Delayed detection of congenital hearing loss.
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Child↗
Biomedical subjects
W Arnold
Publications and source records attributed to W Arnold.
Regional variations in the expression of cytokeratin proteins in the adult human cochlea.
In the adult human cochlea, a cytokeratin (Ck) network exists along the entire surface of the organ of Corti, enclosing it like a shell. Only the surfaces of the outer and inner hair cells are not integrated in this network. In temporal bone specimens, Ck filaments in Hensen's cells were found to be arranged parallel with and closely apposed to the plasma membrane. In the stria vascularis, Cks were identified only in the marginal cells. Cells in Reissner's membrane and spiral prominence showed varying degrees of immunoreactivity to different monoclonal antibodies directed against Cks. A distinct positivity for Cks was found in most spiral ganglion cells, indicating their presence in all cells. The principal pattern of immunoreactivity was the same in the organ of Corti of the entire cochlea. However, a quantitative gradient in the expression of Cks was observed, with more Cks at the apex than at the base. This was correlated to a difference in the number of Hensen's cells between the two regions. The distinct shell configuration of the Ck network in Corti's organ gives it a tonotopically related difference in rigidity which must be of considerable importance for the perception of sound in the cochlea. The absence of Cks in inner and outer sulcus cells gives them cytoskeletal characteristics of mesenchymal cells with a possible regenerative potential.
Adult↗
An Fnr-like protein encoded in Rhizobium leguminosarum biovar viciae shows structural and functional homology to Rhizobium meliloti FixK.
A 1.9 kb DNA region of Rhizobium leguminosarum biovar viciae strain VF39 capable of promoting microaerobic and symbiotic induction of the Rhizobium meliloti fixN gene was identified by heterologous complementation. Sequence analysis of this DNA region revealed the presence of two complete open reading frames, orf240 and orf114. The deduced amino acid sequence of orf240 showed significant homology to Escherichia coli Fnr and R. meliloti FixK. The major difference between ORF240 and FixK is the presence of 21 N-terminal amino acids in ORF240 that have no counterpart in FixK. A similar protein domain is also present in E. coli Fnr and is essential for the oxygen-regulated activity of this protein. Analysis of the nucleotide sequence upstream of orf240 revealed a motif similar to the NtrA-dependent promoter consensus sequence, as well as two DNA regions resembling the Fnr consensus binding sequence. A Tn5-generated mutant in orf240 lost the ability to induce the R. meliloti fixN-lacZ fusion. Interestingly, this mutant was still capable of nitrogen fixation but showed reduced nitrogenase activity.
Amino Acid Sequence↗
[The cytokeratin skeleton of the human organ of Corti and its functional significance].
In the adult human organ of Corti cytokeratin (CK) is expressed by all supporting cells enclosing it like a shell. The pattern of immunoreactivity clearly demonstrates a quantitative gradient in the expression of CK, with more CK at the apex than at the base of the cochlea. Predominantly in the apical cochlear turns, the CK-shell separates the compartment of the inner hair cells from that of the outer hair cells. Ultrastructurally, the supporting cells contain a loose fibrillary network which apically is oriented toward the desmosome chain and which can be clearly distinguished from the well-known tubular filaments (microtubuli). Some supporting cells show centrioles. Both the expression of CK and the presence of centrioles indicate a possible potential for cell regeneration. Ultrastructurally, outer hair cells and Deiters' cells show features of a specialized contact zone which might be of functional significance regarding the contractile abilities of the outer hair cells. In the human organ of Corti, vimentin is expressed only by the inner and outer pillar cells. These cells thus express CK together with vimentin. The distinct shell configuration of the CK network in the organ of Corti gives it a tonotopically related difference in rigidity which not only must be of importance for cochlear perception of sound but also could explain the reduced vulnerability of the ear to low frequencies.
Cytoskeleton↗
[Functional morphology of the outer hair cells of the human: new aspects].
