation of soluble acidic proteins in A431 epidermoid carcinoma cells.

Treatment of [32P]phosphate prelabeled intact human A431 epidermoid carcinoma cells with epidermal growth factor (EGF, 100 ng/ml) or 12-O-tetradecanoylphorbol-13-acetate (TPA, 10(-7)M) resulted in a selective enhancement in the phosphorylation of the following soluble acidic proteins: a phosphoprotein with a molecular weight of 17,000 (pp17; similar notation used throughout) pI approximately 5.5); pp27 (pI approximately 5.5); pp34 (pI approximately 6.2); and pp80 (pI approximately 4.5) as detected by two-dimensional gel electrophoresis. EGF or TPA induced a 4- to 6-fold increase in the phosphorylation of pp17 and a 2- to 4-fold increase in the phosphorylation of pp27, pp34, and pp80 within 15 min after treatment of subconfluent A431 cells. Alkali treatment of the gels removed most of the incorporated [32P] phosphate from the phosphoproteins, including pp27, pp34, and pp80; however, the phosphoester bond in pp17 was stable to alkaline hydrolysis since there was no removal of [32P]phosphate from this protein. Treatment of A431 cells with dibutyryl cyclic adenosine 3':5'-monophosphate (1 mM) also increased the phosphorylation of pp17, pp27, and pp34 but not of pp80. Activation of endogenous calcium- and phospholipid-dependent protein kinase C in the cytosol of A431 cells in a cell-free system resulted in the enhanced phosphorylation of pp27, pp34, and pp80 but not of pp17 while exogenous addition of the catalytic subunit of cyclic adenosine 3':5'-monophosphate-dependent protein kinase to cytosol preparations resulted in the phosphorylation of pp17, pp27, and pp34, but not of pp80. These results demonstrate that at least four soluble acidic proteins are phosphorylated in A431 cells in response to either EGF or TPA in vivo suggesting that these two agents may exert part of their biological effects on A431 cells through a biochemical pathway involving the phosphorylation of several common proteins; moreover, the studies suggest that these four acidic proteins may be substrates in vitro for protein kinase C and/or a cyclic adenosine 3':5'-monophosphate-dependent protein kinase.

Suppression of synthesis and utilization of tropomyosin in mouse and rat fibroblasts by transforming growth factor alpha: a pathway in oncogene action.

Two events which commonly occur during transformation of murine and avian fibroblasts by retroviral oncogenes are production of transforming growth factor alpha (TGF-alpha) and suppression of tropomyosin synthesis. TGF has been proposed as a mediator of transformation through autocrine stimulation. Suppression of tropomyosin synthesis may contribute to the transformed phenotype through destabilization of actin microfilaments and cytoskeletal derangement. To determine whether suppression of tropomyosin synthesis might be a consequence of the action of TGF-alpha we studied tropomyosin synthesis in rat (normal rat kidney) and mouse (NIH3T3) fibroblasts treated with TGF-alpha. In a serum-containing system, addition of TGF-alpha or epidermal growth factor to normal rat kidney monolayers in subnanomolar concentrations induced morphological changes consistent with transformation. These changes were accompanied by prominent suppression of synthesis of Mr 36,000 and 39,000 tropomyosins. Similar suppression was observed in NIH3T3 cells. Inhibition of tropomyosin synthesis began almost immediately after addition of TGF-alpha and became progressively more pronounced during the succeeding 48 h. Suppression of tropomyosin synthesis was correlated with reduced expression of 1.1- and 1.8-kilobase tropomyosin mRNAs in both TGF-treated normal rat kidney cells and v-Ki-ras-transformed NIH3T3 cells. Rapid onset of a specific block in utilization of newly synthesized tropomyosin for formation of cytoskeletal elements was also demonstrated following TGF-alpha treatment. The evidence suggests that this block may be a specific effect of TGF-alpha treatment and that reduced expression of tropomyosin gene products may be either an independent event or a regulatory consequence of the block to utilization. The data support the conclusion that suppression of tropomyosin synthesis in cells transformed by a number of retroviral oncogenes results from the autocrine action of TGF-alpha.