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Biomedical subjects

J Ylikoski

Publications and source records attributed to J Ylikoski.

At least 19 recordsLinked to original sources

Brain-derived neurotrophic factor and neurotrophin 3 mRNAs in the peripheral target fields of developing inner ear ganglia.

In situ hybridization was used to study the site and timing of the expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 5 (NT-5) mRNAs in the developing inner ear of the rat. In the sensory epithelia, the levels of NGF and NT-5 mRNAs were below the detection limit. NT-3 and BDNF mRNAs were expressed in the otic vesicle in overlapping but also in distinct regions. Later in development, NT-3 transcripts were localized to the differentiating sensory and supporting cells of the auditory organ and vestibular maculae. In these sensory epithelia, the intensity of NT-3 mRNA expression decreased in parallel with maturation. The expression of BDNF mRNA was restricted to the sensory cells of both the auditory and vestibular organs, including ampullary cristae. In bioassays, BDNF and NT-3, but not NGF, at physiological concentrations induced neurite outgrowth from the statoacoustic ganglion explants. These results demonstrate that NT-3 and BDNF, rather than NGF and NT-5, are the primary neurotrophins present in the target fields of the cochlear and vestibular neurons. Expression of NT-3 and BDNF mRNAs in the otic vesicle before and during the ingrowth of neurites from the statoacoustic ganglion suggests that NT-3 or BDNF or both may serve as chemoattractants for the early nerve fibers. The results also suggest that these neurotrophins have a role in later development of the cochlear and vestibular neurons.

Animals

Distribution of F-actin and fodrin in the hair cells of the guinea pig cochlea as revealed by confocal fluorescence microscopy.

We double-stained paraformaldehyde fixed guinea pig cochleas with rhodaminated phalloidin to detect F-actin and with a monoclonal antibody against non-erythroid spectrin (fodrin). The hair cells were studied in surface specimens of the organ of Corti with confocal fluorescence microscopy. In serial optical sections, phalloidin stained the stereocilia, cuticular plate, and a circumferential ring beneath it in the inner and outer hair cells (IHCs and OHCs). The cytoplasm of the IHCs and the OHCs was unlabelled, but the infracuticular network of the OHCs in the upper turns showed a strong reaction. The lateral plasma membrane was unreactive with phalloidin in the IHCs and OHCs, except in the basal turn, where a moderate reaction, probably representing actin of Deiter's cups, was seen along the lateral walls of the basal pole of the OHCs. Fodrin was similarly seen in the cuticular plate, in a circumferential ring beneath it, and in the infracuticular network of the apical OHCs. The most interesting finding was the fodrin-specific distinct labelling of the lateral cell surface in the OHCs of the basal cochlear turn. This staining diminished towards the apex and was practically absent in the OHCs located above the level of 15 mm from the round window. The lateral cell surface of IHCs showed moderate fodrin labelling in all cochlear turns. This staining was much weaker than that seen in the basal OHCs. Fodrin labelling revealed deformation from the regular cylindrical shape in midportion of the OHC bodies in the basal turn of the cochlea.

Actins

Preparation of europium-labelled DNA probes and their properties.

A chemical method for labelling DNA with a europium chelate is presented. First, primary aliphatic amino groups are introduced onto DNA in a transamination reaction. The transamination reaction is altered by adjusting temperature and duration of the reaction. Subsequently, the modified DNA is reacted with an isothiocyanate derivative of a Eu chelate. The optimum amount of Eu chelates on a DNA probe is 4-8% of total nucleotides. There is a decrease of 0.7 degrees C in the melting temperature of DNA for each incorporated Eu chelate on 100 bases. Hybridization efficiency is lowered by the introduction of Eu chelates but this effect can be partly overcome by using high DNA probe concentrations. The detection limit of the Eu-labelled probe is 0.15 attomoles of target DNA in a mixed-phase hybridization assay on microtitration wells. In addition to high sensitivity the Eu-labelled probes offer convenience in use and results which are quantitative and easy to interpret.

