Exploring the Lived Experiences of Medication for Opioid use Disorder Treatment: A Qualitative Study among a Crowdsourced Convenience Sample.

Given the effectiveness of medication for opioid use disorder (MOUD) and low engagement of treatment among people who use drugs (PWUD), it is important to better understand how to engage treatment clients with MOUD care. The current study aimed to achieve this goal by using qualitative methodology to characterize the MOUD treatment experiences. Participants (N = 52) were recruited for an online semi-structured interview. Qualitative analysis revealed varied treatment experiences, with the majority expressing irregular and intermittent MOUD treatment engagement. The therapeutic effects of MOUD in curbing withdrawal symptoms in conjunction with counseling services was frequently mentioned, as well as a preference for methadone maintenance treatment (MMT) to buprenorphine or naltrexone. Many participants described barriers to treatment and continuation of care, including failed drug screens for non-opioid drugs, perceived stigma, and physician-initiated discontinuation of treatment. The current study revealed that patients had favorable experiences with MOUD treatment, particularly when supplemented with counseling services.

A longitudinal study of COVID-19 disclosure stigma and COVID-19 testing hesitancy in the United States.

OBJECTIVES: This study examines the relationship between COVID-19 disclosure stigma and COVID-19 testing hesitancy and assesses their changes between November 2020 and 2021. STUDY DESIGN: This was a longitudinal cohort. METHODS: A total of 355 participants completed four study waves between November 2020 and November 2021. Factor analyses and Cronbach's alpha assessed the factor structure and internal consistency of the COVID-19 Disclosure Stigma scale. Paired t-tests and McNemar's Chi-squared test assessed change between the study waves. Multivariable logistic regression models examined the relationship between COVID-19 disclosure stigma and testing hesitancy at four study waves. RESULTS: COVID-19 disclosure stigma declined significantly between the last study waves (P = 0.030). The greatest disclosure concern was reporting a positive test to close contacts (range: 19%-21%) followed by disclosure to friends (range: 10%-15%) and family (range: 4%-10%). Over the course of the four study waves, COVID-19 testing hesitancy when symptomatic ranged from 23% to 30%. Older age, female gender, and having received a COVID-19 vaccine were associated with decreased odds of testing hesitancy. Greater COVID-19 disclosure stigma and more conservative political ideology showed a consistent relationship with increased odds of COVID-19 testing hesitancy. CONCLUSIONS: Study findings suggest that many people anticipate feeling stigmatized when disclosing positive test results, especially to close contacts. A substantial percentage of study participants reported hesitancy to be tested when symptomatic. This study identifies a need for interventions that normalize COVID-19 testing (e.g. engaging leaders with conservative followings), provide strategies for disclosing positive results, and allow anonymous notification of potential COVID-19 exposure.

Influence of work organization and work environment on missed work, productivity, and use of pain medications among construction apprentices.

BACKGROUND: Construction is among the most dangerous industries. In addition to traditional hazards for workplace injury and illness, other threats to health and well-being may occur from work organization and work environment factors, including irregular employment, long commutes, long work hours, and employer policies regarding health and safety. These nontraditional hazards may affect work and health outcomes directly, or through effects on health behaviors. The cumulative impacts of both traditional and nontraditional hazards on health-related outcomes among construction workers are largely unknown. METHODS: We conducted a survey among apprentice construction workers to identify relationships between work organization and environmental factors with five outcomes of economic relevance to employers: missed work due to work-related injury, missed work due to any pain or injury, self-reported workability, health-related productivity, and use of prescription medications for pain. RESULTS: A total of 963 surveys were completed (response rate 90%) in this young (mean age 28) working cohort. Multivariate Poisson regression models found associations between the outcomes of interest and multiple work factors, including job strain, safety behaviors of coworkers, and mandatory overtime. Univariate analysis showed additional associations, including precarious work, and supervisor support for safety. CONCLUSIONS: Findings from this cross-sectional study suggest that work organization and environment factors influence health and work outcomes among young construction trade workers. Future work with longitudinal data will examine the hypothesized paths between work factors, health behaviors, health outcomes, and work outcomes.

Feasibility of Collecting Saliva for Biological Verification of Tobacco Use Status in Dental Practices and Patients' Homes: Results from the National Dental PBRN.

