The influence of laminin-1 (LN) and tenascin-C (TN), extracellular matrix molecules expressed spatially and temporally along the neural growth route from spiral ganglion (SG) neurons to the cochlear ...sensory cells, was evaluated in cultured SG explants from postnatal day 4 rats. Increasing concentrations of LN resulted in a strong, dose-dependent increase in the length of neurites and in a higher number of neural processes, while varying TN concentrations had relatively minor effects on both parameters. The results suggest differential receptor activation by LN and TN. When explants grown on LN were treated with Kistrin, an inhibitor of the alphavbeta3 integrin, the LN-induced increase in neurite length was reduced in a dose-dependent manner. However, the number of extending neurites was not affected, indicating that different receptors mediate this response, perhaps by increasing neuronal survival.
Objective--Neurotrophins and extracellular matrix (ECM) molecules are involved in neurite guidance during the development of spiral ganglion (SG) neurons. Several intracellular signaling molecules ...can be activated by ECMs and neurotrophins via their cognate receptors. In other systems these include the Rho small GTPases, which influence reorganization of the actin cytoskeleton that is required for axon growth. The aim of this study was to determine whether neurotrophin-3 (NT-3)-mediated SG neurite outgrowth on laminin-1 (LN) is dependent on the activation of the small GTPases Rho/Rac/Cdc42. Material and methods--SG explants from postnatal Day 4 rats were cultured on LN with and without NT-3 and increasing concentrations of Clostridium difficile Toxin B, an inhibitor of Rho GTPases. After fixation and immunocytochemical labeling, neurite growth was evaluated. Results--Treatment with C. difficile Toxin B without NT-3 lead to a dose-dependent decrease in the length and number of processes on LN. In contrast, C. difficile Toxin B had no significant effect on NT-3-mediated stimulation of neurite growth on LN, in terms of either number or length. Conclusion--The results suggest that the Rho GTPases (Rho, Rac and Cdc42) are not involved in the pathways linking NT-3 signals to neurite outgrowth, but appear to be involved in LN signaling in these neurons. However, NT-3 can override or bypass LN signaling to promote neurite extension.
This study aimed to analyze the localization and distribution of vessels and of these angiogenic growth factors: basic fibroblast growth factor (FGF-2), transforming growth factor-alpha (TGF-alpha), ...transforming growth factor-beta1 (TGF-beta1), and vascular endothelial growth factor (VEGF) in middle ear cholesteatoma in comparison with normal middle ear mucosa and auditory meatal skin.
Angiogenesis is particularly important in many normal and pathologic processes, including wound healing and inflammation. Because proliferating tissues require an enhanced blood supply, angiogenesis appears to be a prerequisite for the expansion of cholesteatoma.
The expression of FGF-2, TGF-alpha, TGF-beta1, and VEGF was studied by immunohistochemistry. The amount of vessels (collagen type IV staining) was determined by an automatic imaging analyzing system.
The results showed an altered expression and distribution of VEGF, FGF-2, TGF-alpha, and TGF-beta1 in cholesteatoma in relation to middle ear mucosa and auditory meatal skin. The results were consistent with rapidly growing, activated keratinocytes and stromal cells. Vascularization within the perimatrix of cholesteatoma showed a 4.3-fold increase compared with middle ear mucosa and a twofold increase compared with ear canal skin. An increase of 3.2- to 4-fold in the number of vessels was observed. A close relationship was seen between the density of capillaries, degree of inflammation, and expression of the angiogenic factors investigated, and an increased number of microvessels in cholesteatoma tissue.
Angiogenesis enables and supports the sustained migration of keratinocytes into the middle ear cavity. Therefore, it is a pivotal factor in the destructive behavior of middle ear cholesteatoma.
Presbyacusis in humans is an age-related bilateral sensorineural hearing impairment generally associated with degeneration of cochlear hair cells and spiral ganglion cells (SGC) predominantly in the ...basal turn but present in the apical turn. Investigations of cochleas of aged rats and gerbils reveal a large loss of SGCs in the apical as well as the basal turns. Genetically inbred aged mice, on the other hand, seem to have variable amounts of SGC loss beginning in some strains very early in the life span of the animals and greatest in the basal turn.
Theee age groups of wild-caught, then laboratory-bred, mice were investigated to determine the pattern of SGC degeneration. In 18–19-month-old animals the main loss of SGCs occurred in the basal turn (49% loss compared to 2–3 months) followed by the apical turn (31%). The greatest SGC losses in the 28–31-month-old animals were in both the apical (76%) and basal turns (74%). Thus, this strain of mice is similar to other rodents in that both ends of the ganglion are affected by SGC degeneration associated with aging.
To determine if transforming growth factor alpha (TGFα) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair ...cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10−3M) exposure either with or without growth factor pretreatment. After TGFα (500ng/ml) treatment, the intracellular calcium level of hair cells showed a five‐fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGFα in organ of Corti explants.
We evaluated long-term quality of life of patients successfully treated with either laser-assisted microsurgery alone or combined with adjuvant radiotherapy for laryngeal carcinoma.
The study ...included 53 patients who were treated by laser surgery and 16 patients who were treated by laser surgery combined with adjuvant radiotherapy. Quality of life was evaluated with two validated questionnaires: the global EORTC QLQ-C30 and the head and neck specific EORTC QLQ-H&N35. The mean follow-up was 59 months (range 10 to 111 months).
Patients receiving adjuvant radiotherapy showed a significantly lower level of global health status. Surprisingly, the two treatment groups showed close similarities with respect to symptoms specific to the head and neck region. The most frequent complaints were coughing and speech problems in both groups. On the other hand, patients with a follow-up duration of more than or less than five years did not differ significantly with regard to the global health status.
Adjuvant radiotherapy must be selectively utilized in patients treated with laser surgery for laryngeal carcinoma.
