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M Vierbuchen

Publications and source records attributed to M Vierbuchen.

At least 37 records · Page 2Linked to original sources

[Epidermal growth factor receptor (EGF-R) in human breast cancer--a marker of morphologic-functional differentiation].

Epidermal growth factor and some related mitogens elicit a biological response in normal and malignant cells by mediation of a specific receptor, the epidermal growth factor receptor (EGF-R). In recent publications the expression of this receptor, a glycoprotein with extensive sequence homology to the erb B-oncogene, has in human breast carcinoma, been claimed to be an excellent indicator of a poor prognosis, superior to conventional prognostic factors such as nodal status and tumour size. To learn about the functional and prognostic role of EGF-R in breast carcinoma, we screened breast cancer tissue from 91 patients for the expression of the receptor by immunohistochemical means, with a monoclonal antibody. The results were compared to the expression of steroid receptors and to morphological and clinical parameters. We detected EGF-R in normal squamous cells of the skin and in epithelial and myoepithelial cells in non-neoplastic lobuli and ducts of the human breast. EGF-R was found in breast cancer tissues of 22 of the 91 patients. Specific staining was observed mainly in the cell membranes, but also to some extent in the cytoplasm. The distribution pattern of the antigen in terms of intensity of staining and number of specifically stained cells varied widely among different and within different regions of the same tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Endogenous carbohydrate-binding proteins in Pneumocystis carinii.

By using biotinylated neoglycoproteins, the in situ occurrence of endogenous carbohydrate-binding proteins (lectins) in Pneumocystis carinii has been glycohistochemically demonstrated in lung tissue specimens from acquired immunodeficiency syndrome patients with P. carinii pneumonia. While the parasite possessed only a weak to moderate density of receptors for L-fucose and N-acetylated amino sugars, a strong specific binding of beta-D-galactoside and D-mannoside neoglycoproteins was observed on the cyst surface and within intracystic bodies. It is suggested that these endogenous lectins may be involved in the adhesion of P. carinii to the target.

Acetylation↗

Detection of squamous cell carcinoma antigen in normal squamous epithelia and in squamous cell carcinomas of the uterine cervix.

Squamous cell carcinoma (SCC) antigen is a subfraction of tumor antigen TA-4 isolated from a cervical squamous cell carcinoma. The specificity of SCC antigen and the factors influencing its release into serum were evaluated. Antigen concentrations were measured in 157 tissue extracts and in 188 sera of patients with nonmalignant or malignant gynecologic diseases. A commercial radioimmunoassay based on polyclonal antibodies (Abbott Laboratories, North Chicago) was used. Cytosol concentrations were significantly higher (P less than 0.005) in normal squamous epithelia (means = 6040 ng/mg cell protein [CP]) and in squamous cell carcinomas (means = 2483 ng/mg CP) of the exocervix than those in normal columnar epithelia and in adenocarcinomas of the endocervix, endometrium, ovary, and breast (means = 1-508 ng/mg CP). Despite the high antigen concentrations in normal squamous epithelia, elevated serum levels (greater than 2.5 ng/ml) were almost exclusively found in patients with cervical squamous cell carcinomas. The sensitivity of SCC antigen as a marker for primary carcinomas was 61%, increasing from 29% in Stage I to 89% in Stage IV. The positivity rate was higher in women with well-differentiated (78%) and moderately differentiated carcinomas (67%) than in those with poorly differentiated tumors (38%). The results show that SCC antigen is not tumor specific. The release into serum is independent of local tissue content, but is apparently influenced by the infiltrative growth, the mass, and the degree of histologic differentiation of the tumor.

Adenocarcinoma↗

CA 125 in normal tissues and carcinomas of the uterine cervix, endometrium and fallopian tube. I. Immunohistochemical detection.

The distribution of cancer antigen 125 (CA 125) has been investigated in normal tissues and carcinomas of the Müllerian duct by immunohistochemical methods using the monoclonal antibody OC 125. Detection of CA 125 was most intense in cryostat sections and decreased in formalin fixed and paraffin embedded tissues according to the duration of fixation. Enzymatic digestion with neuraminidase or alkaline hydrolysis abolished specific staining suggesting the antigen is a sialylsaccharide bound to protein by alkali-labile linkage. Immunohistochemical staining demonstrated the presence of CA 125 in all normal glandular epithelia of the endocervix, endometrium and fallopian tube in different distribution patterns. In normal endometrium the cellular distribution pattern was related to the menstrual cycle. In endocervical, endometrial and tubal adenocarcinomas CA 125 was found in 73% of cases. In glandular structures the antigen was concentrated at the luminal surface of the tumour cells, in solid tumour areas it was spread throughout the cytoplasm or concentrated in large cytoplasmic vacuoles. The expression of CA 125 was considerably lower in solid tumour areas. These data show that CA 125 is not a true "tumour marker", but a product of female genital mucosae and of their cancerous derivates provided their synthesizing ability is not lost in the course of pathologic differentiation.