Affinity Labels

Spatiotemporal development of cochlear innervation and hair cell differentiation in the rat.

The apical cytoskeleton of cochlear hair cells is largely comprised of actin microfilaments and actin-associated proteins, of which fodrin is one of the most prominent. We studied the development of this mechanosensory apical portion of cochlear hair cells of the rat by fluorescence microscopy using rhodamine conjugated phalloidin to detect F-actin and an antibody against alpha-fodrin. An antibody against the 160 kDa neurofilament polypeptide was used for tracing nerve fibers. The first sign of differentiation of the mechanosensory region, actin-containing stereocilia, was observed on the 19th gestational day in the inner hair cells of the basal coil. The appearance of expression of cytoskeletal actin in the cochlear hair cells proceeded gradientally from basal to apical coil and from inner to outer hair cells. Corresponding maturation sequences were observed in the development of fodrin immunoreactivity in the cuticular plates, but the first evidence of this reactivity was found one day later than the appearance of stereocilia in the hair cells at the same location. Also the penetration of neurofilament-positive neurites into the sensory epithelium followed the same kind of longitudinal and radial maturation gradients throughout the cochlea. Fibers were revealed beneath the sensory cells shortly before the first appearance of differentiation of their mechanosensory region. The results suggest that ingrowing nerve fibers may influence the timing of the apical cytoskeleton differentiation in cochlear hair cells or that both these processes could be controlled by the same external signals that are gradientally expressed throughout the cochlea.

Actins

The comparative efficacy and safety of clarithromycin and amoxycillin in the treatment of outpatients with acute maxillary sinusitis.

The efficacy and safety of clarithromycin and amoxycillin in the treatment of acute maxillary sinusitis were compared in a single-blind, multicentre outpatient study. Fifty patients were randomly assigned to receive either clarithromycin 500 mg 12-hourly or amoxycillin 500 mg 8-hourly orally. Clinical signs and symptoms, sinus culture and blood and urine laboratory profiles were assessed prior to treatment, at four to six days during treatment, and within 48 h of the end of therapy (usually 9-11 days). Patients from whom beta-lactamase producing strains were isolated were excluded from the study. Both antibiotics achieved a clinical success rate of 91% within 48 h post-treatment; radiological resolution or improvement was observed in 91% of patients treated with clarithromycin and 89% of patients who received amoxycillin. Bacteriological cure was achieved in 88% and 91% of evaluable patients for clarithromycin and amoxycillin, respectively. Adverse events were reported for 16% of patients in the clarithromycin group compared to 26% in the amoxycillin group. Gastrointestinal disturbance was the most commonly occurring adverse event in both groups. The results of this study suggest that clarithromycin is as effective and well tolerated as amoxycillin in the treatment of acute maxillary sinusitis.

Acute Disease

Intermediate filaments in the endolymphatic sac of the guinea pig.

The expression of the five main groups of intermediate filaments and their subgroups, especially cytokeratins, was investigated in the guinea pig endolymphatic sac at the light microscopic level using immunohistochemistry. Immunostaining for cytokeratin (PKK1, PKK2, PKK3) was found in the epithelial cell layer of the sac. Vimentin was seen to stain epithelial cell layer as well as subepithelial tissue. These findings may indicate that the cytokeratins are closely related to the inner ear fluid transport. The coexpression of cytokeratin and vimentin seemed to indicate the dual function of absorption and secretion of the endolymphatic sac epithelial cell to regulate the inner ear fluid homeostasis.

Animals

Coexistence of substance P and calcitonin gene-related peptide-like immunoreactivities in the rat vestibular endorgans.

