人体正常涎腺组织中成纤维细胞生长因子受体3的表达

目的　探讨成纤维细胞生长因子受体 3 (FGFR3 )在人体正常涎腺组织中的表达情况。方法　正常成人涎腺标本2 4例 ,其中腮腺、颌下腺和舌下腺标本各 4例 ,唇腺、腭腺、磨牙后腺及舌腺各 3例 ,分别用超敏S P免疫组化法检测不同腺体组织中FGFR3的分布。结果　在腮腺的浆液性腺泡的分泌颗粒及其他混合性腺的浆液性腺泡的分泌颗粒中均可见少量的FGFR3的表达 ,在大唾液腺及小唾液腺的小叶内导管和小叶间导管中均可见中等强度的FGFR3的表达 ,其中以颌下腺中表达较强 ,而在舌下腺中表达较弱 ,在间质结缔组织中均无FGFR3的表达。结论　人体正常涎腺的导管系统中及浆液性腺泡中有FGFR3的表达     

Locally dividing macrophages in normal and inflamed mammary glands.

Goat mammary macrophage division in vivo was assessed by detection of mitotic figures, by autoradiographic measurement of the uptake of 3H thymidine, and by a 96-well proliferation assay. Autoradiography revealed that 3.74 +/- 0.77% of nonstimulated mammary macrophages were actively synthesizing DNA. Eight days of sterile inflammation, induced by lipopolysaccharide or thioglycollate, increased mammary macrophage division (10.9 +/- 2.1%). The division increased within 2 h after inducing inflammation with thioglycollate. After 1 day, the rate of division decreased, and another increase occurred 3-4 days later. The high rate of division was maintained for greater than 60 days after the induction of sterile inflammation. Division was further shown to occur by injecting 3H-thymidine directly into the mammary gland, harvesting the macrophages 1.5 h later, and determining incorporation by autoradiography. The results of all assays of division were in agreement, suggesting they reflected the same event. The dividing cells were nonspecific esterase-positive, adherent, motile, phagocytic, and had morphological characteristics of macrophages.     

Transforming growth factor beta 1 expression in gastric carcinoma.

Many types of human malignant tumor have been reported to amplify transforming growth factor-beta 1 (TGF-beta 1) gene and overexpress its protein. However, little work has been done about the content of TGF-beta 1 protein in tissue and blood of patients with malignant tumors. TGF-beta 1 protein of tissue (n = 29) and serum TGF-beta 1 levels in patients with gastric carcinoma (n = 62) were compared with those in normal subjects (n = 10) using a TGF-beta 1 enzyme-linked immunosorbent assay. Also, expression of TGF-beta 1 mRNA (n = 20) and immunohistochemical distribution of the protein (n = 70) in gastric carcinoma tissues were studied. The immunohistochemical expression of TGF-beta 1 protein was significantly correlated with the tissue TGF-beta 1 content (r = 0.45 : p < 0.05). The content of TGF-beta 1 was 311 +/- 212 ng/g wet carcinoma tissue. TGF-beta 1 mRNA was expressed in gastric carcinoma cells. However, unexpectedly serum TGF-beta 1 levels in patients with gastric carcinoma were lower (97.1 +/- 29.4 ng/ml) than those in normal subjects (140.3 +/- 85.7 ng/ml, P < 0.05). Our results support that the tumor cells directly produce TGF-beta 1 and that semiquantitative immunohistochemical staining method for TGF-beta 1 protein is a validative method for TGF-beta 1 protein quantitation.     

Immunohistological detection of tissue factor in normal and abnormal human mammary glands using monoclonal antibodies

Summary Tissue factor (TF) is the primary cell-bound initiator of the coagulation protease cascade. The cytological distribution of TF in various tissues may be described on the basis of immunohistochemistry with epitope-defined monoclonal antibodies and the extravascular distribution of TF apparently represents a haemostatic envelope ready to activate coagulation when vascular integrity is disrupted. The present study localized TF in human breast cancer tissues when compared with normal breast gland tissues and benign disorders of the mammary gland. By use of a cocktail of three epitopedefined monoclonal antibodies, TF was detected only in the myoepithelia of the resting breast gland. In proliferating disorders like fibrocystic disease or in fibroadenomas, both myoepithelia and luminal epithelia showed TF expression. Of 115 breast cancers 93 reacted with anti-TF, in an inhomogeneous manner in terms of intensity and number of positive cells. There was a tendency for more positive and intensely stained cells to be found in well-differentiated structures such as tubules. Invasive ductal carcinomas exhibiting more positive and more strongly stained cells were less commonly metastatic to lymph nodes when compared with the tumours with no detectable or very low TF immunostaining. A semiquantitatively recorded score of TF immunostaining correlated with the procoagulatory activity measured (7 fibroadenomas and 24 carcinomas). The results of this study suggest that proliferation and differentiation of the mammary gland is associated with enhanced TF expression in the epithelia which are negative for TF staining in the resting gland. Malignant growth is characterized by randomly expressed epithelial TF, which expression is enhanced and more frequent in well-differentiated tumour cells.     