Antigens, Tumor-Associated, Carbohydrate↗

[Topography and mechanisms of adhesion of uropathogenic Escherichia coli bacteria in the human kidney and renal pelvis].

The occurrence and significance of bacterial carbohydrate recognition proteins (bacterial lectins) and endogenous carbohydrate binding proteins (endogenous lectins) of human urothelium as well as kidney tubulus epithelium was analyzed with respect to the adhesion of urotoxogenic Escherichia coli bacteria. Using biotinylated neoglycoproteins, we demonstrated a wide spectrum of endogenous lectins with Galactose-, Mannose-, Fucose-, N-Acetylgalactosamine-, and N-Acetylglucosamine binding activities in the urothelium. In the kidney the distal nephron and especially the medullar collecting ducts exhibited a similar spectrum of endogenous carbohydrate binding activities as detected for the urothelium. Adhesion- as well as inhibition-experiments with selective blocking of either bacterial lectins or endogenous lectins of the target cells by different carbohydrates both reduced the bacterial adhesion. However, maximal inhibition of bacterial adhesion was achieved by simultanous blocking of microbial and target cell lectins with mannose or mannan. From these results it is reasonable to conclude that specific adhesion which may result in an organotropism (urotropism) of E. coli infection is due to a dual recognition mechanism which is accomplished by the combined interaction of the bachterial and host cell lectins with the corresponding carbohydrates of E. coli and that of the target cells respectively. Further studies showed that normal human serum possesses natural antiadhesins which are represented by the glycan parts of the serum-glycoproteins.

Bacterial Adhesion↗

[Lectin histochemistry in the kidney and renal tumors].

In recent years histochemical methods using lectins with diverse carbohydrate binding specificities have proved useful tools for studying the distribution pattern of intracellular and pericellular glycoconjugates at the tissue level. Several studies of human kidneys have shown that the binding sites for certain lectins are strictly confined to various parts of the nephron. This allows the use of lectins as markers for the particular segments. The glomeruli exhibit abundant sialoglycoproteins at the free surface coat of the podocytes as detected by PNA after sialidase representing a major component of the filtration barrier; neoplastic podocytes of glomeruloid bodies in nephroblastomas as well revealed an intense lectin binding despite failing any vascularization. The lectin binding pattern of renal carcinomas varies within a wide range depending on their histological growth pattern. Whereas most renal carcinomas of clear and granular cell type rarely displayed a slight reactivity with lectins at the cell surface and at the luminal aspect of tubulopapillary tumors, a sub-group of carcinomas named chromophobe type exhibited a strong cytoplasmic staining with DBA and PNA after sialidase. Comparative evaluation of normal kidneys revealed an identical binding pattern exclusively in the intercalated cells of the collecting ducts probably indicating a histogenetic origin of these tumors from the collecting duct epithelium. This assumption derives further support from the detection of precursor lesions rarely detected in normal and tumor-bearing kidneys exhibiting the same lectin binding pattern. In accordance with recent observations in the literature the disclosure of a similar lectin binding pattern in renal oncocytomas and their precursor lesions exhibiting oncocytic transformation clearly favors the assumption of an identical histogenetic origin. On the other hand, few cases of a carcinoma mimicking collecting duct epithelium exhibited a broader lectin binding pattern revealing evidence of secretory activity; the histochemical similarities between this unusual carcinoma and transitional cell carcinoma confirmed the suggested origin from the ducts of Bellini. In conclusion, lectin histochemistry may be a useful tool for estimating the characteristics of renal tumors and elucidating their histogenesis.

Epithelium↗

CA 50 and CA 19-9 antigen expression in normal, hyperplastic, and neoplastic thyroid tissue.