Serial sections through the outer hair cells of the human organ of Corti were investigated using high-resolution electron microscopy. Delicate monostratified tubular structures of differing lengths are located on the cytoplasmic side of the hair-cell membrane. They are connected to the cell membrane via short fibers (pillars) arranged in pairs. The tubular structures, which are also termed subsurface cisterns (SSC), constitute an extensive network. This network lines the entire inner surface of the outer hair-cell membrane, and in contrast to the mammals investigated so far, also lines the base of the cell. The postsynaptic cisterns of the efferent synapses are integrated into this system. At the surface of the inner lamina of the cisterns, pores 8.5 nm in diameter are to be found. These are surrounded by protein complexes with a stellate arrangement. Similar protein complexes are located on the inner lamina of the postsynaptic cisterns. Pores 8.5 nm in diameter are also present in the outer lamina of the SSC. These constitute the base for the pillar filaments. At high magnification, the pillars are seen to have a lumen about 6 nm in diameter. Pores about 8 nm in diameter are again to be found where the pillars are anchored in the outer cell membrane. The pillars, consisting of actin, are probably ionic channels, and the pores of the inner lamina of the SSC surrounded by protein complexes are thought to be acetylcholine receptors. Since the postsynaptic cisterns of the efferent innervation of the outer hair cells are part of the overall system of the SSC, and acetylcholine is regarded as the neurotransmitter of efferent innervation, it would seem possible to regulate the subsurface cisterns, as a wall-stabilizing, contractile system, via the efferent innervation. On the basis of serial sections, a three-dimensional, true-to-scale model of the contractile wall system of the human outer hair cell was reconstructed.
Adult↗
[Site and incidence of multiple cancers in patients with squamous cell carcinomas of the upper aerodigestive tract].
The etiology of multiple primary cancers has not been clearly elucidated, although some pathogenic factors are known. The studies reported here include 796 patients who, between January 1970 and March 1989, presented with a carcinoma of the upper aerodigestive system. The charts of 687 patients were analyzed retrospectively; 109 patients were studied prospectively by systematic pretherapeutic panendoscopy. Multiple primary cancers were found in 76 cases (9.5%), 33 patients had synchronous cancers, and 43 had metachronous cancers. In the prospective study, the incidence of multiple cancers was higher (13.7%) than in the retrospective group (8.8%). Synchronous primaries were more frequent in the prospective study (8.2%) than in the retrospective analysis (3.4%). Second primaries were mostly found in the esophagus, the hypopharynx, the buccal cavity, and the lung. The authors also examined whether the anatomic location of the second primary cancer can be related to the site of the first. The five-year survival rate among patients with synchronous cancers (18%) was lower than among patients with metachronous cancers (41%). The prognosis for synchronous cancers deteriorates if the planned treatment has to be modified following the discovery of a second primary. Systematic pretherapeutic panendoscopy should be used to help detect early asymptomatic second primaries which might be missed during clinical examination.
Carcinoma, Squamous Cell↗
Identification of novel proteins unique to either transverse tubules (TS28) or the sarcolemma (SL50) in rabbit skeletal muscle.
Novel proteins unique to either transverse tubules (TS28) or the sarcolemma (SL50) have been identified and characterized, and their in situ distribution in rabbit skeletal muscle has been determined using monoclonal antibodies. TS28, defined by mAb IXE112, was shown to have an apparent relative molecular mass of 28,000 D. Biochemical studies showed that TS28 is a minor membrane protein in isolated transverse tubular vesicles. Immunofluorescence and immunoelectron microscopical studies showed that TS28 is localized to the transverse tubules and in some subsarcolemmal vesicles possibly corresponding to the subgroup of caveolae connecting the transverse tubules with the sarcolemma. In contrast, TS28 is absent from the lateral portion of the sarcolemma. Immunofluorescence studies also showed that TS28 is more densely distributed in type II (fast) than in type I (slow) myofibers. Although TS28 and the 1,4-dihydropyridine receptor are both localized to transverse tubules and subsarcolemmal vesicles, TS28 is not a wheat germ agglutinin (WGA)-binding glycoprotein and does not appear to copurify with the 1,4-dihydropyridine receptor after detergent solubilization of transverse tubular membranes. SL50, defined by mAb IVD31, was shown to have an apparent relative molecular mass of 50,000 D. Biochemical studies showed that SL50 is not related to the 52,000-D (beta subunit) of the dihydropyridine receptor but does bind to WGA-Sepharose. Immunofluorescence labeling imaged by standard and confocal microscopy showed that SL50 is associated with the sarcolemma but apparently absent from the transverse tubules. Immunofluorescence labeling also showed that the density of SL50 in type II (fast) myofibers is indistinguishable from that of type I (slow) myofibers. The functions of TS28 and SL50 are presently unknown. However, the distinct distribution of TS28 to the transverse tubules and subsarcolemmal vesicles as determined by immunocytochemical labeling suggests that TS28 may be directly involved in excitation-contraction coupling. Our results demonstrate that, although transverse tubules are continuous with the sarcolemma, each of these membranes contain one or more unique proteins, thus supporting the idea that they each have a distinct protein composition.
