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Biomedical subjects

G Poulsen

Publications and source records attributed to G Poulsen.

At least 19 recordsLinked to original sources

Reduction in DNA binding activity of the transcription factor Pax-5a in B lymphocytes of aged mice.

Aging has been associated with intrinsic changes of the humoral immune response, which may lead to an increased occurrence of autoimmune disorders and pathogenic susceptibility. The transcription factor Pax-5 is a key regulator of B cell development. Pax-5a/B cell-specific activator protein and an alternatively spliced isoform, Pax-5d, may have opposing functions in transcriptional regulation due to the lack of a transactivation domain in Pax-5d. To study B cell-specific changes that occur during the aging process, we investigated expression patterns of Pax-5a and 5d in mature B cells of young and aged mice. RNase protection assays showed a similar transcriptional pattern for both age groups that indicates that aging has no affect on transcription initiation or alternative splicing for either isoform. In contrast, a significant reduction in the DNA binding activity of Pax-5a but not Pax-5d protein was observed in aged B cells in vitro, while Western blot analyses showed that similar levels of Pax-5a and 5d proteins were present in both age groups. The observed decrease in Pax-5a binding activity correlated with changes in expression of two Pax-5 target genes in aged B cells. Expression of the Ig J chain and the secreted form of Ig mu, which are both known to be suppressed by Pax-5a in mature B cells, were increased in B cells of aged mice. Together, our studies suggest that changes associated with the aging phenotype cause posttranslational modification(s) of Pax-5a but not Pax-5d, which may lead to an abnormal B cell phenotype in aged mice, associated with elevated levels of J chain, and secretion of IgM.

Aging↗

Bioavailability of four oral coenzyme Q10 formulations in healthy volunteers.

The bioavailability of four different Coenzyme Q10 (CoQ) formulations was compared in ten healthy volunteers in a four-way randomised cross-over trial. The included formulations were: A hard gelatin capsule containing 100 mg of CoQ and 400 mg of Emcompress. Three soft gelatin capsules containing: 100 mg of CoQ with 400 mg of soy bean oil (Bioquinon); 100 mg of CoQ with 20 mg of polysorbate 80, 100 mg of lecithin and 280 mg of soy bean oil; and 100 mg of CoQ with 20 mg of polysorbate 80 and 380 mg of soy bean oil, respectively. The result suggests that the soya bean oil suspension of CoQ (Bioquinon has the highest bioavailability. A difference in basic AUC and AUC after p.o. administration of CoQ was observed with respect to sex. A characteristic two peak-pattern was observed at the concentration-time profile.

Administration, Oral↗

Immunolocalization of the retinoblastoma protein in the human eye and in retinoblastoma.

PURPOSE: To determine whether, by employing recent advances in immunocytochemical technique, it is possible to identify reliably the product of the retinoblastoma (RB) susceptibility gene, p110RB1, in formalin-fixed, paraffin-embedded eyes with commercially available primary antibodies. If so, the authors sought to determine the distribution of p110RB1 in normal human eyes and retinoblastomas in hopes of better understanding its function. METHODS: Four antibodies to p110RB1 were tested on normal human and monkey eyes, as well as on six human retinoblastomas. The human tissue was formalin-fixed and paraffin-embedded. Free antigen was used for an absorbed control. The monkey eye had been injected with tritiated (H3) thymidine 24 hours before enucleation. RESULTS: Three of the four antibodies had acceptable reactivity (a polyclonal against the carboxyl-terminal epitope and two monoclonals against epitopes near the amino-terminus). Staining was confined to nucleated cells of the normal eyes and was strongest in the cycling cells of the lenticular and corneal epithelia. Somewhat weaker reactivity was seen in those corneal epithelial cells in S phase as determined by autoradiography for H3-thymidine. Of the six retinoblastomas, three had strong nuclear and cytoplasmic staining and one showed weaker staining in the tumor cells than in the adjacent vascular endothelial cells. Two of the tumors had positive cytoplasmic and negative nuclear staining with an amino-terminal antibody but were completely negative for carboxyl-terminal p110RB1 reactivity. CONCLUSIONS: Using appropriate immunocytochemical techniques, p110RB1 can be identified in paraffin-embedded tissues with commercially available antibodies. The observed staining pattern in retinoblastoma suggests that RB1 transcripts are commonly produced in the tumor cells and that they are sometimes, but not always, capable of nuclear binding. Thus, nuclear binding by the RB1 gene product per se is not sufficient to prevent tumor growth, nor does it indicate the presence of a normal transcript.

