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Biomedical subjects

M Abramson

Publications and source records attributed to M Abramson.

At least 127 records · Page 7Linked to original sources

Role of polymorphonuclear leukocytes in collagenase production in chronic otitis media.

The effect of polymorphonuclear leukocytes on collagenase production by fibroblast-like cells was studied in an in vitro cell culture system. An extract of rat intraperitoneal polymorphonuclear leukocytes induced significant collagenase production by rat skin fibroblast-like cells. Fibroblast-like cells cultured in the presence of polymorphonuclear leukocytes had many conspicuous microspikes on their surface and contained bundles of actin filaments in their cytoplasm. Polymorphonuclear leukocytes appears to be involved in bone resorption by inducing collagenase production by fibroblast-like cells, as well as by releasing their own enzymes involved in bone resorption.

Animals↗

Localization of interleukin-1 in human cholesteatoma.

Recent studies by other investigators have shown that interleukin-1 (IL-1) promotes bone resorption by stimulating various cells. Interleukin-1 not only stimulates collagenase production by fibroblasts and macrophages, but also acts as an osteoclast-activating factor. In this study, IL-1 was localized in human cholesteatoma tissues using both immunoperoxidase and immunofluorescent-staining methods with specific monoclonal antibodies. Highly concentrated IL-1 was found in the epithelial layer and granulation tissue. More specifically, intense staining was seen in basal and spinous cells of the epithelial layer, and in fibroblasts and macrophages of the granulation layer. We also located IL-1 in the normal external ear canal skin; however, the intensity of the staining in the cholesteatoma epithelium was found to be stronger. The presence of IL-1 in the epithelial layer and granulation tissue of the cholesteatoma suggests that IL-1 from the stimulated keratinocytes of the cholesteatoma could be one factor responsible for the markedly increased bone resorption observed in cholesteatoma patients.

Bone Resorption↗

Effects of epidermal Langerhans cell's conditioned medium on keratinocytes: a role of Langerhans cells in cholesteatoma.

Langerhans cells (LCs) are known to play an important role in the immunosurveillance system. In this study, as in others, numerous LCs were detected in the epithelial layer of acquired cholesteatoma by immunohistochemical staining. This finding suggests that cell-mediated immune responses are initiated by LCs in cholesteatoma; however, documentation concerning the microenvironment of LCs-keratinocytes in cholesteatoma is limited. Therefore, we investigated the effects of LCs on keratinocytes in vitro. To study these effects it was necessary to isolate and purify LCs. Our present study revealed that good enrichment and a high degree of purity (95%) of LCs could be obtained from neonatal rat skin using the immunomagnetic beads (Dynabeads M-450) sorting technique. These isolated LCs have the biologic activity of LCs, and Langerhans cells' conditioned medium (LCCM) stimulates DNA synthesis in thymocytes. The effect of LCCM on keratinocytes was then studied. We found that (1) LCCM stimulated DNA synthesis in keratinocytes was then studied. We found that (1) LCCM stimulated DNA synthesis in keratinocytes, but not protein synthesis, and (2) LCCM stimulated the incorporation of 3H-putrescine into keratinocytes by the activation of transglutaminase. Transglutaminase is a known marker of terminal differentiation in keratinocytes. By Western blot analysis, we identified a 17-kd immunoreactive mouse interleukin-1 alpha in LCCM. Our results imply that LCs found in cholesteatoma tissue may play an important role in stimulating both hyper-proliferation and cornification of keratinocytes; two characteristic features of cholesteatoma formation. These stimulatory effects may be due to the release of interleukin-1 or other factors by LCs.

Animals↗

Immunologically induced salpingitis in rats.

Eustachian salpingitis was induced with type II collagen in rats. The inflammatory reaction spread from the tubal submucous layer toward the surrounding tissue. Lymphocytes and plasmacytes were the major cells found in the inflammatory infiltrates. Bone resorption with many osteoclasts and mononuclear cells infiltrating into the muscle were also observed. These findings suggest that an immune response against type II collagen can induce eustachian salpingitis.

