Different reticular elements in rat lymphoid tissue identified by localization of Ia, Thy-1 and MRC OX 2 antigens.

An indirect immunoperoxidase method was used to localize the Ia, Thy-1 and MRC OX 2 antigens in rat lymphoid tissues. The antigens were detected using mouse monoclonal antibodies and all were notable since they were found to be expressed on different dendritic or reticular elements in lymphoid tissue. Ia antigen was present on bone marrow-derived dendritic cells in the T-dependent areas of spleen and lymph nodes in addition to B cells. MRC OX 2 antibody labelled dendritic cells in the follicles of spleen and lymph nodes but not the Ia positive cells in the T-dependent areas. Cells associated with blood vessels including the endothelium of the post capillary venules were also labelled with MRC OX 2 antibody. In contrast, anti-Thy-1 antibody labelled the pericyte sheath surrounding the post capillary venules and connective tissue elements in lymphoid tissues. The odd patterns of distribution of these antigens are discussed with respect to possible functions of the antigens and the cells they label.     

Mouse monoclonal antibodies against rat major histocompatibility antigens. Two Ia antigens and expression of Ia and class I antigens in rat thymus

A rat Ia (RT-1B) antigen (called Ia-A) equivalent to the mouse I-A product has been defined with mouse monoclonal antibodies (W. R. McMaster and A. F. Williams, Eur. J. Immunol. 1979. 9: 426). To identify other Ia antigens mouse monoclonal antibodies were raised against rat spleen glycoproteins depleted of the Ia-A antigen. An IgG antibody (called MRC OX17) was obtained and used to purify a molecule which had a similar structure to the Ia-A antigen and reacted with anti-Ia alloantibodies. There was no cross-reaction between the two Ia glycoproteins in assays with mouse monoclonal antibodies, alloantibodies or rabbit antibodies. In one alloantiserum almost all the detectable anti-Ia antibodies reacted with a mixture of the two Ia glycoproteins. The MRC OX17 antibody did not bind to mouse cells, but rabbit antibodies to the pure rat glycoprotein cross-reacted and recognized determinants mapping to the mouse I-E region. In the thymus the rat Ia-E antigen was on cortical epithelial and medullary reticular cells. An IgG monoclonal antibody (MRC OX18) to isotypic determinants of rat histocompatibility RT-1A antigens was also produced and used to analyze these antigens on thymus cells. The heavily labeled thymocytes were those with characteristics of mature T lymphocytes. Cortical epithelial cells and medullary dendritic-like cells were also RT-1A positive.     

Immunoultrastructural localization of Ia antigens in human endometrium

The distribution of Ia antigens was studied at the light and ultrastructural levels in 34 proliferative and 16 secretory endometria with two monoclonal antibodies using an avidin-biotin-peroxidase complex method. The endothelial cells, many lymphocytes, and various monocytic-macrophagic cells in the endometrial stroma were Ia positive. Furthermore, Ia antigens were localized to normal endometrial epithelium in the proliferative phase, and focally in epithelium adjacent to stromal lymphoid aggregates throughout the cycle. Expression of Ia antigens in the secretory epithelium was focal or absent. At the ultrastructural level, Ia-positive epithelial cells exhibited staining on the plasma membrane, in free and membrane-bound ribosomes, rough endoplasmic reticulum, and occasional perinuclear cisternae. In the endothelial cells and lymphocytes, Ia antigens were also localized to the plasma membrane and rough endoplasmic reticulum. These findings indicate that endometrial epithelium expresses Ia antigens which may be regulated by endometrial lymphoid cells and/or hormones. The plasma membrane expression of Ia antigens by the epithelial cells of endometrium appears to result from active synthesis, and not merely from passive absorption of Ia antigens.     

Estimation of the amount and tissue distribution of rat Thy-1.1 antigen

The distribution and amount of Thy-1.1 antigen expressed in rat and mouse tissues have been studied. When anti-Thy-1.1 antisera were absorbed with various tissues and assayed by cytotoxicity or radioactive binding assays, it was found that antigen was expressed in similar amounts on thymocytes and brain of both species. Lymphocytic leukemia cells from PVG/c rats also expressed as much Thy-1.1 as rat thymocytes. In contrast, Thy-1.1 was only detected in very small amounts on rat lymph node cells or thoracic duct lymphocytes; the level was 20-fold less than the AKR mouse equivalent. Rat spleen cells had larger amounts than other peripheral rat lymphocytes, and had only 2–3 times less antigen than AKR spleen cells. These results were confirmed by direct binding assays which showed that AKR mouse and PVG/c rat thymocytes bound more than 500000 molecules of anti-Thy-1.1 antibody per cell. Autoradiographic analysis showed 90 % of thymocytes, 12 % of spleen cells, and 2 % of lymph node or thoracic duct lymphocytes of the rat to be specifically labeled.     