The immunocytochemical distribution and coexistence of substance P (SP) and calcitonin gene-related peptide (CGRP) in the rat vestibular endorgans were investigated. SP-like immunoreactivity was found in nervous elements beneath and around hair cells. CGRP-like immunoreactivity was also abundantly distributed beneath and within the sensory epithelia. In the present study, double-staining immunocytochemistry revealed that three different types of immunoreactivities: SP-positive/CGRP-negative, SP-negative/CGRP-positive, and SP/CGRP-positive immunostaining can be distinguished. SP/CGRP-immunoreactive fibers were localized within as well as beneath the sensory epithelia. These fibers often penetrated the epithelia and nearly reached the surface. The present immunocytochemical evidence suggests that different types of peripheral nervous systems may exist in the vestibular periphery.

Animals

Expression of neurofilament proteins in the vestibular ganglion cells of the rat.

Vestibular neurons from adult rats were studied by immunofluorescence microscopy using ten polyclonal and monoclonal antibodies reacting with different subunits of neurofilament (NF) polypeptides. Most antibodies strongly immunolabeled axons and dendrites. With the majority of antibodies the vestibular ganglion cells showed two distinct subpopulations: those with intense immunoreactivity and those without it. The intensely immunoreactive somata, staining with anti-70 kDa and anti-200 kDa NF antibodies but not with anti-150 kDa NF antibodies, comprised 32% of the ganglion cells (range: 27-40%). These cells were larger than the weakly immunoreactive majority of cells. Comparisons of adjacent sections revealed that at least a part of the distinctly immunostained cells were the same regardless of the antibody used. Thus, about one-third of the vestibular ganglion cells seem to form a subpopulation containing 200 kDa and 70 kDa subunits of NF polypeptides. Similar compositions of NF subunits have been demonstrated in such cells as the large dorsal root ganglion cells. The high percentage of neuronal somata with phosphorylated subunits of NF polypeptides demonstrated in this study is exceptional in other normal neurons and has been demonstrated only in experimental models and disease states.

Animals

Nonerythroid spectrin (fodrin) is a prominent component of the cochlear hair cells.

We studied the distribution of nonerythroid spectrin, fodrin, in surface preparations and cryosections of the cochlear hair cells as well as isolated hair cells of the guinea pig by using a monoclonal antibody (Mab) reacting with Mr 240 kD alpha-fodrin polypeptide. The Mab gave a strong reaction with the cuticular plate of both the inner and outer hair cells (IHCs and OHCs). Stereocilia were nonreactive and only a weak cell surface reaction was seen in the supporting cells. In the outer hair cells the upper turns of the cochlea, fodrin was observed in a cytoplasmic spiralling structure extending from the cuticular plate towards the cell nucleus. Some labelling was also seen along the cell surface membrane and in the synaptic region. The results suggest that fodrin may be an important constituent in the active processes of hair cells such as cell motility and/or signal transduction.

Animals

Pathological features of the facial nerve in patients with facial palsy of varying aetiology. Light and electron microscopic study.

Facial nerve specimens obtained during reinnervation surgery from 31 patients with facial palsy of varying aetiology were studied. In patients who had a facial palsy after attenuation during acoustic schwannoma removal the facial nerve had normal populations of myelinated nerve fibres in the sensory zone but their numbers and sizes were severely reduced and fibrosis was increased in the motor zone. The latter also had large numbers of endoneurial tubes with thin unmyelinated axons. When the facial nerve had been severed in tumour removal, it had practically no remaining nerve fibres. In three out of four patients with middle ear cholesteatoma, the distal facial nerve stump showed severe fibrosis. In patients with iatrogenic trauma and skull fracture, the distal stump usually showed few myelinated nerve fibres, endoneurial tubes with thin unmyelinated fibres and increased fibrosis. The pathological changes observed indicate that in all cases the motor fibres distal to the lesion have undergone Wallerian degeneration and demyelination and in most a subsequent partial regeneration. However, the regeneration remained incomplete. The distal stump of the facial nerve with numerous endoneurial tubes in most cases of the material presented appear to provide favourable structural preconditions for reinnervation surgery.

Cholesteatoma

Immunohistochemical localization of nonerythroid spectrin (fodrin) in the sensory cells of the vestibular end organs of the rat and guinea pig.

