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S R Ross

Publications and source records attributed to S R Ross.

At least 73 records · Page 4Linked to original sources
PubMed1989

Obesity-linked regulation of the adipsin gene promoter in transgenic mice.

The mouse adipsin gene encodes a member of the serine protease family that is expressed predominantly in adipose tissue and is secreted into the bloodstream. Adipsin expression is sharply down-regulated in several models of genetic and acquired obesity, representing the first example of an adipocyte gene whose expression is greatly altered in this disorder. In this study, we have asked whether a DNA fragment from the adipsin gene can direct tissue-specific expression of a heterologous gene and mediate the suppression of this expression in genetic and chemically induced obesity. Transgenic mice have been constructed with 950 bases of DNA from the 5' flanking region of the adipsin gene linked to the bacterial chloramphenicol acetyltransferase (CAT) gene in a mouse strain bearing a recessive obesity gene (diabetes, db). By crossing db/+ transgenic mice with nontransgenic db/+ mice, we obtained progeny that allowed a direct comparison of CAT expression in the tissues of lean and obese littermates. The lean mice express CAT activity predominantly in adipose tissue, while the obese mice show a marked reduction in CAT expression relative to the lean controls. When similar experiments are performed with an adipsin-CAT fusion gene containing a heterologous AKV (AKR mouse leukemia virus) enhancer, the tissue specificity of CAT expression in lean mice is broadened to include the thymus, spleen, brain, and other tissues; down-regulation occurs in all of these tissues in mice homozygous for the obesity gene or in mice that have been injected with monosodium glutamate (MSG), which induces obesity. These results indicate that 950 bases of the 5' flanking region of the adipsin gene carry information that specifies both expression in adipose tissue and a response to a gene or chemical that induces obesity. These results also suggest that the trans-acting factors that are regulated aberrantly in these forms of obesity are not restricted to adipose tissue and could play a role in obesity-linked dysfunctions observed in other tissues as well.

Animals↗
PubMed1988

Endogenous mouse mammary tumor virus is expressed in several organs in addition to the lactating mammary gland.

We studied the transcription of endogenous mouse mammary tumor virus (MMTV) in transgenic and normal strains of mice of different genetic backgrounds. Although the lactating mammary gland in all strains showed the highest level of MMTV expression, detectable levels of viral RNA were also found in the lungs, kidneys, salivary glands, seminal vesicles and/or prostate gland, testes, and lymphoid tissue in mice which contain different endogenous proviruses. Transcription in transgenic mice containing the MMTV long terminal repeat linked to the simian virus 40 early region also occurred in these same organs. These results indicate that the MMTV long terminal repeat functions in several organs in addition to the lactating mammary gland.

Animals↗
PubMed1988

Requirement for the simian virus 40 small tumor antigen in tumorigenesis in transgenic mice.

To examine the role of simian virus 40 (SV40) large T and small t antigens in tumorigenesis in animals, we generated transgenic mice which expressed either both the SV40 large T and small t antigens or the SV40 large T antigen alone under the control of the mouse mammary tumor virus long terminal repeat. The mouse mammary tumor virus long terminal repeat directs the expression of transgenes in ductal epithelial cells of several organs, including the mammary gland, lung, and kidney, and in lymphoid cells. The mice which expressed both the T and t tumor antigens developed lung and kidney adenocarcinomas, while those which expressed large T alone did not. Both types of mice developed malignant lymphomas with similar frequencies and latency periods. Our results show that the SV40 small t antigen cooperates with the large T antigen in inducing tumors in slowly dividing epithelial cells in the lung and kidney.

Animals↗
PubMed1987

The mouse mammary tumor virus long terminal repeat directs expression in epithelial and lymphoid cells of different tissues in transgenic mice.

A series of transgenic mice was developed that contained the simian virus 40 early region genes under the transcriptional control of the mouse mammary tumor virus long terminal repeat, including the promoter and glucocorticoid response elements. These mice all expressed the transgene in the epithelial cells of a number of different organs, such as lungs, kidneys, and prostate, salivary, and mammary glands, and in Leydig and lymphoid cells. Transcription of the chimeric gene was inducible by glucocorticoids, either after transfection into tissue culture cells or in cells cultured from animals carrying the transgene. Many, but not all, tissues which expressed the simian virus 40 sequences, as determined immunologically and by RNA analysis, developed into tumors, although they showed premalignant features. Since the mouse mammary tumor virus long terminal repeat is expressed in a number of different cell types when inherited through the germ line, the lactating mammary gland-specific transcription of endogenous proviruses must require other factors or sequences to achieve this specificity.

Animals↗
PubMed1985

Glucocorticoid regulation of mouse mammary tumor virus sequences in transgenic mice.

We have introduced a chimeric plasmid, pLTR2TK, containing the mouse mammary tumor virus (MTV) long terminal repeat (LTR) linked to the herpes simplex virus type 1 thymidine kinase gene into the mouse germ line by microinjection. In one mouse line, the thymidine kinase gene is appropriately expressed in the lactating mammary glands of heterozygous females; expression also occurs in the ovaries of these mice. In heterozygous males of this line, and in a male derived from another microinjection, transcription of these new germ line genes occurs in the testes and is specifically stimulated by glucocorticoid hormones. Thus, the MTV LTR may contain elements that allow its expression both in lactating mammary glands and in testicular tissue.