Action and localization of neuropeptide Y in the human fallopian tube

Using indirect immunohistochemistry, neuropeptide Y-like immunoreactivity was found in nerve fibers around blood vessels and in the muscle layers of the human fallopian tube. Apart from a network of immunoreactive nerve fibers in connection with the luminary epithelium of the isthmus, the distribution resembled that of adrenergic, tyroxine hydroxylase immunoreactive, nerve fibers. Neuropeptide Y was found to have a dose-dependent inhibitory action on the adrenergic contractile response to field stimulation in the external longitudinal muscle layer of the isthmus. Furthermore, neuropeptide Y inhibited [3H]noradrenaline release from isthmic preparations during field stimulation, suggesting a prejunctional inhibitory action on adrenergic neurotransmission.     

Distribution of Ia antigens and T lymphocyte subpopulations in rat lungs.

In order to examine the mechanism of specific immunity in the lung, the distribution of Ia antigens and T lymphocyte populations was determined using immunoperoxidase-staining of cryostat sections of lungs from specific pathogen-free rats. BALT was found to be divided into three regions of lymphoid tissue. The central region was primarily composed of B cells, and was surrounded by a peripheral region of T cells (MRC OX-19+) which included both T helper (W3/25+) and T suppressor/cytotoxic (MRC OX-8+) cells. The subepithelial region contained a dense network of W3/25+, non-T cells. A majority of BALT cells, including the lymphoepithelial cells, were Ia+. The alveolar walls were found to contain numerous Ia+ dendritic-shaped cells. Alveolar macrophages found in sections, as well as those collected using bronchoalveolar lavage, were Ia- and W3/25-. Mechanisms for the induction of immunity within both BALT and the alveolar region are proposed.     

Purification of Thy-1-related glycoproteins from human brain and fibroblasts: comparisons between these molecules and murine glycoproteins carrying Thy-1.1 and Thy-1.2 antigens

The purification and partial characterization of glycoproteins from human brain and fibroblasts which are antigenically and structurally related to the Thy-1 glycoproteins of rats and mice is described. In addition, Thy-1 molecules were isolated from the brains of AKR and CBA mice (Thy-1.1 and Thy-1.2, respectively). The molecules were purified from sodium deoxycholate extracts of brain tissue by chromatography on lentil lectin-Sepharose followed by gel filtration, and purification was monitored by radioimmunoassay. Similar molecules were isolated from human brain and fibroblasts using monoclonal antibody columns. Analysis by electrophoresis on 12.5% polyacrylamide gels in sodium dodecyl sulfate (SDS) showed that Thy-1-related molecules from human brain migrate as a doublet with apparent molecular weights of 24700 and 26200. Thy-1 from human foreskin fibroblasts cultured in vitro migrates as a single band of 26500. Thus, human Thy-1 glycoproteins resemble their rat counterparts in exhibiting tissue-specific polymorphism. Amino acid analysis of Thy-1 from human brain and fibroblasts suggests that the polypeptides expressed by different tissues are extremely similar. Thy-1.1 from AKR mouse brain migrates as a doublet on SDS gel electrophoresis with apparent molecular weights of 23700 and 25100, while Thy-1.2 molecules isolated from CBA mouse brain run as a single broad symmetrical band with a molecular weight of 25000. Molecules carrying the Thy-1.1 allotype are readily distinguished from those carrying the Thy-1.2 allotype by the presence of an additional arginine residue. Amino acid compositions of Thy-1 from man and the two mouse strains are similar, but each has unique features. Thy-1 molecules immunoprecipitated from mouse and rat fibroblasts have higher apparent molecular weights than their brain counterparts; the basis of the tissue-specific polymorphism is discussed.     

Amylase in fallopian tube and serous ovarian neoplasms: immunohistochemical localization

We studied the cellular localization of amylase in normal Fallopian tubes and serous ovarian neoplasms using an indirect immunoperoxidase technique. The primary antiserum was against human pancreatic amylase, and was found to inhibit ovarian tumor amylase as well. Amylase was present in normal endosalpingeal epithelium and in the epithelial cells of benign, borderline, and malignant serous ovarian tumors. A mucinous cystadenoma was also studied and contained no amylase. This localization suggests that amylase production by serous ovarian neoplasms reflects the endosalpingeal differentiation of these tumors. Antibody to amylase may be potentially useful in distinguishing serous ovarian tumors from other forms of ovarian neoplasia.     