Indirect immunofluorescence method was used to study presence and localization of nonerythroid spectrin (fodrin) in the vestibular sensory epithelia. Cryosections of the vestibular organs were treated by monoclonal antibody (mAb) reacting with mammalian fodrin. Strong mAb labelling was observed in the cuticular plate of the vestibular hair cells. The stereocilia were nonreactive and supporting cells showed only a weak reaction. Fodrin seems to have similar localization in the inner ear hair cells as actin (except stereocilia) and it appears to be the major component of the membrane skeleton in the inner ear hair cells. Fodrin-associated membrane skeleton may be involved in the hair cell function in several different ways.

Animals

Serological evidence of viral or Mycoplasma pneumoniae infection in acute maxillary sinusitis.

Evidence for the involvement of viruses, Mycoplasma pneumoniae, and Chlamydia spp. was studied by the complement fixation test in paired sera from 310 young adults (297 men and 13 women) with acute maxillary sinusitis. The diagnosis of acute sinusitis was confirmed by radiography and sinus puncture. Elevated antibody titres were found in 102 patients (33%). A four fold or greater titre rise was detected in 21.5%, and a high stable titre suggestive of recent viral infection was present in a further 11.5%. Adenovirus, influenza A and B viruses, and Mycoplasma pneumoniae accounted for most of the elevated antibody titres. Elevated titres were found in 79 (32%) of the 245 patients with purulent maxillary sinusitis (pathogenic bacteria isolated in sinus secretion) and in 23 (35%) of the 65 patients with non-purulent sinusitis (no pathogenic bacteria isolated). About 90% of the fourfold or greater titre rises in bacteriologically negative cases were due to adeno- or influenza viruses. A fourfold rise in antibody titre was also found in 7 of 101 control patients (7%). The results of this study suggest that respiratory viruses and Mycoplasma pneumoniae may be potential etiological agents in acute maxillary sinusitis, either alone or in combination with the common bacterial pathogens of sinusitis.

Adolescent

Bacterial flora in the nasopharynx and nasal cavity of healthy young men.

The bacterial flora of the nose and nasopharynx was studied in 86 healthy young men. Common pathogens (Haemophilus influenzae and Streptococcus pneumoniae) were isolated from only 6% of all 172 nasal cavities. The same pathogens were isolated from 27% of 86 nasopharyngeal samples. H. influenzae dominated over S. pneumoniae both in the nose and the nasopharynx. No culture either from the nose or nasopharynx grew Streptococcus pyogenes. Potentially pathogenic bacteria, non-group-A hemolytic streptococci and various groups of Neisseria meningitidis were isolated from the nasopharynx in 20% of the subjects. According to the present study healthy adults do not carry group-A hemolytic streptococci in the nose and seldom if ever in the pharynx. Thus, isolation of S. pyogenes by bacterial culture is suggestive of a bacterial infection by this agent at these sites. Isolation of hemolytic streptococci other than group A from the pharynx does not necessarily indicate bacterial infection, and the same holds true for H. influenzae and S. pneumoniae.

Adolescent

The bacteriology of acute maxillary sinusitis.

Sinus secretions obtained by antral aspiration from 347 patients with acute maxillary sinusitis were examined bacteriologically. Special attention was paid to the method by which anaerobic bacteria could be recovered. On the total, 485 sinus secretion samples were examined, of these 336 were aspirates, 149 yields of injection-aspirations. Aerobic bacteria were cultured from 263 aspirates and from 100 injection-aspiration samples. Only anaerobes were recovered from 6 sinuses. Bacterial culture was negative in 115 sinuses (24%). The most common pathogens isolated were Haemophilus influenzae (50.5%), Streptococcus pneumoniae (18.5%), Streptococcus pyogenes (5%) and Branhamella catarrhalis (1.5%). A true anaerobic infection was considered to be present in only 7 sinuses (1.5%) indicating that anaerobes are not a significant cause of acute maxillary sinusitis. According to this study the most common pathogen in acute maxillary sinusitis in young adults is H. influenzae. From this follows that in such patients aminopenicillins may be a more appropriate choice than conventional penicillin in the antimicrobial treatment of acute maxillary sinusitis.