Acid Phosphatase↗

Effect of endotoxin on keratin production of keratinocytes in vitro.

The rate of keratin protein accumulation appears to be a crucial factor in the pathogenesis of middle ear cholesteatoma. The effect of endotoxin on keratin production of keratinocytes was studied. Endotoxins are lipopolysaccharides contained within the cell wall of gram-negative bacteria. Various concentrations of endotoxin were added to keratinocytes derived from newborn rats. Syntheses of keratin proteins were studied by incorporation of 3H-leucine into each protein fraction. Extraction of keratin proteins with various salt solutions showed that endotoxin stimulated keratinocytes to produce keratohyalin granules and its related proteins as well as proteins in the stratum corneum (keratin proteins). These findings suggest that accumulation of keratin debris in cholesteatoma may result from the effect of infection in the epithelial cells.

Animals↗

Type II collagen-induced otospongiosis-like lesions in rats.

Otospongiosis-like lesions were induced in rats by immunizing them with type II collagen. After seven months' immunization, the rats were killed and processed for histologic study. We found otospongiotic lesions in the bony cochlea, vestibule, semicircular canal, and in the regions near the oval window and round window. The spongiotic lesions in the otic capsules were similar to human otospongiosis and were characterized by the following types of microscopic appearances. 1) The classic type showed enlarged vascular spaces with congestion, macrophages, fibroblasts, and sometimes osteoclasts. 2) The fibrotic type showed vascular spaces filled with fibrous tissues. 3) The osteoporotic type had a porous appearance and was devoid of content. 4) The sclerotic type showed bone spaces partially or entirely being replaced by new bone with blue mantles and a mosaic appearance. Some spongiotic lesions showed a mixture of the above types. The findings suggest that this animal model may provide important information to help understand the process of human otosclerosis.

Acid Phosphatase↗

Asthma management: how effective is it in the community?

BACKGROUND: The National Asthma Campaign (NAC) was launched in Australia in 1989 with the major objective of improving asthma management through the implementation of a six-step asthma management plan. AIM: The objective of the present study was to analyse the management of asthma in a cohort of adults with self-reported asthma 10 years after the commencement of the NAC. METHODS: The subjects were participants in the laboratory phase of a cross-sectional epidemiological study conducted in Melbourne in 1999-2000. Participants completed the detailed European Community Respiratory Health Survey, which included specific questions about their asthma management. Participants were included in this analysis if they had a positive response to the question 'Have you ever had asthma?'. This resulted in a total of 435 subjects. RESULTS: Of the subjects with self-reported asthma, over half of the participants reported that a doctor had ever measured their breathing (52.9%). However, only 10.1% of participants reported that they owned a peakflow meter (PFM) and only 13.3% reported that they had ever been given a written action plan. In comparison with data reported from 1993, doctor measurement of lung function has decreased significantly (P < 0.000 1), as has PFM ownership (P < 0.0001) and, importantly, possession of a written action plan (P = 0.0004). CONCLUSIONS: Asthma management among adults still falls well short of NAC guidelines. The decline in some key features over recent years suggests that new management and dissemination strategies are required.

Adult↗

Associations between health and air pollution in time-series analyses.

The objective of this study was to determine the contribution of cyclic geophysical and sociocultural factors and of meterological and pollutant variations to explained variance in asthma admissions. A Poisson regression-type quasi-Fourier generalized linear model was built. We constructed an extended family of models to study the contribution of each variable. Daily observations of children's admissions for asthma were conducted during 2 y in hospitals in Melbourne, Australia. Pollutant data (i.e., fine particles, sulfur dioxide, nitrogen dioxide, and ozone) and meterological data (i.e., maximum and minimum temperatures, mean humidity, and mean barometric pressure) were collected. The result of the final model accounted for 57% of the variance in admissions. The contribution of pollution, with all periodic patterns estimated by Poisson ANOVA, was 14%, even though no pollutant alone made a significant contribution to explained variance. Autocorrelation analysis of residuals showed that the model accounted reasonably well for autocorrelation effects.

Adolescent↗

Collagenase activity in epidermoid carcinoma of the oral cavity and larynx.