The occurrence of the tumor-associated carbohydrate antigens defined by the monoclonal antibodies (moabs) C 50 and 19-9 has been studied by immunoperoxidase staining of formalin-fixed and paraffin-embedded tissue specimens from normal, hyperplastic, adenomatous, and carcinomatous thyroid tissues. Epithelial expression of these antigens was observed neither in normal nor in hyperplastic thyroid tissue. The antigens were expressed in only 1 of 26 follicular adenomas and the staining in this case was weak and restricted to a few cells. In contrast, the expression of this antigens is marked and progressive in carcinomatous tissues. A high proportion, 48 of 52 papillary carcinomas demonstrated C 50 reactivity, whereas 25 of these tumors expressed the CA 19-9 antigen. Of 25 follicular carcinomas, 15 gave a positive staining for the CA 50 and 6 for the CA 19-9 antigen. CA 50 antigen expression was still detected in tumor cells lacking the CA 19-9 antigen and C 50 reactive material was found in all tissue specimens from medullary carcinomas tested, whereas CA 19-9 antigen staining was consistently negative. This indicates that the moab C 50 which reacts, like the moab 19-9, with the sialylated Lewisa (Lea) blood group determinant also binds to other antigens apart from the sialylated Lea in CA 19-9 antigen negative tumor cells. Although, the functional significance of CA 50 and CA 19-9 antigen expression remains to be investigated, these results suggest that the demonstration of these antigens could provide additional differential diagnostic parameters for the characterization of hyperplastic and neoplastic lesions of the thyroid gland. Further clinical studies will show whether these carbohydrate antigens are useful serum markers for the monitoring of thyroid carcinomas.

Adenocarcinoma↗

Differentiation of plasma cell infiltrates in the bone marrow. A clinicopathological study on 80 patients including immunohistochemistry and morphometry.

In 80 patients immunohistochemical, morphometrical and clinical studies were performed on routinely referred trephine biopsies of the bone marrow showing an abnormal increase in plasma cells. From the approximately determined density of plasma cell infiltrates two main groups were distinguished, the first with an involvement exceeding 20% and the second with less than 10% of the total marrow area involved. The first group (n = 30; 324 +/- 130 plasma cells per square millimeter bone marrow) consisted of patients with frank malignant myeloma (MM) by clinical and histomorphological diagnosis. The second group (n = 50; 132 +/- 54 plasma cells per square millimeter bone marrow) with plasmacytic differentiation of infiltrates, had to be further divided into one component with evidence for initial or residual MM following chemotherapy (n = 27), another with obviously monoclonal gammopathy of undetermined significance--benign monoclonal gammopathy (BMG, n = 6), and a final set of cases with a reactive plasmacytosis mostly associated with an inflammatory condition (n = 17). There was an excellent agreement between the intracellular immunoglobulin staining as defined by the immunoperoxidase technique and the serum or urinary M-component detected by immunoelectrophoresis. In MM significant correlations were found between osteoclastic activity (number of osteoclasts specifically stained by acid phosphatase) per trabecular bone area, presence of lytic bone defects and the density of plasma cell infiltrates in the marrow. This latter feature corresponded well with the titer of secreted serum M-components measured by quantitative immunoelectrophoresis. Using morphological data alone, BMG cases could not be discriminated with any certainty from initial or residual plasmacytic MM. They consequently need a prolonged clinical follow up to clarify the nature of the lesions.

Bone Marrow↗

Immunohistochemical study of distribution of estrogen receptors in corpus and cervix uteri.

An immunohistochemical assay based on monoclonal antiestrophilin antibodies has been used to localize estrogen receptor (ER) in frozen sections of normal human endometrial, myometrial and cervical tissues from menstruating, hormonally treated, pregnant and postmenopausal women. Specific staining was confined to the cellular nuclei. In proliferative phase endometrium, postmenopausal emdometrium, and endometrium from patients treated with hormone ERs were easily detected in most glandular and stromal cells. After ovulation and in early pregnancy a quick and distinct decrease of ER expression was noted. This was especially the case with the more superficial layers of endometrium (endometrium functionalis), the majority of whose cells had either weak localization of ER or none at all. In the endometrium basalis, however, the reduction of ER localization turned out to be more moderate. More then half of the epithelial and stromal cells displayed nuclear staining, partly strong. The myometrium of the corpus uteri showed a similar ER localization and dependence on hormonal stage when compared with the endometrium functionalis. The endocervical mucosa displayed a high degree of ER expression in the proliferative phase, in postmenopausal women and in women who had been treated with hormones. Unlike the endometrium and myometrium, the endocervical glands underwent minimal changes in nuclear ER content during the menstrual cycle. Although the endocervical stroma showed cyclic alterations in ER levels, their reduction after ovulation was less marked than in the corresponding endometria. In cervical squamous epithelium ER localization was predominantly confined to the basal layers. In the course of cellular maturation, specific nuclear staining vanished. In the proliferative phase, after the menopause and in early pregnancy, the basal, parabasal and intermediate cells were specifically stained. In the postovulatory phase, However, nuclear staining was confined to the basal and parabasal cells. Hormonally treated squamous epithelia almost completely lacked nuclear ER localization.

