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Biomedical subjects

A Schrott-Fischer

Publications and source records attributed to A Schrott-Fischer.

At least 37 records · Page 2Linked to original sources

Dendritic cells in precancerous lesions of the larynx.

OBJECTIVES: Hyperplastic lesions of the laryngeal mucosa can eventually develop into squamous cell carcinoma The relationship between dendritic cell infiltration of head and neck cancers and prognosis is well known. Surprisingly, data regarding dendritic cell infiltration in precancerous lesions are not available today. It was the purpose of our study to extend these observations and to investigate in more detail the density and distribution of dendritic cells in pre-cancerous lesions. STUDY DESIGN: Retrospective survey by immunohistochemistry. METHODS: For this study we investigated paraffin-embedded tissue sections of 41 specimens. Histological diagnosis disclosed precancerous lesions of the larynx in 34 cases and in 7 cases, squamous cell carcinoma Immunohistochemical study was performed using antibodies against the cell surface markers S-100, HLA-DR, CD20, CD45 RO, CD45 RA, and Lag. Typical dendritic cell distributions of the immunostained specimens were photographed and measured on a quantitative basis. The medical histories of the patients were then analyzed retrospectively. RESULTS: HLA-DR+ cells could be detected in 14 of 16 cases in mild dysplastic lesions. The infiltration of the dysplastic lesions was sparse compared to cases with higher-graded dysplastic lesions. The distribution patterns of the dendritic cells in specimens with severe dysplastic lesions, but squamous cell carcinoma were extremely similar and markedly different from those in grades I and II specimens. Memory T lymphocytes (CD45 RO+) were detected more often in the group with severe dysplastic lesions (8 of 9 cases) than in the group with squamous cell carcinoma (3 of 8 cases). The inverse became evident for CD20 and CD45 RA immunolabeling. CONCLUSIONS: Few dendritic cells were found in the precancerous lesions. This may suggest that these early lesions (grades I and H) are not efficiently monitored by the immune system. Therefore they may develop into carcinomas unimpaired by cytotoxic T cells. As the degree of malignancy rises (grade III), more dendritic cells infiltrate the tumor.

Aged↗

Dendritic cells in selected head and neck tumors.

Specimens from 17 head and neck tumor patients were immunohistochemically stained with monoclonal antibodies against HLA-DR, CD1a, RFD1, LAG, CD3, CD4, CD8, CD45RO, CD68, and cytokeratin to identify the nature and distribution of dendritic cells (DCs), T cells, and macrophages. Small numbers of DCs were present in all but 2 specimens. They were located between the tumor cells and in the stroma, especially in areas of inflammatory cell infiltration. Variable numbers of T lymphocytes (cytotoxic and memory type) occurred in the same locations. Numerous macrophages were found in the epithelium, in the stroma, and in the vicinity of tumor cells. The presence of DCs in head and neck tumors indicates that the organism has activated the immune surveillance system and is trying to present tumor antigens. Considering the sparsity of DCs in the malignant tissues, the T cell response can be only limited.

Antibodies, Monoclonal↗

[Immunocytochemical study of gamma-aminobutyric acid-ergic innervation in the end-organs of human vestibule].

OBJECTIVE: To investigate gamma-aminobutyric acid-ergic (GABAergic) innervation in the end-organs of human vestibule. METHODS: A modified pre-embedding immunostaining technique of immunoelectron microscopy were applied to accomplish this study with a polyclonal antibody to gamma-aminobutyric acid. RESULTS: GABA-immunoreactive products were confined to the nerve terminals, which were rich in synaptic vesicles and the non-myelinated fibers. The GABA-immunoreactive nerve fibers synapse with afferent calices surrounding the type I hair cells. CONCLUSION: This study shows that GABAergic fibers of human vestibular end-organs belong to the vestibular efferent system.

Humans↗

Immunohistochemical investigation of enkephalins in the human inner ear.

