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Biomedical subjects

R A Weiss

Publications and source records attributed to R A Weiss.

At least 307 records · Page 17Linked to original sources

Monoclonal antibody analysis of keratin expression in epidermal diseases: a 48- and 56-kdalton keratin as molecular markers for hyperproliferative keratinocytes.

The polypeptide composition of epidermal keratin varies in disease. To better understand the biological meaning of these variations, we have analyzed keratins from a number of human epidermal diseases by the immunoblot technique using AE1 and AE3 monoclonal antikeratin antibodies. The results reveal a continuous spectrum of keratin expression ranging from one closely resembling the normal in vivo pattern to one almost identical to cultured epidermal keratinocytes. Specifically, a 50-kilodalton (kd) (AE1-positive) and a 58-kd (AE3-positive) keratin are present in all diseases, supporting the concept that they represent "permanent" markers for keratinocytes. A 56.5-kd (AE1) and a 65-67-kd (AE3) keratin, previously shown to be markers for keratinization, are expressed only by lesions retaining a keratinized morphology. A 48-kd (AE1) and a 56-kd (AE3) keratin are present in all hyperproliferative (para- or nonkeratinized) disorders, but not in normal abdominal epidermis or in ichthyosis vulgaris which is a nonhyperproliferative disease. These two keratins have previously been found in various nonepidermal keratinocytes undergoing hyperproliferation, suggesting that these keratins are not epidermis-specific and may represent markers for hyperproliferative keratinocytes in general. In various epidermal diseases, there is a reciprocal expression of the (keratin) markers for hyperproliferation and keratinization, supporting the mutual exclusiveness of the two cellular events. Moreover, our results indicate that, as far as keratin expression is concerned, cultured human epidermal cells resemble and thus may be regarded as a model for epidermal hyperplasia. Finally, the apparent lack of any major, disease-specific keratin changes in the epidermal disorders studied so far implies that keratin abnormalities probably represent the consequence, rather than the cause, of these diseases.

Antibodies, Monoclonal↗

Human retroviruses in health and disease.

Before 1980, infectiously transmitted human retroviruses were unknown. Since then three types of human T-lymphotropic viruses (HTLVs) have been discovered and are under intensive study. Further types may well come to light. HTLV-I is etiologically associated with adult T-cell leukemia-lymphoma (ATLL), HTLV-II has been isolated from a patient with hairy T-cell leukemia, and HTLV-III is the cause of acquired immune deficiency syndrome (AIDS). Viruses related to HTLVs occur in several species of macaque monkeys. It appears that only a small minority of infected subjects develop the associated malignancy or immunodeficiency. Little is known of HTLV transmission, although it is clear that the viruses can be transmitted sexually and also iatrogenically through blood. HTLV-I and HTLV-II appear to be highly conserved across different human host populations, whereas HTLV-III shows greater polymorphism and elicits different immune responses. HTLVs have a tropism for T-helper/inducer cells. While HTLV-I and HTLV-II can penetrate many cell types and the T-cell tropism may reside in the activity of the X gene product following infection, initial infection of HTLV-III is restricted to cells bearing the T4 cell surface antigen. The T4 antigen is an essential component of the receptor for the virus, which is consistent with its tropism and the nature of the immunodeficiency it causes.

Antibodies, Viral↗

Pseudotype viruses bearing envelope antigens of Japanese isolates of human T-cell leukemia viruses type I.

We tried to transmit human T-cell leukemia virus type I (HTLV-I) into non-lymphoid cells and found that S+L- CCC cat cells were permissive for HTLV-I. Using these HTLV-positive cat cells, vesicular stomatitis virus (VSV) pseudotypes bearing envelope antigens of Japanese isolates of HTLVs were prepared and their reactivities with human or rabbit serum were examined. Japanese HTLV2M, HTLV10Y, and HTLVMT-2 pseudotypes and American HTLVPL pseudotype were neutralized by sera of Japanese and American patients with adult T-cell leukemia/lymphoma (ATL) and rabbit antisera against HTLV. Each serum showed similar antibody titers against different pseudotypes. Thus, envelope antigens of four HTLVs that reacted with the human and rabbit sera were considered to belong to a single serotype.

