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Biomedical subjects

H J Kahn

Publications and source records attributed to H J Kahn.

At least 37 records · Page 2Linked to original sources

Overexpression of p53 is a late event in the development of malignant melanoma.

Overexpression of the p53 gene product has been observed in a high percentage of malignant melanomas. To evaluate the role of this protein in the development of melanoma, we examined p53 expression in benign, premalignant, and malignant melanocytic lesions. Using the antibodies DO-7 and 1801, which recognize both wild-type and most mutant forms of the p53 protein, we analyzed by immunohistochemical staining 26 benign nevi, 34 dysplastic nevi from patients at low risk for the development of melanoma, 22 dysplastic nevi from patients at high risk for the development of melanoma, 61 primary melanomas (including 15 that arose from dysplastic nevi), and 10 metastatic melanomas. Expression of the p53 protein was not observed in any of the benign or dysplastic nevi. Of the primary melanomas only 3 (5%) demonstrated nuclear staining, whereas 70% of the metastatic melanomas showed a positive reaction for p53. These data suggest that overexpression of the p53 gene product is a late event in the progression of melanoma and consequently indicate that expression of this protein cannot be used as a marker to identify patients at high risk for the subsequent development of melanoma.

Antibodies↗

Lymphocyte and macrophage subsets in active and inactive lesions of lichen planus.

Lichen planus (LP) is a mucocutaneous disease for which the etiology and pathogenesis are poorly understood. We performed an immunohistochemical study on formalin-fixed tissue sections of 10 cases of LP using subsets of antibodies to lymphocytes (LCA, CD3, OPD4-CD4, L26, LN1 and Leu-7), and monocyte-macrophages [lysozyme, KP1-Mac, Factor XIIIa (FXIIIa) and S-100 protein]. Six cases showed typical histological features of active LP, two cases showed features of active and inactive LP, and two cases showed only inactive LP. In active LP, scattered T cells (CD3+ and pan T cells) were present in the epidermis, whereas large numbers of CD3+ T cells were present at the dermoepidermal junction and in the dermis. Approximately 40% of the T cells at the dermoepidermal junction were of the helper/inducer subset, whereas approximately 80% of those in the dermis were CD4 positive (helper/inducer T cells). Occasional B cells were present in the dermis only. Increased numbers of S-100-positive Langerhans cells, macrophages expressing lysozyme, and FXIIIa dendritic cells were present in the epidermis and dermis. The inactive lesions showed the presence of a few epidermal Langerhans cells and a mild infiltrate of T cells (helper/inducer subset). These results suggest that in addition to different subsets of T cells and macrophages, including Langerhans cells, dermal dendritic cells expressing Factor XIIIa and lysozyme-positive histiocytes play an important role in lichen planus. They may participate in the destruction and subsequent regeneration of the basal layer of the epidermis, or alternatively may be activated as a result of destruction of the basement membrane in LP.

CD4-Positive T-Lymphocytes↗

Lymphocyte markers on formalin-fixed tissue in Jessner's lymphocytic infiltrate and lupus erythematosus.

Clinical and histological differentiation between Jessner's lymphocytic infiltration of the skin (JLI) and lupus erythematosus (LE) may be difficult. Previous immunohistochemical studies using monoclonal antibodies on frozen sections have shown that the majority of inflammatory cells in JLI and LE are T lymphocytes, whereas B lymphocytes are few or absent. We have performed an immunohistochemical study on formalin-fixed, paraffin-embedded tissue sections from seven patients with JLI and five with LE using monoclonal antibodies MT1 (pan T-cells), OPD4 (helper/inducer T-cells CD4), MT2 (mantle zone B and some T-cells), MB2 (pan B-cells), L26 (pan B-cells), and LN1 (germinal centre B-cells). In both diseases, the-majority of the inflammatory cells were T lymphocytes (MT1 positive), confirming the results others have obtained on frozen material. OPD4 positive cells were detected in varying numbers in all cases. However, the percentage of B lymphocytes tended to be higher in JLI than LE. LN1 was the most useful B-cell marker in distinguishing JLI from LE. However, a combination of MT2 and LN1 gave the most significant difference. We conclude that immunohistochemical analysis using a panel of monoclonal antibodies to T and B lymphocytes may be useful in differentiating JLI from LE, although there is still considerable overlap.

Adult↗

Expression and amplification of neu oncogene in pleomorphic adenomas of salivary gland.