Enkephalins are generally considered as neuropeptides in the central and peripheral nervous system of mammals bound to three large precursor molecules. Several animal studies demonstrated the distribution of met- and leu-enkephalin-like immunoreactivities in neurons and terminals of the lateral olivocochlear system. The immunostainings in the medial system are more controversial. No data about the presence of different enkephalin sequences in the vestibular efferent terminals are known. In the present study, the ultrastructural localization and distribution of immunoreactivities for six different antibodies against met- and leu-enkephalins in the human cochlear and vestibular periphery were investigated. A modified method of pre-embedding immunoelectronmicroscopy was applied. Met- and leu-enkephalin-like immunoreactivities were observed in the efferent terminals of the human outer and inner hair cell region. Using different met- and leu-enkephalin antibodies, the distribution of immunoreactivities remained similar. In the five human vestibular endorgans, enkephalin-like immunostaining was absent.

Antibodies↗

Ultrastructural localization of ChAT-like immunoreactivity in the human vestibular periphery.

Acetylcholine (ACh) has long been considered a neurotransmitter candidate in the efferent vestibular system of mammals. Recently, choline acetyltransferase (ChAT), the synthesizing enzyme for ACh, was immunocytochemically localized in all five end-organs of the rat vestibule (Kong et al. (1994) Hear. Res. 75, 192-200). However, there is little information in the literature concerning the cholinergic innervation in the vestibular periphery of man. In the present study the ultrastructural localization of the ChAT-like immunoreactivity in the human vestibular periphery was investigated in order to reveal the cholinergic innervation in the human vestibular end-organs. A modified method of pre-embedding immunoelectron microscopy was applied. It was found that the ChAT-like immunoreactivity was located in the bouton-type vesiculated nerve terminals in the vestibular neurosensory epithelia of man. These ChAT-like immunostained nerve terminals make synaptic contacts either with afferent chalices surrounding type I vestibular sensory hair cells, or with type II vestibular sensory hair cells. These results show that the ChAT-like immunoreactivity in the human vestibular periphery is confined to the efferent vestibular system. The ChAT-containing efferents innervate both type I hair cells and type II hair cells, making postsynaptic and presynaptic contacts, respectively. This study presents evidence that ACh is a neurotransmitter candidate in the efferent vestibular system of man.

Acoustic Maculae↗

Ultrastructural localization of GABA-like immunoreactivity in the human utricular macula.

In the vertebrate vestibular periphery, gamma-aminobutyric acid (GABA) has long been presumed to be a neurotransmitter candidate. However, experimental reports about the localization and function of GABA in the vestibular systems of vertebrates are contradictory. In addition, there is no information in the literature concerning the localization of GABA in the human vestibular periphery. The present study investigates the ultrastructural localization of GABA-like immunoreactivity in the human utricular macula. A modified pre-embedding immunostaining electron microscopy technique was applied using two different commercially available polyclonal antibodies to GABA. GABA-like immunoreactivity is confined to the vesiculated nerve fibers and terminals of the human vestibular neurosensory epithelia. The GABA-containing nerve terminals make asymmetrical axo-dendritic synapses with the afferent chalices surrounding the type I sensory hair cells. Type I and type II hair cells as well as afferent chalices are devoid of GABA-like immunoreactive staining. The present study demonstrates that GABA exists in the human vestibular periphery, and that GABA is a neurotransmitter candidate of the human efferent vestibular system.

Acoustic Maculae↗

Activated and non-activated eosinophils in patients with chronic rhinosinusitis.

Nasal polyps develop out of an oedematous swelling of the mucous membrane, which is probably a localized mediator-dependent reaction of the mucous membrane in the lamina propria. Among other things, eosinophil cationic protein (ECP) is released from activated eosinophils. In previous studies, ECP was considered as measuring the degree of allergic dermatological illnesses and therapy was given accordingly. A group of 54 patients with massive polyposis requiring functional endoscopic sinus surgery was examined. After surgery they were treated with local and systemic cortisone. Polypous tissue samples were collected and counted for the number and ratio of activated and non-activated eosinophils, and the serum titre of ECP was measured simultaneously using a fluoroimmunoassay (test kit, Kabi Pharmacia, Sweden). The aim of the study was to evaluate the activity of the disease and to gain hints for a specific therapy. The presence of these eosinophils was demonstrated by immunohistochemical methods, using EG1 antibodies against non-activated and EG2 antibodies against activated (i.e. secreted form of ECP) eosinophils. Depending on the duration of treatment with systemic and local corticosteroids, there was a considerable decrease in activated eosinophils and the level of serum ECP. Consequently, cortisone can be applied in the treatment of eosinophilic nasal polyps. As the number of activated eosinophils in the tissue is an indicator for the activity of the chronic inflammation it can be deduced from our study that local and/or systemic cortisone application successfully stops the growth of eosinophilic nasal polyps. The number and ratio of activated and non-activated eosinophils seem to be reliable indicators for the activity of chronic polyposis.