Animals↗

Productive infection and cell-free transmission of human T-cell leukemia virus in a nonlymphoid cell line.

Human T-cell leukemia virus (HTLV), American PL isolate, was transmitted by cocultivation and by cell-free filtrates to a nonlymphoid human osteogenic sarcoma (HOS) cell line, designated HOS/PL, but not to nine other lines bearing receptors for HTLV. HOS and HOS/PL cells are not dependent on interleukin-2 and do not express interleukin-2 receptors that are recognized by anti-Tac monoclonal antibody. HTLV released by the Japanese MT2 cell line was also transmitted to HOS cells. The infected HOS cells release substantial titers of progeny HTLV which is antigenically indistinguishable from parental virus and is able to transform T cells.

Antigens, Surface↗

Human T-cell leukemia virus type I: induction of syncytia and inhibition by patients' sera.

HTLV-producing T-cell lines induce cell fusion when co-cultivated with a wide variety of indicator cells, suggesting that HTLV envelope antigens interact with the membranes of many cell types. Serum antibodies from adult T-cell lymphoma-leukemia (ATL) patients inhibited the formation of syncytia, and sera from British, American and Japanese ATL patients inhibited cell fusion induced by American and Japanese HTLV isolates equally well. No serological cross-inhibition of syncytium induction was found between HTLV and bovine leukosis virus, Moloney murine leukemia virus and simian sarcoma-associated virus. A simple syncytium inhibition test in microtiter plates has been developed to provide a rapid screen for antibodies presumed to be specific to HTLV envelope glycoproteins.

Animals↗

Rhodotorula rubra peritonitis in patients undergoing continuous ambulatory peritoneal dialysis.

Although still uncommon, fungal peritonitis is being reported with increasing frequency in patients with renal failure who are undergoing long-term peritoneal dialysis. Although most cases have involved Candida albicans, other opportunistic pathogens have been reported as well. Recently, three patients were seen with serious peritoneal infections due to Rhodotorula rubra, a "nonpathogenic" fungus. In two patients, peritoneal fibrosis made further peritoneal dialysis impossible. The third patient died from complications of peritonitis. Environmental cultures revealed a possible common-source outbreak. Literature review reveals that infection due to this organism is most unusual and occurs only in the hospital setting in patients with serious compromise of host defenses.

Adolescent↗

The use of monoclonal antibody to keratin in human epidermal disease: alterations in immunohistochemical staining pattern.

A monoclonal antikeratin antibody, designated AEl, was used to stain frozen sections of normal and abnormal human skin by the immunofluorescence and peroxidase-antiperoxidase techniques. In normal human epidermis and ichthyosis vulgaris, a nonproliferative epidermal disease, this antibody selectively stained epidermal basal cells. Very different staining patterns were observed in various other epidermal diseases. A suprabasal staining pattern was observed in psoriasis (16 cases), verruca (9), seborrheic keratosis (5), actinic keratosis (2), as well as the epidermis adjacent to certain epidermal neoplasms (4). Basal cell carcinoma (7) showed weak, homogeneous staining. In contrast, a disorganized pattern consisting of cells with various staining intensities was observed in Bowen's disease (2) and squamous cell carcinoma (4). Although the biochemical basis for these altered staining patterns remains to be elucidated, these results provide further evidence that epidermal keratin expression can be affected by various disease states. Moreover, our data suggest that a common alteration in keratin expression, as defined by the suprabasal AEl staining pattern, exists in psoriasis and a number of other benign hyperproliferative epidermal diseases.

Animals↗

Keratin classes: molecular markers for different types of epithelial differentiation.

