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Biomedical subjects

K Heikinheimo

Publications and source records attributed to K Heikinheimo.

At least 37 records · Page 2Linked to original sources

Developmental and cyclic adenosine 3',5'monophosphate-dependent regulation of inhibin subunit messenger ribonucleic acids in human fetal testes.

Inhibin subunit messenger ribonucleic acids (mRNAs) are expressed during the gonadal development of rodent, ovine, and bovine fetuses. We investigated the expression of inhibin subunit mRNAs in human fetal gonads between 13 and 25 weeks of gestational age. In testes, the alpha-subunit mRNA was highly expressed at the beginning of the second trimester and its expression level slightly decreased thereafter. Also the beta B-subunit mRNA was detected throughout this time period but no significant developmental change could be observed. Northern analysis showed a 1.6-kilobase (kb) transcript for alpha-chain, as well as two bands of about 5.0 and 4.5 kb for the beta B-subunit. A human Leydig cell tumor also expressed the 1.6-kb alpha-subunit. By filter hybridization studies, the beta A-chain mRNA could not be observed in testes and none of the three inhibin subunits were detectable in the ovaries at this developmental stage. However, reverse-transcription polymerase chain reaction analysis revealed the expression of all three inhibin subunit mRNAs in testes. As studied by in situ hybridization, inhibin alpha-subunit hybridization signal was most intense in seminiferous tubules and weaker hybridization was observed in interstitial cells of the fetal testis. In primary cultures of fetal testicular cells, dibutyryl cAMP (0.2 mmol/L) stimulated alpha- and beta B-mRNAs. It augmented alpha- and beta B-mRNA accumulation up to 6- and 2.5-fold, respectively. Thus, we conclude that: 1) during the second trimester of gestation, human fetal testes express all three inhibin subunit mRNAs, although the beta A-chain expression appears to be low; 2) during this developmental stage inhibin subunit mRNAs are not detectable in ovaries; 3) in human fetal testes, the alpha-chain mRNA is localized to both intratubular and interstitial cells; 4) in cultured human testicular cells, inhibin alpha- and beta B-subunit mRNAs are regulated by a cAMP-dependent pathway.

Animals↗

Transforming growth factor-alpha (TGF-alpha) and insulin gene expression in human fetal pancreas.

Transforming growth factor-alpha (TGF-alpha) mRNA is expressed in several pancreatic cancer cell lines, but its expression during normal fetal pancreas development has not been studied. We investigated the expression of TGF-alpha, its receptor (EGF-R) and insulin mRNA and their corresponding peptides in human fetal pancreata (15-20 gestation weeks). Polymerase chain reaction (PCR) and RNAase protection analysis revealed that TGF-alpha and insulin mRNAs were detectable in pancreas during the developmental span studied. In northern blot analysis a single band of 4.8 kilobases (kb) corresponding to the TGF-alpha transcript and a 0.6 kb for the insulin mRNA were detected in the pancreas. Using in situ hybridization, TGF-alpha mRNA expression was seen in a low copy number in both the exo- and endocrine pancreas. By immunohistochemistry TGF-alpha-immunoreactive cells were detected in the ducts, acini and islets showing that the mRNA was translated into protein. By contrast, insulin transcripts were detected in a high copy number, restricted to the islets of Langerhans. However, monoclonal insulin antibody detected less insulin containing cells than could be expected from the mRNA pattern suggesting that fetal beta-cells rapidly secrete insulin instead of storing it in the secretory granules. Alternatively, the translation of insulin mRNA could be inefficient. By double labeling the pancreas sections with polyclonal TGF-alpha antiserum and monoclonal insulin antibody the TGF-alpha- and insulin-like immunoreactivity was localized to beta-cells. Furthermore, mRNA for the TGF-alpha receptor, EGF-R, together with EGF-R-immunoreactive cells were also present in pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)

ErbB Receptors↗

Expression of different cytokeratin subclasses in human chordoma.

A detailed immunohistochemical characterization of different cytokeratin subclasses was performed on frozen tumour tissue from three classical chordomas. Simple epithelium cytokeratins Nos 8, 18, and 19 were detected in all tumour cells while cytokeratin No. 7 was not found. Cytokeratins characteristic of squamous differentiation, including keratinization, were generally lacking, with the exception of the varying expression of cytokeratin No. 4. Vimentin was found in all the tumours, while they lacked desmin immunoreactivity. The present study indicates the co-expression of vimentin and cytokeratins, predominantly of the simple epithelium type. In addition, chordoma cells have the ability to express cytokeratins characteristic of squamous differentiation. This finding corresponds well to the electron microscopic findings of tonofilament bundles ending in well-developed desmosomes.

Antibodies, Monoclonal↗

Distribution of extracellular matrix proteins in odontogenic tumours and developing teeth.