Distribution of cytoskeletal and contractile proteins in normal and tumour bearing salivary and lacrimal glands

Summary We have evaluated by means of immunocytochemistry the distribution of various cytoskeletal and contractile proteins (cytokeratins, vimentin, desmin and -smooth muscle actin) in 23 salivary or lacrimal gland primary tumours (15 pleomorphic adenomas and 8 carcinomas in pleomorphic adenoma), one third of which contained areas of normal gland. Normal epithelial luminal cells were stained by cytokeratin antibodies with a general specificity, while myoepithelial cells were selectively stained by a monoclonal antibody (SK2-27) reacting in immunoblots with cytokeratin polypeptides 14, 16 and 17, according to the classification of Moll et al. (1982) and by an antibody directed against -smooth muscle actin (Skalli et al. 1986). In pleomorphic adenomas, both epithelial and myoepithelial cells displayed typical topographic distributions; moreover, myoepithelial cells showed two distinct cytoskeletal phenotypes. These findings could account in part for the heterogeneity of aspects observed in this tumour. In carcinomas, malignant cells were always positive to cytokeratin antibodies with general specificity and myoepithelial cells were absent as judged by anticytokeratin SK2-27 and anti--smooth muscle actin immunostainings. However, interestingly, there was in all cases a strong positivity for -smooth muscle actin in stromal cells, similarly to what has previously been described for mammary carcinoma (Skalli et al. 1986). Our findings may be useful for the interpretation of the histogenesis of salivary and lacrimal tumour and stromal cells.     

Solitary fibrous tumour of the major salivary glands

We report four cases of solitary fibrous tumours which involved the parotid (two cases), submandibular, and sublingual glands of two men and two women ranging in age from 46 to 81, mean 66 years. The tumours presented as painless, firm masses which involved the substance of the salivary gland in each case. All have had an uneventful clinical course after local excision. Awareness of this entity is important to avoid confusion with haemangiopericytoma.     

大鼠皮肤创伤修复过程中转化生长因子β1和β3的表达

背景：转化生长因子β在组织创伤修复中发挥核心和关键作用。 目的：观察转化生长因子β1和转化生长因子β3在大鼠皮肤瘢痕性创伤愈合过程中表达量及表达部位的变化。 方法：制备大鼠皮肤全层切伤模型,长度1.5-2.0 cm,深及筋膜层。于伤后0 h,12 h,1 d,2 d,3 d,4 d,5 d,6 d,7 d处死大鼠,取损伤部位皮肤,采用免疫组织化学染色检测各时间点转化生长因子β1和转化生长因子β3的表达,并进行定量分析。 结果与结论：免疫组织化学染色显示,在创伤愈合的早期阶段(伤后1-5 d),转化生长因子β1和转化生长因子β3免疫阳性颗粒主要出现在上皮细胞、上皮基底层细胞胞浆、巨噬细胞等免疫细胞胞浆及肉芽组织中;随着创伤修复时间的持续,免疫阳性颗粒主要出现在真皮层的成纤维细胞及细胞外基质中。其中转化生长因子β1的表达在创伤后1-5 d最强,而转化生长因子β3在创伤后六七天时开始明显表达。可见在大鼠皮肤瘢痕性创伤愈合过程中,转化生长因子β1的表达先于转化生长因子β3,提示转化生长因子β1与胶原形成及创伤修复关系密切,而转化生长因子β3在愈合后期表达量有升高趋势,其可能与创伤后期的组织改建密切相关。     

Vascular endothelial growth factor is constitutively expressed in normal human salivary glands and is secreted in the saliva of healthy individuals

The expression of vascular endothelial growth factor (VEGF), a specific mitogen for endothelial cells, was examined in salivary glands and in normal saliva. In normal salivary glands, VEGF mRNA and protein were strongly present in acinar cells, whereas little or no VEGF was found in ductal cells. In chronically inflamed glands, VEGF protein was in addition present in ductal elements and in infiltrating mononuclear cells. No difference of VEGF expression was observed between benign and malignant salivary gland tumours. By ELISA, whole saliva of 24 healthy individuals contained up to 2·5 ng/ml (mean 1·4 ng/ml; SD 0·77 ng/ml) of VEGF, confirming the constitutive secretion of this cytokine by human salivary glands. Western blot analysis of normal saliva under non-reducing conditions detected anti-VEGF reactive protein moieties of ≈46 kD, corresponding to VEGF secreted by cells in tissue culture. Additional anti-VEGF reactive proteins of ≈60 and 90 kD were detected in the saliva of some individuals. The presence of considerable quantities of VEGF in normal human saliva suggests an important role for this cytokine in the maintenance of the homeostasis of mucous membranes, with rapid induction of neoangiogenesis by salivary VEGF helping to accelerate wound healing within the oral cavity. Moreover, salivary VEGF may permeabilize intraglandular capillaries and thus participate in the regulation of saliva production itself. Copyright © 1998 John Wiley & Sons, Ltd.     