Animals↗
Biogenesis of transverse tubules: immunocytochemical localization of a transverse tubular protein (TS28) and a sarcolemmal protein (SL50) in rabbit skeletal muscle developing in situ.
To study the biogenesis of transverse tubules, the temporal appearance and distribution of TS28 (a specific marker of transverse tubules absent from the sarcolemma in adult skeletal muscle; 28,000 Mr) and SL50 (specifically associated with the sarcolemma and absent from the region of the transverse tubules in adult rabbit skeletal muscle) (Jorgensen, A.O., W. Arnold, A. C.-Y. Shen, S. Yuan, M. Gaver, and K.P. Campbell. 1990. J. Cell Biol. 110:1173-1185) were determined in rabbit skeletal muscle developing in situ (day 17 of gestation to day 15 newborn) by indirect immunofluorescence labeling. The results presented show that the temporal appearance and subcellular distribution of TS28 is distinct from that of SL50 at the developmental stages examined. TS28 was first detected in some, but not all, multinucleated myotubes on day 17 of gestation. At this stage of development, SL50 and the Ca2(+)-ATPase of the sarcoplasmic reticulum were already present in all myotubes. TS28 first appeared in discrete foci mostly confined to the cell periphery of the myotubes. At subsequent stages of development (days 19-24 of gestation), TS28 was also found in shoft finger-like structures extending obliquely and transversely from the cell periphery towards the center of the myotubes. 1-2 d after birth, TS28 was observed in an anastomosing network composed of transversely oriented chickenwire-like networks extending throughout the cytoplasm and interconnected by longitudinally oriented fiber-like structures. As development proceeded, the transversely oriented network became increasingly dominant. By day 10 of postnatal development, the longitudinally oriented component of the tubular network was not regularly observed. At none of the developmental stages examined was TS28 observed to be uniformly distributed at the cell periphery. SL50, like TS28, first appeared in discrete foci at the cell periphery. However, shortly after its first appearance it appeared to be distributed along the entire cell periphery. Although the intensity of SL50 labeling increased with development, it remained confined to the sarcolemma and was absent from the interior regions of the myofibers, where transverse tubules were present at all subsequent developmental stages examined. Immunoblotting of cell extracts from skeletal muscle tissue at various stages of development showed that SL50 was first detected on day 24 of gestation, while TS28 was not detected until days 1-2 after birth. Comparison of these results with previous ultrastructural studies of the formation of transverse tubules supports the idea that the temporal appearance and subcellular distribution of TS28 correspond very closely to that of the distribution of forming transverse tubules in rabbit skeletal muscle developing in situ.(ABSTRACT TRUNCATED AT 400 WORDS)
Aging↗
Biotransformation of moclobemide in humans.
The structure of the urinary metabolites formed after moclobemide administration in human was elucidated, and the pattern compared with that in the plasma. The metabolic pathways of moclobemide were also compared with those of structurally related substances. After oral moclobemide administration, on average 95% of the dose was recovered in the urine within 4 days, with a mean of 92% being excreted during the first 12 h. The drug is extensively metabolized: less than 1% of the dose was excreted unchanged. A total of 19 metabolites, accounting together for about 64% of the dose, was isolated and all metabolites accounting for more than 1% of the dose were identified. Consistent with other morpholine-containing compounds, metabolic pathways of moclobemide include mainly oxidative attack on the morpholine moiety, leading to a multitude of oxidation products. Four primary metabolic reactions were identified: morpholine N-oxidation, aromatic hydroxylation, morpholine C-oxidation and deamination. The major metabolites in urine are 4 carboxylic acids (M7A and M7B, M8, M9) that account for 49% of the dose. Only 2 metabolites (M3, M10) were found to be hydroxylated on the aromatic nucleus. They were excreted completely as conjugates of glucuronic and/or sulfuric acid. Conjugation in general, however, seems to be of minor importance in the overall biotransformation of the drug. The metabolite pattern in plasma was found to be qualitatively but not quantitatively similar to that observed in urine. Almost all of the main urinary metabolites were found in plasma as well. The unchanged parent compound and 2 primary oxidation products of the morpholine ring (M1, M15), which were present in urine only in trace amounts, could easily be detected in plasma.