Blood Proteins↗

Ultrastructural localization of GABA-like immunoreactivity in the vestibular periphery of the rat.

Gamma-aminobutyric acid (GABA) is presumed to be a neurotransmitter candidate in the vestibular periphery of mammals. However, experimental reports about the localization of GABA in afferents or efferents of the vestibular systems are contradictory. It is an open question whether there are species differences in the amammalian vestibular system. The present study was designed to investigate the ultrastructural localization of GABA-like immunoreactivity in the vestibular periphery of the rat. A modified preembedding immunoelectron microscopy technique was applied using a polyclonal antibody to GABA as a marker. GABA-like immunoreactivity was revealed in the vestibular periphery of the rat, confined to the vesiculated nerve fibers and terminals of the rat vestibular neurosensory epithelia. Type I hair cells and type II hair cells as well as efferent chalices are devoid of GABA-like immunoreactive staining. These findings indicate that GABA is a neurotransmitter candidate of the efferent vestibular system of the rat.

Acoustic Maculae↗

[Immunocytochemical study of cholinergic innervation in the neurosensory epithelia of human vestibule].

OBJECTIVE: To investigate the cholinergic innervation of the neurosensory epithelia of human vestibule. METHODS: A modified preembedding immunostaining technique for immunoelectronmicroscopy was applied to this study. A polyclonal antibody to choline acetyltransferase (ChAT) was used as the marker of cholinergic fibers. RESULTS: ChAT-immunoreactive products were restricted to the nerve fibers and terminals which were rich in synaptic vesicles. The ChAT-immunoreactive fibers synaps with afferent chalice as well as with type II sensory hair cells. CONCLUSION: This study demonstrates that cholinergic fibers innervate the neurosensory epithelia of human vestible. The cholinergic fibers of human vestibular sensory epithelia belong to the vestibular efferent system.

Aged↗

Innervation of cholinergic vestibular efferent system in vestibular periphery of rats.

The innervation of cholinergic efferent fibers in the vestibular endorgans of the rats was investigated using a modified preembedding immunostaining technique of immunoelectron microscopy. A monoclonal antibody to choline acetyltransferase (ChAT) was used as a marker of cholinergic fibers. It was found that there were four types of cholinergic innervation in the vestibular endorgans of the rat: (1) cholinergic nerve endings formed axo-dendritic synapses with afferent chalice surrounding the type I sensory hair cells; (2) cholinergic nerve endings formed axo-somatic synapses with type II hair cells; (3) cholinergic fibers synapse with afferent nerve fibers and (4) a synaptic contact developed between cholinergic nerve endings. The results demonstrated that a multiform innervation of the cholinergic efferents exists in the rats vestibular periphery.

Acetylcholine↗

Quantitative evaluation of cochlear neurons and computer-aided three-dimensional reconstruction of spiral ganglion cells in humans with a peripheral loss of nerve fibres.

Quantitative data on human cochlear neuronal elements were collected from various regions in five patients with high-tone hearing loss due to presbycusis and in two patients with normal hearing. The number of nerve fibers was assessed in the spiral lamina and in the inner acoustic meatus together with counts of spiral ganglion cells. The results show that the number of neurons decreased peripherally, i.e., with increasing distance from the central nervous system in patients with high-tone hearing loss due to presbycusis. In two patients with normal hearing no significant difference in the number of neurons was found in the lamina spiralis as compared to the inner acoustic canal. Computer-aided 3-dimensional reconstruction of the human spiral ganglion displayed large bipolar neurons (type I cells), but also large ganglion cells with one missing axon. The results may indicate that a slow retrograde degeneration occurs from the periphery towards the spiral ganglion in presbycusis. Transmission electron microscopy analysis of freshly fixed human spiral ganglions displayed interneural connections. It is speculated whether a trophic supply from other neurons at the level of the spiral ganglion can prevent or delay further degeneration of the central axon.