Immunohistochemical demonstration of insulin-like growth factor I (IGF-1) in normal and pathological human pituitary glands.

The authors have studied the presence and distribution of Insulin-Like-Growth-Factor-1 (IGF-1) in 5 autopsied normal and 20 surgically removed human pituitary adenomas, employing a peroxidase-anti-peroxidase method. IGF-1 could be demonstrated in all cases, with variation of cells immunostaining from 60% in normal pituitary gland to 100% in corticotroph cell adenoma.     

Immunoglobulin-containing cells in normal human labial salivary glands

The distribution of immunoglobulin-containing cells within 8 normal human labial salivary glands was studied using an immunoperoxidase technique. Cell counts revealed that IgA-containing cells pre-dominated in all specimens and that the mean percentage class ratios for IgG:IgA:IgM:IgD cells were 4:92:3:1. IgE cells were rare and only detected in one gland. The density of IgA cells (191 cells/mm2 of labial gland section) was greater than those previously reported for the parotid and submandibular glands. These results support the view that minor salivary glands play an important role in the synthesis and secretion of salivary antibody.     

Actin containing cells in normal human salivary glands

Summary A study of actin distribution in human salivary glands was performed, using smooth muscle antibodies from a patient with active chronic hepatitis.Immunoperoxidase labelling methods were found to give a good staining intensity for actin containing cells. The peroxidase antiperoxidase (PAP) method gave a stronger reaction than the double layer method, but the latter was sensitive enough for our purpose and was less time consuming. Sections from formalin fixed and paraffin embedded specimens were negative for actin staining while frozen sections showed good staining results. Sections from specimens which were washed for 12 h at 4 ° C showed less background staining.Strong staining was found in myoepithelial cells lying around the acini, intercalated ducts and parts of the striated ducts. The number of myoepithelial cells around acini increased in the following order: the parotid gland, the submandibular gland, the sublingual gland and the small glands of the lip. This distribution indicates the importance of myoepithelial cells in the process of physical expression of saliva. Cytoplasmic staining in the basal epithelial cells of the striated ducts illustrates that these cells may be involved in some sort of secretion. This staining might also suggest a histogenetic origin for myoepithelial cells.     

Nerve growth factor receptor in tumours of the human nervous system. Immunohistochemical analysis of receptor expression and tumour growth fraction

The expression of nerve growth factor receptor (NGFr) was investigated by means of immunohistochemistry in 135 tumours of the human central and peripheral nervous system. The results were compared to the proliferative activity of the tumours as determined by immunostaining for the proliferation-associated antigen Ki-67. Immunoreactivity for NGFr was most consistently observed in tumours derived from the neural crest such as neurinomas, neurofibromas and ganglioneuromas. In tumours of the central nervous system, NGFr-immunostaining was particularly strong in pilocytic astrocytomas while the majority of other gliomas were either NGFr-negative or contained only a minor fraction of NGFr-positive tumour cells. Among all other investigated tumours including medulloblastomas, pituitary adenomas and meningiomas only exceptional cases demonstrated a significant number of positive tumour cells. Choroid plexus papillomas and metastatic carcinomas were always NGFr-negative. Our results indicate that NGFr-expression in tumours of the human nervous system is heterogenous with respect to tumour type and appears to be unrelated to proliferative activity.     

Muscle-specific protein expression in normal salivary glands and pleomorphic adenomas: an immunocytochemical study with biochemical confirmation.

Normal salivary gland myoepithelia are contractile cells with hybrid epithelial/myogenic ultrastructural features. It is known that these cells co-express the intermediate filaments cytokeratin, vimentin, and occasionally GFAP. This complex cytoskeletal immunophenotype is also reflected in multiple morphologic cell types of pleomorphic adenoma. At present, the myofilament complement of normal and neoplastic myoepithelium is not well defined. We have evaluated the expression of desmin and smooth and sarcomeric muscle actins in 11 normal salivary glands (six snap-frozen and five methacarn fixed) and 26 pleomorphic adenomas (11 snap-frozen and 15 methacarn fixed) by ABC-immunoperoxidase method. Two of 11 frozen pleomorphic adenomas contained the muscle-specific intermediate filament desmin, which is not found in the normal glands. This novel finding was confirmed by gel electrophoresis and immunoblot. Using specific antibodies, normal gland myoepithelial cells consistently contained muscle actin isoforms of the smooth muscle type but not sarcomeric muscle actins. Muscle actin expression by the neoplastic cells of pleomorphic adenoma was found in 13 of 26 tumors (six of 11 frozen tumors (desmin negative) and seven of 15 methacarn fixed tumors). In comparison to the normal myoepithelial cell, the transformed myoepithelial-like cells of pleomorphic adenoma are not always characterized by a muscle actin cytoskeleton. Expression of desmin intermediate filaments in pleomorphic adenomas appears to be a rare event that is independent of a muscle actin cytoskeleton.     