Administration, Oral↗
Evaluation of the commercially available HepProbe kit for detection of hepatitis B virus DNA in serum.
The commercially available HepProbe kit involving the use of a 32P-labeled RNA probe was evaluated for its sensitivity, specificity, and reproducibility in detecting hepatitis B virus (HBV) DNA in patient serum by dot blot hybridization. The level of detection was 0.3 pg, corresponding to 3 x 10(4) genomes in 50 microliters of serum. A total of 181 serum samples were tested; 53 (82%) of 65 patients positive for both hepatitis B surface antigen and hepatitis e antigen were positive for HBV DNA compared with only 12 of 74 (16%) hepatitis B surface antigen-positive but hepatitis e antigen-negative individuals. In addition, among all patients positive for HBV DNA, there was a statistically significant correlation between the concentration of HBV DNA in serum and the presence or absence of hepatitis e antigen. None of the 42 hepatitis B surface antigen- and hepatitis e antigen-negative patients tested was positive for HBV DNA. Reproducibility was 87%, with all discordant results representing borderline positives. The results indicate that HepProbe can be employed as a sensitive and reliable assay for HBV DNA in patient serum.
DNA, Viral↗
The epithelium of the human endolymphatic sac: immunohistochemical characterization.
A panel of monoclonal and polyclonal antibodies has been used to study the epithelium of the extraosseous part of the human endolymphatic sac (ES) by immunohistochemistry. The ES epithelium reacted with several epithelial markers such as Lu-5, different anticytokeratins, antiepithelial membrane antigen, and anticarcinoembryonic antigen. Unexpectedly, all epithelial cells also revealed a strong positive reaction for the mesenchymal marker vimentin and for S-100 protein. 'Neuroendocrine', a neurosecretory antigen, and neuron-specific enolase reactivity was detected in a few epithelial cells. The results support the assumption that the ES epithelium is metabolically active and capable of secretion and resorption. These findings are in keeping with results of functional experiments in animals. The demonstration of neurosecretory antigen and neuron-specific enolase in some cells indicate that the epithelium may also have paracrine functions.
Antibodies, Monoclonal↗
Human endolymphatic sac: evidence for a role in inner ear immune defence.
In an immunohistochemical study, monoclonal and polyclonal antibodies have been used to identify cells and structures in the extraosseous part of endolymphatic sacs (ES) which were removed at autopsy from 30 persons. Intraluminal, intraepithelial, intravascular and perisaccular cells expressed the leukocyte common antigen. Immunostaining with antibodies against the CD4 and CD8 antigens revealed the predominance of CD4-positive T lymphocytes in the ES. A few lymphoid cells were found to express the major histocompatibility antigen class II. Interdigitating cells of the Langerhans type were rarely found in the epithelial layer. B lymphocytes were present in the lumen and the stroma of the ES and IgA- or IgG-containing cells in the stroma only. IgA, secretory component and the J chain were detected within epithelial cells and in the lumen of the ES. Macrophages were observed in the lumen and the stroma. Our findings are in accordance with previously published data in animals and man and give further evidence of an important role of the ES in inner ear immune defence.
Antibodies, Monoclonal↗
Analytical electron microscopy and monoclonal antibody techniques applied to the human inner ear.
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Adolescent↗
Methods for cellular and subcellular visualization of intermediate filament proteins in the human inner ear.
