Biomedical subjects
L Saxén
Publications and source records attributed to L Saxén.
Oral polio vaccination during pregnancy: lack of impact on fetal development and perinatal outcome.
Prompted by a nascent epidemic of poliomyelitis in Finland, a mass vaccination program with live oral poliovirus vaccine (OPV) was implemented in February and March 1985. The final rate of coverage was approximately 94%. Pregnant women were included, and a cohort study was launched to evaluate any harmful effects of OPV on the developing embryo. All records of births to mothers who were pregnant during the period of vaccination and whose infants were delivered at the three major hospitals in the Helsinki area were reviewed. Within the study cohort, mothers were grouped into three categories according to their trimester of pregnancy during the program. In addition, two reference cohorts were evaluated; these cohorts consisted of infants delivered at the same hospitals during the second half of 1984 and of 1986, respectively. Each of the three categories in the study cohort included approximately 3,000 children, while each reference cohort included approximately 6,000 children. Data were analyzed on the rate of intrauterine growth and the prevalences of stillbirth, neonatal death, congenital malformation, premature birth, perinatal infection, and neurological aberration. No differences were documented among the study and reference cohorts or among the three categories within the study cohort. Thus, under the conditions described here, the inclusion of pregnant women in programs of mass vaccination with OPV appears to be safe.
[Hans Spemann, the founder of modern developmental biology].
Hans Spemann (1869-1941), Nobel laureate of 1935, is one of the most remarkable biologists of the 20th century and the founder of modern experimental embryology (developmental biology). His embryonic separation experiments contributed greatly to the long-lasting debate between the advocates of the theories of preformation vs. epigenesis, and his subsequent transplantation experiments laid the basis of the concept of embryonic induction. The first of these classic experiments can be precisely dated to May 8, 1921, when one of Spemannn's students, Hilde Pröscholdt, performed a transplantation experiment with a fragment of a new gastrula blastopore lip. The dates, operation strategies and findings have recently been confirmed when the original experimental protocols and slides were found. The findings and the idea of induction were published in 1924, and this fundamental paper is still widely quoted. As shown by a citation analysis, the article is today collecting an increasing number of quotations reflecting a Renaissance of the field. For the Finnish school of development biology, Spemann and his basic ideas have been of pivotal importance.
Neuronal characteristics in embryonic renal stroma.
The metanephric mesenchyme is considered a homogeneous population of predetermined, but pluripotent cells with a nephrogenic bias. By an inductive stimulus, the mesenchyme is programmed to differentiate into the various epithelial phenotypes of the secretory nephron. A fraction of the mesenchymal cells, however, remains in the interstitium between the nephrons and differentiates into spindle-shaped, clear-cytoplasmic renal stroma. We have analyzed the molecular nature of these cells in order to discover the specific cell types that could be involved in the morphogenetic processes during kidney differentiation. In situ hybridization reveals neurofilament light protein mRNA, and immunohistology shows neurofilament light and medium proteins in the stromal cells around kidney tubules. By immunohistochemistry these peritubular stromal cells can be distinguished from the neuronal cells of the renal microganglion: the peritubular stromal cells are neurofilament-positive but L1 neural cell adhesion protein-negative, whereas the neuronal cells with axonal extension are both neurofilament-positive and L1 neural cell adhesion protein-positive. Proliferation index of the stromal cells was low as compared to tubular cells, as shown by bromodeoxyuridine incorporation.
Oral polio vaccination during pregnancy: no increase in the occurrence of congenital malformations.
To examine the possible association between maternal vaccination with oral polio-virus and congenital malformations of the child, use was made of a nationwide mass vaccination in Finland. During a restricted period in 1985, a vaccination with trivalent oral poliovirus was implemented with coverage of 94% of the population. The study population was chosen from three major hospitals in the Greater Helsinki Region in Finland which deliver over 95% of the children of their catchment area. One study and two reference cohorts were delineated; the former consisted of pregnancies that were in their first trimester during the vaccination period. The two reference cohorts included mothers from the same hospitals whose pregnancies were likewise in the first trimester during the corresponding time period in 1984 and 1986, i.e., 12 months before and after the study period. Each cohort consisted of approximately 3,000 mothers/children whose delivery and hospital records were manually perused by trained nurses. All the structural malformations reflecting an impaired organogenesis during the sensitive first trimester were monitored. A total of 209 (2.3%) such malformations were recorded and characterized. There were no differences between the study and reference cohorts (risk ratio = 0.7, 95% confidence interval 0.5-1.0). According to the authors' power estimate, an additional prevalence greater than 0.5% would have been detected. The authors conclude that administration of oral poliovirus vaccine during early pregnancy was not associated with an elevated risk of congenital malformations.