OBJECTIVE: To evaluate the feasibility of collecting and analyzing saliva samples from dental practices and patients' homes for biochemical verification of tobacco use status. BASIC RESEARCH DESIGN: Sub-study within single-arm, multi-center, longitudinal clinical study. CLINICAL SETTING: Dental practices in the South Central region of the United States National Dental Practice-Based Research Network and patients' homes. PARTICIPANTS: Fifty-five patients recruited from 30 dental practices. INTERVENTIONS: Participants in the sub-study were instructed on saliva collection for cotinine analysis in dental practices where they enrolled in the primary study. Saliva was collected at the practices and then from patients' homes. MAIN OUTCOME MEASURES: Feasibility for dental practice collection was define as 80% of enrolled participants having analyzable samples. For patients' home collection, feasibility was defined as 70%. RESULTS: Forty-seven samples (i.e., 86% of those enrolled) collected in dental practices were analyzable. Twenty-one samples (i.e. 38% of those enrolled) collected in patients' homes were analyzable. CONCLUSIONS: Collecting saliva samples for cotinine analysis from dental practices, but not from patients' homes, was feasible. Dental practices may provide an advantageous setting for biochemically verifying tobacco use status as part of clinical trials for tobacco cessation.

Standardisation of defined approaches for skin sensitisation testing to support regulatory use and international adoption: position of the International Cooperation on Alternative Test Methods.

Skin sensitisation is the regulatory endpoint that has been at the centre of concerted efforts to replace animal testing in recent years, as demonstrated by the Organisation for Economic Co-operation and Development (OECD) adoption of five non-animal methods addressing mechanisms under the first three key events of the skin sensitisation adverse outcome pathway. Nevertheless, the currently adopted methods, when used in isolation, are not sufficient to fulfil regulatory requirements on the skin sensitisation potential and potency of chemicals comparable to that provided by the regulatory animal tests. For this reason, a number of defined approaches integrating data from these methods with other relevant information have been proposed and documented by the OECD. With the aim to further enhance regulatory consideration and adoption of defined approaches, the European Union Reference Laboratory for Alternatives to Animal testing in collaboration with the International Cooperation on Alternative Test Methods hosted, on 4-5 October 2016, a workshop on the international regulatory applicability and acceptance of alternative non-animal approaches, i.e., defined approaches, to skin sensitisation assessment of chemicals used in a variety of sectors. The workshop convened representatives from more than 20 regulatory authorities from the European Union, United States, Canada, Japan, South Korea, Brazil and China. There was a general consensus among the workshop participants that to maximise global regulatory acceptance of data generated with defined approaches, international harmonisation and standardisation are needed. Potential assessment criteria were defined for a systematic evaluation of existing defined approaches that would facilitate their translation into international standards, e.g., into a performance-based Test Guideline. Informed by the discussions at the workshop, the ICATM members propose practical ways to further promote the regulatory use and facilitate adoption of defined approaches for skin sensitisation assessments.

Pathogenesis of Enterococcal Spondylitis Caused by Enterococcus cecorum in Broiler Chickens.

Enterococcal spondylitis (ES) is a disease of commercial broiler chickens, with a worldwide distribution. Symmetrical hind limb paralysis typical of ES results from infection of the free thoracic vertebra (FTV) by pathogenic strains of Enterococcus cecorum . To determine the pathogenesis of ES, birds with natural and experimental ES were studied over time. In natural disease, case birds (n = 150) from an affected farm and control birds (n = 100) from an unaffected farm were evaluated at weeks 1-6. In control birds, intestinal colonization by E. cecorum began at week 3. In case birds, E. cecorum was detected in intestine and spleen at week 1, followed by infection of the FTV beginning at week 3. E. cecorum isolates recovered from intestine, spleen, and FTV of case birds had matching genotypes, confirming that intestinal colonization with pathogenic strains precedes bacteremia and infection of the FTV. Clinical intestinal disease was not required for E. cecorum bacteremia. In 1- to 3-week-old case birds, pathogenic E. cecorum was observed within osteochondrosis dissecans (OCD) lesions in the FTV. To determine whether OCD of the FTV was a risk factor for ES, 214 birds were orally infected with E. cecorum, and the FTV was evaluated histologically at weeks 1-7. Birds without cartilage clefts of OCD in the FTV did not develop ES; while birds with OCD scores ≥3 were susceptible to lesion development. These findings suggest that intestinal colonization, bacteremia, and OCD of the FTV in early life are crucial to the pathogenesis of ES.

Biometrical evaluation of the performance of the revised OECD Test Guideline 402 for assessing acute dermal toxicity.