Summary--Tumor invasion requires the breadkdown of the main structural protein, collagen. A series of fourteen epidermoid carcinomas of the larynx and oral cavity produced a collagen dissolving enzyme in vitro as demonstrated by the breakdown of 14C-labeled collagen. Oral cavity tumors showed greater activity than laryngeal carcinomas while both sites were more active than uninvolved mucosa from the same patients. Tumor associated collagenase activity, in common with previously described collagenases, can only be demonstrated in vitro and requires protein synthesis. Maximum tumor collagenase occurred at 24 hours in vitro and then declined as compared with the maximum collagenase at 72 hours in vitro produced by oral cavity mucosa. The 14 patients in our series were ranked in order of the collagenase activity of their tumors. At 18 months after the diagnosis, four of the six patients with the most active tumors were dead of cancer and one patient was alive with persistent cancer. High collagenase activity may be a factor in the clinical aggressiveness of epidermoid carcinomas of the head and neck.

Biopsy↗

Surgical anatomy of the guinea pig ear.

Summary--The basic anatomy of the guinea pig ear is outlined as background for a description of two surgical approaches to the guinea pig temporal bone. These approaches provide acess to the external, middle and inner ear without significant blood loss or mortality. The superior approach, made by incision at the superior anterior attachment of the auricle and removing the lateral wall of the epitympanic space, exposes the round window, epitympanum, lateral canal, and external auditory canal, leaving the tympanic membrane intact. The inferior approach through the neck exposes the cochlea, Eustachian canal, horizontal and posterior semicircular canals, tympanic membrane, and ossicles.

Animals↗

Experimental aural cholesteatoma causing bone resorption.

A series of experiments were carried out on 55 guinea pigs in four groups to study the conditions fostering bone resorbin epidermal cysts. The first group had free grafts of canal wall skin applied to the cochlea with and without talc application. The second group had canal skin flaps applied to the cochlea with and without subsequent talc application. The third group had talc applied either to the tympanic membrane or on the cochlea. The fourth group had a canal skin flap inserted into a mucosal pocket in the bulla. The animals were killed three to four months after surgery and the temporal bones were prepared for histology. Epidermal cysts were found at the cochlea in 8 of 55 animals. Cochlear fistulas were found in 6 of 55 animals. The fistulas were associated with epidermal cysts in three cases, otitis media in two cases, and talc granuloma in one case. These experiments show that migrating skin attached to a source of epithelium is capable of inducing bone resorption. Chronic foreign body granulomas and chronic sepsis are also capable of resorbing bone. These three conditions all produce a layer of undifferentiated connective tissue containing chronic inflammatory cells lying against the resorbing bone.

Animals↗

Bone resorption in chronic otitis media.

Bone resorption is an important aspect of chronic otitis media contributing to many complications of this disease. It is postulated that the mechanism of this localized destructive process is chemical in origin. Collagenase, lysosomal enzymes, prostaglandins, and other cell mediators are thought to induce bone resorption, but the site of action and cellular origin of these substances remains unclear. In this report, we demonstrate the location and attempt to delineate the cellular origin of two enzymes, collagenase and the lysosomal enzyme acid phosphatase in guinea pig temporal bones and human ossicles from ears containing chronic otitis media. Tissue localization of these enzymes identifies sites of active bone resorption and demonstrates the cells initiating this process. Using immunohistochemical and immunocytochemical techniques, collagenase was seen surrounding mononuclear inflammatory cells of granulation tissue at bone resorbing margins and at the periphery of osteocyte lacunae adjacent to resorbing areas. Electron microscopic data suggests that collagenase is an extracellular enzyme foun at the periphery of osteocytes. In addition, abundant acid phosphatase activity was seen in the same cells that exhibited collagenase staining, lending credence to the destructive function of these cells. The chronic inflammatory reaction found in chronic otitis media appears to activate bone destruction through the dynamic activity of mononuclear inflammatory cells and stimulates bone cells to increase their destructive biochemical functions.