Antibodies, Monoclonal↗

[Clinical aspects and prognosis of granulosa cell tumors of the ovary].

Symptoms, tumour morphology and clinical course were reviewed in 26 women treated at the department of obstetrics and gynaecology of the University of Cologne between 1965 and 1986 for granulosa cell tumours of the ovary. At the time of diagnosis 8 women were in a pre- and 18 in a postmenopausal state. The most common symptoms were irregular haemorrhages, in rare cases lower abdominal pain. Effects of raised estrogen stimulation were seen in 80% of patients. In 24 pre-operative patients, a lower abdominal tumour was diagnosed. 20 patients had lesions of stage I, 5 of stage III and one of stage IV. 21 tumours exceeded 5 cm median diameter. Polymorphic tumours were seen in 16 cases. 14 tumours had a high mitotic activity. Hysterectomy and bilateral salpingoovariectomy were performed in most cases, followed by additional irradiation in 9 and by chemotherapy in 4 cases. Only 3 patients were treated by unilateral salpingoovariectomy. To date 14 patients have no evidence of disease, one suffers from tumour progression and 9 died of the tumours. 2 women died for other reasons. The 5-year survival rate is 70%, the 10-year survival rate 64%. Old age, late progression of tumour stage, tumour diameter exceeding 5 cm, polymorphic tumours and high mitotic index correlated to the worsening prognosis. However, a poor result was also seen in monomorphic tumours with low mitotic activity. The nature of granulosa cell tumours can not be predicted by clinical or morphological criteria. Therefore it is suggested, that all granulosa cell tumours should be considered as malignant.

Adolescent↗

Occurrence and distribution of glycoconjugates in human tissues as detected by the Erythrina cristagalli lectin.

We applied a horseradish peroxidase-Erythrina cristagalli agglutinin (HRP-ECA) conjugate for histochemical staining of tissue sections from various formalin-fixed, paraffin-embedded human tissue specimens. The HRP-ECA conjugate showed broad reactivity, but there was a distinct distribution of native (not masked by sialic acid) and sialic acid-masked ECA binding sites in the various organs. Free ECA binding sites could be detected on red blood cells, lymphocytes of thymus, tonsil, lymph node, and in mucous substances of different organs. Independent of blood group type, the vascular endothelium exhibited strong ECA reactivity. Free ECA binding sites occurred in the cytoplasm of Kupffer's cells in liver, in histiocytic cells of thymus, lymph node, tonsil, and in bone marrow. Podocytes of kidney glomerulus, syncytiotrophoblasts of placenta, megakaryocytes in bone marrow, myelin sheath of nerve, medullary thymocytes, and hepatocytes, as well as islet cells of pancreas, contained only sialic acid-capped ECA binding sites. Inhibiting studies with galactose, lactose, and N-acetyl-lactosamine, as well as other sugars, revealed that this lectin is specific for galactosyl residues. In comparison to galactose and lactose, N-acetyl-lactosamine exhibited the highest inhibitory activity on lectin binding, supporting the concept that this lectin is most reactive with N-acetyl-lactosamine-type (type 2 chain) glycoconjugates.

Blood Vessels↗

Renal oncocytoma. II. Lectin and immunohistochemical features indicating an origin from the collecting duct.

The present study is aimed to gain more insight into the histochemical properties of renal oncocytomas. Ten oncocytomas and normal kidneys were investigated using several lectins (peanut agglutinin--PNA, Dolichos biflorus agglutinin--DBA and Ulex europaeus agglutinin--UEA) and antibodies against epithelial membrane antigen (EMA), Tamm-Horsfall glycoprotein (THG) and lysozyme. Lectin histochemistry revealed a characteristic binding pattern in renal oncocytomas, with strong DBA-binding and, in some cases, a weaker staining with UEA apparent in the cytoplasm of the oncocytes. PNA binding sites were evident only after enzymatic cleavage of sialic acid by neuraminidase. Comparative evaluation of normal kidneys exhibiting a strict compartmentalization of saccharide moieties in the various nephron segments revealed a similar binding pattern exclusively in interspersed collecting duct epithelium. This striking resemblance suggests that renal oncocytomas may originate from the collecting duct system. Further support for this assumption has been provided by the demonstration of strong cytoplasmic EMA reactivity in the oncocytes. In normal kidneys prominent labeling for EMA was apparent in the very same interspersed cells of the collecting ducts. THG and lysozyme failed to react in renal oncocytomas. In accordance with observations recently reported in the literature, these results clearly favor a histogenetic origin of renal oncocytomas from the collecting duct epithelium.