A comprehensive biometrical assessment was conducted to compare the performance of multiple test designs for acute dermal systemic toxicity to support the animal welfare update to the original OECD Test Guideline (TG) 402 for acute dermal toxicity. The test designs evaluated included: (1) two, three, or five animals per dose group (2) evident toxicity or lethality endpoints and (3) absence or presence of a one-animal sighting study. The revision of TG 402 respected the 3R principles (replace, reduce, refine) of animal testing. The results demonstrate that the TG 402 test design can be optimised with reduced animal numbers per test group, such that a scenario of two animals per group following a sighting study at a starting dose of 200 mg/kg bw (unless further information is available to better define the starting dose) would provide a classification which in most cases is conservative, without compromising both the statistical ability of the study to assess dermal toxicity, or the relevant classification outcome.

Novel approach for selective reduction of NNN in cigarette tobacco filler and mainstream smoke.

Research conducted during past decades to reduce the level of the tobacco specific nitrosamine N-nitrosonornicotine (NNN) and its precursor nornicotine in tobacco yielded identification of three tobacco genes encoding for cytochrome P450 nicotine demethylases converting nicotine to nornicotine. We carried out trials to investigate the effect of using tobaccos containing three non-functional nicotine demethylase genes on the selective reduction of NNN in cigarette tobacco filler and mainstream smoke. Our results indicate that the presence of non-functional alleles of the three genes reduces the level of nornicotine and NNN in Burley tobacco by 70% compared to the level observed in currently available low converter (LC) Burley tobacco varieties. The new technology, named ZYVERT™, does not require a regular screening process, while a yearly selection process is needed to produce LC Burley tobacco seeds for NNN reduction. The reduction of NNN observed in smoke of blended prototype cigarettes is proportional to the inclusion level of tobacco having ZYVERT™ technology. Inclusion of Burley tobacco possessing the new trait into a typical American blend resulted in a selective reduction of NNN in cigarette smoke, while the levels of other Harmful and Potentially Harmful Constituents (HPHC) currently in the abbreviated list provided by the US Food and Drug Administration are statistically equivalent in comparison with the levels obtained in reference prototype cigarettes containing LC Burley.

Development of targeted messages to promote smoking cessation among construction trade workers.

Blue-collar workers, particularly those in the construction trades, are more likely to smoke and have less success in quitting when compared with white-collar workers. Little is known about health communication strategies that might influence this priority population. This article describes our formative work to develop targeted messages to increase participation in an existing smoking cessation program among construction workers. Using an iterative and sequential mixed-methods approach, we explored the culture, health attitudes and smoking behaviors of unionized construction workers. We used focus group and survey data to inform message development, and applied audience segmentation methods to identify potential subgroups. Among 144 current smokers, 65% reported wanting to quit smoking in the next 6 months and only 15% had heard of a union-sponsored smoking cessation program, despite widespread advertising. We tested 12 message concepts and 26 images with the target audience to evaluate perceived relevance and effectiveness. Participants responded most favorably to messages and images that emphasized family and work, although responses varied by audience segments based on age and parental status. This study is an important step towards integrating the culture of a high-risk group into targeted messages to increase participation in smoking cessation activities.

Comparative efficacy of tannin-free grain sorghum varieties for the control of necrotic enteritis caused by Clostridium perfringens in broiler chickens.

A 28-day battery cage study was conducted to test the efficacy of tannin-free grain sorghum varieties fed to Cobb 500 male broiler chickens (n = 512) and challenged with Eimeria maxima (EM) and Clostridium perfringens (CP). Birds were fed 1 of 8 treatments (corn, red/bronze, white/tan, or U.S. No. 2 sorghum) and were grouped by challenge method (challenged with EM/CP or unchallenged). On d 14, birds in the challenge group were orally inoculated with ∼5,000 oocysts of EM, and on d 19, 20, and 21, birds were given a broth culture of CP with ∼108 CFU/mL once daily. On d 21, three birds were scored for the degree/presence of necrotic enteritis (NE) lesions. Birds and feed were group weighed (d 0, 14, 21, and 28) to calculate average feed intake (FI), body weight gain (BWG), and adjusted feed conversion ratio (AdjFCR). Intestinal integrity was assessed through histological analysis of intestinal tissues, and change in transcriptome was determined using mRNA-sequencing on intestinal mucosa. Relative concentrations of secondary metabolites in grain sorghum were determined by LC-MS/MS analysis. Data were analyzed as a 2-way ANOVA with factors of treatment, challenge and their interaction. Regardless of challenge from 14 to 21 d, birds on the corn, white/tan, and U.S. No. 2 treatments were more efficient than those fed red/bronze treatment (P = 0.0026). From 14 to 28 d, BWG was significantly higher for the white/tan treatment (P = 0.024) compared to the red/bronze treatment. At 21 d, a significant interaction was observed for lesion score (P = 0.0001) in which, challenged birds fed red/bronze and white/tan treatments had reduced intestinal lesions compared to U.S. No. 2 and corn treatments. No differences among treatments were observed in jejunum morphology, but differential expression analysis showed an upregulation in defense response to bacteria and biotic stress in the challenged red/bronze treatment compared to the challenged corn. This study demonstrated improved gut health and minimal impact on growth and efficiency of broilers fed select grain sorghum varieties when challenged with EM/CP.