Distribution of dendritic cells in normal human salivary glands

Dendritic cells (DC) are believed to contribute to development of autoimmune sialadenitis, but little is known about their distribution in normal salivary glands. In this study, DC were identified and their distribution was determined in normal human parotid and submandibular glands. For light microscopy, salivary gland sections were stained with H&E or immunocytochemically using antibodies to DC markers. Transmission electron microscopy (TEM) was used to evaluate the ultrastructural characteristics of DC. In H&E sections, elongated, irregularly shaped nuclei were occasionally seen in the striated and excretory duct epithelium. Immunolabeling with anti-HLA-DR, anti-CD11c and anti-S100 revealed DC with numerous processes extending between ductal epithelial cells, often close to the lumen. Morphometric analyses indicated that HLA-DR-positive DC occupied approximately 4-11% of the duct wall volume. Similar reactive cells were present in acini, intercalated ducts and interstitial tissues. TEM observations revealed cells with indented nuclei containing dense chromatin, pale cytoplasm with few organelles, and lacking junctional attachments to adjacent cells. These results indicate that DC are abundant constituents of normal human salivary glands. Their location within ductal and acinar epithelium suggests a role in responding to foreign antigens and/or maintaining immunological tolerance to salivary proteins.     

Transforming growth factor beta 1 as a prognostic factor in pulmonary adenocarcinoma.

AIMS--To evaluate the efficacy of transforming growth factor beta (TGF-beta) for the prognosis of pulmonary adenocarcinoma. METHODS--TGF-beta was detected immunohistochemically using the avidin-biotin-peroxidase complex technique in resected pulmonary adenocarcinomas from 88 patients. RESULTS--Of the 88 patients, 39 were TGF-beta negative and 45 TGF-beta positive. The five year survival rate was 56% for the TGF-beta negative and 16% for the TGF-beta positive group. CONCLUSIONS--TGF-beta can be used as a prognostic factor in pulmonary adenocarcinoma.     

Phosphatase enzymes. Cytochemical study of pleomorphic adenoma and normal human salivary glands.

Human parotid glands, submandibular glands, and pleomorphic adenomas were examined by electron microscopic histochemistry. All epithelial cells of the normal salivary glands showed plasma membrane adenosine triphosphatase (ATPase) and inosine diphosphatase (IDPase) activity. However, myoepithelial cells reacted most intensely. Pleomorphic adenomas showed epithelial cells within solid and ductal portions of the tumors that were variably reactive for both ATPase and IDPase. Histochemical examination of the epithelial cells in the myxoid portions of the tumors did not provide conclusive evidence as to the nature of their progenitor cells. Surface-associated phosphatases (alkaline phosphatase, ATPase, and IDPase) cannot be reliably used as histochemical markers of salivary gland myoepithelial cells. Therefore, morphological and phosphatase histochemical studies that intend to examine the role of myoepithelial cells in salivary gland neoplasms must be interpreted with care.     

Immunohistochemical expression of epidermal growth factor receptor in salivary gland tumours

Summary Immunohistochemical localization of epidermal growth factor receptor (EGFR) in normal salivary glands and tumours (108 cases) was studied using a monoclonal antibody. In the normal salivary glands, EGFR was occasionally detected in ductal segments of intercalated, striated, and excretory ducts, but not in acinar cells. The frequency of positive EGFR staining in salivary gland tumours was not high: pleomorphic adenoma, 33.8%; mucoepidermoid tumour, 25.0%; adenolymphoma, 44.4%; and sialoadenocarcinoma, 66.6%. Pleomorphic adenomas showed positive staining for EGFR on the luminal side of luminal cells and in squamous metaplastic cells of tumour tissue. Some modified myoepithelial cells were also reactive whereas outer spindle tumour cells were unstained. Adenolymphomas regularly exhibited positive EGFR staining in the cell membrane; mucoepidermoid carcinoma displayed positive staining in cell membranes in epidermoid tumour cells and cytoplasmic staining in mucous-secreting tumour cells. Sialocarcinomas revealed cell membrane staining and whole cytoplasmic staining for EGFR. The immunohistochemical localization of EGFR could be classified into two types, one the cell membrane-positive type found in epithelial tumour cells, and the second the cytoplasmic positive type seen in normal ductal cells, the luminal tumour cells of pleomorphic adenomas and mucous-secreting tumour cells.