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L Saxén

Publications and source records attributed to L Saxén.

At least 19 recordsLinked to original sources
PubMed1992

Epithelial-mesenchymal interactions in murine organogenesis.

Reciprocal, sequential interactions between embryonic epithelial and their mesenchymal stroma guide the cytodifferentiation and organization of both components. These morphogenetic interactions and their consequences are examined in two model systems in vitro: the mouse metanephric blastema and the tooth rudiment. Experimental approaches include dissection and recombination of the interacting tissues, localization of molecular changes by immunohistology and in situ hybridization. An early response of the mesenchyme is increased proliferation of cells in the vicinity of the epithelial inductor and their subsequent aggregation (condensation). In the kidney model disruption of this aggregation or prevention of assembly of the programmed cells results in impaired cytodifferentiation. If the cells are allowed to reaggregate, a phenotype is expressed not unlike that seen in normal in vivo conditions. Our present interest is focused on the early metabolic events associated with the condensation phenomenon. The cell surface proteoglycan syndecan and the matrix glycoprotein tenascin are expressed in the condensed mesenchyme and may mediate cell-matrix interactions. The expression patterns of certain growth factors suggest functions in signal transduction.

Animals↗
PubMed1992

Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney.

Induction of the embryonic kidney mesenchyme is followed by formation of cell aggregates which subsequently transform into epithelial tubules. Syndecan, which binds various matrix components and growth factors, is a candidate molecule to be involved in this process. We have analyzed the changes in the expression of syndecan during tubule morphogenesis by using in situ hybridization and slot-blot analysis. The expression pattern of syndecan was compared with the distribution of cell proliferation analyzed by immunohistochemistry. Furthermore, the expression of syndecan during formation of the pretubular aggregates was studied in hanging-drop cultures of experimentally induced mesenchymal cells. Syndecan mRNA was expressed in the metanephric mesenchyme prior to induction, was intensely present during formation of the pretubular cell aggregates, but was lost during maturation of the nephron. Slot-blot analyses of the kidney mesenchymes (11-day kidney) cultured in a transfilter situation with a heterotypic inductor tissue that triggers a complete tubulogenic program in the nephric mesenchyme during the first 24 hr suggested the presence of syndecan mRNA in the uninduced mesenchymes with no change during induction. Expression of mRNA was stimulated later (13-day kidney) followed by subsequent decrease. Immunoisolation of sulfate-labeled syndecan, however, revealed a marked stimulation in the induced kidney mesenchyme during the first 24-hr inductive period when the DNA level still remained constant. In hanging-drop cultures where either induced or uninduced mesenchymal cells were dissociated and reaggregated, syndecan was detected only in the induced and aggregating mesenchymal cells. Double-immunostaining demonstrated a close correlation between syndecan expression and cell proliferation analyzed by bromodeoxyuridine incorporation. Thus, it appears that syndecan expression in the mesenchyme is initially induced post-transcriptionally and later during differentiation at the mRNA level. Syndecan may have a dual function during early kidney morphogenesis; it may be involved in cell aggregation through its adhesive properties, and it may contribute to proliferation of the induced mesenchymal cells by binding growth factors.

Animals↗
PubMed1992

The accident at Chernobyl and trisomy 21 in Finland.

Our objective was to explore whether the radiation fallout in Finland after the accident at the Chernobyl nuclear power plant in April 1986 led to an increased incidence of trisomy 21. In this geographic and temporal cohort study, the country was divided into three zones according to the amounts of radioactive fallout and internal radiation caused by two cesium isotopes. The 518 cytologically verified cases of trisomy 21 were divided into a control group (conceived before the accident), and a study group of children whose expected dates of birth were in the post-accident years 1987-1988, i.e., pregnancies commenced after May 1986. The cases were also divided into three subgroups according to the zones of radiation. There were no significant differences in prevalence of trisomy 21 between the control and study groups nor between the three zones in spite of the significant differences in the levels of radiation and in the body burden that prevailed throughout the study period. Power estimates showed that in the two zones of lower radiation, an increase of 0.5% in the prevalence would have been detected with a power of 0.85, and in the somewhat smaller zone of the highest radiation, with a power of 0.70. The study lends no further support to the view that the low radiation fallout in western Europe would have been causally associated with trisomy 21.

Accidents↗
PubMed1992

Puberty-associated gingivitis.