Adult

Neural control of the middle ear mucosa.

Neurogenic inflammation is assumed to be an important local defence mechanism against noxious stimuli in various parts of the body. Recent experimental evidence suggests substance P(SP) to be the mediator of this mechanism in the respiratory tract. Immunohistochemically, SP has earlier been reported to be present in the middle ear mucosa of the cat and guinea pig. Our earlier study demonstrated SP-like immunoreactive (SPLI) nerve fibres in the middle ear mucosa and tympanic nerve of the rat, guinea pig and man. This study shows that in experimental animals, many neuron cell bodies of the sensory ganglia of the glossopharyngeal nerve show SPLI. It is suggested that SP may be involved in the neurogenic inflammatory reaction leading to the mucosal middle ear disease.

Animals

Does impulse noise induce vestibular disturbances?

The effect of impulse noise on postural stability was evaluated in 54 subjects from the Finnish army, who were suffering from acute hearing loss caused by exposure to firearms noise. For referents we used 20 non-exposed army recruits and 39 civilian volunteers. The effects of vision, pressoreceptor function and proprioception were stepwise excluded or altered, leaving mainly the vestibular guidance of postural control intact. Since the postural perturbation was fairly smooth during these instances we assume that the condition evaluates mainly the function of the otolith organs in guiding stance. We found no difference in any of the test conditions used, between normal controls, army controls and impulse noise exposed subjects. Furthermore, there was no dose response with body sway and severity of hearing loss. The results indicate that impulse noise may not be the cause of significant functional changes in the vestibular system that can account for noise-induced postural instability.

Adult

Acute tonsillitis in young men: etiological agents and their differentiation.

Group A beta-hemolytic streptococci were found in 38% of 257 young men in military service with acute tonsillitis. Of the 108 patients tested also for viral antibodies, 42% showed a 4-fold rise in antibody titers. Adenovirus was the most frequent (31%) nonstreptococcal agent, followed by Epstein-Barr virus (6%), and influenza virus (5%). Non-group A streptococci were isolated in about the same proportion (18%) as in healthy control subjects. Other data also suggested that these bacteria were carried and not true infecting organisms. Group A streptococci and adenovirus occurred in mixed infection in 9% of the 108 cases. In group A streptococcal tonsillitis compared to others, white blood cell counts were higher (13.3 vs. 8.3 x 10(9)/l, p less than 0.01), C-reactive protein was higher (70 vs. 48 mg/l, p less than 0.01), tonsillitis was more often non-exudative (p less than 0.05), and the duration of fever was shorter (2.2 vs. 3.5 days, p less than 0.01), while there was no difference in the height of the fever or erythrocyte sedimentation rate.

Adenoviridae Infections

Acute acoustic trauma in Finnish conscripts. Etiological factors and characteristics of hearing impairment.

Etiological factors and otological and audiological findings were analysed retrospectively in 361 Finnish conscripts who had suffered acute acoustic trauma (AAT) from firearms shooting during their military service. The most common cause of AAT was shooting with hand-held weapons without ear-protectors (50%). Other common causal weapons were antitank guns (25%) and cannons (12%). Explosions had caused AAT in one-tenth of the cases. The tympanic membrane had been ruptured in 22 subjects (6%). The frequency at which hearing loss was severest was most commonly 6.0 kHz, followed by 8.0 kHz and 4.0 kHz in that order. Speech frequencies were involved in about 25% of the ears. A flat type of audiometric configuration was observed in about 20% and a rising type (low-tone loss) in about 5% of the ears. Impulse noise from large-calibre guns seemed to cause low-tone hearing loss more often than shooting with hand-held weapons.

Adult