Biomedical subjects

A Schrott-Fischer

Publications and source records attributed to A Schrott-Fischer.

At least 19 recordsLinked to original sources

PubMed2006

First localization and biochemical identification of chromogranin B- and secretoneurin-like immunoreactivity in the fetal human vagal/nucleus solitary complex.

The human vagal/nucleus solitary complex is a primary visceral relay station and an integrative brain stem area which displays a high density of chromogranin B- and secretoneurin-like immunoreactivity. In this study, we localized and biochemically identified these proteins during prenatal development. At prenatal week 11, 15, 20 and 37, we performed a chromatographic analysis to identify the molecular forms of PE-11, a peptide within the chromogranin B sequence, and secretoneurin, a peptide within secretogranin II. Their localization was studied with immunocytochemistry, and was compared to that of substance P which is well established as a functional neuropeptide in the vagal/nucleus solitary complex. At prenatal week 11, chromogranin B-, secretoneurin- and substance P-like immunoreactivities were detected consisting of varicosities, varicose fibers and single cells. At the same time, PE-11 and secretoneurin appeared as a single peak in chromatographic analysis. Prohormone convertases PC1- and PC2-like immunoreactivities were also present at week 11. In general, the density for each peptide increased during later fetal stages with the highest density at week 37. These results demonstrate that each chromogranin peptide is expressed during human fetal life in neurons of the vagal/nucleus solitary complex indicating that these peptides could be important during prenatal development.

Chromogranin B↗

PubMed2006

Effect of age and sex on maturation of sensory systems and balance control.

Maintenance of postural balance requires an active sensorimotor control system. Current data are limited and sometimes conflicting regarding the influence of the proprioceptive, visual, and vestibular afferent systems on posture control in children. This study investigated the development of sensory organization according to each sensory component in relation to age and sex. A total of 140 children (70 males, 70 females; mean age 10y [SD 4y]; age range 3y 5mo-16y 2mo) and 20 adults (10 males, 10 females; mean age 30y 6mo [SD 8y 4mo]; age range 17y 2mo-49y 1mo) were examined using the Sensory Organization Test. Participants were tested in three visual conditions (eyes open, blindfolded, and sway-referenced visual enclosure) while standing on either a fixed or a sway-referenced force platform. Mean equilibrium scores for the six balance conditions showed rapid increases and maturation ceiling levels for age-related development of the sensorimotor control system. Proprioceptive function seemed to mature at 3 to 4 years of age. Visual and vestibular afferent systems reached adult level at 15 to 16 years of age, revealing differences between young males and females. Characterizing balance impairments can contribute to the diagnostic evaluation of neuromotor disorders.

Adolescent↗

PubMed2003

Neuronal responses in the inferior colliculus of mutant mice (Bronx waltzer) with hereditary inner hair cell loss.

Bronx waltzer mice lose a great proportion of their cochlear inner hair cells during early development. Hair cell counts revealed that these mice lacked on average 86% of their inner hair cells. Outer hair cells were present in a normal number, but appeared disarranged. The effect of this inner hair cell loss on the properties of central auditory neurons was investigated by recording neuronal responses in the inferior colliculus. Neuronal thresholds were on average elevated by 40 dB compared to CBA controls. The frequency tuning curves of the mutants were broad, and in part (18.5%) multi-peaked. The tonotopy found in the inferior colliculus of the Bronx waltzer mice appeared diffuse. Both the driven and spontaneous discharge rates were not statistically significantly different from the controls. However, the average first spike latency was significantly longer in the Bronx waltzer mice.

Animals↗

PubMed2003

Role of class D L-type Ca2+ channels for cochlear morphology.