Bovine neuronal vesicular glutamate transporter activity is inhibited by ergovaline and other ergopeptines.

l-Glutamate (Glu) is a major excitatory neurotransmitter responsible for neurotransmission in the vertebrate central nervous system. Vesicular Glu transporters VGLUT1 and VGLUT2 concentrate (50mM) Glu [Michaelis constant (measuring affinity), or K(m),=1 to 4mM] into synaptic vesicles (SV) for subsequent release into the synaptic cleft of glutamatergic neurons. Vesicular Glu transporter activity is dependent on vacuolar H(+)-ATPase function. Previous research has shown that ergopeptines contained in endophyte-infected tall fescue interact with dopaminergic and serotoninergic receptors, thereby affecting physiology regulated by these neuron types. To test the hypothesis that ergopeptine alkaloids inhibit VGLUT activity of bovine cerebral SV, SV were isolated from cerebral tissue of Angus-cross steers that were naive to ergot alkaloids. Immunoblot analysis validated the enrichment of VGLUT1, VGLUT2, synaptophysin 1, and vacuolar H(+)-ATPase in purified SV. Glutamate uptake assays demonstrated the dependence of SV VGLUT-like activity on the presence of ATP, H(+)-gradients, and H(+)-ATPase function. The effect of ergopeptines on VGLUT activity was evaluated by ANOVA. Inhibitory competition (IC(50)) experiments revealed that VGLUT-mediated Glu uptake (n=9) was inhibited by ergopeptine alkaloids: bromocriptine (2.83±0.59µM)

Foot shock facilitates reward seeking in an experience-dependent manner.

Animals organize reward seeking around aversive events. An abundance of research shows that foot shock, as well as a shock-associated cue, can elicit freezing and suppress reward seeking. Yet, there is evidence that experience can flip the effect of foot shock to facilitate reward seeking. Here we examined cue suppression, foot shock suppression and foot shock facilitation of reward seeking in a single behavioural setting. Male Long Evans rats received fear discrimination consisting of danger, uncertainty, and safety cues. Discrimination took place over a baseline of rewarded nose poking. With limited experience (1-2 sessions), all cues and foot shock suppressed reward seeking. With continued experience (10-16 sessions), suppression became specific to shock-associated cues, foot shock briefly suppressed, then facilitated reward seeking. Our results provide a means of assessing positive properties of foot shock, and may provide insight into maladaptive behaviour around aversive events.

Variability of TSNA in U.S. Tobacco and Moist Smokeless Tobacco Products.

Tobacco-specific nitrosamines (TSNAs) have been of concern to the public health community for decades and their reduction through agricultural practices, plant breeding, and tobacco processing has also been a decades-long industry effort. Despite those efforts, TSNAs, though lower, continue to be constituents of concern in tobacco products. This paper examines the TSNA levels of dark air-cured, dark fire-cured, and burley tobaccos purchased in the United States by U.S. Smokeless Tobacco Company LLC (USSTC) and of nine finished USSTC moist smokeless tobacco products. TSNA values of the incoming purchased tobaccos and the finished products showed considerable variability. For the incoming tobaccos, the coefficient of variation was generally more than 100 % for each tobacco type and for each of the measured TSNAs. The relative TSNA variability of the finished tobacco products was also considerable, averaging approximately 25 %. It was also found that the measured values for the finished products averaged well above the proposed FDA NNN proposed product standard of 1.0 µg/g dry weight. Because of the large variability in NNN values, products would have to average well below FDA's proposed product standard to be consistently compliant.

