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Biomedical subjects

H A Gerber

Publications and source records attributed to H A Gerber.

At least 37 records · Page 2Linked to original sources

c-erbB-2 protein expression in node negative breast cancer.

We investigated the expression of c-erB-2 protein in two matched groups of breast cancer patients, one with and one without relapse. 37 patients with relapse were compared with 42 patients without recurrence for time of observation, adjuvant treatment, age, menopausal status and estrogen receptor content. Paraffin-embedded sections were stained with the polyclonal antibody 21N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein. The staining of c-erbB-2 was measured on a scale of 0 to 3+. C-erbB-2 staining was negative in 16 (38%) patients in the relapse-free group, and in 8 (22%) of the patients with metastases. Neither disease-free survival (DFS) nor overall survival (OS) were dependent upon the extent of c-erbB-2 expression. An analysis by estrogen receptor (ER) status (i.e. positive or negative) and by c-erbB-2 expression (i.e. positive or negative) revealed that patients with ER-positive primaries and negative c-erbB-2 have the longest disease-free survival (DFS) and overall survival (OS). We conclude that c-erbB-2 expression might be clinically useful only if other prognostic variables (e.g. estrogen receptor content in the tumor) are also considered.

Adult↗

Overexpression of the c-erbB-2 protein in human breast tumor cell lines.

The c-erbB-2 proto-oncogene is amplified in a high percentage of primary human breast tumors, suggesting that the overexpression of this gene may be involved in the development of human breast cancer. We have investigated five human breast tumor cell lines and have detected amplified c-erbB-2 gene copies in two of them. This amplification leads to overexpression of the c-erbB-2 protein. In addition, two other cell lines have elevated protein levels without gene amplification, suggesting that other mechanisms can lead to overexpression of the c-erbB-2 protein. These results are similar to those that we obtained during a study of primary breast tumors (Berger et al.: Cancer Res 48:1238-1243, 1988). These breast tumor cell lines should be useful for an analysis of c-erbB-2 expression and of the mechanisms that in some cases lead to overexpression.

Blotting, Southern↗

Heterogeneous malignant non Hodgkin's lymphomas as a causative disorder in lethal midline granuloma.

The present report describes the results of a combined morphological, enzyme- and immunohistochemical analysis of nine cases of malignant non Hodgkin's lymphomas (NHL) clinically presenting as lethal midline granuloma. In a previous report written before antibodies directed against B and T lymphocytes were available, a histiocytic origin of such neoplasms had been suggested. A panel of antibodies reactive with most B cells (L26, MB1, KiB3) and a majority of T cells (MT1, UCHL1) was applied on paraffin sections of formalin fixed tissues as well as antibodies directed against leukocyte common antigen (LCA), myeloid/histiocyte antigen (MAC 387), lysozyme, alpha-1-antitrypsin, alpha-1-antichymotrypsin, S-100 protein, prekeratin and immunoglobulin light chains. Enzyme histochemistry included tests for non-specific acid esterase, acid phosphatase, beta-glucuronidase and chloroacetate esterase. As a result, five T, two B and two unclassified (malignant histiocytosis probable) NHL were identified, indicating distinct heterogeneity of NHL as causative disorders in lethal midline granuloma.

Adolescent↗

In vitro pemphigus vulgaris model using organotypic cultures of human epidermal keratinocytes.

Using the Combi-ring-dish (CRD), a new culture device, organotypic cultures of human epidermal keratinocytes were grown on bovine eye lens capsules. In these highly differentiated cultures, typical suprabasal acantholysis was induced by pemphigus vulgaris antibodies. This in vitro pemphigus vulgaris model may be used to analyse keratinocyte-derived factors causing acantholysis in experimental pemphigus.

Acantholysis↗

Hormonotherapy of meningiomas with medroxyprogesterone acetate. Immunohistochemical demonstration of the effect of medroxyprogesterone acetate on growth fractions of meningioma cells using the monoclonal antibody Ki-67.

The effect of medroxyprogesterone acetate (MPA) on growth fractions of ex vivo meningiomas is demonstrated in using the Ki-67 monoclonal antibody in three cases of meningiomas operated on in two stages and in meningioma specimens from a group of eight patients operated on in one single stage after MPA therapy. Growth fractions in samples from five meningioma patients not treated with MPA were determined for comparison. In the three cases of two-stage operation of the tumors, the percentage of Ki-67-positive cells in meningioma tissue was lower by a factor of 6, 5, and 3, respectively, after MPA therapy. In meningioma specimens from patients receiving no MPA therapy, Ki-67-positive cells were present in 1.02 +/- 0.48%; in samples from MPA-treated tumors the percentage of Ki-67-positive cells was 0.41 +/- 0.40 (different at p less than 0.02 [Wilcoxon's test]). In comparison to our previously published data on untreated meningiomas analyzed for progesterone receptors (PR), MPA significantly reduced the PR activity. There was no obvious correlation between PR activity and potential suppression of the tumor growth fraction. It is concluded that MPA is attractive because it reduces the growth fractions of most meningiomas and might be suitable for adjuvant hormonotherapy.