Animals↗
PubMed1984

Dyskeratosis congenita with pancytopenia and horseshoe kidney.

Dyskeratosis congenita is an X-linked ectodermal dysplasia characterized by hyperpigmentation, nail dystrophy, and leukoplakia. Pancytopenia develops in 50% of patients. We have reported another case with serious pancytopenia and the previously unreported occurrence of horseshoe kidney, and have discussed the similarities and differences between dyskeratosis congenita and Fanconi's anemia.

Adolescent↗
PubMed1984

Developing performance-appraisal systems.

The development and applications of performance-appraisal systems for hospital pharmacy personnel are discussed. The need for a performance-appraisal system is explained from the perspectives of the employee, the manager, and the hospital. Ethical standards that should be considered by managers during the appraisal process are listed. Performance standards are a key component of a performance-appraisal system and should be developed jointly by management and staff. Types of appraisal methods, personnel who should conduct appraisals, and the frequency at which appraisals should be conducted are discussed. Potential biases in appraisal methods and the preparation for and conduct of employee appraisals are discussed. A performance-appraisal system should be designed to meet the needs of employees, managers, and the hospital. Such a system will be more effective if it ensures the regular, frequent flow of data on employee performance, the systematic comparison of these data with previously agreed-upon expectations, and the frequent reporting of the results of these comparisons to both employees and managers.

Employee Performance Appraisal↗
PubMed1984

Managing training programs for pharmacy employees.

Principles for managing training programs for supportive personnel and new pharmacist employees in hospital pharmacy departments are discussed, and ongoing staff development activities are described. General management objectives of training programs are outlined. Training programs for supportive personnel should include general theory, such as basic pharmacology and metric conversions, and practice in the specific skills required for the job. The practical component of the training program should be based on a job analysis, and behavioral objectives of the training program should be developed. Various approaches for structuring and monitoring training programs for supportive personnel are described. Besides mastering specific practice skills, new pharmacist employees must become thoroughly familiar with the pharmacy department's policy and procedure manual. Hospital pharmacy managers should implement ongoing activities for developing the decision-making, interpersonal, and practice skills of staff pharmacists. Well-organized training programs can effectively raise the performance standards of pharmacy departments and decrease the time spent in monitoring, evaluating, and correcting performance deficiencies of the staff.

Feedback↗
PubMed1982

Multiple specific binding sites for purified glucocorticoid receptors on mammary tumor virus DNA.

Glucocorticoid hormones selectively stimulate the rate of transcription of integrated mammary tumor virus (MTV) sequences in infected rat hepatoma cells. Using two independent assays, we find that purified rat liver glucocorticoid receptor protein binds specifically to at least four widely separated regions on pure MTV proviral DNA. One of these specific binding domains, which itself contains at least two distinct receptor binding sites, resides within a fragment of viral DNA that maps 110-449 bp upstream of the promoter for MTV RNA synthesis. Three other binding domains lie downstream of the promoter and within the MTV primary transcription unit. Restriction fragments bearing separate binding domains have been introduced into cultured cells; transformants have been recovered in which the introduced fragments are expressed under glucocorticoid control. Thus, it appears that this assay will be useful for assessing the biological significance of the receptor binding sites detected in vitro.

Animals↗
PubMed1981

Mammary tumor virus DNA contains sequences required for its hormone-regulated transcription.

Glucocorticoids regulate the rate of transcription of integrated murine mammary tumor virus (MTV) genes in most clones of MTV-infected rat hepatoma tissue culture (HTC) cells. To determine whether hormonal regulation is mediated from flanking cellular sequences or rather from within the viral DNA, we analyzed the relative rates of transcription of MTV and adjacent HTC sequences in two lines of infected HTC cells, J2.15 and J2.17, each of which contains a single insertion of MTV DNA. In addition, we measured in uninfected HTC cells the transcriptional rates of the corresponding "preinsertion fragments," which may be viewed as the equivalent sequences bearing deletions of MTV DNA; the two genomic segments into which integration occurred in the two lines are unrelated. Previous work showed that glucocorticoids induce the accumulation of MTV RNA in J2.17, whereas viral transcripts are not detected in J2.15, RNA pulse-labeling experiments indicate that glucocorticoids stimulate that rate of MTV gene transcription in J2.17 but not in J2.15; in contrast, no labeled RNA hybridizing to flanking sequences was detected either in the uninfected or in the infected cells. We conclude that the host site of integration cells. We conclude that the host site of integration of MTV need not be transcriptionally active or hormonally responsive to permit viral gene expression. Furthermore, these rate measurements indicate that glucocorticoid-stimulated MTV RNA synthesis in J2.17 does not reflect readthrough transcription from a regulated cellular promoter. This notion is independently supported by transcript mapping experiments showing that the 5' terminus of nuclear MTV RNA is at a site on MTV DNA approximately 1.2 kb downstream from the host-viral junction. Thus our data are consistent with the presence of a hormone-responsive element within the provirus.

Animals↗