Host cell reactivation studies with epidermal cells of mice sensitive and resistant to carcinogenesis.

Primary epidermal cells from AKR, BALB/c, CD-1, and SENCAR mice, listed in order of least to most sensitive to epidermal carcinogenesis by initiation and promotion protocols, were found to be equally competent to "reactivate" herpes simplex virus type 1 irradiated by germicidal ultraviolet radiation. Nontumorigenic BALB/c epidermal cell lines selected in vitro for resistance to terminal differentiation after in vivo or in vitro treatment with initiating doses of carcinogens showed virus survival curves similar to those of primary cells. Similarly, primary cultures which were allowed to grow to confluency following a single treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (100 ng/ml) retained normal host cell reactivation. Host cell reactivation studies with mouse dermal fibroblasts could not be done because of the failure of the herpes simplex virus to infect these cells and produce plaques. These results demonstrate that survival of ultraviolet light-damaged virus in primary epidermal cells in culture is unrelated to whether the cells are derived from mice sensitive or resistant to epidermal carcinogenesis. Furthermore, virus survival is not changed by tumor promoter treatment or by treatment with initiating doses of carcinogens which results in differentiation-resistant cells.

Inhibition of 12-O-tetradecanoylphorbol-13-acetate induction of epidermal transglutaminase activity by protease inhibitors.

Pretreatment of primary mouse epidermal cell cultures with chymostatin, a protease inhibitor, blocked the increase in transglutaminase (R-glutaminyl-peptide:amine gamma-glutamyltransferase, EC 2.3.2.13) activity resulting from treatment with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or with retinoic acid. This inhibitory effect was dependent upon both the concentration of chymostatin used and preincubation time and was eliminated when chymostatin was inactivated by NaBH4 reduction. Five other protease inhibitors, antipain, leupeptin, pepstatin, aprotinin, and soybean trypsin inhibitor, also suppressed TPA induction of transglutaminase activity. However, neither chymostatin, nor antipain, nor leupeptin reduced protein synthesis as measured by incorporation of labeled leucine into acid-precipitable products, while pepstatin, aprotinin, and soybean trypsin inhibitor inhibited protein synthesis markedly. L-1-Tosylamide-2-phenylethylchloromethyl ketone, on the other hand, strongly inhibited protein synthesis but did not inhibit the increase of transglutaminase activity after TPA exposure, and elastatinal inhibited neither TPA action nor protein synthesis. Chymostatin did not block phorbol ester binding to epidermal cells or TPA-mediated reduction of epidermal growth factor binding. These results suggest that the apparent induction of intracellular transglutaminase activity is mediated by a chymostatin-sensitive protease, while both phorbol ester binding and the reduction by TPA of epidermal growth factor binding at the cell membrane were independent.

Association of resistance to terminal differentiation with initiation of carcinogenesis in adult mouse epidermal cells.

Primary adult mouse epidermal cells were maintained as a monolayer culture with a high proliferation rate in fibroblast-conditioned medium with low Ca2+ concentration (less than 0.1 mM). Terminal differentiation of the cultures was induced by raising the Ca2+ level in the medium above 0.1 mM. Treatment of adult mouse epidermal cells either in vivo or in vitro with 7,12-dimethylbenz(a)anthracene or N-methyl-N'-nitro-N-nitrosoguanidine yielded colonies which were resistant to terminal differentiation induced by Ca2+. The number of resistant colonies was dependent upon the dose of each carcinogen used whether exposure was in vivo or in vitro. Cultures derived from skin initiated in vivo with 7,12-dimethylbenz(a)anthracene, a strong initiator, resulted in more colonies than were derived from skin initiated with N-methyl-N'-nitro-N-nitrosoguanidine, a moderately potent initiator. Two mouse strains, BALB/c and SENCAR, which differ in sensitivity to skin carcinogenesis, yielded similar numbers of Ca2+-resistant colonies following carcinogen exposure. However, colonies developed spontaneously from untreated SENCAR cells (the sensitive strain), but not from BALB/c cells (the resistant strain). These results support the concept that cells resistant to terminal differentiation are initiated cells. The results also suggest that initiation may occur spontaneously in SENCAR skin, a finding consistent with the reported occurrence of tumors in mice of this strain receiving promoters without exogenous initiator.

A model for initiated mouse skin: suppression of papilloma but not carcinoma formation by normal epidermal cells in grafts on athymic nude mice.