Antibodies, Monoclonal↗

Fibronectin in pemphigus.

In the skin organ culture model of pemphigus, fibronectin concentrations of 300 and 500 micrograms/ml inhibited pemphigus plasma-induced acantholysis and intraepidermal binding of the pemphigus antibodies examined by direct immunofluorescence. A direct interaction of fibronectin with pemphigus antibodies could not be demonstrated by chromatography of pemphigus plasma on immobilized fibronectin or by incubation with fibronectin and subsequent precipitation with antifibronectin. We then measured fibronectin concentrations in the plasma of 15 patients suffering from various types of pemphigus and presenting different activities of their disease. Immunoreactive fibronectin levels in untreated patients with active disease were generally in the low normal or even clearly in the subnormal range. They had the tendency to decrease when the disease subsided during therapy with high doses of glucocorticoids, sometimes in combination with azathioprine. The fibronectin concentration in the blister fluid of a patient with acute, untreated pemphigus vulgaris was similar to that in a plasma sample taken at the same time. Skin biopsies of pemphigus patients exhibited an essentially normal fibronectin pattern in direct immunofluorescence. We discuss a possible protective role of fibronectin in pemphigus e.g., by reducing the permeability for pemphigus antibodies in the dermal-epidermal junction zone.

Acantholysis↗

Production and characterization of monoclonal antibodies against human neuroblastoma.

MAb were derived from mice immunized with cells of the human neuroblastoma line IMR-32. Five hybridomas were selected according to their selective binding to human cell lines, tumors and normal tissues. One of them, CE7, reacted with all sympatho-adrenomedullary cells (neuroblastoma, ganglioneuroblastoma, ganglioneuroma, pheochromocytoma, adrenal medulla, sympathetic ganglion cells). Weak cross-reactivities were observed with melanocytes and with some human melanoma and glioma cell lines. The antigen recognized by CE7 was markedly expressed on neuroblastoma tumors of all histological grades, independently of the adrenergic or cholinergic nature of these cells. MAb derived from clones AD2, BC1, BC4 and CB10 bound variably to some, but not to all, neuroblastoma cells. By using these MAb, 3 phenotypes of neuroblastoma lines could be distinguished. The binding profiles of these types, however, showed no correlation with origin of the cell lines or stage of the disease.

Animals↗

The role of gut-associated lymphoid tissues in the generation of immunoglobulin-bearing lymphocytes in sheep.

Experiments were designed to examine the relative contributions of Peyer's patches and mesenteric lymph nodes to the population of circulating immunoglobulin-bearing lymphocytes in sheep. The ileum, with more than 90% of the total Peyer's patches, the mesenteric lymph nodes, or both, were removed from lambs at different stages of development and the composition of the cell populations in lymph from different sources and in the blood was examined. Lambs which had had the ileum removed before or within a few days of birth were deficient in small lymphocytes bearing membrane immunoglobulin. This deficit remained for at least the first year of the animals' lives. Neither the removal of mesenteric lymph nodes nor removal of the ileum had any statistically significant effect on the total output of cells or on the population of IgA-producing cells in lymph draining from the gut.

Aging↗

High doses of antigen-nonspecific IgG do not inhibit pemphigus acantholysis in skin organ cultures.

A patient suffering from severe pemphigus vulgaris was treated using large-volume plasma exchange in combination with an immunosuppressive regimen. As some recent reports have shown evidence that polyclonal, polyspecific human IgG in high doses through the i.v. route (IGIV) protect target platelets in idiopathic thrombocytopenic purpura from attack by antiplatelet autoantibodies and/or immune complexes, we also administered IGIV to this pemphigus-vulgaris patient. In order to test the hypothesis that IGIV might protect in vitro-cultured human skin from acantholysis induced by pemphigus antibodies, studies with skin organ cultures were carried out using plasma from another pemphigus-vulgaris patient who had undergone plasma exchange. The preincubation of either the skin explants or the pemphigus plasma with various concentrations of IGIV (ranging from 0.15 to 15 mg/ml in the culture medium) did not prevent acantholysis induced by the pemphigus plasma nor did it inhibit the binding of the specific antibodies visualized by direct immunofluorescence. Thus, the assumption that IGIV may coat the pemphigus antigens on epidermal cells making them inaccessible to pathogenic autoantibodies was not substantiated by our tests in vitro; likewise, the hypothesis of functionally blocking autoantibody activity by means of anti-idiotype effects of IGIV cannot be supported.