Amplification of the neu oncogene and overexpression of its product was found to be a potential marker for aggressive biological behavior in breast cancer. However, the expression of the neu oncoprotein in normal breast ducts and myoepithelial cells has also been demonstrated. Hence, we examined normal salivary gland tissue and 15 cases of pleomorphic adenoma for the expression of the neu oncoprotein by immunohistochemistry using two polyclonal antibodies and 12 cases for the amplification of the neu oncogene using slot blot hybridization. Immunohistochemistry in the normal salivary gland revealed positive staining of all ductal cells. In the pleomorphic adenomas all cellular elements stained to a variable degree. The positive staining was seen in the ductal cells, in the solid sheets, and in chondroid, myxoid, and metaplastic foci. The normal salivary gland and 11 of 12 cases of pleomorphic adenoma showed no increase in copy number of the neu oncogene, whereas one case showed threefold amplification. These results indicate that the neu oncoprotein is expressed but the neu copy number is not increased in normal salivary gland epithelium and in most pleomorphic adenomas. The threefold amplification of the gene in one case may indicate an aggressive biological behavior.

Adenoma, Pleomorphic↗

Subcellular localization of HMFG2 in breast carcinomas: an immunohistochemical and immunoelectron microscopic study.

Malignant transformation of human cells is associated with morphological and biochemical alterations. We have studied the distribution and pattern of staining of HMFG2 (human milk fat globulin) in normal breast, benign breast lesions, and 137 primary and metastatic breast carcinomas. Immunohistochemical staining was performed with an antibody to HMFG2 using the indirect peroxidase technique. Three patterns of staining were noted: 1) secretion and luminal staining (in normal breast, most benign breast lesions and some breast carcinomas); 2) plasma membrane staining (in breast carcinomas); 3) intracytoplasmic staining (in breast carcinomas). Immunoelectron microscopy was also performed on normal breast, infiltrating duct, and lobular carcinomas. Immunoelectron microscopy showed localization of the gold particles on the electron dense granules of the HMFG2 protein. These were localized along the surface of the extracytoplasmic lumina in normal breast ducts/acini and breast carcinomas, whereas localization was also noted within the intracytoplasmic lumina in cancer cells only. These results show that there is altered localization of milk fat globulin in breast cancer cells associated with membrane internalization and formation of intracytoplasmic lumina. This contributes to the understanding of the phenotypic alterations associated with malignant transformation in breast cancer.

Breast Diseases↗

Altered distribution of desmin filaments in hypertrophic cardiomyopathy: an immunohistochemical study.

Hypertrophic cardiomyopathy (HCM) is characterized by myofiber hypertrophy and disarray. Intermediate filaments play an important role in maintaining of normal cell shape. Desmin filaments have been detected in adult cardiomyocytes, and vimentin and keratin filaments in cardiomyocytes during embryonic development. The pattern of arrangement of intermediate filaments in HCM has not been reported. We examined the distribution of intermediate filaments in formalin-fixed tissue sections of the disarrayed myofibers from 10 hearts with HCM using an immunohistochemical technique and antibodies to desmin, vimentin, and high and low molecular weight keratins. The controls consisted of subaortic tissue from surgically explanted hearts of patients with ischemic heart disease. In the ischemic hearts, desmin was detected in the Z bands and intercalated disks. In all HCM cases, three patterns of staining for desmin were noted: (a) individual myocytes showing a parallel arrangement along Z bands; (b) focal myofibers with decreased or complete loss of labeling of Z bands; and (c) individual myocytes with intense granular cytoplasmic staining especially in disarrayed myofibers. No staining for vimentin or keratins was noted in the cardiomyocytes from either the HCM or ischemic cases. The altered arrangement of desmin filaments in the disarrayed cardiac muscle fibers may play a role in the altered contractility that occurs in patients with HCM.

Adult↗

The correlation of Ki67 growth factor and ERICA in breast cancer.

Estrogen receptor (ER) status is an accepted prognostic indicator for breast cancer when measured by either the biochemical or immunohistochemical (ERICA) methods. Moreover, ERICA was found to be a better predictor of survival in human breast cancer than the biochemical assay for ER. The antibody to Ki67 recognizes the growth fraction of proliferating cells. We examined 100 primary breast cancers to investigate the relationship between ER status as measured by ERICA and Ki67 reactivity. Of the 56 ERICA positive cases, 47 (84%) were Ki67 negative whereas 30 of the 44 ERICA negative tumors were Ki67 positive (68%). There was evidence of a significant inverse relationship between ERICA and the growth fraction (77% of cases, p less than 0.001). In addition, a cluster of ERICA-positive Ki67-positive tumors that were larger and occurred in older patients was identified as a subset that might require aggressive therapy. Our results suggest that Ki67 may be an important additional criterion for predicting the biological behaviour of breast cancers.