Animals↗

Tympanosclerosis of the drum in secretory otitis after insertion of grommets. A prospective, comparative study.

In 193 consecutive children with bilateral secretory otitis, intubation and adenoidectomy were performed on the right ear and paracentesis on the left. Changes in the ear drum were analysed at re-evaluation one to three years after operation. In ears that had been intubated, tympanosclerosis occurred significantly more frequently (48 per cent) than in ears that had not been intubated (10 per cent). The frequency of atrophy of the pars tensa was the same. Of the right ears, 10 per cent were re-intubated, compared with 23 per cent of the left ears. The cause of the increased frequency of tympanosclerosis in the intubated ears must be mechanical, as decreased movements of the drum with inflammatory fibrous hyperplasia impede spontaneous normalization and promote hyalinization and calcification. The hearing was found to be similar in ears with and without tympanosclerosis.

Child↗

Repetitive tympanometric screenings of two-year-old children.

240 healthy 2-year-old children were examined with tympanometry in November, February and May. One the whole, the tympanograms were somewhat improved at the spring evaluation compared with the winter evaluation. The type of tympanogram changed in half of the ears at each evaluation. In total, 64% of the ears have changed type at the three evaluations. The type B tympanogram, indicating a flat curve and secretory otitis, was improved in 64% of the ears that were originally type B, while in many other ears the tympanogram deteriorated to type B, such that 12,3% of the ears had secretory otitis at the first investigation, 14.6% at the second, and 11.3% at the third. Thus, in total 26.3% of the ears had at least one period of type B tympanogram or middle ear effusion and only 26.1% of the ears had a middle ear pressure of between 0 and 99 mmH2O at all three evaluations. Due to the large spontaneous normalization in this as well as in other materials, it may be assumed that 75--90% of all children have had at least one episode of secretory otitis.

Acoustic Impedance Tests↗

[Spontaneous normalisation and frequency of secretory otitis (author's transl)].

In two-year-old children from two communities of Copenhagen five repetitive tympanometries were performed. In winter a prevalence of secretory otitis between 11% and 14% of investigated ears in summer of 7% was found. The results of tympanometry changed very much between the repetitive investigations thus every time 50% of ears changed the tympanogram type. The rate of spontaneous normalisation of secretory otitis was calculated to 75%. The total frequence of secretory otitis is very high and 50% of all ears have during the first three years of life in at least one period had middle ear effusion.

Acoustic Impedance Tests↗

Etiologic factors in secretory otitis.

We investigated the possible etiologic factors of secretory otitis and dysfunction of the Eustachian tube in 278 healthy 2-year-old children based on screening tympanometry and medical history. We found that catarrhalia was the most frequent etiologic factor, with acute otitis being the second most frequent factor. It was demonstrated that secretory otitis may develop without a preceding infection of the middle ear. It is probable that dysfunction of the tube plays a primary role in the development of secretory otitis. Allergy did not seem to be an etiologic factor. Antibiotic treatment does not promote the development of secretory otitis, but is probably unable to prevent it. Parental disposition could not be related to the children's ear diseases.

Acute Disease↗

Tympanometry in 2-year-old children. Seasonal influence on frequency of secretory otitis and tubal function.

Repetitive screening tympanometry performed in 240 healthy 2-year-old children showed that tympanometric conditions are significantly better in the summer season than in the spring or winter. A very large tendency to spontaneous normalization of the tympanogram type B was demonstrated. Only 16% of the ears that had type B at the first investigation in November had the same type in August. Simultaneous with the normalization of some ears others deteriorated, thus in November type B tympanogram was found in 12%, in February 14.6%, in May 11.3%, and in August 7.2% of all ears investigated. Due to the large variability in the tympanometric conditions which are predominantly caused by catarrhalia, 28.6% of the ears have had type B tympanogram at least once during the period from November to August, while only 1.6% have had type B at all four investigations. The large spontaneous recovery of secretory otitis, demonstrated in the present study, indicates that the child should be observed for a period before implementation of surgical treatment.

Acoustic Impedance Tests↗

Screening tympanometry during the first year of life.