Aging↗

Nerve fibre interaction with large ganglion cells in the human spiral ganglion. A TEM study.

A TEM study was performed on freshly fixed human spiral ganglions (HSG) biopsied during skull base surgery. Well preserved tissue specimens were obtained for ultrastructural analysis. The investigation revealed that nerve fibres frequently form contacts with the large ganglion cells (type I cells). In the areas of contact, membrane specializations occurred, consisting of symmetric or asymmetric densities often alternating from one cell to the other with a reduced intercellular distance (approximately 10 nm). High power TEM showed the intercellular cleft to contain an extra dense line resulting in a pentalaminar structure. The dense line appeared on the side of the membrane protein concentration. Protein densities jutted into the cytoplasm along the intracellular face spreading into a diffuse cytoplasmic web physically related to accumulating mitochondria. This indicated a concentration of oxygen-dependent metabolic activity in these regions. It is believed that the nerve junctions are involved in electric transmission between type I ganglion cells. The neural junctions were morphologically different from synaptic contacts between small human ganglion cells (type II cells) and nerve fibres which have been suspected of sharing the olivocochlear bundle as their origin.

Axons↗

Quantitative evaluation of myelinated nerve fibres and hair cells in cochleae of humans with age-related high-tone hearing loss.

In this study 9 human temporal bones from 8 individuals were fixed with Karnovsky solution by perilymphatic perfusion within 1-3 h after death and examined using the "block-surface method' (Spoendlin and Brun, 1974; Spoendlin and Schrott, 1987) and the "micro-dissection method' (Johnsson and Hawkins, 1967). The audiogram of 7 individuals showed high-tone hearing loss, typical for sensory-neural presbycusis. The inner (IHC) and outer hair cells (OHC) and the myelinated nerve fibers in the osseous spiral lamina were counted to correlate audiometric curves with hair-cell and nerve-fibre densities. The "block-surface' method allows accurate hair-cell and myelinated nerve-fibre enumeration with maximal preservation of cochlear structures. The most significant change in the cochlea was not the expected loss of hair cells but an evident loss of nerve fibres in the spiral lamina along the entire length of the cochlea. This loss of nerve fibres was found to be age-related. Reductions up to 30-40% in comparison to normal-hearing middle-aged persons were found in cochleae from persons older than 60 years. In 2 cases only 13% of the fibres remained in some regions of the cochlea. The hair-cell counts showed a reduction of approximately 80% of the OHCs, mainly in the apical parts of the cochlea, and only little differences in the number of IHCs as compared with a group of normal-hearing middle-aged persons. We conclude that neither loss of hair cells nor primary degeneration of nerve fibres alone can fully explain the high-tone loss. Probably injuries of hair cells or neuronal elements at the cellular level can cause threshold elevation.

Aged↗

Dendritic cells in the normal human tympanic membrane.

Dendritic cells (DCs) are antigen-presenting cells that possess an outstanding capacity to initiate primary immune responses. They reside in the tissues in an immunologically immature state. Upon antigenic challenge in vivo or short-term culture in vitro, they undergo a maturation process and turn into mature "lymphoid DCs." Langerhans cells (LCs) of the epidermis were identified as members of this DC system. They have been demonstrated in cholesteatoma matrix and in inflamed tympanic membranes, but the normal tympanic membrane was hitherto thought to be devoid of them. To clarify this question, we removed 12 normal tympanic membranes postmortem and processed them for a sheet preparation. The epidermal layers were peeled off and immunostained with the following monoclonal antibodies: HLA-DR, OKT6/CD1a, and LAG (specific for the Birbeck granules of LCs). Two tympanic membranes were also processed for routine electron microscopy. In all epidermal sheets a dense network of DCs could be demonstrated. They showed a positive immunostaining reaction with HLA-DR, but a negative one with OKT6 and LAG. Thus, they differ in their immunohistochemical properties from typical epidermal LCs. At the ultrastructural level, DCs could also be identified, but without the typical Birbeck granules. This explains the negative reaction with the LAG antibody. These findings were extended and supported by a tissue culture examination of three normal tympanic membranes. After 3 days, typical "veiled" cells (ie, mature DCs), showing positive immunostaining with HLA-DR, could be recovered from the culture medium. In an oxidative mitogenesis assay, these cells displayed strong stimulatory capacity for resting T lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Movement↗

Immunocytochemical detection of choline acetyltransferase in the human organ of Corti.

