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  • 1
    In: Toxicologic Pathology, SAGE Publications, Vol. 43, No. 3 ( 2015-04), p. 343-353
    Abstract: Histopathologic examination of the immature ovary is a required end point on juvenile toxicity studies and female pubertal and thyroid function assays. To aid in this evaluation and interpretation of the immature ovary, the characteristic histologic features of rat ovary through the developmental periods are described. These histologic features are correlated with published changes in neuroendocrine profiles as the hypothalamic–pituitary–gonadal axis matures. During the neonatal stage (postnatal day [PND] 0–7), ovarian follicle development is independent of pituitary gonadotropins (luteinizing hormone [LH] or follicle-stimulating hormone [FSH]), and follicles remain preantral. Antral development of “atypical” follicles occurs in the early infantile period (PND 8–14) when the ovary becomes responsive to pituitary gonadotropins. In the late infantile period (PND 15–20), the zona pellucida appears, the hilus forms, and antral follicles mature by losing their “atypical” appearance. The juvenile stage (PND 21–32) is the stage when atresia of medullary follicles occurs corresponding to a nadir in FSH levels. In the peripubertal period (PND 33–37), atresia subsides as FSH levels rebound, and LH begins its bimodal surge pattern leading to ovulation. This report will provide pathologists with baseline morphologic and endocrinologic information to aid in identification and interpretation of xenobiotic effects in the ovary of the prepubertal rat.
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2056753-4
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  • 2
    Online Resource
    Online Resource
    SAGE Publications ; 2005
    In:  Toxicologic Pathology Vol. 33, No. 7 ( 2005-12), p. 803-803
    In: Toxicologic Pathology, SAGE Publications, Vol. 33, No. 7 ( 2005-12), p. 803-803
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2005
    detail.hit.zdb_id: 2056753-4
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  • 3
    Online Resource
    Online Resource
    SAGE Publications ; 2012
    In:  Toxicologic Pathology Vol. 40, No. 2 ( 2012-02), p. 237-247
    In: Toxicologic Pathology, SAGE Publications, Vol. 40, No. 2 ( 2012-02), p. 237-247
    Abstract: The liver is the primary hematopoietic organ of the mammalian body during the fetal stage. The postnatal liver retains immunologically important functions and contains a substantial population of immunologically active cells, including T and B lymphocytes, Kupffer cells, liver-adapted natural killer (NK) cells (pit cells), natural killer cells expressing T cell receptor (NKT cells), stellate cells, and dendritic cells. The liver is the major site of production of the acute phase proteins that are associated with acute inflammatory reactions. Kupffer cells have an important role in the nonspecific phagocytosis that comprises a major component of the barrier to invasion of pathogenic organisms from the intestine. Hepatic NK and NKT cells are important in the nonspecific cell killing that is important in resistance to tumor cell invasion. The liver has a major role in deletion of activated T cells and induction of tolerance to ingested and self-antigens. Disposal of waste molecules generated through inflammatory, immunologic, or general homeostatic processes is accomplished via the action of specific endocytic receptors on sinusoidal endothelial cells of the liver. Age-related changes in sinusoids (pseudocapillarization), autophagy, and functions of various hepatic cell populations result in substantial alterations in many of these immunologically important functions.
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2012
    detail.hit.zdb_id: 2056753-4
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  • 4
    Online Resource
    Online Resource
    SAGE Publications ; 1994
    In:  Toxicologic Pathology Vol. 22, No. 2 ( 1994-03), p. 213-221
    In: Toxicologic Pathology, SAGE Publications, Vol. 22, No. 2 ( 1994-03), p. 213-221
    Abstract: Pharmaceutical companies exist today in a hostile legal and regulatory environment. The threat of product liability in the pharmaceutical industry has risen to the point where it stifles research and development, especially for contraceptive and psychotropic drugs. Regulatory sanctions against the industry are more likely now than in the past since the Food and Drug Administration (FDA) has placed significant emphasis on regulatory inspection and enforcement. Industrial pathologists play a critical role in defending their company in product liability litigation and from regulatory sanctions. In-house and contract pathologists should be prepared to give expert testimony in court and ensure that an effective document retention policy is implemented. Pathologists should know the limits of the FDA's inspection authority and be aware of the “pitfalls” of the FDA's new Fraud Policy. In addition to keeping abreast of science, industrial pathologists today can best serve the pharmaceutical industry if they maintain an awareness of legal issues that pose a threat to the future success of the industry.
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1994
    detail.hit.zdb_id: 2056753-4
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  • 5
    In: Toxicologic Pathology, SAGE Publications, Vol. 37, No. 4 ( 2009-06), p. 547-552
    Abstract: Hibernomas are rare neoplasms originating in brown adipose tissue of humans and other animal species, including laboratory animals. Background incidence values for these tumors in all common strains of laboratory rats are generally accepted as being 〈 0.1%. Between April 2000 and April 2007, however, sixty-two hibernomas (an overall prevalence of 3.52%) were observed in a total of 1760 Sprague-Dawley rats assigned to three carcinogenesis bioassays at two separate research laboratories. All rats were obtained from Charles River’s breeding facilities in either Portage, Michigan, or Raleigh, North Carolina. Tumors (twenty-nine benign and thirty-three malignant) were randomly distributed among test article–treated and control groups and were considered to be spontaneous. Most tumors originated in the thoracic cavity, and they were usually described as soft, mottled to tan masses with nodular to lobulated profiles. Immunohistochemical procedures for uncoupling protein 1 (UCP1) confirmed brown adipose tissue as the site of origin rather than white fat. The marked increase in hibernomas in our studies suggests that greater numbers of spontaneous hibernomas may be sporadically encountered in future carcinogenesis studies with Sprague-Dawley rats. The increased potential for hibernomas to arise as spontaneous neoplasms has important implications in studies involving peroxisome proliferators–activated receptor (PPAR) drugs, lipophilic environmental chemicals (e.g., polychlorinated biphenyls), and other molecules or physiologic processes (e.g., β-adrenergic stimulation) that may target brown fat adipocytes.
