Micropuncture techniques were used to study receptor-mediated endocytosis of alpha 2-macroglobulin bound to colloidal gold (alpha 2M-gold) by principal cells in the proximal caput epididymidis of control and efferent duct-ligated rats. The pathway of receptor-mediated endocytosis of alpha 2-macroglobulin-gold in vivo was similar to that which occurs in vitro. Alpha 2-macroglobulin-gold was taken up and internalized in coated pits and coated vesicles and was localized sequentially in uncoated vesicles (endosomes), tubular-vesicular structures, multivesicular bodies, and lysosomes. However, a 100-fold excess of alpha 2-macroglobulin did not displace the uptake of alpha 2-macroglobulin-gold in principal cells from control rats. In contrast, uptake of alpha 2-macroglobulin-gold by principal cells from efferent duct-ligated rats was six-fold greater than in control rats, and could be displaced to control levels by a 100-fold excess of alpha 2-macroglobulin. It is suggested that the inability of a 100-fold excess of alpha 2-macroglobulin to displace uptake of alpha 2-macroglobulin-gold in control rats was due to the normal saturation of apparent alpha 2-macroglobulin receptors on principal cells. The effect of efferent duct ligation was to remove the high levels of endogenous alpha 2-macroglobulin, which depleted the receptors of alpha 2-macroglobulin, thereby allowing a higher uptake of alpha 2-macroglobulin-gold in the efferent duct-ligated rats.

Animals↗

PubMedDate not supplied

Axon conduction velocity modified by reinnervation of mammalian muscle.

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Animals↗

PubMedDate not supplied

Immunoglobulin E in chronic middle ear effusions: conmparison of RIST, PRIST, and RIA techniques.

To investigate the possible role of allergy in otitis media with effusion (OME), the immunoglobulin E (IgE) content of 138 middle ear effusions (MEE) and paired serum samples from patients with chronic otitis media with effusion was determined. The initial 62 paired specimens were assayed for IgE by the radioimmunosorbent test (RIST), while the later 76 paired specimens were assayed for IgE by the paper radioimmunosorbent test (PRIST). When the results obtained by these two techniques were compared, it was noted that the PRIST procedure gave significantly lower IgE values for effusions than the RIST method. When the effusion-to-serum ratios (E/S ratios) were computed from the PRIST data, the E/S ratio was less than one, while RIST data gave an E/S ratio greater than one. The results obtained with the PRIST procedure were confirmed by double antibody radioimmunoassay for IgE. Thus, the PRIST procedure appears to measure the IgE content of MEE more accurately, and the results obtained by this procedure fail to support the concept of allergy as a major causative factor in OME.

Adolescent↗

PubMedDate not supplied

Antibody activity in otitis media with effusion.

Bacteria were isolated from a high percentage of the effusions from patients with otitis media with effusion (OME, serous otitis media). In an attempt to determine if the isolated bacteria were involved in the disease process, we analyzed the serum and effusion of 25 OME patients for the presence of antibacterial antibodies by the indirect immunofluorescence antibody method. Specific antibody activity was detected in 20 of 25 effusions (80%) and 19 of 22 sera (86%). IgG antibodies were the most frequently found class of antibodies in both sera and effusions, but IgA antibodies were detected more frequently in the effusions than in the sera. Hemophilus influenzae, Streptococcus pneumoniae, and diphtheroids were the most frequently isolated organisms, and antibody activity to all bacterial species isolated was detected. The results support the concept that the isolated bacteria are not contaminants but are actively involved in the disease process.

Antibodies, Bacterial↗

PubMedDate not supplied

Antibiotic-resistant bacteria in otitis media with effusion.

Eighty-two bacterial isolates recovered from the middle ear effusions (192) of children with otitis media with effusion (OME) were tested for antibiotic sensitivity. Nearly 50% of all bacteria isolated were found to be resistant to penicillin, and in particular, 61% of the Haemophilus isolates were penicillin-resistant; 48% of the Haemophilus isolates were ampicillin-resistant. In addition, we we compared the bacterial recovery rate from effusions of patients who were receiving antibiotics with those who were not. Among patients who were receiving antibiotics, 33% of the effusions were culture positive, while 82% of the effusions were culture positive in the patients who were not given antibiotics. These results are discussed with respect to the possible role of bacteria in the pathogenesis of OME.

