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Biomedical subjects

P L Larsen

Publications and source records attributed to P L Larsen.

At least 37 records · Page 2Linked to original sources
PubMed1992

The early stages of polyp formation.

The purpose of this study is to describe polyp formation in the mucosa of the middle ear as a possible model for the pathogenesis of nasal polyps. In 65 Wistar rats, the eustachian tube was occluded on the left side for up to 20 months; 60 right-sided, nonoccluded ears served as controls. Following occlusion, the middle ear mucosa was examined for signs of polyps. Signs of polyp formation or fully developed polyps were seen in 14 (22%) of the middle ears, and were only seen in middle ears with signs of actual or previous infection. It was established that the first stages of polyp formation include epithelial rupture, proliferation of fibrous tissue through the epithelial defect, and epithelialization of the prolapsed fibrous tissue by proliferation and migration of epithelial cells from the surrounding epithelium until there is full epithelial covering of the polyp. This report discusses whether the described middle ear model may form basis for the explanation of the pathogenesis of nasal polyps.

Animals↗
PubMed1991

Origin of nasal polyps.

The nasoethmoid complexes from 6 patients with nasal polyps were systematically examined. First, the location and place of the origin of the polyps were recorded and photographed. The polyps and their places of origin were removed, serial sectioned, and examined. In all 6 patients, the polyps originated from the nasal mucosa. Most of the polyps extended laterally from the mucosa into the anterior part of the middle meatus. Several polyps originated from the mucosa near the ethmoid cell ostium or directly from the mucosa lining the edge of the ostium. The ostia themselves were not blocked by the polyps, and there was no indication of polyp formation in the ethmoid cells.

Aged↗
PubMed1991

Polyp formation by experimental tubal occlusion in the rat.

The purpose of this study was to show the early stages of polyp formation, as part of our studies on the pathogenesis of nasal polyps. Two and 4 weeks after experimental tubal occlusion in 18 Wistar rats, 13 showed signs of bacterial infection, respective acute otitis media. In the majority of these rats polypouslike protrusions of the middle ear mucosa were found in whole-mount specimens. All polypouslike protrusions were investigated by cross sections, which revealed localised accumulation of fluid and inflammatory cells in the lamina propria. The polyps were covered with a flattened epithelium, compared to the epithelium in the surroundings. In some of the bigger polyps the apical part was without epithelial covering. The findings suggest that the epithelium by fast polyp growth may be distended and may burst, or that a primary epithelial defect has not been sufficiently covered.

Animals↗
PubMed1990

Goblet cell density in nasal polyps.

The goblet cell density was determined in 29 nasal polyps from 22 patients by use of the periodic acid Schiff-alcian blue whole-mount method. The distribution of goblet cells was found to be extremely irregular, ranging from areas completely devoid of goblet cells to areas with a relatively high density. The median density varied from 280 cells/mm2 to 10,000 cells/mm2. The total median density for all 15 polyps located anteriorly in the nose was 3,450 cells/mm2, compared with 6,050 cells/mm2 for 14 posteriorly located polyps. The density was highest in pseudostratified, cylindric epithelium, although great variations occurred among the different areas with this type of epithelium. The goblet cell density may be influenced by several factors, such as the airflow, type and thickness of the epithelium, and whether the genesis of the nasal polyps is infectious or allergic, in addition to polyp growth, size, and age.

Basement Membrane↗
PubMed1989

The whole-mount method as a technique for measuring experimental changes in airway goblet cell number.

The whole-mount staining method for mucous membranes was introduced as an experimental technique for measuring goblet cell density and for estimating the degree of goblet cell hyperplasia in the trachea of experimental animals. By this technique it was demonstrated that a single intratracheal instillation of lysed extract from human neutrophilic granulocytes in rats after 3 weeks caused a three-fold increase in the density of tracheal goblet cells as compared to control animals receiving saline. The increase is of 3-6 times greater magnitude than previously reported in similar experiments where the number of goblet cells was calculated from cross sections in a traditional manner. It was further shown that the increase in goblet cell density could be prevented if prednisone was given to the animals prior to and during the experiment. It is concluded that the whole-mount preparation method is a useful tool in the quantitation of airway goblet cells in experimental settings, and that it appears to be a more sensitive method than the traditionally used cross section techniques.

Animals↗
PubMed1989

Nasal polyps: epithelium and goblet cell density.