Voltage-gated Ca(2+) channels formed by subunits (class D Ca(2+) channels) tightly regulate neurotransmitter release from cochlear inner hair cells (IHCs) by controlling the majority of depolarisation-induced Ca(2+) entry. We have recently shown that the absence of these channels can cause deafness and degeneration of outer hair cells (OHCs) and IHCs in alpha1D-deficient mice (alpha1D(-/-)) (Platzer et al., 2000. Cell 102, 89-97). We investigated the time-dependent patterns of degeneration during postnatal development in the alpha1D(-/-) mouse cochlea using light and electron microscopy. At postnatal day 3 (P3), electron microscopy revealed no morphological aberrations in sensory cells, in afferent as well as in efferent nerve endings. But at P7 we observed a beginning degeneration of afferent nerve fibres by electron microscopy. By P15, we found a loss of OHCs in apical turns but electron microscopy revealed no ultrastructural changes in IHCs and efferent axons as compared to C57 black control animals (C57BL). We demonstrated by serial ultrathin sectioning of 15 days old alpha1D(-/-) mice that intact efferent nerve fibres formed direct contacts with IHCs as the degeneration of afferent nerve fibres progressed. We also saw a notable degeneration of spiral ganglion cells at P15. By 8 months, nearly all spiral ganglion and sensory cells of the organ of Corti were absent. Random ultrathin sectioning gave the impression that synaptic bodies abundant in wild-type animals were absent in nearly all alpha1D(-/-) mice investigated. We conclude that besides presumably reduced synaptic bodies the absence of class D L-type Ca(2+) channels does not prevent morphological development of the cochlea until P3 but may cause cochlear degeneration thereafter. The observed pattern of degeneration involves afferent nerve fibres (P7) followed by cell bodies in the spiral ganglion (P15), OHCs (P15) and IHCs (after P15).

Aging↗

PubMed2003

Distribution of catestatin-like immunoreactivity in the human auditory system.

Chromogranin A (CgA) belongs to the family of chromogranin peptides which are contained in large dense-core vesicles. The novel CgA fragment catestatin (bovine CgA(344-364); RSMRLSFRARGYGFRGPGLQL) is a potent inhibitor of catecholamine release by acting as a nicotinic cholinergic antagonist. Catestatin is a recently characterized neuropeptide, consisting of 21 amino acids, which might play an autocrine regulatory role in neuroendocrine secretion through its interaction with different nicotinic acetylcholine receptor subtypes. This study investigates for the first time the distribution of this peptide in the human auditory system using immunohistochemistry. A high density of catestatin-like immunoreactivity (catestatin-LI) is located in the spiral ganglion cells. In the dorsal cochlear nucleus, a high density of catestatin-LI consists of varicose fibers, immunoreactive varicosities and immunoreactive neurons. A moderate density is detected in the ventral cochlear and the medial vestibular nucleus. A low density is found in the inferior colliculus and superior olivary complex. The study indicates that catestatin is distinctly distributed in the auditory system, suggesting a role as a neuromodulatory peptide. Further studies should elucidate a possible interaction with other neurotransmitters in the auditory system.

Aged↗

PubMed2002

Localization of efferent neurotransmitters in the inner ear of the homozygous Bronx waltzer mutant mouse.

Naturally occurring mutant mice provide an excellent model for the study of genetic malformations of the inner ear. Mice homozygous for the Bronx waltzer (bv/bv) mutation are severely hearing impaired or deaf and exhibit a 'waltzing' gait. Functional aspects of cochlear and vestibular efferents in the bv/bv mutant mouse are not well known. The present study was designed to evaluate several candidates of efferent neurotransmitters or neuromodulators including choline acetyltransferase (ChAT), gamma-aminobutyric acid (GABA), and calcitonin gene-related peptide (CGRP) in the inner ear of the bv/bv mutant mouse. Ultrastructural investigations at both light and electron microscopic level were performed. Ultrastructural morphologic evaluations of the cochlea and the vestibular end-organs were also undertaken. It is demonstrated that ChAT, GABA and CGRP immunoreactivities are present in the cochlea and in vestibular end-organs of bv/bv mutant mice. In the organ of Corti, immunoreactivity of ChAT, GABA and CGRP is confined to the inner spiral fibers, tunnel-crossing fibers, and the vesiculated nerve endings synapsing with outer hair cells. Interestingly, immunoreactivity was detectable even where inner hair cells appeared missing. Results also revealed malformations of the outer hair cells with synaptic contacts to efferent nerve endings consistently intact. In the neurosensory epithelia of the vestibular end-organs, the presence of ChAT, GABA, and CGRP immunoreactivity was localized at the vestibular efferents, with the exception of the macula of saccule. In one 8-month-old macula of utricle where the depletion of hair cells appeared highest, ChAT immunostaining was still discernible. Ultrastructural investigation demonstrated that vesiculated efferent nerve endings make synaptic contact with the outer hair cells in the organ of Corti and with type II hair cells in the vestibular end-organs. The present study provides further support that the efferent system in the bv/bv mutant inner ear is morphologically as well as functionally mature. These findings also demonstrate that if and when the onset of efferent degeneration in the bv/bv mutant inner ear occurs, it transpires subsequent to pathological conditions in the hair cells. The present findings give further indication that the efferent systems of the bv/bv mutant inner ear are independent of the afferent systems in many aspects including development, maturation as well as degeneration.