The preservation of antigenicity for monoclonal antibodies (mAbs) directed against the five classes of intermediate filament proteins and their subgroups was analysed in inner ear specimens from both early embryonic (6-8 gestation-week-old) human labyrinths and inner ears from newborn CBA/CBA mice. After initial fixation in 2% paraformaldehyde, the specimens were embedded in either polyvinyl alcohol (PVA) or the low viscosity acrylic resin LR White. Both embedding media allowed sectioning at room temperature with a specimen thickness of 0.5-1 microns, which gives a resolution at the subcellular level in the light microscope. Immunoreactivity occurred in the PVA-embedded material, but not in specimens embedded in LR White. However, considerably fewer mAbs showed immunostaining in the PVA-embedded material than in both cryofixed-cryosectioned or paraformaldehyde-fixed-cryosectioned human inner ears. Immunoelectron microscopy using colloidal gold (particles 10 nm in diameter) was successful in the PVA-embedded (but not the LR White-embedded) material.
Acrylic Resins↗
Cytoskeletal network of intermediate filament proteins in the adult human vestibular labyrinth.
The cytoskeleton of adult human vestibular hair cells lacks intermediate filament (IF) proteins, whereas in fetal material immunoreactivity for cytokeratin (cks; a subclass of IFs) occurs in both types of hair cells. The shift in the cytoskeletal composition can be hypothesized to their onset of physiological function. Since the IFs are extremely rigid intracellular structures, they provide considerable mechanical stability. The entire cytoplasm of all supporting cells in the epithelial lining of all five vestibular organs is filled with cks. In this way most vestibular hair cells become compartmentalized, each with a rigid shell surrounding it. The distinct delineation of IF proteins in adult tissues, in contrast to fetal inner ear organs in which often a rather general cytoplasmic expression occurs, probably reflects their anatomical basis for their function.
Ear, Inner↗
Immunohistochemistry of otosclerosis.
Immunoglobulins G (IgG) and A (IgA) were found in plasma cells, osteocytes, chondrocytes and in connective tissue of active otosclerotic (= otospongiotic) lesions. The application of antibodies against paramyxovirus and rubella virus antigens reproducibly determined the expression of these antigens at different sites in the otosclerotic stapes, but also in the epithelial cells of the overlying middle ear mucosa. By using specific T-lymphocyte and B-lymphocyte markers, about 80% of the lymphocytes present in the otosclerotic footplate were revealed to be T-lymphocytes. There was neither deposition of immunoglobulins nor any expression of viral antigens in non-otosclerotic footplates which were investigated as controls.
Adolescent↗
[Lung embolism caused by vaseline following insertion of a venous catheter].
Pulmonary embolism usually is due to natural causes, most often to obstruction of pulmonary arteries by blood clots breaking loose from venous thrombi forming in the leg or pelvis. Clots of other cellular material such as tumor fragments or fatty tissue (this especially in case of severe soft tissue and skeletal trauma), but also foreign material can give rise to this- often times lethal-condition. This is a report of foreign-body pulmonary embolism with obstruction of mainly the right lower lobe pulmonary arteries due to white vaseline embolism, probably responsible for the patient's premature surmise. Clinical history, therapeutic measures and course of disease--including radiographic and laboratory findings are being presented. Autopsy revealed massive pulmonary embolism to the right lower lobe due to a whitish greasy substance, which was chemically identified to be white vaseline. Additionally, this zone of infarction also showed signs of severe pneumonia with abscess formation resembling that of necrotizing infarction and therefore felt to be related to the foreign body embolism. Histology showed evidence of pneumonia and also inflammatory changes of the pulmonary arteries in form of additional formation of endothelium with involvement of the internal elastic layer. Finally, several possible causes for this case of pulmonary vaseline embolism are being discussed. The exact mechanism remains unclear; but in view of the course of disease, some radiographic findings as well as those of autopsy and histology, it seems most likely that the vaseline embolism was connected to transjugular catheterization rather than to the two other mechanisms also described.
Catheterization, Central Venous↗
[Initial clinical experiences with the cervical spine titanium locking plate].
The titanium CS (cervical spine) locking plate is a system that takes account not only of biochemical aspects, in the choice of material, but also new biomechanical aspects. With the help of a new hollow screwing system, such stability is achieved that in many cases there is no need for a second, dorsal, operation. Ten patients, most of whom had unstable fractures, have so far been treated. No complications attributable to this implantation system were observed. A further step in the attainment of security and stability by operative treatment of cervical spine disorders has been achieved with this system.
Bone Plates↗