The density of goblet cells was determined in 14 anterior and 15 posterior nasal polyps using the whole-mount method. The specimens were then serial cut and the type of epithelium was determined in nine localities in each polyp. The goblet cell density was correlated to the epithelial type. Pseudostratified, cylindrical epithelium was the prevailing type, occurring in 62% of anterior localities and 78% of posterior localities. Transitional types of epithelium were found in 33% of the anterior and 19% of the posterior localities. Stratified squamous epithelium occurred in 5% and 3%, respectively. The goblet cell density was highest in hyperplastic pseudostratified epithelium, whereas it was four times lower in transitional epithelium and even lower in squamous epithelium. Marked differences in the distribution of epithelium and goblet cell density were found between anterior and posterior polyps, illustrating that the epithelium constantly changes under the influence of air current, contact with other polyps, infection, growth, and age of the polyp as well as other unknown factors.

Cell Count↗
PubMed1988

Mapping protein-DNA interactions in vivo with formaldehyde: evidence that histone H4 is retained on a highly transcribed gene.

We have used formaldehyde-mediated protein-DNA crosslinking within intact cells to examine the in vivo chromatin structure of the D. melanogaster heat shock protein 70 (hsp70) genes. In agreement with previous in vitro studies, we find that the heat shock-mediated transcriptional induction of the hsp70 genes perturbs their chromatin structure, resulting in fewer protein-DNA contacts crosslinkable in vivo by formaldehyde. However, contrary to earlier in vitro evidence that histones may be absent from actively transcribed genes, we show directly, by immunoprecipitation of in vivo-crosslinked chromatin fragments, that at least histone H4 remains bound to hsp70 DNA in vivo, irrespective of its rate of transcription. The formaldehyde-based in vivo mapping techniques described in this work are generally applicable, and can be used both to probe protein-DNA interactions within specific genes and to determine the genomic location of specific chromosomal proteins.

Animals↗
PubMed1988

IgD in nasopharyngeal secretions and tonsils from otitis-prone children.

Quantification of IgD was performed by ELISA in 180 plasma samples and 83 nasopharyngeal secretions (NPS) from children aged 2-162 months with varying degrees of recurrent otitis media. Furthermore, in 24 of the children the density of the IgD-immunocytes (IgD-cells) was calculated in immunoenzyme-stained cross-sections of their nasopharyngeal tonsils (NPT). Owing to a considerable variation of the IgD cell density throughout the NPT, a semi-quantitative counting system was applied. An irregular distribution of plasma IgD was observed during childhood and maximum levels were found between 48 and 72 months of age. However, an even distribution of plasma IgD was found among the four groups of children investigated. Based on calculations of the transudation of albumin from plasma to the NPS the amount of locally produced IgD in NPS (NPS-IgD (local] was estimated to 88% (range 41-99%). Significantly higher levels of NPS-IgD (local) were found in otitis-prone children than in the other groups. Moreover, a positive correlation was calculated between levels of NPS-IgD (local) and NPT-IgD cell density, indicating that NPT, being the local lymphoepithelial tissue, also functions as an important source of NPS-IgD. NPS-IgD was not found to be associated with secretory component, indicating a passive transfer of IgD through the mucosal membranes. Our results support the hypothesis of an association between the occurrence of IgD in the mucosa and secretions of the upper respiratory tract with localized inflammatory events.

Acute Disease↗
PubMed1988

Cholesteatomas of the temporal bone. Preoperative C-T versus peroperative findings.

In a series of 25 ears with chronic otitis media the correlation between findings obtained by preoperative C-T of the temporal bone and observations made at surgery was evaluated. The study was performed "blindly", i.e., neither the radiologist nor the surgeon had any knowledge of the other's findings. Cholesteatoma prediction varied with location. Similar observations were made in respect to granulation tissue and erosions. A relatively high percentage of false positives and false negatives was found even in this rather small sample. To obtain better results by C-T, close co-operation and exchange of information between clinician and radiologist appears necessary, along with an explorative attico-antrotomy as a regular part of the operation.

Adolescent↗
PubMed1987

Adenovirus E1A gene autorepression: revertants of an E1A promoter mutation encode altered E1A proteins.

Revertants have been isolated from Ad3hr15, a mutant of human adenovirus type 3 that carries a defective E1A promoter. Transcription of these revertant E1A genes is restored--from nil for Ad3hr15 mutant to levels exceeding that of the wild-type virus. The mutant Ad3hr15 virus and the revertants all have an aberrant E1A promoter that contains two short tandem duplications of viral DNA sequence. The E1A gene-coding region of the mutant is the same as that for wild-type adenovirus type 3, whereas the revertants are characterized by short in-frame deletions within the 5' exon region of their E1A genes. Location of these reverting, second-site deletions is discussed in relation to E1A gene autoregulation and the evolved diversity of E1A-related oncogenic potential among different human adenoviruses.

Adenovirus Early Proteins↗
PubMed1986

An E1A mutant of adenovirus type 3: Ad3hr15 has reiterated DNA sequences 5' to its E1A gene.