Keratins are a group of water-insoluble proteins (molecular weight range 40-70 K) that form 10-nm tonofilaments in a wide variety of epithelial cells. The subunit composition of the keratin filaments varies with cell type, period of embryonic development, stage of histologic differentiation, cellular growth environment, and disease state. To better understand the functional significance of individual keratin species, we have generated three monoclonal antikeratin antibodies to different subsets of keratins and used these antibodies to localize specific keratins in normal human epidermis by a combination of immunohistochemical and biochemical techniques. The results indicate that the 50 K and 58 K keratins are present in all cell layers including the relatively undifferentiated basal layer, whereas the 56.5 K and 65-67 K keratins are associated only with the more differentiated cells above the basal layer. In a separate series of experiments, we used the monoclonal antibodies to survey the keratins expressed by various nonepidermal epithelia. The data show that keratins can be divided into at least seven major classes according to their immunologic reactivity and size. Among the keratin classes, the 50 K and 58 K classes appear to be characteristic of all stratified squamous epithelia, whereas the 56.5 K and 65-67 K classes are unique to the keratinized epidermis. These findings suggest that specific keratin classes, as defined by monoclonal antibodies, may serve as useful markers for different types of epithelial differentiation (simple versus stratified, keratinized versus nonkeratinized).

Animals↗

Renal failure in childhood.

Renal failure in infants and children requires prompt and thorough diagnostic evaluation for reversible causes and careful medical management. Congenital malformations of the renal parenchyma and urinary drainage system must be excluded in any child, even the adolescent. The management of these patients requires close cooperation with the (pediatric) urologist. These children are at highest risk for the development of complications, such as growth failure, osteodystrophy, and urinary tract infections. Prolonged progressive renal insufficiency in this group must be anticipated. In contrast, acquired renal insults may result in acute, reversible renal failure. Awareness of the hemodynamic or nephrotoxic insults that can result in ARF, and appropriate diagnostic and therapeutic maneuvers, may minimize morbidity and mortality. CRF presents the physician with long-term and complex challenge of medical management. Dietary and drug therapy can be remarkably effective in reducing the complications of CRF. Rehabilitation with successful renal transplantation is an attainable goal for most uremic children.

Acute Kidney Injury↗

Immunohistologic cellular phenotypes of lymphoproliferative disorders. Comprehensive evaluation of 564 cases including 257 non-Hodgkin's lymphomas classified by the International Working Formulation.

The plethora of classifications for non-Hodgkin's lymphomas (NHLs) and controversy regarding the merits of the individual classification schemes has led to the articulation of an International Working Formulation for NHL classification by a working group sponsored by the National Cancer Institute. This classification is based on both architectural and cytologic features and has been shown to have clinical relevance, but it is not an immunologic approach. With the use of frozen sections and both polyclonal and monoclonal antibodies, a comprehensive immunohistologic study was made of 564 biopsy specimens 1) for determination of the utility of the principle of monoclonality in differentiating benign from malignant lymphoproliferative disorders, 2) for definition of the immunohistochemical phenotypes of histologically benign and malignant cellular proliferations, and 3) for evaluation of the immunologic phenotype of 257 non-Hodgkin's lymphomas classified by the International Working Formulation. Two hundred seven "reactive benign" lymphoproliferations demonstrated polyclonal immunostaining. Monoclonal kappa light chain immunostaining was demonstrated in 3 of 4 cases classified as atypical hyperplasia, two of which had coexistent NHL or subsequently developed overt NHL. Frozen tissue sections were found to be essential for demonstration of immunoglobulin and glycoprotein membrane antigens. The results of immunohistochemical studies were readily integrated with the International Formulation. Although diffuse mixed and small lymphocytic lymphomas were immunologically heterogeneous (both T- and B-cell), follicular lymphomas were invariably of B-cell type, and immunoblastic lymphomas originating from homogeneous T- and B-cell populations were identified.

Antibodies, Monoclonal↗