The distribution of two cellular fibronectins (cFn), tenascin, laminin, as well as type VII collagen was studied in 14 benign odontogenic tumours of epithelial (ameloblastoma) and epithelial-ectomesenchymal (ameloblastic fibroma) origins, as well as in developing human teeth by immunocytochemical means using monoclonal antibodies (Mabs). An extradomain sequence-A-containing form of cFn (EDA-cFn) was seen in the extracellular matrix (ECM) of all tumours studied and in the mesenchyme of the developing tooth germs, indicating that cFn in these tissues are predominantly produced locally. A form of cFn containing an oncofetal domain (Onc-cFn), hitherto found only in carcinomas, was detected focally in the stroma of most ameloblastomas but was absent from ameloblastic fibromas and tooth germs. Tenascin was strongly expressed in the basement membrane (BM) zone of all odontogenic tumours and in that of the early tooth germs. Focal absence of laminin and type VII collagen from the BM of some ameloblastomas and the presence of Onc-cFn in the ECM of most ameloblastomas may correlate with their aggressive behaviour. The results also suggest that EDA-cFn and tenascin are involved in epithelial-mesenchymal interactions during tooth development and in odontogenic tumours.

Adolescent↗

Expression of p21RAS in odontogenic tumors.

Using an immunohistochemical assay 10 benign odontogenic tumors were evaluated for expression of the HRAS- and KRAS-encoded gene products p21RAS. Overexpression of p21RAS was found in ameloblastomas, ameloblastic fibromas and odontogenic myxomas compared with normal human developing teeth. The highest expression was noted in a recurrent plexiform ameloblastoma in which almost 100% of the tumor cells were brightly reactive. In general, p21RAS was preferentially expressed in ectodermal cells of odontogenic tumors, consistent with the findings in the tooth germs. The significance of p21RAS expression is considered in relation to the biological behavior of ameloblastomas.

Gene Expression↗

Cytoskeletal gene expression in normal and neoplastic human odontogenic epithelia.

In situ and Northern hybridization was carried out to study cytokeratin (Ck) 1, 4, 8, 18, and 19 and vimentin (Vim) gene expression in 13- to 24-week-old human fetal tooth germs, including overlying oral epithelium and odontogenic tumors (N = 6) of epithelial (ameloblastoma) and epithelial-ectomesenchymal (ameloblastic fibroma) origin. The results were compared with immunocytochemistry using monoclonal antibodies. A relatively strong expression of simple epithelial Ck 19 mRNA, together with low, but significant expression of Ck 8 and 18 mRNAs, was demonstrated in all normal and neoplastic odontogenic epithelia studied. Transcripts for squamous differentiation marker, Ck 4, and for terminal differentiation marker, Ck 1, were detected suprabasally in the fetal oral epithelium, focally in the dental lamina but not in the enamel organ. Ck 4 mRNA was expressed variably in most odontogenic tumors studied, whereas Ck 1 mRNA was detected in one ameloblastoma only. Vim mRNA was not found in the fetal oral epithelia, dental lamina or the enamel organ, but a distinct immunoreactivity with monoclonal antibodies to Vim was seen in the stellate reticulum cells of the enamel organ. The epithelium of most ameloblastomas showed a focal Vim mRNA and polypeptide expression. In addition to Vim, the neoplastic ectomesenchymal cells of ameloblastic fibroma coexpressed low amounts of simple epithelial Cks 8, 18, and 19. The results indicate that the differentiation and cytoskeletal gene expression programs of odontogenic epithelia upon neoplastic transformation are not fully retained. Most ameloblastomas and ameloblastic fibromas show differentiation parameters reminiscent of dental lamina. Ameloblastomas seem to form a heterogenous group of tumors, which may originate from odontogenic epithelial cells at various differentiation levels. The origin of ameloblastic fibroma is more closely related to the tooth germ proper.

Ameloblastoma↗

In situ hybridization using single-stranded antisense RNA probes in oral pathology research.

In situ hybridization is a new molecular biological technique which has made it possible to demonstrate messenger RNA (mRNA) transcription of a specific gene in tissue sections and in cell preparations. In addition to the immunocytochemical methods widely used to locate gene products, e.g. a protein, nucleic acid hybridization techniques are having growing impact in pathological research. Increasing availability of cloned nucleotide sequences of human genes and the recent development of very sensitive and specific hybridization methods is rapidly expanding the field of gene function studies in cell and tumour biology. As with immunocytochemical techniques, hybridization techniques require proper controls for specificity. A basic knowledge of molecular biology is essential to determine the optimal conditions for successful hybridization and to interpret the results correctly.

Antisense Elements (Genetics)↗

Non-Hodgkin's lymphomas presenting through oral symptoms.