Spemann's organizer: models and molecules.
Explore the source record for details and available documents.
Metronidazole in the treatment of localized juvenile periodontitis.
Systemic metronidazole and tetracycline were compared as adjunctive agents in the treatment of localized juvenile periodontitis (LJP). 27 patients with Actinobacillus actinomycetemcomitans-positive (Aa) LJP were treated with scaling and rootplaning, control of oral hygiene and periodontal surgery if indicated. The patients were randomly divided into 3 equal groups: the 1st group had metronidazole 200 mg x 3 x 10 days, the 2nd tetracycline 250 mg x 4 x 12 days, the 3rd group received no medication and served as a control. 6 patients had periodontal surgery. 4 sites with the most advanced bone loss as determined on radiographs were selected in each subject for test sites. Gingival index, gingival bleeding after probing (GB), probing depth (PD), suppuration, and radiographic bone loss were registered, and subgingival Aa was selectively cultured. GB and PD > or = 4 mm were registered in the whole dentition as well. All parameters were monitored at baseline and at 6 and 18 months after treatment. By the end of the study, Aa was suppressed to below detection level at all test sites only in the metronidazole group, at 17/26 sites (4 patients) in the tetracycline group and at 19/26 sites (6 patients) in the control group. Clinically, all groups showed improvement. In conclusion, metronidazole was more effective than tetracycline in the suppression of Aa and the suppression of Aa appeared to produce better clinical results.
Specific antibodies against Actinobacillus actinomycetemcomitans in serum and saliva of patients with advanced periodontitis.
The aim of the present study was to discover any possible correlation between specific antibodies against Actinobacillus actinomycetemcomitans (A.a.) in serum and saliva. The test group consisted of 38 patients aged 31-68 yr (mean 49) with advanced periodontitis. Twenty-nine subjects aged 23-67 yr, without periodontal destruction, formed a control group with a reference level of specific salivary antibodies against A.a. A subgingival plaque sample for culturing A.a., a specimen of stimulated whole saliva, and a sample of venous blood were taken from each subject of the test group. Specific IgG and IgA antibodies against A.a. were determined from serum and stimulated whole saliva by means of the ELISA test. Fifteen of the patients (39%) had cultivable A.a. Six of the 15 A.a. culture-positive patients and one of the 29 reference subjects exhibited very high antibody titers against A.a. in saliva. Specific IgG and IgA antibodies in saliva correlated highly significantly with the corresponding antibody values in serum among the patients in the test group. It was concluded that among patients with severe adult periodontitis, the less invasive saliva sample has a diagnostic value equal to that of the serum sample concerning specific antibodies against A.a.
Increased rate of salivary epidermal growth factor secretion in patients with juvenile periodontitis.
We compared salivary epidermal growth factor (EGF) concentrations in patients with juvenile periodontitis (JP) and periodontally healthy controls. In initial screening of 45 JP patients and a group of healthy controls, significantly higher salivary EGF concentrations were measured in the JP patients. Subsequently, 17 JP patients who had high EGF concentrations in some of their salivary samples were chosen, and a group of age- and sex-matched controls was selected. We then examined their EGF concentrations and EGF secretion rates under standardized conditions in stimulated and unstimulated saliva and studied the expression of EGF receptor (EGF-R) in their gingival tissues. The results showed that the mean EGF concentration (pmol/ml) was slightly higher in JP patients than in controls. However, the difference was statistically significant only in stimulated saliva and when calculated per milligram salivary protein. When EGF release was measured as the rate of EGF secretion (pg/min), significantly higher values were observed in JP patients than in controls both in unstimulated and stimulated saliva. Immunofluorescence microscopy (IF) of gingival samples from JP patients and their controls revealed no quantitative or qualitative differences in the expression of EGF-R. Our results demonstrate the complex nature of salivary EGF release. The elevated rate of salivary EGF secretion in JP patients may be associated with the pathogenetic mechanisms of juvenile periodontitis.
[Incidence of Down syndrome and prenatal diagnosis during the years 1984-88 in Finland].
Explore the source record for details and available documents.
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.
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.
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.
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.
[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.
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.
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.