In a 2-yr follow-up study gingival condition was related to oral hygiene and different stages of puberty in 88 14-yr-old Finnish schoolchildren. Visible plaque and gingival bleeding after probing were determined from six teeth, at four sites each. Bitewing radiographs were taken from the molar areas. These examinations were repeated 2 yr later. The pubertal stage of the subjects was determined at the age of 14 by the school physician based on the classification of Tanner according to breast development (M) in girls and genital development (G) in boys. All subjects were in the somatic period of puberty at the time of the baseline examination. No radiographically detectable bone loss was found in either of the examinations. There was no difference in the gingival bleeding tendency at various pubertal stages when all subjects were included or when boys and girls were compared separately. Instead, a highly significant correlation was found between gingival bleeding and visible plaque, both at the baseline and 2 yr later. The results indicate that from the age of 14 to 16 the influence of oral hygiene on the gingival condition may be more important than that of the rising level of steroid hormones.

Adolescent↗
PubMed1992

[3H]-adenine metabolism and radiation damage during in vitro development of the kidney.

We followed the early post-induction changes in nucleic acid synthesis of the metanephric kidney anlage in vitro. Enhanced incorporation of [3H]-thymidine and [3H]-adenine was detected, but several factors were shown to influence the interpretation of such in vitro experiments. The incorporation is dependent not only on the stage of development of the target organ but also on its transfer to organ culture, as early rudiments require an "adaptive" pre-cultivation to stabilize their metabolism; at more advanced stages growth and DNA synthesis proceed without delay. Another potential artifact is radiation damage which is caused by the incorporated radioisotope and can be detected in prolonged cultures. A [3H]-adenine pulse of more than 1 microCi/ml for 2 hr leads to definite growth retardation, and a 10-microCi/ml pulse causes extensive cell death and atrophy on a 4- to 6-day subculture. The radiation damage is dose-dependent and of variable severity in the different cell lineages within the organ. Since the radioisotope doses were in the range of those commonly used for monitoring cell proliferation and metabolism, we stress the risk of obtaining artifactual results, especially in prolonged cultures after pulse-labeling.

Adenine↗
PubMed1992

Differential expression of gap junction mRNAs and proteins in the developing murine kidney and in experimentally induced nephric mesenchymes.

The expression of three gap junction (GJ) proteins, alpha 1 (Cx43), beta 1 (Cx32), and beta 2 (Cx26), and their transcripts were examined during the ontogeny of the mouse and rat kidney. These proteins were expressed in two non-overlapping patterns. The alpha 1 GJ protein was first observed in mesenchymal cells in the 12-day mouse kidney. By day 14 and thereafter, the alpha 1 protein was detected in the transient S-shaped bodies, but not in the podocytes of the maturing glomeruli. After birth the antigen was retained in a small subset of secretory tubules. The beta 1 and beta 2 GJ proteins were similar in their developmental patterns. They were first detected in a small subset of secretory tubules in the subcortical zone of day 17 embryos. These tubules were identified by immunohistochemical markers to be proximal. At birth, practically all proximal tubules expressed the two antigens. This analysis of GJ proteins was consistent with the results of S1 nuclease protection assays showing that, while the alpha 1 mRNA appeared early during kidney development and declined around birth, the two beta mRNAs appeared later and became intensified during the last days of intrauterine development. In experimentally induced metanephric mesenchymes, a transient expression of the alpha 1 GJ protein was seen during the segregation of the tubular anlagen. beta 1 and beta 2 GJ proteins were not detected in such induced mesenchymes cultivated up to 7 days. These observations provide evidence for the cell-specific utilization of different GJ genes during different stages of kidney organogenesis. The alpha 1 gene is activated during the early segregation of the secretory tubule and might contribute to its compartmentalization, while the beta 1 and beta 2 gene products are not detected until advanced stages of development. The latter gene products might be correlated with the physiological activity of the proximal tubules in vivo, as they are not expressed in experimentally induced tubules detectable with markers for proximal tubules.

Animals↗
PubMed1991

Anencephaly and maternal common cold.

To study the risk of anencephaly related to common cold during pregnancy, a case-control study was made. The series comprised 393 Finnish mothers of anencephalic children and their time-area-matched controls in the period 1964 through 1982. Seventy mothers of anencephalic infants and 17 controls had reported common cold in the first trimester [adjusted odds ratio 4.5; 95% confidence interval (2.2-9.1)]. Reported common cold in the second trimester was not associated with anencephaly. As suggested by our previous cohort study in the same population, a true viral influenza resembling "common cold" might not explain the observed association.