Ampicillin↗

PubMedDate not supplied

Experimental otitis media in chinchillas.

Otitis media was induced in chinchillas by intrabullar injection of type 3 Streptococcus pneumoniae. It was found that the severity of a primary infection was related to the dose of bacteria injected, and animals that had recovered from a primary infection were resistant to reinfection with type 3 S pneumoniae. Middle ear effusions from infected animals contained antibodies to type 3 pneumococcal polysaccharide, whereas the sera of these animals lacked this antibody, suggesting that resistance to reinfectin was due to local immune mechanisms. This idea was tested by immunizing chinchillas by various routes. Animals immunized with formalin-killed type 3 S pneumoniae by intramuscular injection (to stimulate the systemic immune system) or by intranasal inoculation (to stimulate the secretory immune system) were found to be susceptible to infection with type 3 pneumonococcus, while animals immunized by inoculation of bacterial suspension directly into the middle ear were resistant to infection. In addition, we found that ampicillin treatment of a primary infection blocks the development of resistance since antibiotic-treated animals were susceptible to reinfection with the type 3 pneumococcus. These results indicate that chinchillas develop an immunity to pneumococcal otitis media following recovery from primary infection and that this immunity is mediated primarily by local immune mechanisms rather than systemic immune responses.

Ampicillin↗

PubMedDate not supplied

Experimental otitis media with effusion: an immune-complex-mediated response.

The possibility that immune complexes cause otitis media with effusion (OME) has been previously proposed. In order to test this hypothesis we developed an animal model in which immune complexes were injected into the middle ears of chinchillas and the animals killed at various time intervals thereafter. Moderate inflammatory changes were seen in animals killed four hours postinjection, whereas intense inflammation was observed in those killed at 24 hours. Inflammatory changes observed included capillary dilatation with increased capillary permeability, migration of polymorphonuclear leukocytes into the sub-mucosa, hemorrhage, and damage to and actual disruption of the subepithelial basement membrane. These changes are consistent with a complement-mediated acute inflammatory reaction. Although no definite conclusion can be made concerning the etiologic role of immune complex in OME, our findings show that immune complexes can cause acute inflammatory changes in the middle ear of the experimental animal.

Animals↗

PubMedDate not supplied

Inhibitory action of tetrandrine on macrophage production of interleukin-1 (IL-1)-like activity and thymocyte proliferation.

Tetrandrine is a bisbenzylisoquinoline alkaloid which has been shown to exhibit antifibrotic activity against silicosis. Tetrandrine is characterized by its strong binding to alveolar macrophages and inhibition of particle-induced respiratory burst activity in these phagocytes. In contrast, tubocurine and tubocurarine are structurally similar to tetrandrine but exhibit little effect on fibrosis or activation of alveolar macrophages. The objective of the present study was to test the effect of tetrandrine on macrophage production of monokines in response to occupational dusts, and to determine tetrandrine's effect on monokine-medicated cell growth using a mouse thymocyte proliferation assay and lipopolysaccharide (LPS) as a positive control. Stimulation of alveolar macrophages by respirable silica dust resulted in a release of monokines which caused a fourfold increase in thymocyte proliferation. Coal dust, on the other hand, had no effect on macrophage production of this cytokine. Tetrandrine was found to exhibit a dose-dependent inhibition of monokine release from both silica and LPS-stimulated alveolar macrophages. In experiments where thymocytes were directly treated with tetrandrine, a dose-dependent inhibition of thymocyte proliferation was noted with both interleukin-1-(IL-1) specific and nonspecific mitogenic (concanavalin A) actions. In contrast to the inhibitory potency of tetrandrine, tubocurarine was found to have no effect on either the production of monokines by LPS-stimulated alveolar macrophages or IL-1-mediated thymocyte proliferation. These results provide a correlation between the antifibrotic effect of tetrandrine and inhibition of macrophage activation.

Alkaloids↗