Biomarkers, Tumor↗

Acalculia: an historical review of localization.

This article reviews the brain localization of calculation disorders (acalculia) beginning with Gall's claim in the early 19th century for a "center" of calculation. A renewed interest in the subject arose around the time of Henschen during the first quarter of the 20th century. A summary of the cases of acalculia since Henschen leads to the conclusion that regardless of the functional modular nature of calculation ability, there is neither a localized region nor a specific hemisphere uniquely underlying the disorder.

Brain↗

Lysozyme in abnormal dermal elastic fibers of cutaneous aging, solar elastosis and pseudoxanthoma elasticum.

Staining of elastic fibres with antilysozyme antibodies has been noted previously. In this study, we examined the staining pattern of dermal elastic fibres in aging, solar elastosis, and lesional skin of pseudoxanthoma elasticum (PXE) using an antibody to lysozyme and the indirect-peroxidase technique. To assess the effects of aging, sun-protected skin (buttock) from a younger and an older group of patients was used. Sun damage was studied in skin specimens from varying sun-exposed body regions (trunk; head and neck). No staining was seen in sun-protected skin from younger individuals, whereas sun-protected skin from older persons had scattered positive fibres. Solar elastotic material was intensely positive and the number of positive fibres appeared to correlate with the amount of sun damage. Abnormal elastic fibres in PXE also stained positively, but less intensely, than fibres in solar elastosis. This study shows that changes in the elastic fibres due to degenerative processes or genetic factors results in altered antigenic expression of the fibres. This may be an epiphenomenon secondary to changes in proteoglycans, which are known to occur with solar elastosis and PXE, or may represent an adaptive phenomenon to maintain the elastic properties of the altered fibres or to decrease their antigenicity.

Adolescent↗

Immunohistochemical demonstration of actinically damaged elastic fibers in keratoacanthomas: an aid in diagnosis.

The inclusion of elastic fibers within the epithelium of keratoacanthomas is a phenomenon suggested to be an aid in differentiating this lesion from squamous cell carcinoma. Antilysozyme antibodies have recently been noted to stain actinically damaged elastic fibers but not those from sunprotected skin. In this study, 54 keratoacanthomas and 46 squamous cell carcinomas were stained with a histochemical elastic tissue stain and polyclonal antibody to lysozyme using an immunoperoxidase technique. Elastic fibers were demonstrated in keratoacanthomas (37/54, 68%) significantly more often than squamous cell carcinomas (12/46, 26%) (p less than 0.001) using both techniques. This study confirms that the inclusion of elastic fibers occurs significantly more often in keratoacanthomas than squamous cell carcinomas. These elastic fibers were also actinically damaged, suggesting a role for sun damage in the evolution of keratoacanthoma.

Adult↗

Heterogeneity in expression of S100 beta mRNA in human melanoma and pleomorphic adenoma demonstrated by in situ hybridization.

S100 protein is a widely used immunohistochemical marker for identification of a number of tumors including malignant melanoma and pleomorphic adenoma of the salivary gland. To extend the detection techniques for S100 protein to the level of its mRNA, sections of malignant melanoma and pleomorphic adenoma were hybridized in situ with a 35S-labeled anti-sense RNA probe complementary to the mRNA for the beta subunit of human S100 protein. Both tumors were labeled with the anti-sense RNA probe but not with a sense RNA probe. In addition, sections of normal and tumor tissues which were known not to express S100 protein on the basis of immunohistochemical studies were not labeled with the anti-sense RNA probe. These results established the specificity of the in situ hybridization technique for the detection of S100 protein mRNA. Although most of the tumor cells in both malignant melanoma and pleomorphic adenoma were labeled with the anti-sense RNA probe, unlabeled tumor cells were also present in their vicinity, suggesting there was a heterogeneity among the cells in both tumor types with respect to S100 protein mRNA expression.

Adenoma, Pleomorphic↗

Immunoreactivity of S100 beta in heart, skeletal muscle, and kidney in chronic lung disease: possible induction by cAMP.