Anencephaly↗
PubMed1991

Pregnancy outcome in Finland after the Chernobyl accident.

The explosion at the Chernobyl nuclear power plant caused radioactive fallout in Finland in April-May 1986. The fallout was unevenly distributed geographically, and, accordingly, the country was divided into 3 fallout zones. Whole-body radioactivity measurements of randomly chosen persons showed that the regional differences prevailed throughout the following 2 years. Data for legal abortions, registered congenital malformations as well as preterm births and stillbirths of malformed children were collected. The corresponding expected figures were obtained from statistics from 1984 and 1985. No differences in the expected/observed rates of the above parameters were detected.

Abnormalities, Radiation-Induced↗
PubMed1991

Collagenase activity in gingival crevicular fluid of patients with juvenile periodontitis.

The nature and origin of collagenases in gingival crevicular fluid of juvenile periodontitis patients was investigated. Gingival crevicular fluid collected from deep untreated periodontal pockets of juvenile periodontitis patients was found to contain only vertebrate collagenase (EC 3.4.24.7) activity that cleaved soluble type-I and -III collagens into 3/4 and 1/4 length fragments, as analyzed by SDS-polyacrylamide gel electrophoresis. Type II collagen was degraded at a markedly slower rate. This substrate specificity is indicative of collagenases produced by fibroblasts, epithelial cells and macrophages. We have previously found that collagenase in gingival crevicular fluid of adult periodontics patients appears to be mainly derived from polymorphonuclear leukocytes (PMN). The reasons for the apparent difference in collagenase source between the groups were investigated. We examined whether the pathogen characteristic for juvenile periodontitis, Actinobacillus actinomycetemcomitans, can release collagenase from normal human PMNs. All 10 A. actinomycetemcomitans strains tested, freshly isolated from the subgingival plaque of juvenile periodontitis patients, caused release of collagenase from PMNs in vitro. These results suggest that the lack of normally functioning PMNs in the periodontium of juvenile periodontitis patients may result in a colonization of bacteria that activate the resident periodontal cells to produce increased amounts of collagenase.

Aggregatibacter actinomycetemcomitans↗
PubMed1991

Immunohistochemical localization of epidermal growth factor receptors in human gingival epithelia.

Epidermal growth factor (EGF) is a small molecular weight polypeptide which is thought to have important functions in epithelial growth and differentiation and in wound healing. EGF exerts its action on cells through binding to a cell surface receptor. Using immunohistochemistry and a monoclonal antibody (mAb) directed against the EGF receptor, we have examined gingival specimens of periodontally healthy individuals and patients with adult adult (AP) and juvenile periodontitis (JP), as well as epithelial cell rests of Malassez. EGF receptors were expressed at high levels on the cell surface of basal cell layers of gingival epithelium. In normal junctional epithelium, on the other hand, specific labeling was faint or negative, indicating that receptors are poorly expressed or absent in these cells. No differences were detected between uninflamed gingival specimens of periodontally healthy subjects and of patients with JP. Instead, in biopsies of inflamed tissue from AP patients, an intense cell surface labeling was revealed in proliferating epithelial cells. Moreover, the epithelial cell rests of Malassez bound the antibody intensely. The results suggest that EGF is involved in control of epithelial growth and differentiation in periodontal tissues.

Adolescent↗
PubMed1991

Recovery of A. actinomycetemcomitans from teeth, tongue, and saliva.

The recovery of actinobacillus actinomycetemcomitans simultaneously from subgingival sites around teeth and dorsum of the tongue and/or saliva was examined in 293 subjects at 444 visits; 295 paired samples were available from subgingival sites and tongue, 171 paired samples from subgingival sites and stimulated saliva, and 137 paired samples from subgingival sites and unstimulated saliva. Sixty-one subjects were periodontally healthy (mean age 20.3 years); 55 exhibited localized juvenile periodontitis (mean age 21.8 years); 176 adult periodontitis (mean age 46.7 years); and 1 prepubertal periodontitis (age 10 years). When A. actinomycetemcomitans was recovered from subgingival sites, it was also found in 56.3%, 69.9%, and 35.9% of the paired samples from tongue, and stimulated and unstimulated saliva, respectively. No difference in the detection rate of A. actinomycetemcomitans from tongue or stimulated saliva was seen between the subjects with healthy or diseased periodontium. When A. actinomycetemcomitans was not recovered from subgingival sites, it was cultured in 6.8%, 2.0%, and 1.4% of the paired samples from tongue, and stimulated and unstimulated saliva, respectively. In search for noninvasive, inexpensive, and easily run sampling methods for the recovery of oral A. actinomycetemcomitans samples from stimulated saliva and tongue may prove useful in clinical periodontology.