150 healthy children were regularly investigated with tympanometry during the first year of life. Normal middle ear pressure was found in nearly all children at birth. At the age of 6 months, 62% of the ears had a pressure of 0-99 mmH2O. In 37% the pressure was between -100 and -350 mmH2O and 1% had flat curves. At the age of 9 months, the tympanograms further deteriorated and at 12 months, only 40% of the ears had a pressure of 0 to -99 mmH2O, 28% had a pressure of -100 to -199 mmH2O, 19% a pressure of -200 to -350 mmH2O and 13% had flat curves, indicating secretory otitis. At 1 year, the tympanograms were worse than in any other age group investigated so far. The dominant cause of the reduced middle ear ventilation was catarrhalia, the frequency of which increased during the period from 6 to 12 months.

Acoustic Impedance Tests↗

[Tuba aperta].

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Adult↗

Tympanometry in 2-year-old children.

Screening tympanometry was performed in 278 healthy 2-year-old children (556 ears) born the first 10 days of every month in 1976 in two municipalities from Copenhagen County. A middle ear pressure between 0 and -99 mm H2O was found in 49.6%, between -100 and -199 in 19.4%, between -200 and -300 in 20.1%, and flat curves in 10.8%. The latter group also otoscopically gave evidence of middle ear effusion. The results reveal the highest incidence of tubal dysfunction and middle ear effusion for this age group in contrast to any other age group. However, a large spontaneous recovery from secretory otitis was also noted. No differences were found between sexes, right ear/left ear, the socio-economic factors, or whether the children lived in houses or apartments. Children who were nursed in public nurseries had a significantly higher incidence of secretory otitis than those nursed in private nurseries or at home.

Acoustic Impedance Tests↗

Screening tympanometry in newborn infants and during the first six months of life.

Tympanometry was performed in 151 healthy children at birth and at 3 and 6 months of age. At birth 10.5% of the ears had a pressure of -100 mmH2O, and 0.3% a pressure of -125 mmH20. The pressure in most of these ears later became normalized. At 3 months of age 17.9% had a pressure of -100 mmH2O or less, and at 6 months of age 39.2%. At 6 months of age 1.3% of the ears had flat curves and middle ear effusion, and 9.6% had a pressure between -200 and -300 mmH2O. The pressure changes and their cause were analysed. Catarrhalia occurred in 23% of the infants before 3 months of age and in 60% in the 3-6 month period. This is an important though not the only etiological factor for the reduced ventilation in the middle ear, which probably occurs via oedema of the tubal mucosa and mild internal tubal occlusion. Ventilation was significantly reduced at 3 months of age in catarrhal girls, and in catarrhal boys at 6 months of age.

Acoustic Impedance Tests↗

Tubal function in chronic secretory otitis media in children.

In 100 children (150 ears) with chronic secretory otitis media the function of the Eustachian tube during treatment with grommet was investigated by air equalisation methods. Tubal function proved poor in the great majority at the beginning of the treatment, but towards its completion there was some improvement. After extrusion of the grommet, tubal function was investigated on the same material by tympanometry. 34% had normal middle-ear pressure initially, and 43% 12-18 months after closure of the perforation. There was no relation between tubal function shown by air equalisation methods and by tympanometry, and the air equalisation methods proved of less value than tympanometry in assessing the course and prognosis of secretory otitis. The pathogenetic theories - the ex vacuo and the secretory theory - are discussed in relation to the chronic tubal dysfunction found to be the most common direct cause of the disease.

Acoustic Impedance Tests↗

Secretory otitis media. Late results of treatment with grommets.

In 108 children (184 ears) with chronic secretory otitis treated with grommets, the condition at one-to-five years follow-up was compared with that at five-to-eight years follow-up. At the latter time, hearing was extremely good, 97.5% of the ears having a speech reception threshold (SRT) of 20 dB or less. However, only 67% of patients could be classified as cured by normal tympanometry. The remaining ears showed a negative middle-ear pressure of 100 to 300 mm H2O (25%), recurrent accumulation of secretion (1.6%), adhesive otitis (3.3%), perforation (1.7%), or cholesteatoma (1%). The eardrum was normal in 44% of patients, while in 25% it was diffusely atrophic, lax, or retracted.

Adenoidectomy↗