Search PubMed⌕ Search

Biomedical subjects

R Stern

Publications and source records attributed to R Stern.

At least 181 records · Page 10Linked to original sources
PubMed1988

The fibroblast-like nature of myofibroblasts.

The myofibroblast is found in normal tissue as well as in a wide variety of pathological processes. We have cultured myofibroblasts and dermal fibroblasts and have found that they secrete similar type-specific procollagens into the culture media. These were primarily type I and III procollagens with a predominance of type I procollagen. These patterns are distinctly different from those of smooth muscle cells, which synthesize predominantly type III procollagen. Cultured fixed cells were also examined by immunohistochemistry. Both myofibroblasts and fibroblasts stained positively with antibodies to type I and III procollagens. Reaction to type V procollagen antibodies was prominent only in the myofibroblast, as was immunostaining with anti-muscle actin antibodies. Immunostaining with desmin antibodies was negative in both cell types. By electron microscopy, the myofibroblast had well-developed dense microfilament fibers of 40-80 degrees that were prominent in the long axes of the cells near the cellular margins. Although the myofibroblast has properties of both smooth muscle cells and fibroblasts, it appears to be most likely a modified fibroblast that has undergone differentiation, probably in response to specific signals from the extracellular matrix.

Actins↗
PubMed1988

Identification of the plasma membrane proteolipid protein as a constituent of brain coated vesicles and synaptic plasma membrane.

We have analyzed brain coated vesicles and synaptic plasma membrane for the presence of the plasma membrane proteolipid protein. Coated vesicles were isolated from calf brain gray matter with a final purification on Sephacryl S-1000 and reisolated twice by chromatography to ensure homogeneity. Fractions were analyzed by gel electrophoresis, immunoblotting for clathrin heavy chain, and by electron microscopy. Using an immunoblotting assay we were able to demonstrate the presence of the plasma membrane proteolipid protein in these coated vesicles at a significant level (i.e., approximately 1% of the bilayer protein of these vesicles). Reisolation of coated vesicles did not diminish the concentration of the protein in this fraction. Removal of the clathrin coat proteins or exposure of the coated vesicles to 0.1 M Na2CO3 showed that the plasma membrane proteolipid protein is not removed during uncoating and lysis but is intrinsic to the membrane bilayer of these vesicles. These studies demonstrate that plasma membrane proteolipid protein represents a significant amount of the bilayer protein of coated vesicles, suggesting that these vesicles may be a transport vehicle for the intracellular movement of the plasma membrane proteolipid protein. Isolation of synaptic plasma membranes proteolipid adult rat brain and estimation of the plasma membrane proteolipid protein content using the immunoblotting method confirmed earlier studies that show this protein is present in this membrane fraction at high levels as well (approximately 1-2%). The level of this protein in the synaptic plasma membrane suggests that the synaptic plasma membrane is one major site to which these vesicles may be targeted or from which the protein is being retrieved.

Animals↗
PubMed1988

Partial characterization of a soluble mitogenic factor from medulloblastoma.

To determine how medulloblastoma cells might influence the proliferation and phenotype of normal stromal cells, normal human leptomeningeal cells were treated in culture with medulloblastoma-conditioned medium; their ability to incorporate tritiated thymidine and synthesize collagen was measured. The treated leptomeningeal cells had a significantly greater uptake of tritiated thymidine and grew faster than control leptomeningeal cells. Immunofluorescence studies demonstrated a greater intensity of staining for procollagen type III in the cell layer of the treated cultures than in control cultures; diethylaminoethyl (DEAE)-cellulose chromatography of the medium showed that the treated cells synthesized predominantly type III collagen, whereas control cells synthesized type I collagen. Analysis of the medulloblastoma-conditioned medium revealed that the soluble factor responsible for these effects in an acid- and heat-stable protein. The increased proliferation and altered collagen synthesis induced in leptomeningeal cell cultures by a soluble factor from a medulloblastoma are examples of how tumor and stromal elements interact, and may be related to the process of desmoplasia often observed in medulloblastomas in vivo.

Cell Division↗
PubMed1988

The extracellular matrix of the central and peripheral nervous systems: structure and function.