In the mammalian cochlea acetylcholine has been considered a major neurotransmitter of the lateral and medial efferent fibers. The aims of the present study were to investigate the expression of ChAT in the human cochlea and to develop a new method for immunohistochemical investigations in the human cochlea both at the light and electronmicroscopic level. We thus examined the ChAT-like immunoreactivity in the human inner ear using light and electron microscopy with a pre-embedding technique. Our present results agree with the previously published data acquired in rodent species. The ChAT-like immunostaining could be found in the inner spiral fibers, the inner spiral bundle, tunnel crossing fibers and at the base of the outer hair cells. No staining was noted in the negative controls experiments, while rat cochleas used as positive controls showed the usual ChAT-like immunostaining as described above. The main difference between human and rat cochleas was that the efferent nerve supply seems to be less pronounced in the human cochleas.

Animals↗

Localization of chat-like immunoreactivity in the vestibular endorgans of the rat.

In vertebrates acetylcholine (ACh) has been generally considered as a neurotransmitter of the vestibular efferent system. The precise localization and innervation of the cholinergic nerve endings in the vestibular sensory periphery is still unknown. We examined choline acetyltransferase (ChAT)-like immunoreactivity in all five endorgans of the rat vestibule with light and electron microscopy using a modified pre-embedding immunostaining technique. The results were: (1) ChAT-like immunoreactivity was widespread in all five endorgans of the vestibule and confined to the vesiculated efferent nerve endings. (2) Two types of ChAT-like immunostained nerve endings can be identified according to their size and innervation pattern: a large nerve ending and a small--middle size one. (3) Vestibular endorgans differ in their ChAT-like immunoreactivity: staining is dense in the macula of the utricule and the three ampullary cristae, but less so in the macula of the saccule. (4) We found also a regional difference of the ChAT-like immunostaining in ampullary crista. ChAT-like immunostained nerve endings were predominant in the periphery close to the semilunar plane, and less in density in the central area. These findings demonstrate that ACh is a major neurotransmitter in the vestibular efferent system.

Animals↗

A study of neurotransmitters in human inner ear. Preservation of human temporal bone and value of organ donation for inner ear research.

Twenty-nine human temporal bones (TBs) from 3 different groups of patients were used to investigate an effective preservation method of the inner ear and to study the suitability of TBs from organ donors for human inner ear research. Inner ears were fixed by perilymphatic perfusion and immersion fixation. Choline acetyltransferase (ChAT) and gamma-aminobutyric acid (GABA) activities were detected either by an indirect immunostaining method or by the peroxidase-anti-peroxidase (PAP) technique. The results show that the cytoarchitecture of the sensory epithelia is excellently preserved in specimens fixed within 2 h after death. ChAT- and GABA-immunoreactivities were revealed in the efferent nerve endings and fibers of the cochlea. Morphological preservation of the sensory epithelia was also good in specimens fixed within 5 h after death. However, inner ear sensory epithelia of organ donors that had died from head trauma and were in the definite brain death state for at least 7 1/2 h were severely damaged and showed cellular debris due to autolysis, although they were fixed within 2 1/2 h after death. The mechanisms underlying this damage of the sensory epithelia are discussed.

Adult↗

A quantitative study of nerve fibers in the human facial nerve.

The facial and intermediate nerves were quantitatively evaluated in seven patients who died from systemic malignancies not involving the facial nerve. In addition, five of the specimens were also qualitatively evaluated by measuring the total and axon diameters of the facial and intermediate nerve fibers. In two cases the facial nerve fibers were counted at five different levels. The total number of myelinated nerve fibers in the facial nerve varied from 7500 to 9370. The total number of myelinated nerve fibers in the intermediate nerve varied between 3120 and 5360. The peak diameter of the facial nerve axon was between 4 and 6 microns, and was between 2 and 3 microns in the intermediate nerve. When comparing nerve segments at different anatomical levels, the largest amount of nerve fibers was found at the level of the middle mastoid portion. However, this number did not reach the amount of nerve fibers counted in the internal acoustic meatus.

Adult↗