Animals↗

PubMed2002

Electrophysiological characteristics of inferior colliculus neurons in mutant mice with hereditary absence of cochlear outer hair cells.

One strain of homozygous Kit(W-v) mice (formerly known as W(v)/W(v)) lack 98% of the cochlear outer hair cells (OHCs) from birth. Inner hair cells (IHCs) and supporting cells develop normally. Thus, this strain is an attractive model to study the effect of complete OHC absence on central frequency representation. Frequency threshold curves were recorded along the tonotopic axis of inferior colliculus (IC) in mutant and control mice of the genetic background strain (C57BL/6J) and a different outbred strain (NMRI/wild mouse hybrids) known to be free of any cochlear pathology. The average threshold level of neurons in the mutants was 100 dB sound pressure level, 60 dB higher than in C57BL/6J and NMRI mice. Their tuning curves lacked the sharply tuned tip. In the C57BL/6J mice, although younger than four months, abnormal tuning curves were found for about 30% of the neurons, especially in the high frequency range. No abnormal tuning curves were found in the NMRI mice. The bandwidth of the tuning curves, measured at 10 dB above threshold, was on average 1.27 octaves in mutants, 0.62 octaves in C57BL/6J mice, and 0.34 octaves in NMRI mice. The range for the high cut-off frequency of the tuning curves at 10 dB above threshold was 6.4-61.1 kHz in the NMRI and 7-59.5 kHz in C57BL/6J. In the mutants, the range was limited to 11.1-41.7 kHz. The tonotopic gradient based on the cut-off frequency was less steep in the IC of the mutants than in both control groups.

Action Potentials↗

PubMed2001

N-chlorotaurine, a novel endogenous antimicrobial agent: tolerability testing in a mouse model.

OBJECTIVE: To investigate the tolerability of N-chlorotaurine, a new antimicrobial agent, by application to the middle ear in a mouse model. METHODS: Five BALB/c mice were each injected through the tympanic membrane with 5 microL of 0.1%, 1.0%, and 10% N-chlorotaurine and compared with animals in which 0.9% isotonic sodium chloride solution, 0.2% gentamicin sulfate, and 0.25% trimethyltin chloride were instilled. Auditory brainstem responses to clicks were evaluated repeatedly between 4 and 75 days after injection, and histologic investigations of the inner ear were performed subsequently. Three additional groups of mice were injected with isotonic sodium chloride solution, 1.0% N-chlorotaurine, and 0.25% trimethyltin, and brainstem responses to tone bursts of 8, 16, and 32 kHz were tested. In addition, the middle ear was examined histologically. RESULTS: Mice treated with isotonic sodium chloride solution, 0.1% N-chlorotaurine, and 0.2% gentamicin sulfate did not show changes in response threshold. Treatment with 1.0% and 10% N-chlorotaurine caused a reversible increase in auditory brainstem response threshold by 20 dB 4 days after application because of local irritation around the perforation of the tympanic membrane. In contrast, 0.25% trimethyltin showed a permanent elevation of auditory brainstem response threshold of 10 to 15 dB and a scattered loss of outer hair cells predominantly in the apical turn. No alterations of the inner ear were observed in the other treatment groups. The mucous membrane of the middle ear remained unaffected in all test groups. CONCLUSION: Application of N-chlorotaurine to the middle ear is well tolerated without adverse effects and may be a useful new endogenous antimicrobial agent for local treatment of otologic infections.

Animals↗

PubMed2001

Selective aspects of human pathology in high-tone hearing loss of the aging inner ear.