The extracellular matrix (ECM) is the naturally occurring substrate upon which cells migrate, proliferate, and differentiate. The ECM functions as a biological adhesive that maintains the normal cytoarchitecture of different tissues and defines the key spatial relationships among dissimilar cell types. A loss of coordination and an alteration in the interactions between mesenchymal cells and epithelial cells separated by an ECM are thought to be fundamental steps in the development and progression of cancer. Although a substantial body of knowledge has been accumulated concerning the role of the ECM in most other tissues, much less is known of the structure and function of the ECM in the nervous system. Recent experiments in mammalian systems have shown that an increased knowledge of the ECM in the nervous system can lead to a better understanding of complex neurobiological processes under developmental, normal, and pathological conditions. This review focuses on the structure and function of the ECM in the peripheral and central nervous systems and on the importance of ECM macromolecules in axonal regeneration, cerebral edema, and cerebral neoplasia.

Brain Edema↗
PubMed1987

Inhibition of growth and induction of differentiation in a malignant human glioma cell line by normal leptomeningeal extracellular matrix proteins.

We devised a model system to study the effects of extracellular matrix proteins on the malignant phenotype of an anaplastic glioma cell line, U 343 MG-A. Well-characterized cultures derived from normal human leptomeninges were grown to confluence and maintained for 2 weeks. The leptomeningeal cells were then removed with base and detergent, leaving behind an extracellular matrix enriched in laminin, fibronectin, type I and IV collagen, and procollagen III. U 343 MG-A tumor cells planted on top of this normal extracellular matrix were profoundly growth inhibited compared with glioma cells grown on plastic alone. Glioma cells grown on the extracellular matrix developed multiple, slender processes and assumed a more differentiated astrocytic phenotype; immunostains for glial fibrillary acidic protein revealed a more extensive intracytoplasmic network of intensely staining filaments than in control glioma cells. When glioma cells grown on the extracellular matrix were analyzed by an enzyme-linked immunosorbent assay for glial fibrillary acidic protein, the amount of this intermediate filament per cell was increased 20-fold compared with glioma cells growing on plastic. The growth and differentiation of U 343 MG-A glioma cells in flasks coated with purified fibronectin or laminin was not significantly perturbed; however, glioma cell cultures grown in flasks coated with purified type I or IV collagen showed decreased cellular proliferation, stellate cell formation, and increased levels of glial fibrillary acidic protein per cell compared with glioma cells growing on plastic. Gelatin gel analysis showed that U 343 MG-A glioma cells growing on plastic secreted a 65,000-D metalloproteinase that was not secreted by glioma cells grown on the leptomeningeal extracellular matrix. We conclude that in this system, the extracellular matrix of a normal human leptomeningeal culture substantially inhibited the proliferation of and induced differentiation in an anaplastic glioma cell line. Our analysis of single components of the extracellular matrix suggests that these effects may be mediated in part by type I and IV collagen. The mechanism by which the leptomeningeal extracellular matrix inhibits glioma cell proliferation may be by diminishing tumor-associated protease secretion so that the degradation of extracellular matrix macromolecules in the tumor cell microenvironment is prevented and tumor cell migration becomes less likely.

Cell Differentiation↗
PubMed1987

Myopathy complicating the acquired immune deficiency syndrome.

A case of Acquired Immunodeficiency Syndrome complicated by a severe myopathy is reported. All efforts aimed at documenting an infectious etiology for the myopathy were negative. The relationship of myopathy to AIDS is discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Cirrhosis: US images with narrow band filtering.

A new type of ultrasound (US) image was created by first recording unfiltered, backscattered ultrasonic amplitudes to a standard dynamic range prior to narrow band digital filtration of the ultrasonic signal and mapping of the resultant filtered ultrasonic envelope amplitudes. Unlike unfiltered images, those created by narrow band digital filtration permit differentiation between phantoms with different scattering characteristics and normal from cirrhotic human liver in vivo. Significantly different image statistics for normal and cirrhotic liver (P less than .002) were demonstrated in preliminary clinical trials.

Humans↗
PubMed1986

Characterization of rabbit stromal fibroblasts derived from red and yellow bone marrow.

