Subchronic toxicity studies with the leukotriene D4 antagonist RG 12525.

Preclinical safety studies with the leukotriene D4 antagonist RG 12525 were conducted by the oral route in mice, rats, and monkeys. Oral administration of RG 12525 was repeated daily in studies up to 6 months in duration. RG 12525 was shown to have limited high-dose toxicity after repeated oral administration.

Proliferative pituitary lesions in rats treated with salmon or porcine calcitonin.

Calcitonin, the serum calcium-lowering hormone, has been used in the treatment of hypercalcemia of malignancy and postmenopausal osteoporosis in humans for several years without any adverse effects. Recent studies in rats have indicated that calcitonin may be associated with morphologic effects on the pituitary. A large study was performed on 2 strains of rats, Sprague-Dawley (SD) and Fischer-344 (F-344), with 2 types of calcitonin, salmon-derived (sCT) and porcine-derived (pCT) calcitonin to evaluate possible effects on the pituitary.

Glycoprotein hormone alpha-subunit-producing pituitary adenomas in rats treated for one year with calcitonin.

Calcitonin, a calcium-lowering hormone, has been associated with an increased incidence of nonfunctioning pituitary tumors in rats. In this study, rats were treated with calcitonin (80 IU/kg/d) for 52 weeks. After treatment with calcitonin, immunohistochemistry and in situ hybridization analyses demonstrated that most pituitary tumors expressed the glycoprotein hormone alpha-subunit.

Spindle cell carcinoma of the conjunctiva. An immunohistochemical and ultrastructural study of six cases.

Six cases of conjunctival spindle cell carcinoma, a rare variant of squamous cell carcinoma, were studied. The median age of the three men and three women was 63.5 years.

Establishment of cell lines from somite stage mouse embryos and expression of major histocompatibility class I genes in these cells.

To study the regulation of MHC class I gene expression during embryonic development, we have characterized a number of clonal cell lines derived from somite stage mouse embryos that were established with or without infection by several transforming retroviruses in combination with murine leukemia viruses. Unlike embryonal carcinoma (EC) cells that have been used as a model for early embryos, the cell lines derived from somite stage embryos are negative for stage specific embryonic Ag-1 and do not appear to differentiate after retinoic acid treatment. Morphology varies from clone to clone and is distinct from that of F9 and other EC cells.

Immunohistochemical localization of hepatitis B surface antigen and hepatitis B core antigen in tissue sections. A source of false positive staining.

The occurrence of apparent false positive immunoperoxidase staining for hepatitis B surface antigen (HBsAg) led to the evaluation of several commercial antisera for usefulness in the diagnosis of hepatitis B by immunohistochemistry. One commercial antibody to hepatitis B core antigen (HBcAg) was tested and found to give sensitive and specific staining, with only a few false negatives and no false positives. Of three antibodies to HBsAg, one gave good staining results that were consistent with serologic data; one had many false positive stains due to contaminating antibodies to plasma proteins; and one (a monoclonal antibody) had many false negatives, probably due to its restricted antigenic specificity.

Spindle-cell carcinoma of the aerodigestive tract. An immunohistochemical analysis of 21 cases.

Immunohistochemical analysis of 21 prototypic mucosal spindle-cell carcinomas of the aerodigestive tract was performed at the Armed Forces Institute of Pathology (AFIP) to establish the usefulness of selected immunohistochemical markers in distinguishing spindle-cell carcinoma from other mucosal spindle-cell neoplasms. Immunoreactive keratin could be demonstrated in only 13/21 (62%) of cases. Coexpression of keratin and vimentin was demonstrated in 10/17 (59%) of the tumors evaluated for both of these intermediate filaments.

Lymphoid interstitial pneumonia: clinicopathological and immunopathological findings in 18 cases.

Eighteen patients with lymphoid interstitial pneumonia (LIP) were studied. The diagnosis was established by the microscopic finding of interstitial infiltrates of lymphocytes and plasma cells. Forty-seven% of patients also had germinal centres, while 72% showed interstitial giant cells.

Kupffer cells in hepatocellular adenomas.