Defective variants of adenovirus type 3 (Ad3) have been isolated from a heterogeneous, high multiplicity passage stock of the virus. A strikingly defective variant, Ad3hr15, fails to propagate on normally permissive A549 cells, yet has greater infectivity than wild type Ad3 in the adenovirus type 5 (Ad5) DNA-transformed 293 cell line. Investigation of its genomic alterations revealed that Ad3hr15 bears two short tandem duplications of viral DNA sequences near its left end, 5' to the E1A gene. The variant also bears a large tandem triplication at its right end. Marker rescue experiments with plasmid-cloned left end DNA sequences of Ad3 implicate that the duplications 5' to E1A are responsible for the Ad3hr15 defect and the E1A structural gene of the variant is functional. Northern analysis revealed no detectable E1A transcripts early after Ad3hr15 infection of A549 cells. The 293 cell line, however, supports high levels of transcription of the Ad3 E1A gene by the mutant Ad3hr15 E1A promoter.

Adenovirus Early Proteins↗
PubMed1986

Autoregulation of adenovirus E1A gene expression.

We examined E1A gene expression by two evolutionarily divergent human adenoviruses, type 5 (subgroup C) and type 3 (subgroup B). Adenovirus type 3 (Ad3)-infected A549 cells contained much larger amounts of E1A-specific RNA than adenovirus type 5 (Ad5)-infected cells, from very early (3 h) through the late stages (20 h) after infection. The appearance of such abundant Ad3 E1A transcripts was delayed after infection of Ad5 E1A-expressing 293 cells, suggesting a down regulation of the Ad3 E1A gene by Ad5 E1A gene products. In a reciprocal manner, coinfection of A549 cells led to typically early and intense Ad3 E1A transcription and strongly inhibited transcription of the Ad5 E1A gene. Transient expression assays were developed so that the autoregulation of the E1A gene could be studied apart from the more complex background of infected cells. The DNA sequence surrounding the transcription start site of the Ad3 E1A gene was placed 5' to the sequence which encodes the bacterial chloramphenicol acetyltransferase gene. Cotransfection of HeLa cells with Ad3 or Ad5 E1A-expression plasmids increased the expression of the Ad3 E1A promoter-driven chloramphenicol acetyltransferase gene. Taken together, these results suggest dual autoregulatory features of adenovirus E1A gene expression. The positive and negative effects appear to be temporally distinguished under different conditions, both in viral infection and in transient assays with plasmid-cloned genes.

Acetyltransferases↗
PubMed1985

Spontaneous reiterations of DNA sequences near the ends of adenovirus type 3 genomes.

Repeated passage of adenovirus type 3 in HeLa cells has led to a novel stock of variant genomes. Most of the DNA molecules in this stock are characterized by deletions and substitutions of DNA sequences near the left end of the adenovirus type 3 genome map, as reported earlier (C.C. Robinson and C. Tibbetts (1984) Virology 137, 276-286). In this report the characterization of the variant genomes is extended and reveals elongated DNA molecules bearing tandem repetitions of viral DNA sequences near the left and right ends of the viral DNA. Evidence is also presented supporting the cellular DNA origin of short insert sequences found in substitution variants. The elongated variants are of interest because of their novel repeated DNA structures. The locations of these aberrant sequences raise questions about their potential impact on viral gene expression.

Adenoviruses, Human↗
PubMedDate not supplied

DNA content in adenoid cystic carcinomas.

BACKGROUND: A retrospective study was performed on 51 patients with adenoid cystic carcinomas to see whether DNA ploidy, tumor stage, and histopathologic grading correlated with prognosis. METHODS: Histopathologic grading was performed according to Szanto et al and DNA content was estimated from archived material using the technique by Hedley et al. RESULTS: Thirty-nine tumors were DNA diploid and 12 were DNA aneuploid. Histologic grade III was more often associated with DNA aneuploidy than the lower grades (p = 0.011). DNA ploidy also correlated with clinical stage (p = 0.011). Log-rank analysis and Cox regression analysis of treatment failures revealed significant findings for S-phase value and DNA ploidy. CONCLUSIONS: Our results indicate that DNA ploidy estimations, S-phase value, and histologic grading are prognostic factors in adenoid cystic carcinomas. These examinations should therefore be incorporated in the evaluation of patients with adenoid cystic carcinomas.

Adult↗
PubMedDate not supplied

Nasal glands and goblet cells in chronic hypertrophic rhinitis.

Partial turbinectomies were done in 13 patients suffering from chronic hypertrophic rhinitis. The mucous membranes were fine-dissected, and mucous elements were stained and counted using the PAS-alcian blue whole-mount method. Cross-sections were made from the whole-mount specimens. There was a great variety of epithelial types. Comparison of the density of mucous elements in normal patients and patients with chronic hypertrophic rhinitis revealed no statistically significant differences.

Adult↗