Rabbit stromal fibroblasts subcultured from red and yellow bone marrow and implanted beneath the renal capsule form ossicles the hemic cellularity of which mirrors the cellularity of the marrow used for culture. Although the cultured red and yellow marrow cells are similar in fine-structural appearance, they differ strikingly in enzymatic content of alpha-naphthylbutyrate esterase, which is abundant only in the cells derived from yellow marrow. Other observers (20, 21) have proposed that stromal fibroblasts are preadipocytes, and this data suggests that those derived from yellow marrow have the phenotype of more differentiated adipocytes. On the other hand, fibroblasts derived from red and yellow bone marrow show no differences in their profiles of procollagen synthesis. Both types of fibroblasts secrete type III procollagen as the major species, with a I/III ratio of 1:3; in contrast, rabbit dermal fibroblasts have a prominent peak of type I procollagen. The similarity of stromal cells derived from red and yellow bone marrow in procollagen synthesis suggests that the collagen part of the extracellular matrix is not the only basis for their intrinsic difference in capacity for hematopoiesis.

Animals↗
PubMed1986

Collagen and elastin synthesis in human stroma and breast carcinoma cell lines: modulation by the extracellular matrix.

The desmoplastic response to breast carcinoma is being studied. The stimulation of stromal cell proliferation by a preformed breast tumor matrix was shown. An additional mechanism for stimulating scleroprotein deposition is described here. On a per-cell basis, the synthesis of collagen and elastin was increased by 50% and 70%, respectively, in fibroblasts grown on the preformed breast tumor matrix compared to the same cells grown on plastic or on their own preformed matrix. Breast tumor cells themselves synthesized small amounts of collagen and elastin compared to fibroblasts. These levels were unchanged when breast tumor cells were grown on the preformed matrix of fibroblasts. Addition of steroid hormones to cultured cells grown on plastic or on preformed matrices in various combinations, did not change the levels of either collagen or elastin synthesis. The matrix of human breast tumor cells exerts a dual effect; it is mitogenic for fibroblasts, and also stimulates the level of collagen and elastin synthesis, events that could contribute to the formation of the desmoplastic response to human breast cancer in situ.

Breast Neoplasms↗
PubMed1986

Severe cutaneous reactions among American travelers using pyrimethamine-sulfadoxine (Fansidar) for malaria prophylaxis.

In 1982, the fixed combination of pyrimethamine and sulfadoxine (Fansidar) became available in the United States, and was recommended for use in travelers at risk of acquiring chloroquine-resistant Plasmodium falciparum. Prior to that time, no reports of severe cutaneous reactions had appeared in the medical literature despite widespread use for more than 8 years in both Europe and malarious areas of the developing world. In the fall of 1984, the Centers for Disease Control received reports of 4 cases of toxic epidermal necrolysis (including 3 fatalities) among Americans who had used pyrimethamine-sulfadoxine (PYR/SDX) for the prevention of malaria. Subsequent investigation into severe cutaneous reactions associated with the use of this drug by American travelers detected 24 cases of erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. Twenty-three of the 24 patients concurrently used chloroquine. Seven patients died. No risk factors in the development of these reactions other than the use of PYR/SDX could be identified. Among American travelers, we estimate that these reactions occur in 1 per 5,000-8,000 users, and that fatal reactions occur in 1 per 11,000-25,000 users. This higher than expected incidence necessitates that the use of PYR/SDX for the prevention of malaria be reconsidered. In the United States it is now recommended that the routine weekly use of the drug be reserved for those travelers at highest risk of acquiring chloroquine-resistant P. falciparum, when alternate prophylactic regimens are not deemed appropriate.

Adolescent↗
PubMed1986

Collagenases in human breast carcinoma cell lines.

The intense stromal response to some human tumors is termed the desmoplastic reaction. It is found with most human breast carcinomas. Dissolution of this response, containing predominantly fibrous proteins such as collagen and elastin, can occur with treatment. We have undertaken a study of the collagenases of the breast tumor desmoplastic reaction using a tissue culture model composed of human breast tumor cell lines and various human fibroblasts. The breast tumor cells had the higher collagenase activity, particularly the ZR75-31A cell line. Activity was 10-fold higher than that of the stromal cells. The enzyme was secreted into the media and required trypsin pretreatment for activity to be manifest. Partial purification was achieved of the major collagenase species. The protein was a metalloprotease and, like other mammalian collagenases, had a relative molecular weight of 60,000. Classical 3/4 and 1/4 cleavage products of the triple helical collagen substrate were demonstrated, typical of most mammalian collagenases. Only types I and III collagens were suitable substrates for this enzyme, with no apparent preference between the two. The breast tumor collagenases were not responsive to hormones; however, stimulation of activity was apparent in the absence of proteolytic pretreatment. This may represent conversion of the procollagenases of the breast tumor cells to the active form by an estrogen-sensitive plasminogen activator secreted by the same tumor cells.