Accompanied with aging, the thresholds for high frequency sounds may elevate and result in a progressive hearing loss described as presbycusis. Based on correlations between audiometric measures of aged patients and histologic findings garnered from postmortem examinations, four types of presbycusis have been characterized: sensory-neural, neural, strial, and conductive [Schuknecht, H.F., Gacek, M.R., 1993. Ann. Otol. Rhinol. Laryngol. 102, 1--16]. Otopathologic changes to the inner ear as a direct function of age, however, remain controversial. The focus of this investigation involves the pathological impact on remaining sensory structures in patients having sensory--neural degeneration. The current study presents seven human temporal bones extracted from patients aged 53--67 years with high-tone hearing loss and with no known history of extraordinary environmental events involving head or noise trauma, acoustic overstimulation, or ototoxicity. In previously published findings of these specimens, all but one temporal bone failed to demonstrate a meaningful correlation between audiometric measurements and loss of functional hair cell populations with secondary retrograde degeneration of nerve fibers. Using the block surface method, electron microscopic micrographs demonstrate ultrastructural changes in the cuticular plate, stereocilia, pillar cells, stria vascularis, and the spiral ligament. In all pathological specimens, the greatest incidence of degeneration was seen at the cuticular plate. Conclusively, our findings present three implications in the aging human cochlea: firstly, audiometric measures that represent a high-tone hearing loss may take various forms with respect to ultrastructural patterns of degeneration and surviving structures; secondly, the incidence of lipofuscin and lysosome granules does not correlate with the degree of hearing loss and; thirdly, as shown only in guinea pigs [Anniko, M., 1988. Scanning Microsc. 2, 1035--1041], high-tone hearing loss can be associated with deformation of the cuticular plate.

Adult↗

PubMed2001

Estrogen receptors in the normal adult and developing human inner ear and in Turner's syndrome.

The influence of estrogens, the female sex hormone, on the ear and hearing is yet not fully investigated, though some studies have suggested that estrogens may influence hearing functions. The presence of estrogen receptors alpha and beta has earlier been shown in the inner ear of mice and rats. The aim of this study was to map possible estrogen receptors in the human inner ear. Inner ear tissue from human adults, aborted human normal fetuses and fetuses with Turner's syndrome were collected. Paraffin embedded sections of adult and fetal inner ears were immunostained with antibodies against estrogen receptors alpha and beta. Estrogen receptor alpha containing cells were found in the adult human inner ear only in the spiral ganglion, and estrogen receptor beta in the stria vascularis solely. The human fetal inner ear tissue from both normal and Turner fetuses showed a very weak staining of estrogen receptor alpha in the spiral ganglion cells, but no specific labeling of the Kölliker's organ of Corti at 13, 14 and 18 weeks of age. No staining of estrogen receptor beta was seen in the fetal inner ear.

Adult↗

PubMed2001

Connexin 26 in human fetal development of the inner ear.

Specialized for intercellular communication, gap junctions have been theorized to provide a means (the epithelial and connective tissue gap junction systems) by which fluid and ions might be transported for maintenance of high levels of endolymphatic K+ [Kikuchi et al., 1994. Acta Otolaryngol. 114, 520-528] in the inner ear. A primary constituent of these gap junctions is connexin 26 (Cx26), a protein encoded by the gene GJB2 and found in both epithelial and connective tissue cells. It has been shown that a mutation in Cx26 accounts for 50% of patients with autosomal recessive nonsyndromic hearing loss. In the present study, we document the emergence and distribution features of Cx26 through various stages (weeks 11-31) of gestation in human, fetal cochleae. Comparative patterns of Cx26 distribution are also presented in the mature rat. The cochleae were fixed in 4% paraformaldehyde within 2 h post mortem. Immunohistochemical studies were performed using a rabbit polyclonal antibody raised against synthetic peptide and corresponding with amino acids 108-122. Specimens were mounted into paraffin sections. Results show that Cx26-like immunoreactivity is evident at a prenatal age of 11 weeks and maintains a high intensity of reactivity through 31 weeks of gestation. The appearance of this reactivity seemed to modulate in parallel with the onset of development and histological maturation as well as provide functional maintenance. In the human fetal cochlea, Cx26-like immunoreactivity distribution resembled adult patterns by fetal week 20. At the completion of morphological development by week 31, reactivity appeared to achieve an adult profile of distribution. Descriptions and discussion of Cx26 distribution patterns are presented in detail.