Hepatocellular adenomas are usually visualized as defects on technetium-99m-sulfur colloid liver scans, a fact which has been attributed to the absence of phagocytic Kupffer cells in the tumors. To determine whether this is true, seven hepatocellular adenomas were subjected to immunoperoxidase staining for lysozyme, a marker of mononuclear phagocytes. The Kupffer cells were counted in the tumors and surrounding non-neoplastic liver.

Effect of thymosin immunostimulation with and without corticosteroid immunosuppression on chimpanzee hepatitis B carriers.

Carriers of hepatitis B surface antigen (HBsAg) are at a high personal risk of developing chronic hepatitis, cirrhosis, and primary hepatocellular carcinoma, and they pose a potential health threat to others. Accordingly, erradication of the carrier state is an important therapeutic goal. Several categories of drugs have been evaluated for this purpose, with, at best, limited success.

Sarcomas and sarcomatoid neoplasms of the major salivary gland regions. A clinicopathologic and immunohistochemical study of 67 cases and review of the literature.

Sixty-seven cases of sarcomas and sarcomatoid neoplasms of the major salivary gland regions were studied in order to determine the clinical and histomorphologic features and biologic behavior. Fifty-seven of these proved to be sarcomas and the two most common types were malignant schwannoma (11) and fibrosarcoma (9). Nine sarcomas could not be subclassified morphologically.

Lymphomatoid granulomatosis: a clinicopathologic study of 42 patients.

We studied the histological and clinicopathological findings in 42 patients who had lymphomatoid granulomatosis (LYG). In addition to small round lymphocytes, small to intermediate lymphocytes with serpentine nuclei, large immature mononuclear lymphoid cells, abundant histiocytes, and vascular invasion by the cell infiltrate were observed in all cases. Fifty percent of lesions had occasional "atypical" cells with multi-lobed nuclei.

Estrogen receptor protein in bone and soft tissue tumors.

Thirty-three histologically diverse bone and soft tissue tumors were analyzed biochemically for the presence of estrogen receptor protein (ERP) and progesterone receptor by means of a conventional, commercially available, steroid-binding assay (dextran-coated charcoal method) on fresh frozen tissue. These results were compared with analysis of ERP by using a specific monoclonal antibody both in an enzyme immunoassay and on frozen tissue sections by using immunohistochemical procedures. Frozen tissue sections were also examined for the presence of estrogen and progesterone receptors using fluorescein-labeled steroids.

Lung neoplasms in rodents after chronic administration of dimethyl hydrogen phosphite.

Dimethyl hydrogen phosphite (DMHP), an intermediate in the production of insecticides or herbicides, was administered by p.o. gavage for 2 yr to male Fischer 344/N rats and male and female B6C3F1 mice at doses of 0, 100, or 200 mg/kg and to female Fischer 344/N rats at doses of 0, 50 or 100 mg/kg.

Coexpression of keratin and desmin in a carcinosarcoma involving the maxillary alveolar ridge.

Immunohistochemical determination of the class of intermediate filaments (keratins, vimentin, desmin, neurofilaments, and glial fibrillary acidic protein) expressed by tumors has become an important diagnostic procedure for the histogenetic classification of neoplasms. A case of a poorly differentiated malignant neoplasm of the maxillary alveolar ridge which coexpressed keratin and desmin types of intermediate filaments is reported. These intermediate filaments have been associated with epithelial and muscle cell differentiation, respectively.

Pigmented dermatofibrosarcoma protuberans (Bednar tumor). A pathologic, ultrastructural, and immunohistochemical study.

Described by Bednar as a "storiform neurofibroma," pigmented dermatofibrosarcoma protuberans is a rare neoplasm accounting for approximately 1-5% of all cases of dermatofibrosarcoma protuberans (DFSP). The lesion commonly presents as an exophytic, multinodular neoplasm of the dermis or subcutaneous tissue. It occurs predominantly in blacks.

Combined hepatocellular-cholangiocarcinoma. A histologic and immunohistochemical study.

Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation. In a review of 24 cases of this tumor, three histologic types were encountered. Four cases were Type I or "collision tumors," apparently a coincidental occurrence of both hepatocellular carcinoma and cholangiocarcinoma in the same patient.

A search for cytomegalovirus and herpes viral antigen in brains of schizophrenic patients.