Malacoplakia of the ovary,fallopian tube and uterus: a case associated with diabetes mellitus

Malacoplakia is a chronic xanthogranulomatous inflammation that most commonly affects the urinary tract and the gastrointestinal system of middle-aged women. It is rarely encountered in a female genital tract, and only a handful of cases of malacoplakia of the ovary have been described. We report an unusual case of malacoplakia extensively involving the ovary, fallopian tube and uterus of a 47-year-old woman with poorly controlled diabetes mellitus. Escherichia coli was cultured from the ovarian lesion. To our knowledge, such an extensive female genital malacoplakia associated with diabetes mellitus has not been reported before. Widespread or atypical site malacoplakia occurring in a patient with systemic disease may result from a diminution of macrophagocytic function, either under the influence of the systemic illness or related to corticosteroid excess. We propose that diabetes mellitus without appropriate medical control may have resulted in impaired leukocyte function which, when combined with E. coli infection, led to the development of extensive malacoplakia in the genital tract of this patient.     

Key features of extrauterine pelvic serous tumours (fallopian tube, ovary, and peritoneum)

Key features of extrauterine pelvic serous tumours (fallopian tube, ovary, and peritoneum) Ovarian serous carcinoma (OSC) is the most common of the ovarian epithelial malignancies, and accounts for most of the mortality. Traditionally, ovarian cancer has been considered to be one disease; however, it is now apparent that it actually consists of many different entities. OSC can be further segregated into two processes: high-grade serous carcinoma (HGSC) and low-grade serous carcinoma. This classification is supported by molecular changes, morphological appearance, clinical behaviour, and distinct precursor lesions. This review will describe in detail these features of OSC, differential diagnosis, prognosis, and recent challenges to the existing hypotheses regarding the origin of these tumours. Special attention will be paid to HGSC and its relationship with BRCA abnormalities, especially those seen in hereditary breast and ovarian cancer syndrome. Finally, treatment options based on specific molecular targets will be discussed.     

The subcellular localization of rat photoreceptor-specific antigens

The subcellular localization of three photoreceptor antigens (RET-P1, rhodopsin and RET-P2) has been studied by electron microscopic immunocytochemistry of rat retinas. Localization was also examined by determining the amount of RET-P1 and RET-P2 antigen in various subcellular fractions. RET-P1 and RET-P2 antigens were further characterized by immunoblotting of crude retina membrane proteins which had been separated by one-dimensional gel electrophoresis. RET-P1 antigen has been detected with a monoclonal antibody that reacts with the perikarya, inner segments, and outer segments of adult rat photoreceptors by peroxidase immunolabelling of fixed tissue sections. Analysis at the electron microscopic level has shown that RET-P1 antigen is located on the external face of the inner and outer segment plasma membrane. A monoclonal antibody against purified bovine rhodopsin (RHO-C7) labels the outer segments of rat retinas by peroxidase immunocytochemistry. Ultrastructural antibody localization indicates that this particular determinant of rhodopsin is exposed on the external face of the plasma membrane of outer segments and may also be expressed on the surface of the inner segments. RET-P2 antibody labels only the outer segments of adult rat photoreceptors by peroxidase immunocytochemistry. The light microscopic labelling of RET-P2 antibody in the presence, but not in the absence, of detergent suggests that it is an intracellular antigen. The results of both ultrastructural labelling and biochemical fractionation are consistent with the localization of RET-P2 antigen on the internal face of the plasma membrane and/or the cytoplasmic face of the disc membranes. RET-P2 antigen was found to be a protein (or glycoprotein) of apparent molecular weight 38 000 +/- 3000.     

Metastases to the ovary arising from endometrial,cervical and fallopian tube cancer: recent advances