Acid Phosphatase↗

Collagenase activity in squamous cell carcinoma of the human parotid gland.

A collagenase obtained from a single squamous cell carcinoma of human parotid gland was purified to homogeneity by procedures including precipitation with ammonium sulfate, gel filtration, ion-exchange chromatography with DEAE-cellulose, and extraction from polyacrylamide gel after electrophoresis. The parotid tumor collagenase had a molecular weight of approximately 68,000 and appeared similar to other mammalian collagenases in many respects such as action on collagen and response to common collagenase inhibitors. Analysis of specimens of various human parotid gland tumors revealed that the levels of collagenase activity were higher in squamous cell carcinoma than in nonsquamous tumors. A high level of collagenase activity from squamous cell carcinoma suggests that collagenase may promote local connective tissue destruction associated with tumor invasion and lymph node metastasis.

Adenoma, Pleomorphic↗

Histology, pathogenesis, and treatment of cholesteatoma.

Factors present in cholesteatoma connective tissue induce bone resorption in chronic otitis media. The presence of skin and its products appears to exacerbate the destructive influence of connective tissue. One exacerbating factor is pressure, shown in an animal model to increase bone resorption by influencing the subepithelial connective tissue. Consideration of pathogenic factors provides a rationale for modifications in the treatment of middle ear cholesteatoma.

Animals↗

Effects of pressure on bone resorption in the middle ear of rats.

Laminaria, a hygroscopic seaweed, was used to induce pressure within the rat tympanic cavity. Resorption of the bulla and cochlear walls occurred in all animals within 2 weeks. Cochlear fistulas were observed in four of nine animals after 2 weeks and in nine of 11 animals after 3 weeks. Preswelled laminaria inserted in the same area induced minimal bone resorption after 2 and 3 weeks. In animals given indomethacin following insertion of laminaria, both granulation-tissue formation and bone resorption were inhibited. Collagenase appeared localized in the inflammatory granulation tissue in the bone-resorption area, especially in fibroblasts, mononuclear cells, and osteoclasts. Results of this study suggested that pressure created by laminaria caused bone resorption by stimulating osteoclasts and granulation tissue.

Animals↗

Collagenase in human head and neck tumors and rat tumors and fibroblasts in monolayer cultures.

Invasive tumors must release collagenase to break down the surrounding host connective tissues. The cellular origin of this enzyme is still unclear. We used anticollagenase antibodies to localize collagenase in the human head and neck tumor and rat tumor tissues. Collagenase appeared to be localized in the tumor connective tissue stroma but not in tumor cells. The rat skin fibroblasts in monolayer culture treated with the rat tumor cell-conditioned medium demonstrated marked extranuclear and particulate staining. Fibroblasts without treatment showed no staining. Tumor cells in the culture also showed no staining. Assay of culture media demonstrated that only fibroblasts with the addition of the tumor cell-conditioned medium produced collagenase. These findings suggest the following: collagenase is produced by fibroblasts which are harbored in the connective tissue stroma, but not by tumor cells; cellular interaction between tumor cells and fibroblasts appears to be involved in breakdown of the host connective tissue for tumor cell invasion; and tumor cells release soluble factors which stimulate production of collagenase by fibroblasts.

Animals↗

Localization of collagenase in chronically inflamed guinea pig temporal bone.

Bone destruction, commonly associated with chronic otitis media, requires collagen degradation. Collagenase, a neutral protease, appears to be an essential component in the process of collagen breakdown. Collagenase was identified within chronically inflamed and normal guinea pig temporal bones using an immunohistochemical technique with fluorescein isothyocyanate and peroxidase-antiperoxidase labels. Localization of the enzyme identifies sites of matrix resorption. Collagenase was found in osteoclasts, osteocytes, mononuclear inflammatory cells, and at resorbing margins. Inflammation increased the intracellular collagenase content of inflammatory bone osteocytes when compared to normal osteocytes using a microspectrofluorometer. It appears that the inflammatory process directly influences bone destruction through the action of mononuclear inflammatory cells and indirectly by stimulating bone cells to increase their proteolytic enzyme production.

Animals↗