Adult↗

PubMed2001

Dendritic cell vaccines for cancer therapy.

Dendritic cells (DC) are professional antigen-presenting cells whose primary function is the initiation of immune response. Based on the finding that the immune system usually fails to identify and kill cancer cells, DC have been recently used as vaccines for stimulation of tumour-specific immunity. This review focuses on pitfalls related to DC-based vaccination against solid tumours and on improvement of this immunotherapeutic approach for routine treatment of cancer disease.

Adjuvants, Immunologic↗

PubMed2001

Immunohistochemical and morphological studies on the human fetal cochlea: a comparative view on methods.

The preservation of morphology and antigenicity can vary uncontrollably with human fetuses since these rely heavily on immediate fixation of the temporal bone following spontaneous abortion. Once good fixation is established, there is the question of the approach taken for morphologic and immunohistochemical studies. To achieve maximal preservation for the purpose of studying normal and pathologic fetal cochleae, commonly used preparation methods for analyzing the cochlea were reviewed and compared for both immunohistochemical and morphologic studies. Cochleae obtained after spontaneous abortion ranged from the 9th gestational week to birth. Four different methods were compared for morphologic study: the block surface method; a microslicing technique; paraffin; and celloidin sectioning. For immunohistochemical study, three methods were compared: pre-embedding; paraffin; and frozen sectioning. For morphologic preservation, the block surface method gave best overall results, showing good representation of the fetal cochlea for surface preparation, light, and electron microscopy. Celloidin sectioning was also found to show good light microscopic results for both the middle and inner ear. To achieve optimal results, preservation quality, fixation procedures, and antibody all contribute to the efficacy of a methods choice.

Antibodies↗

PubMed2001

Cerebro-oculo-facio-skeletal syndrome as a human example for accelerated cochlear nerve degeneration.

BACKGROUND: Cerebro-oculo-facio-skeletal (COFS) syndrome is a rare autosomal-recessive disorder that includes microcephaly, severe mental retardation, and multiple congenital anomalies. Otologic findings are usually limited to descriptions of the auricles. PATIENT AND METHODS: The authors report inner ear histopathologic findings of a deceased 13-year-old patient with COFS. A histologic study of the inner ear in COFS syndrome has not yet been described. This patient was documented as having a profound bilateral sensorineural hearing loss at the age of 2 years. RESULTS: Histologic evaluation revealed accelerated neural and neuronal degeneration at the cochlear and retrocochlear levels. Remaining myelinated nerve fibers, counted in the spiral lamina, had degenerated by up to 97% when compared with normal innervation densities. Afferent nerve fibers innervating inner hair cells were completely absent, whereas medial efferent fibers to outer hair cells were found. Vestibular nerve fibers were less affected. CONCLUSION: The authors report inner ear findings that differ from animal models of primary cochlear neural degeneration and that resemble the pattern of hereditary cochlear nerve degeneration reported in Friedreich's ataxia.

Abnormalities, Multiple↗

PubMed2001

Goldenhar's syndrome: congenital hearing deficit of conductive or sensorineural origin? Temporal bone histopathologic study.

BACKGROUND: Oculoauriculovertebral dysplasia (OAVD) (Goldenhar's syndrome) is a congenital syndrome with ipsilateral deformity of the ear and face, epibulbar lipodermoids, coloboma, and vertebral anomalies. Goldenhar's anomaly has often been associated with a degree of congenital hearing deficits, almost always of a conductive origin, but a sensorineural component is also suspected in some cases, evident through malformations of the inner ear. PATIENTS AND METHODS: Both temporal bones of a 10-day-old deceased patient with oculoauriculovertebral dysplasia were examined by light microscopy. RESULTS: The ear deformities included deformity of the auricle, atresia of the external auditory canal, and malformation of the tympanic cavity and ossicles. Abnormalities of the stria vascularis and the semicircular canals were also demonstrated. Further inner ear deformities were not identified in this case. CONCLUSION: These histopathologic findings appear to confirm the conductive component of the congenital hearing deficit, but a sensorineural component could not be omitted. The ear alterations favor early developmental field defects. The causes of this condition are controversial. Recent results in genetic research pertaining to the MSX class genes permit better understanding of the variety, variability, and different degrees of severity of the anomalies described here.