Actinobacillus↗
PubMed1990

The long-term efficacy of systemic doxycycline medication in the treatment of localized juvenile periodontitis.

The presence of Actinobacillus actinomycetemcomitans in the deep periodontal pockets of patients with localized juvenile periodontitis has been causally associated with active periodontal destruction. Thus, eradication of this microorganism has become the goal of treatment. It has been postulated that such eradication cannot be achieved without systemic antimicrobial treatment. The efficacy of a semisynthetic tetracycline (doxycycline) in a double-blind follow-up study of 14 patients with localized juvenile periodontitis was evaluated. For assessment of the periodontal status, probing depth and bleeding after probing at 4 sites of all teeth were recorded. The treatment consisted of instruction in oral hygiene, scaling and root planing, periodontal surgery and systemic medication for 2 weeks with either doxycycline (Doximycin) or placebo. A. actinomycetemcomitans was cultivated from subgingival samples taken from 4 sites. The periodontal condition and the prevalence of A. actinomycetemcomitans were monitored at the baseline and at 2, 8 and 20 months. The periodontal condition improved in both groups; the only significant difference was a greater reduction in the prevalence of A. actinomycetemcomitans 8 months after treatment with doxycycline as compared with the placebo.

Actinobacillus↗
PubMed1990

The immediate efficacy of adjunctive doxycycline in treatment of localized juvenile periodontitis.

A randomized, double-blind, placebo-controlled study on the immediate clinical and microbiological efficacy of doxycycline (100 mg for 14 days) was carried out to determine the benefit of adjunctive medication in 16 patients with localized juvenile periodontitis. Measurements of gingival fluid flow, probing depths, bleeding on probing and suppuration were determined at 2 periodontal sites with and 2 without radiographic attachment loss, at weeks 0, 1, 3 and 8. Subgingival bacterial samples were taken with curettes from the same sites. Spirochaetes were searched for by dark-field microscopy. Actinobacillus actinomycetemcomitans, pigmented and non-pigmented Bacteroides spp., Capnocytophaga, Fusobacterium and Actinomyces spp. were cultured on various selective and non-selective media. Bacterial species found at least in 50% of the patients and comprising on average 5% or more of the cultivable flora were included in the analysis. Neither short-term clinical nor microbiological efficacy beyond that of a course of mechanical debridement alone was found by using systemic medication with doxycycline in patients with localized juvenile periodontitis.

Actinobacillus↗
PubMed1990

Phagocyte function in juvenile periodontitis.

We studied the chemotaxis of peripheral blood polymorphonuclear leukocytes (PMNs) and monocytes and the production of tumor necrosis factor alpha by monocytes of patients with juvenile periodontitis (JP). As a group, the patients' PMNs showed significantly increased chemotaxis determined by counting the number of migrating cells within a 3-microns-pore-size filter. Determined as distance of migration within the filter, as chemotactic increment based on checkerboard analysis, as leukotactic index calculated on the basis of distance of migration and cell count at different depths within a 3-microns-pore-size filter, as distance of migration under agarose, and as the number of PMNs migrating across a 5-microns-pore-size filter, the chemotactic migration rates of PMNs of patients were similar to those of controls. Evaluation of the data on an individual basis suggested that in terms of PMN chemotaxis some patients were hyperresponsive and some were hyporesponsive. Chemotaxis, spontaneous migration, and the rates of lipopolysaccharide-induced tumor necrosis factor alpha production by JP monocytes were similar to those of control cells. Our results give credence to the view that there are minor aberrations in the functions of JP phagocytes, but the extent to which these aberrations are relevant to accumulation of PMNs at sites of infection and inflammation in vivo and possibly contribute to the pathogenesis of JP remains unclear.

Adolescent↗
PubMed1990

Influenza epidemics and anencephaly.

To explore the postulated association between maternal influenza and congenital defects of the central nervous system, 14 virologically verified epidemics in Finland, 1969-82, were studied. Mothers of 248 anencephalic children were grouped into those whose first trimester had occurred during an epidemic period and those whose pregnancy had commenced during a non-epidemic period. No significant differences in prevalence of anencephaly were noted in these groups.

Adult↗