Acantholysis↗

Thymic lymphopoiesis: protected from, or influenced by, external stimulation?

The mechanisms regulating thymic lymphopoiesis are still a matter of debate. Intracortical proliferation and differentiation of thymocytes are thought to be controlled by locally produced humoral factors and close contact with epithelial, possibly also phagocytic, cells, and restricted by products of the major histocompatibility complex. The observation of a translocation of intraabdominally introduced PVP-coated silica particles (Percoll) via parathymic lymph vessels and through the thymic capsule into the cortical parenchyma demonstrates that the thymic cortex is accessible to materials carried with the transcapsular flux of interstitial fluid, and that this barrier is less effective than the blood-thymus barrier. The proliferative activity of cortical thymocytes following an intraabdominal injection of particulate tetanus toxoid was compared in sites adjacent to, and distant from, parathymic lymph nodes. Absolute numbers of DNA-synthesizing thymocytes were found to be much higher in cortical areas close to the lymph nodes, where lymphatic vessels are most numerous, than on the opposite sides of the thymic lobes. Taken together, these findings indicate that--in addition to intrinsic control mechanisms--cortical thymocyte production may be influenced by peripheral stimulation to some extent, and that materials from sites which are drained by parathymic lymph nodes may be important in this respect.

Animals↗

Factor VIII-related antigen in malignant hemangioendothelioma of the thyroid: additional evidence for the endothelial origin of this tumor.

Malignant hemangioendothelioma of the thyroid gland, which most often originates in a hemorrhagic nodule, is a well-known entity in European alpine regions with endemic goiter. In other parts of the world it very rarely has been diagnosed. This tumor may display considerable morphologic variation and often has been interpreted as a variant of undifferentiated carcinoma. In 13 out of 20 thyroid tumors, classified by light microscopy as malignant hemangioendothelioma, Factor VIII-related antigen, a marker for endothelial cells, was demonstrated in neoplastic cells with the help of immunohistochemical technics applied to conventional paraffin sections. In one case, in which material suitable for electron microscopy was available, Weibel-Palade bodies were found in tumor cells. These findings add strong support to the notion of an endothelial origin of this neoplasm.

Aged↗

Differentiation of B lymphocytes in sheep. I. Phenotypic analysis of ileal Peyer's patch cells and the demonstration of a precursor population for sIg+ cells in the ileal Peyer's patches.

The ileal Peyer's patches (IPP) of sheep may be a primary lymphoid organ for b cells since they have a number of important features in common with the bursa of Fabricius of chickens. We have examined the surface phenotype of IPP cells. Approximately 90% to 95% of IPP cells are 'low sIgM+'; that is, they have surface IgM, but in much smaller amounts than peripheral B cells, which are 'high sIgM+'. IPP cells with sIgG or sIgA are very rare. Upon exposure to a tumour promotor, phorbol myristate acetate (PMA), in vitro, low sIgM+ cells differentiated into high sIgM+ cells. The amount of Ia-like antigens on the surface also increased after PMA treatment. Approximately 5% of IPP cells bore no identifiable markers. However, these cells could also be induced into high sIgM+ cells upon exposure to PMA; this may indicate the presence of precursors of sIgM+ cells within the IPP. While PNA (peanut agglutinin) binds strongly to the vast majority of IPP cells, it binds very little, if at all, to B cells obtained from the periphery, unless they have been treated with neuraminidase; this suggests that cells in the B lineage retain their PNA receptors, but that these become masked by sialic acid on mature B cells.

Animals↗

Uptake by enterocytes and subsequent translocation to internal organs, eg, the thymus, of Percoll microspheres administered per os to suckling mice.

The translocation of Percoll microspheres (mean diameter 20-30 nm) from the intestinal lumen through the epithelial layer to internal organs was examined in suckling mice using transmission electron microscopy. Repeated administration of this material by gavaging for 7 consecutive days resulted in a heavy particle load of vacuolated enterocytes. A limited amount of Percoll was transported to the subepithelial tissue of both the villous mucosa and Peyer's patches where microspheres were found endocytosed, predominantly by macrophages. Even smaller numbers of particles reached mesenteric lymph nodes and, occasionally, milky spots of the omentum. Minor Percoll aggregates were easily found in Kupffer cells of the liver, indicating hematogenous translocation. Small numbers of particles were regularly detected in perivascular macrophages of the thymic cortex, which are in close contact with surrounding lymphocytes. We conclude that the thymic cortex is not totally inaccessible to particulate matter of the intestinal content.

Animals↗