The introduction of genomic studies has enabled assessment of the clonality of synchronous tumours involving the ovary and other sites in the female genital tract in a definitive way. This has led to the abandonment of conventional approaches to primary site assignment, and the recognition that most such synchronous neoplasms are clonally related single tumours with metastatic spread, rather than independent primary tumours. These discoveries have implications for diagnostic practice, analogous to the gradual change over the last few decades in our approach to mucinous neoplasms of the ovary metastatic from the gastrointestinal tract. In this review, we first examine the routes of metastasis to the ovary, and then discuss the diagnostic and clinical implications of concurrent ovarian carcinomas arising in combination with endometrial, endocervical and tubal carcinomas. It is proposed that cases of primary low-grade endometrioid endometrial carcinoma with a secondary unilateral ovarian tumour, both with indolent characteristics, may be classified as ‘FIGO stage IIIA-simulating independent primary tumours’, with a comment that conservative management would be appropriate. It should be recognised that human papillomavirus-associated endocervical adenocarcinomas may result in synchronous or metachronous ovarian metastases that appear to be unrelated to the primary tumour, and that these may be managed conservatively in the absence of other sites of disease. In cases of tubo-ovarian high-grade serous carcinoma, tubal intraepithelial or contralateral adnexal involvement should count as a pelvic disease site for staging purposes.     

Primary carcinoma of the fallopian tube coexisting with benign cystic teratoma of the ovary

Primary carcinoma of the fallopian tube is a rare malignancy of the female genital tract and infrequently diagnosed before an operation. The majority of patients have extensive disease at the time of diagnosis. We have experienced incidentally a case of a carcinoma of the fallopian tube coexisting with a benign cystic teratoma of the ovary in a 25-year-old woman. We report this case with a brief review of literatures.     

Ultrastructural localization of alkaline and acid phosphatases in the human fallopian tube epithelium during the menstrual cycle

Ultrastructural and cytochemical methods were utilized to study the human Fallopian tube fimbrial epithelium during the different stages of the menstrual cycle. Alkaline phosphatase reaction product was located along the apical and lateral plasma membranes of the secretory cells only, regardless of the stage of the cycle. The ciliated cells were almost devoid of any reaction product at all stages of the cycle. Acid phosphatase reaction product depicted the lysosomes. These appeared as electron-dense bodies, of almost equal numbers in the ciliated and the secretory cells at all stages of the cycle. Thus the number of lysosomes did not vary appreciably during the different stages of the menstrual cycle. Many lipid droplets were found in both cells; these were rimmed by acid phosphatase reaction product, and some were partially enveloped by electron-dense bodies containing acid phosphatase deposits. Acid phosphatase deposits were also found on the inner face of Golgi vesicles.     

Identification of lymphocyte subsets in the human fallopian tube.

PROBLEM: Immunohistochemical investigations for the detection of lymphocyte subsets in the human oviduct have been performed. Knowledge about local immunity especially cell-mediated immunity, in the fallopian tube has been, up to now, limited. As an essential structure for the human reproduction process, the tubal mucous membrane is exposed to a variety of antigens. METHOD: A total number of 20 tubal biopsies obtained from fertile women during gynecological operations like tubal ligations or hysterectomy were examined by the immunoperoxidase technique. Seven specimens were obtained during the proliferative phase, ten during the secretory phase and three during a caesarean section with tubal ligations. RESULTS: It could be established that the presence of lymphocytes in the oviductal mucous membrane is physiological. These cells can be identified by their typical immunohistochemical patterns. There were no significant differences of the type and number of lymphocytes in the mucosa within the phases of menstrual cycle. The dominant cell types in the tubal mucosa were the CD3+ and CD8+ lymphocytes. CONCLUSIONS: It can be suggested that the lymphocytes in the tubal mucosa may involved in the process of immune tolerance, which could realize the transport of sperms and blastocysts through the oviduct under normal conditions without activation of local immune mechanisms. The lymphoid tissue of the oviduct is a specialized form of mucosal-associated lymphoid tissue (MALT).     

Gene structure and chromosomal localization of the mouse homologue of rat OX40 protein

The OX40 protein is expressed only on activated rat CD4⁺ T blasts and is a member of a superfamily of cell surface molecules which includes CD40, CD30, CD95 (Fas), CD27, 4-1BB antigens and the receptors for tumor necrosis factor (TNF) and nerve growth factor (NGF). The proteins of this group are related to each other by having three to six repeats of a cysteine-rich sequence in their extracellular domains. Members of this family of receptors have also been shown to bind to ligands which are structurally related to TNF. The mouse homologue of the rat OX40 protein was cloned at the cDNA and genomic levels. The gene structure shows that there are several intron/exon borders shared between OX40 and CD27, CD40, TNF receptor type I, CD95 and 4-1BB genes. This group of genes is less closely related structurally to the gene structure of the NGF receptor. The gene encoding murine OX40 has been placed on mouse chromosome 4, in an area which contains the genes for TNF receptor type II and 4-1BB, and is syntenic with a region of human chromosome 1 which contains human TNF receptor type II, OX40, and CD30 genes.