Goldenhar Syndrome↗

PubMed2000

Congenital deafness and sinoatrial node dysfunction in mice lacking class D L-type Ca2+ channels.

Voltage-gated L-type Ca2+ channels (LTCCs) containing a pore-forming alpha1D subunit (D-LTCCs) are expressed in neurons and neuroendocrine cells. Their relative contribution to total L-type Ca2+ currents and their physiological role and significance as a drug target remain unknown. Therefore, we generated D-LTCC deficient mice (alpha1D-/-) that were viable with no major disturbances of glucose metabolism. alpha1D-/-mice were deaf due to the complete absence of L-type currents in cochlear inner hair cells and degeneration of outer and inner hair cells. In wild-type controls, D-LTCC-mediated currents showed low activation thresholds and slow inactivation kinetics. Electrocardiogram recordings revealed sinoatrial node dysfunction (bradycardia and arrhythmia) in alpha1D-/- mice. We conclude that alpha1D can form LTCCs with negative activation thresholds essential for normal auditory function and control of cardiac pacemaker activity.

Acoustic Stimulation↗

PubMed2000

Co-distribution patterns of chromogranin B-like immunoreactivity with chromogranin A and secretoneurin within the human brainstem.

As members of the chromogranin family, chromogranin A, chromogranin B, and secretogranin II are acidic proteins found in large, dense core vesicles. They are endoproteolytically processed to smaller peptides and released after neuronal stimulation. Using immunocytochemistry, this study closely examines chromogranin B-like immunoreactivity within the human brainstem and then takes a comparative view of co-distribution patterns by chromogranin B, chromogranin A, and secretogranin II. We used an antiserum raised against a synthetic peptide (PE-11) present in the chromogranin B molecule. Secretogranin II was localized with an antiserum against secretoneurin, a 33 amino acid peptide, found within the secretogranin II precursor. Like chromogranin A and secretoneurin, chromogranin B is expressed through all levels of the human brainstem. Chromogranin B was exclusively detected in neuronal structures. The medial part of the substantia nigra pars reticulata, the nucleus interpeduncularis, the area of the central gray, and the raphe complex displayed a high density of PE-11-like immunoreactivity. Furthermore, a prominent staining was found in the medial, dorsal and gelatinous subnuclei of the solitary tract and the dorsal motor nucleus of vagus. The substantia gelatinosa of the caudal trigeminal nucleus and spinal cord were also very strongly PE-11-immunopositive. In conclusion, chromogranin B and secretogranin II showed similar distributions while neuronal localization typically differed from chromogranin A aside from a few exceptions. These findings may provide a framework for future research in revealing a functional role of chromogranin peptides in the human brainstem.

Adult↗

PubMed2000

Structural/audiometric correlations in a human inner ear with noise-induced hearing loss.

A morphological analysis was performed on a human cochlea removed during skull base surgery. The patient experienced a noise-induced hearing loss following 30 years of mechanical exposure. The tissue was processed according to the block surface technique and the organ of Corti, osseous spiral lamina and spiral ganglion were analyzed at different levels. There was a circumscribed lesion approx. 10 mm from the round window extending to about 13 mm. At this site, the dominant pathological feature was the loss of outer hair cells that was comprehensive in the centermost area and partial in the peripheral region of the damage. The degradation of inner hair cells was less severe with signs of cell atrophy yet with limited loss. Outer pillar cells were often collapsed leading to deformation of the acoustic ridge. The Deiters cells were often present and physically interactive with remaining nerve fibers. In the reticular lamina, surgical manipulation and dissection resulted in tears which may be attributed to a reduction of intercellular strength between cells. In the damaged area, there was a 45% loss of myelinated nerve fibers measured at the osseous spiral lamina. Pathological changes could not be observed in the spiral ganglion with certainty although the type II cells innervating the outer hair cells were often difficult to discern.

Audiometry↗