The peroxidase-antiperoxidase method was employed to search for evidence of cytomegalovirus (CMV) or herpes simplex virus (HSV) antigen in the brains of 25 patients with a diagnosis of schizophrenia, 25 nonschizophrenic neuropsychiatric patients, and 16 nonpsychiatric control subjects. Brain specimens from patients with acute CMV and herpes encephalitis served as positive controls. Although early results with low-titer CMV antisera suggested immunoreactivity in specific brain regions of a small number of schizophrenic and control cases, the present studies with high-titer anti-CMV IgG did not give a positive immunoperoxidase reaction in sections from the basal forebrain, hypothalamus, or midbrain.

Keratin in epithelioid sarcoma. An immunohistochemical study.

Intermediate-sized filaments have been noted in epithelioid sarcoma by previous investigators, two of whom have reported that the filaments represent vimentin. We utilized polyclonal antibodies directed against keratin and immunoperoxidase techniques (PAP) to stain 32 of the more than 300 cases accumulated at the AFIP . All of our material was formalin-fixed, paraffin-embedded.

Differentiation of vascular prostheses in dogs with serial tests of in vivo platelet reactivity.

Three different vascular prostheses (standard weight knitted Dacron, double velour knitted Dacron, and expanded polytetrafluoroethylene) were implanted in the aortas of dogs, and serial determinations of platelet survival and platelet serotonin were monitored at 12-week intervals for 1 year. Prostheses were then removed and luminal coverage with endothelialized neointima and production of prostacyclin were measured. Changes in platelet survival were correlated with changes in platelet serotonin, and both measurements reflected in vivo platelet reactivity with the vascular prostheses.

Value of S-100 protein in the diagnosis of soft tissue tumors with particular reference to benign and malignant Schwann cell tumors.

Two hundred and two benign and malignant soft tissue lesions were studied for the presence of S-100 protein by means of the peroxidase-antiperoxidase technique on formalin-fixed, paraffin-embedded tissue. Virtually all benign nerve sheath tumors (neurofibroma, neurilemoma, and granular cell tumor) contained numerous immunoreactive S-100-positive cells. Only one-half (18 of 36) of malignant schwannomas contained the protein, suggesting that its presence is an expression of differentiation in Schwann cell tumors.

DEET (N,N-diethyltoluamide) does not affect sperm number, viability and head morphology in male rats treated dermally.

DEET (N,N-Diethyltoluamide) was applied dermally to groups of 80 Sprague Dawley rats 5 days/week for 9 weeks (63 days), at three dose levels, (100, 300, and 1000 mg/kg). The undiluted material was applied with micropipettes to shaved patches. There was no run off and the material wet out onto the skin.

The antithrombotic nature of vascular prosthetic pseudointima.

Morphologic functional, and biochemical studies were performed on pseudointima obtained from woven Dacron aortic prostheses harvested from eight dogs 2 to 3 years after placement. In vivo platelet reactivity with prostheses was assessed by serial 51Cr-platelet survival measurements which documented that platelet survival returned towards normal but never attained preoperative levels. The extent of luminal coverage of prosthesis with pseudointima of the time of harvest was 60.

Pathogenesis of acute toxoplasmosis in specific-pathogen-free cats.

Systemic toxoplasmosis was produced in specific-pathogen-free cats by intravenous inoculation with Toxoplasma gondii tachyzoites. Infectious organisms were recovered from all tissues studied, but the number of organisms recovered from liver, lungs and spleen was 10-fold to 10,000-fold higher than from heart and brain. The occurrence and severity of Toxoplasma-induced lesions correlated with the number of infectious organisms recovered from the various tissues.

Elaboration of chemotactic substances by alveolar cells: possible mechanisms for the initial neutrophilic response in feline caliciviral pneumonia.

In vitro experiments established that the interaction of feline calicivirus (FCV) with alveolar macrophages and pneumocytes results in the generation of chemotactic factors that produce directed migration of neutrophils in Boyden chambers. Factors were produced independent of immune mechanisms and of discernible serum factors. Lysates of noninfected alveolar macrophages and pneumocytes did not possess chemotactic activity, indicating that chemotactic factors were not preformed in these cells.