Breast Neoplasms↗
PubMed1986

Elastases in human breast carcinoma cell lines.

Elastosis, the deposition of large amounts of elastin, is characteristic of the desmoplastic reaction to human breast carcinoma. Dissolution of the elastin often occurs following treatment regimens that involve steroid hormones or their antagonists. Elastinolytic activities must be invoked to account for the loss of this elastin-cotaining stroma. We have utilized a tissue culture model to explore the molecular aspects of this phenomenon. The elastases of several human fibroblast and breast carcinoma cell lines were examined. The tumor cells had 10- to 30-fold higher elastase activity than did the fibroblasts. Three separate elastinolytic activities were observed in the tumor cell lines, and partial purification was achieved. The effect of steroid hormones on these elastases was examined. No stimulation of activity was found with any of the hormones, in any combination. However, there was marked inhibition of elastase with estradiol, progesterone, and dexamethasone of the ZR75-1 cell line. This is the estrogen receptor positive line that is estrogen responsive. The corticosteroids also inhibited the elastases of the estrogen receptor positive, non-responder cell line ZR75-30. No effect was seen on the elastases of receptor negative cells ZR75-31A with any of the steroid hormones. Stimulation of elastinolytic activities in these tumor cells must occur by some as yet unidentified pathway.

Breast Neoplasms↗
PubMed1985

Cutaneous reactions to nonsteroidal anti-inflammatory drugs. A review.

The nonsteroidal anti-inflammatory drugs are one of the most commonly prescribed classes of drugs used in medical practice. This review discusses the diverse cutaneous reactions associated with nonsteroidal anti-inflammatory drugs. Adverse cutaneous reactions occur most frequently with benoxaprofen, piroxicam, sulindac, meclofenamate sodium, zomepirac sodium, and phenylbutazone. The most serious adverse cutaneous reactions, Stevens-Johnson syndrome and toxic epidermal necrolysis, appear to be most often associated with sulindac and phenylbutazone. Tolmetin and zomepirac sodium, two structurally similar pyrrole derivatives, have been associated with a disproportionate number of cases of anaphylactoid reactions. Among the currently marketed nonsteroidal anti-inflammatory drugs, piroxicam appears to have the highest rate of phototoxic reactions. This phototoxic eruption is most often vesiculobullous.

Acetates↗
PubMed1985

Cutaneous drug reactions: pathogenesis and clinical classification.

Cutaneous drug reactions may be classified with respect to pathogenesis and clinical morphology. They may be mediated by immunologic and nonimmunologic mechanisms. Immunologic reactions require host immune response and may result from IgE-dependent, immune complex-initiated, cytotoxic, or cellular immune mechanisms. Nonimmunologic reactions may result from nonimmunologic activation of effector pathways, overdosage, cumulative toxicity, side effects, ecologic disturbance, interactions between drugs, metabolic alterations, or exacerbation of preexisting dermatologic conditions. Certain defined, cutaneous, morphologic patterns are frequently associated with cutaneous drug reactions. These include urticaria, photosensitivity eruptions, erythema multiforme, disturbance of pigmentation, morbilliform reactions, fixed drug reactions, erythema nodosum, toxic epidermal necrolysis, lichenoid eruptions, and bullous reactions. In addition, certain drugs cause defined cutaneous syndromes. These include iodides and bromides, hydantoins, corticosteroids, antimalarial agents, gold, cancer chemotherapeutic agents, tetracyclines, thiazides and sulfonamides, nonsteroidal anti-inflammatory agents, and coumarin. The criteria for evaluation of possible drug reactions are presented and reviewed.

Adrenal Cortex Hormones↗