S100 protein is a calcium-binding protein composed of two subunits S100 alpha and S100 beta, which are expressed selectively by specific cell types. The distribution of S100 beta was examined among various tissues obtained at autopsy from 18 subjects with chronic lung disease and 10 control subjects. The presence of S100 beta in individual cell types was demonstrated by immunoperoxidase staining using polyclonal and monoclonal antibodies specific for S100 beta. In the 10 control subjects, positive staining was seen in a number of cell types that normally produce S100 alpha and S100 beta, (e.g., glial cells, melanocytes, chondrocytes) or only S100 beta, (e.g., Schwann cells). There was no staining of myocardial cells, skeletal muscle fibers, or kidney tubules, which normally produce S100 alpha but not S100 beta. In contrast, in the 18 subjects with chronic lung disease, all of the above cell types stained positively for S100 beta, showing that in these subjects cell types that ordinarily expressed only S100 alpha also expressed S100 beta. We suggest that the observed induction of S100 beta in these cell types seen in subjects with chronic lung disease was mediated by an elevation of cAMP levels secondary to bronchodilator therapy with beta-adrenergic agonists and phosphodiesterase inhibitors.

Chronic Disease↗

S-100 protein antibodies do not label normal salivary gland myoepithelium. Histogenetic implications for salivary gland tumors.

Neoplastically modified myoepithelial cells have a key role in developing the histologic characteristics of some salivary gland tumors. S-100 protein expressed in certain of these tumors is suggested to support this role, as the principal component in the human salivary gland reported to be S-100 protein-positive is myoepithelium. Confirmation of such an important aspect is required. Immunoperoxidase staining of parotid salivary gland shows considerably different patterns obtained with antibodies to S-100 protein, neuron-specific enolase, and neurofilaments compared with those for muscle-specific actin and cytokeratin 14; many more cells and their processes associated with acini and ducts are evident with the latter two antibodies. Double immunofluorescent staining with antibodies to either S-100 protein or neuron-specific enolase combined with muscle-specific actin does not reveal colocalization of these antigens in myoepithelial cells. The former localize only to nerve fibers adjacent to, but separate from, acini, and the latter only to myoepithelial cells. It is apparent that S-100 protein staining of the rich network of unmyelinated nerves in the interstitial tissues, evident ultrastructurally, has been misinterpreted as myoepithelium. This result has important implications for histogenetic classifications of salivary gland tumors.

Epithelium↗

Discourse analysis in neuropsychology: comment on Chapman and Ulatowska.

This paper discusses a recent article by Chapman and Ulatowska (1989, Brain and Language, 36, 651-658) on discourse analysis in aphasia. As such, the research in this area is interdisciplinary drawing from neuropsychology, as well as cognitive psychology, and, in part, aging. We illustrate problems that can arise when theoretical constructs and methodological considerations in this interdisciplinary approach are not rigorously observed. It is argued that definitive conclusions regarding the functional organization of the brain and discourse can be offered only when discourse analysis uses the state of the art from neuropsychology and cognitive psychology.

Adult↗

Immunohistochemistry of intravascular papillary endothelial hyperplasia.

Intravascular papillary endothelial hyperplasia is an interesting endothelial proliferation, the nature of which has aroused some controversy. Five cases were studied by light microscopy and by immunohistochemistry using antibodies to Factor VIII-related antigen (FVIII-rAg), ferritin, alpha 1-antitrypsin, alpha 1-antichymotrypsin and vimentin and were compared with conventional intravascular organizing thrombi. The results show a similar progression of the immunophenotype of the endothelial cells in both entities: they are initially positive for ferritin, then acquire vimentin positivity and only display FVIII-rAg positivity in advanced ("mature") lesions. This suggests that intravascular endothelial hyperplasia is closely related to organizing thrombi and is probably a peculiar form thereof.

Adult↗

Monoclonal antibody MT1: a marker for Langerhans cell histiocytosis.

Langerhans cells and their pathologic counterparts can be identified in paraffin sections using immunohistochemical staining for S-100 protein. This procedure is useful in confirming a diagnosis of Langerhans cell histiocytosis (LCH). However, many other cell types are also positive for S-100 protein. Positive staining for CD1 (Leu 6) supports a diagnosis of LCH, but requires frozen tissue. A panel of antibodies would be desirable in confirming a diagnosis of LCH, particularly if these antibodies could be used on paraffin-embedded material. We studied the pattern of staining for commercially available monoclonal antibodies MT1, MT2, MB2, and LN1, which were originally marketed as lymphocyte markers, using paraffin-embedded tissue sections of cases of LCH. In all 20 cases pathologic Langerhans cells stained positively with MT1 only. Various other S-100 protein-positive lesions were also examined with MT1 and were consistently negative for MT1. Other cutaneous histiocytic and mast cell lesions were positive with MT1, but S-100 protein negative. Our results demonstrate that the monoclonal antibody MT1 serves as an additional marker for LCH and, together with S-100 protein, would make up a diagnostic panel of antibodies for LCH to be used on routine paraffin-embedded sections.

Antibodies, Monoclonal↗