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
    detail.hit.zdb_id: 2056753-4
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  • 6
    Online Resource
    Online Resource
    SAGE Publications ; 2005
    In:  Toxicologic Pathology Vol. 33, No. 1 ( 2005-01), p. 52-62
    In: Toxicologic Pathology, SAGE Publications, Vol. 33, No. 1 ( 2005-01), p. 52-62
    Abstract: The liver has a number of important functions in innate and adaptive immunity. Contributions to the innate (nonspecific) immune system include production of acute phase proteins, nonspecific phagocytosis of particles, nonspecific pinocytosis of molecules, and nonspecific cell killing. Hepatic involvement in innate immunity contributes to the systemic response to local inflammation, clearance of particles and soluble molecules from the circulation, and killing of invading cells such as neoplastic cells. Liver involvement in the adaptive (specific) immune system includes deletion of activated T cells, induction of tolerance to ingested and self-antigens, extrathymic proliferation of T cells, and deletion of many of the signaling and effector molecules. Hepatic involvement in adaptive immunity allows clearance of activated T cells and signaling molecules following inflammatory reactions, and promotes immunologic tolerance toward potentially antigenic proteins that are absorbed from the intestinal tract. The liver is a major site of extrathymic T cell development, which assumes increasing significance with aging in mammals. Perturbations in hepatic structure or function can result in significant ramifications in both the innate and adaptive immune systems.
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2005
    detail.hit.zdb_id: 2056753-4
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  • 7
    Online Resource
    Online Resource
    SAGE Publications ; 2009
    In:  Toxicologic Pathology Vol. 37, No. 4 ( 2009-06), p. 474-480
    In: Toxicologic Pathology, SAGE Publications, Vol. 37, No. 4 ( 2009-06), p. 474-480
    Abstract: Metrial glands are normal structures located in the mesometrial triangle of the pregnant rat uterus from gestational day (GD) 8 through termination of pregnancy. Metrial glands are composed of a dynamic mixed cell population of granulated metrial gland (GMG) cells, endometrial stromal cells, trophoblasts, blood vessels, and fibroblasts. Collections of similar cells may be seen in association with pseudopregnancy and other hormonal disturbances. Granulated metrial gland cells are the hallmark cell of the metrial gland. They are bone-marrow-derived, perforin-positive, natural killer cells that proliferate in the pregnant uterus. Understanding the normal histogenesis of the metrial gland and recognizing the possible existence of GMG cells and a reactive metrial gland in the nonpregnant state are important when examining any uterine lesion that contains granulated cells. This report demonstrates that the cellular composition, morphology, and immunohistochemical staining profile of normal metrial glands are similar to reported granular cell neoplasms in rats and mice. The possibility of a non-neoplastic lesion involving the metrial gland should be considered when proliferative lesions involving granulated cells are observed in the uterus of mice and rats from nonclinical toxicity studies. Positive immunohistochemical staining for perforin and S100 would assist in the classification of such lesions as a reactive metrial gland or decidual reaction.
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2009
    detail.hit.zdb_id: 2056753-4
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  • 8
    Online Resource
    Online Resource
    SAGE Publications ; 1992
    In:  Toxicologic Pathology Vol. 20, No. 4 ( 1992-11), p. 617-627
    In: Toxicologic Pathology, SAGE Publications, Vol. 20, No. 4 ( 1992-11), p. 617-627
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1992
    detail.hit.zdb_id: 2056753-4
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  • 9
    Online Resource
    Online Resource
    Elsevier BV ; 2016
    In:  Food and Chemical Toxicology Vol. 91 ( 2016-05), p. 191-201
    In: Food and Chemical Toxicology, Elsevier BV, Vol. 91 ( 2016-05), p. 191-201
    Type of Medium: Online Resource
    ISSN: 0278-6915
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 1483645-2
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  • 10
    In: Toxicologic Pathology, SAGE Publications, Vol. 43, No. 3 ( 2015-04), p. 326-342
    Abstract: Histopathologic examination of the testis from juvenile rats is often necessary to characterize the safety of new drugs for pediatric use and is a required end point in male pubertal development and thyroid function assays. To aid in evaluation and interpretation of the immature testis, the characteristic histologic features of the developing rat testis throughout postnatal development are described and correlated with published neuroendocrine parameter changes. During the neonatal period (postnatal day [PND] 3–7), seminiferous tubules contained gonocytes and mitotically active immature Sertoli cells. Profound proliferation of spermatogonia and continued Sertoli cell proliferation occurred in the early infantile period (PND 8–14). The spermatogonia reached maximum density forming double-layered rosettes with Sertoli cells in the late infantile period (PND 15–20). Leptotene/zygotene spermatocytes appeared centrally as tubular lumina developed, and individual tubules segregated into stages. The juvenile period (PND 21–32) featured a dramatic increase in number and size of pachytene spermatocytes with the formation of round spermatids and loss of “infantile” rosette architecture. In the peri-pubertal period (PND 32–55), stage VII tubules containing step 19 spermatids were visible by PND 46. The presented baseline morphologic and endocrinologic information will help pathologists distinguish delayed development from xenobiotic effects, determine pathogenesis when confronted with nonspecific findings, and identify sensitive time points for targeted study design.
    Type of Medium: Online Resource
    ISSN: 0192-6233 , 1533-1601
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2056753-4
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