Biography:

In the past Dirck L. Dillehay has collaborated on articles with Charles Lindamood and Keith A. Fowler. One of their most recent publications is In vitro effects of retinoids on murine thymus-dependent and thymus-lndependent mitogenesis. Which was published in journal Cellular Immunology.

More information about Dirck L. Dillehay research including statistics on their citations can be found on their Copernicus Academic profile page.

Dirck L. Dillehay's Articles: (4)

In vitro effects of retinoids on murine thymus-dependent and thymus-lndependent mitogenesis

AbstractThe effects of three retinoids: all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), and N-(4-hydroxyphenyl)retinamide (4-HPR) on murine splenic lymphocyte proliferative responses to mitogens were evaluated. The responses to T-cell mitogens, PHA and Con A, and a T-cell-dependent B-cell mitogen, PWM were significantly potentiated by these retinoids. However, proliferative responses to a B-cell mitogen, Escherichia coli LPS were unaffected or inhibited. All three retinoids at concentrations ranging from 10−6 to 10−15M significantly potentiated Con A-induced proliferative responses. In response to PWM, 10−13M RA, 10−12M 13-cis RA, and 10−11M 4-HPR were the lowest concentrations producing significant potentiation. Endpoint concentrations of retinoids significantly potentiating responses to PHA were; 10−9M RA, 10−8M13-cis RA, and 10−6M 4-HPR. These responses were independent of retinol contained in fetal calf serum supplemented medium since responses were reproduced in serum-free medium devoid of retinol. Optimal potentiation by retinoids of responses to these T-cell-dependent mitogens were found at superoptimal concentrations of mitogen suggesting a selective inhibition of T-suppressor cells. Thus, potentiation of T-cell-dependent mitogen responses provides the most sensitive biological assay yet described for detection of retinoid activity and is a reproducible system to explore the cellular and molecular mechanisms of retinoid-mediated immunopotentiation.

Toxicologic and immunologic evaluations of N-(all-trans-retinoyl)-dl-leucine and N-(all-trans-retinoyl)glycine

AbstractSprague-Dawley rats were dosed by gavage daily for 28 days with 5, 15, or 50 mg/kg of N-(all-trans-retinoyl)-dl-leucine (RL), N-(all-trans-retinoyl)glycine (RG), or all-trans-retinoic acid (RA). On the basis of mortality incidence, fracture incidence, body weight, and histopathologic effects, RG was slightly to moderately less toxic than RA, and RL was significantly less toxic than RA or RG. Doses that had no effect on weight loss and produced no bone fractures were approximately 5 and 15 mg/kg/day for RA administered to males or females, respectively; greater than 15 mg/kg/day for RG administered to males or females; and greater than 50 mg/kg/day for RL administered to males or females. At these doses, RA and RG produced effects, detectable at the microscopic level, of lymphoid hyperplasia and hematopoietic cell proliferation in the spleen, lymphoid hyperplasia in lymph nodes, necrosis of the cortex of the thymus, hypertrophy of the zona fasciculata of the adrenal, a periportal pattern of cytoplasmic vacuolization in hepatocytes, hematopoietic cell proliferation in the liver, epithelial hyperplasia and subacute inflammation in the forestomach, and osteodystrophy. Serological alterations consisted of reduced serum albumin levels and elevated levels of triglycerides and alkaline phosphatase. For RL, similar microscopic effects, dependent on dose level and sex, were observed in spleen, thymus, adrenal, and liver. In vitro, RL was as active as RA in potentiating pokeweed mitogen-induced lymphocyte proliferation; RG was inactive. This study indicates that, relative to RA and RG, RL has less toxicity but similar immunological effects. Since RL and RG expressed little or no binding affinity for cellular RA-binding protein, the immunological effects of these retinoids may be expressed by mechanisms not linked to this protein.

Animal ModelOverexpression of Aromatase Leads to Development of Testicular Leydig Cell Tumors: An in Vivo Model for Hormone-Mediated Testicular Cancer

Despite recent advances in diagnosis and treatment of testicular cancer, its causes remain unknown. The most common conditions known to be associated with testicular cancer are cryptorchidism, infertility, and overexposure to pesticides or radiation. Recent studies also indicate hormones may play a crucial role in testicular tumorigenesis. Our studies show that about half of the male transgenic mice overexpressing aromatase in testis were infertile and/or had larger than normal testicles. Gross pathology and histological analysis showed the mice to have Leydig cell tumors, unilaterally or bilaterally. Serum estradiol levels for transgenic mice were at least twice as high as those for nontransgenic mice. Expression of aromatase and estrogen receptor were also very high in testicular tissue of transgenic mice compared to nontransgenic mice. Consistent with increased estrogenic activity in the testicular tissue, we also saw an increase in the levels of genes involved in cell cycle that are regulated by the estrogen. To obtain a better understanding of the biological significance of testicular tumorigenesis, a reliable animal model is necessary to clarify the mechanisms and correlations associated with human cancers. Here we describe such a model, which shows that overexpression of aromatase results in increased estrogen production and a changed hormone milieu, leading to the induction of testicular cancer (Leydig cell tumors). This predictable and useful model is a potential tool for the study of testicular tumorigenesis, hormonal carcinogenesis, synergistic action of other carcinogens on hormone-induced tumors, and tumor dependency on endocrine factors.

Adult urologyIntravesical suramin in the prevention of transitional cell carcinoma

AbstractObjectives.To examine the effects of intravesical suramin on N-methyl-N-nitrosurea (MNU)-induced bladder tumors in Fischer 344 rats.Methods.Multiple cohorts of female rats received four biweekly intravesical instillations of MNU. A control group received no other treatment, the experimental group received 25 mg/kg intravesical suramin twice a week beginning at week 6.Results.After 18 weeks from the first instillation of MNU, 60% to 65% of control animals developed papillary transitional cell carcinoma, compared with only 0% to 10% of the suramin-treated animals (P = 0.01 to P = 0.0007). There was no local or systemic toxicity observed.Conclusions.Intravesical suramin is an effective chemopreventative therapy for transitional cell carcinoma in vivo with minimal toxicity.

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