The availability of a skin grafting system on nude mouse hosts and of epidermal cell lines which form papillomas when grafted has made possible the creation of a model for initiated skin in vivo from cultured cells. When grafted with 6-8 x 10(6) primary dermal fibroblasts, 10 x 10(6) primary epidermal cells form an apparently normal skin, and cell line SP-1 (0.5 x 10(6) cells) forms papillomas. Cell line SP-1 was derived from papillomas produced on SENCAR mice by initiation with 7,12-dimethylbenzaadaa]anthracene and promotion with 12-O-tetradecanoylphorbol-13-acetate. Grafting of 0.5 x 10(6) SP-1 cells along with 10 x 10(6) SENCAR newborn primary epidermal cells resulted in a 90% reduction in the average papilloma volume per mouse compared to controls without primary epidermal cells. Suppression occurred specifically with epidermal cells, either cultured or freshly prepared, and was not seen when an equivalent number of SENCAR primary dermal fibroblasts was grafted in place of epidermal cells. Nor did suppression occur when primary epidermal cells were replaced with a carcinogen-altered cell line, SCR722. SCR722 cells have a normal-skin phenotype when grafted. Furthermore, suppression of tumor formation did not occur when a malignant variant of SP-1 cells replaced benign SP-1 cells in grafts. Repeated treatment of suppressed grafts with 12-O-tetradecanoylphorbol-13-acetate resulted in an increased number of mice with papillomas and a larger mean papilloma volume per mouse compared to controls treated with solvent alone, whereas treatment of nonsuppressed grafts of papilloma cells with promoter produced no change in tumor size. These results support the concepts that normal epidermal cells suppress the growth of initiated cells and that repeated treatment with phorbol ester tumor promoters overcomes the suppression, leading to benign tumor formation.

Similar effects of phospholipase C and phorbol ester tumor promoters on primary mouse epidermal cells.

Interaction of tumor promoting phorbol esters with specific high affinity receptors is probably essential for many of the biological responses elicited by these agents. Since diacylglycerols which can be produced enzymatically from phospholipids by phospholipase C are postulated to be the physiological ligands for the phorbol ester receptor, we have examined primary cultures of mouse epidermal basal cells exposed to phospholipase C (Clostridium perfringens) for several biological and biochemical responses characteristic of treatment with 12-O-tetradecanoyl-phorbol-13-acetate, the most potent phorbol ester tumor promoter. Formation of diacylglycerols by treatment with phospholipase C was demonstrated by the dose-dependent release of radioactive diacylglycerols in cells prelabeled with [3H]arachidonic acid. Treatment with phospholipase C at 0.05 units/ml for 30 min led to the morphological changes and to the reduction in epidermal growth factor binding (90%) associated with 12-O-tetradecanoylphorbol-13-acetate treatment. Continuous treatment at the same dose led to the induction of the enzymes ornithine decarboxylase and transglutaminase with a time course and extent similar to the inductions by 12-O-tetradecanoylphorbol-13-acetate. Treatment with phospholipase C at 0.1 enzyme unit/ml yielded substantial suppression of the binding affinity of phorbol-12,13-dibutyrate for its receptors without reduction in total number of binding sites, consistent with the production by phospholipase C of a competitive inhibitor of phorbol ester binding. Several diacylglycerols at concentrations of 250 microM and above effectively competed for phorbol-12,13-dibutyrate binding, reduced epidermal growth factor binding, and to a lesser extent induced ornithine decarboxylase and transglutaminase. These results support the hypothesis that diacylglycerols can act through the phorbol ester receptors and thus produce biological and biochemical responses similar to those of the phorbol esters.

Spontaneous adrenal tumors in the aged, ovariectomized NIH swiss mouse without enhanced retrovirus expression.

A high incidence of adrenal tumors was observed in aged female NIH Swiss mice which had been ovariectomized at 2 to 4 weeks of age but not in nonovariectomized controls. Although tumors weighing more than 1 g were not infrequent in the oldest (> 24 months) animals, adrenal glands did not appear macroscopically abnormal before the age of 18 months. Histologically, however, focal or diffuse abnormalities were found in essentially every gland examined from mice over 12 months of age, including glands of normal size. Since the NIH Swiss mouse has been shown to contain an endogenous xenotropic virus whose expression is under hormonal control, the adrenal tumors were examined in detail for evidence of abnormal viral expression. We were unable, by a variety of techniques, to demonstrate elevated expression of type C virus in these adrenal tumors.