Adenoma↗

Renal oncocytoma. I. Cytochrome c oxidase in normal and neoplastic renal tissue as detected by immunohistochemistry--a valuable aid to distinguish oncocytomas from renal cell carcinomas.

Using a polyclonal antibody raised against bovine heart cytochrome c oxidase, the occurrence of this mitochondrial marker enzyme has been investigated in 63 kidney tumors (ten renal oncocytomas, 43 renal cell carcinomas and ten tubulopapillary adenomas) as well as in normal renal tissue by an immunoperoxidase method (PAP-technique). The differentiation between renal oncocytomas and mitochondria-rich carcinomas represents a problem of histopathology since these tumors have a different prognosis and require different patient managements. The strong immunoreactivity in renal oncocytomas contrasted with the much weaker reactivity in renal carcinomas and adenomas. Even mitochondria-rich (granular cell type) carcinomas exhibited only moderate staining intensity. Furthermore, single strongly stained oncocytes or small complexes were sometimes detected in normal renal tissue. The demonstration of marked differences in enzyme content between renal oncocytomas and granular cell carcinomas renders this method suitable for unequivocal distinction between these renal neoplasms. The antibody proved to be a valuable marker for detecting "true" oncocytic transformation in renal tumors and was useful in defining even single oncocytes or small oncocytic lesions.

Adenoma↗

Exogenous enzymatic modulation of lectin binding sites in human tissue. Development of hemolysis in hemolytic-uremic syndrome (HUS) considering alteration of the glycocalyx in the erythrocyte membrane.

FITC-labelled lectins (DBA, PNA, RCAI, UEAI) with different carbohydrate specificity were used to look for possible alterations of the glycocalyx of erythrocyte membrane in patients with hemolytic uraemic syndrome (HUS; n = 34) in comparison with controls (n = 66). These investigations revealed that patients with the blood group A, B and O possess a significantly higher amount of sialic acid covered binding sites for PNA (p less than 0.05) on the membrane of red blood cells than controls, as measured by quantitative fluorescence microscopy. This significant difference was additionally found for sialic acid substituted RCAI binding sites on B erythrocytes (p less than 0.05). Without pretreatment of red blood cells with neuraminidase a significant difference between HUS patients and controls was observed for PNA on A, for RCAI on O and for UEAI on A erythrocytes. The measured values are influenced by contamination of red blood cells with serum glycoproteins as could be assessed by the lower values on washed erythrocytes. As a whole the results indicate that the composition of the glycocalyx in red blood cells of HUS patients seems to be altered and that the pathogenesis of this syndrome is additionally influenced by serum factors. With the exception of UEAI that possesses a significant higher amount of binding sites on washed erythrocytes of blood group O the other lectins used are not suitable for the demonstration of blood group specificity.

Blood Group Antigens↗

Endogenous as well as exogenous hormonal modulation of lectin binding sites in normal and neoplastic tissue of rat mammary gland.

Free and sialic acid conjugated binding sites for the lectin from Arachis hypogaea (peanut agglutinin, PNA) have been histochemically demonstrated in normal rat mammary tissue and in N-nitrosomethylurea (NMU) induced mammary tumors of rats. The lectin binding sites were predominantly associated with secretory activities of the normal and neoplastic breast tissue (secretory PNA binding sites). In normal breast tissue and in NMU induced mammary tumors the expression of secretory PNA binding sites was reduced after ovariectomy and by the antiestrogen tamoxifen. Estrogen stimulated the formation of free and sialic acid conjugated PNA binding sites in the presence of prolactin. In rat mammary tumors the estrogen induced formation of PNA binding sites was accompanied by an increase of the progesterone receptor concentration in the tumors. Comparative lectinhistochemical, morphological, and biochemical studies on NMU induced rat mammary tumors revealed that the expression of secretory PNA binding sites was associated with a good histologic differentiation and the presence of steroidhormone receptors. Endocrine therapeutic studies showed that tumors responding to therapy possessed higher amounts of secretory PNA binding sites than unresponsive tumors. Therefore secretory PNA binding sites represent a useful histochemical marker for hormone dependence in NMU induced mammary tumors.

Animals↗