Non-Hodgkin's lymphomas (NHL) presenting through oral symptoms are rare. Between 1976 and 1987, a total of 17 cases (7 male, 10 female) were diagnosed in our departments. The first symptom was an intraoral tumour mass in 9 cases, loosening of teeth in 2 cases and paraesthesia in another 2. Most tumours (13/17) were located in the lower jaw. In only 5 cases had the referring physician or dentist suspected malignancy. In 3 cases, the histological diagnosis was Burkitt's lymphoma. The grade of malignancy was classified as low in 4 cases, intermediate in 3 and high in 8. None of the patients was HIV-positive. Nine patients died of their disease within 1-132 months (mean 18.3 months).

Adolescent↗

A longitudinal study of occlusal interferences and signs of craniomandibular disorder at the ages of 12 and 15 years.

Occlusal interferences and signs of craniomandibular disorder (CMD) were studied longitudinally in 167 Finnish adolescents at the ages of 12 and 15 years in order to evaluate their importance for orthodontic diagnosis. Of the adolescents sampled 16.8 per cent had received orthodontic treatment. The results showed that occlusal interferences and signs of CMD are quite common. Of the 12-year-olds 25.7 per cent and 30.5 per cent of the 15-year-olds showed palpatory tenderness of the muscles of mastication. Clicking sounds were recorded for 6 per cent of the 15-year-olds. Opening capacity increased with age. Only tow of the adolescents at the age of 12 and none at the age of 15 fulfilled the criteria of functionally optimal occlusion. The number of occlusal interferences increased between 12 and 15 years of age. Both occlusal interferences and clinical signs of CMD were inconsistent in nature. Mediotrusion contracts and protrusion interferences were found to be the most stable occlusal interferences at adolescence. As to pain on mouth opening, the symptom group at the age of 15 consisted of entirely new individuals. No single sign or CMD symptom, nor combination of them, was consistent enough for inclusion in orthodontic screening indices. However, even though the symptomatology changed, only a few of those considered to be symptomatic at the age of 12 were asymptomatic at the age of 15. In accordance with the present state of knowledge, it would thus seem appropriate to add a general statement about the presence or absence of CMD signs and/or symptoms to orthodontic screening indices.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

A botryoid odontogenic cyst with multiple recurrences.

A botryoid odontogenic cyst (BOC) which recurred 4 times over a period of 9 years is presented. Immunocytochemical comparison of cytokeratin composition of the cyst epithelium with that of the overlying oral epithelium showed distinct differences. The cyst epithelium expressed keratins typical of both simple and nonkeratinizing squamous epithelia. The keratin profile of BOC is in line with previous findings on odontogenic epithelia, thus confirming its odontogenic origin.

Epithelium↗

Symptoms of craniomandibular disorder in a sample of Finnish adolescents at the ages of 12 and 15 years.

Subjective symptoms of craniomandibular disorder (CMD) were studied longitudinally in 167 children at the ages of 12 and 15 in order to investigate their importance for orthodontic diagnosis. The results showed that symptoms are quite common in adolescents (64-67 per cent). However, most of the adolescents experienced their symptoms only occasionally. Frequent occurrence of various, single symptoms of CMD varied from 0 to 7.2 per cent. Recurrent headache was reported by 24 per cent of the adolescents at the age of 12, and by 22 per cent of them at the age of 15. The number of reported symptoms did not increase between the ages of 12 and 15 years, which is in agreement with other studies. The symptoms of CMD did not appear to be consistent. Locking of the joint was found to be the most stable symptom. About 50 per cent of those reporting TMJ-clicking, unexplainable ear symptoms or bruxism at the age of 12, had lost this symptom by the age of 15. For pain on mouth-opening, the symptom group at the age of 15 consisted of entirely new individuals. Because of their inconsistent nature during the final stages of occlusal development, too much attention should not be paid to single occurrences of CMD symptoms. In individual cases, however, important information for diagnosis and treatment planning can be obtained. Symptoms of craniomandibular disorder, recurrent headache, and oral parafunctions should be elicited and recorded at annual dental check-ups of children and adolescents.

Adolescent↗

Patterns of expression of intermediate filaments in ameloblastoma and human fetal tooth germ.

Monoclonal antibodies (Mab) were used to study the expression of cytokeratins and vimentin in various histological types of ameloblastoma and in human fetal tooth germ. The ameloblastoma and the tooth germ epithelia showed characteristics of both simple glandular and stratified squamous epithelial cells. Cytokeratin No. 18 was detected focally in most ameloblastomas studied but not in fetal odontogenic epithelia. Cytokeratins Nos. 8 and 19 were expressed in all epithelial elements of ameloblastomas and tooth germs. Only two tumors showed focally characteristics of keratinizing epithelia also seen in dental lamina but not in the enamel organ. All tumors except the granular cell ameloblastoma showed a variable coexpression of vimentin and cytokeratins in their neoplastic epithelia. A similar coexpression was detected in the stellate reticulum cells of the developing tooth. Ameloblastoma and human tooth germ epithelia share complex pattern of cytokeratin polypeptides together with coexpression of vimentin. The results strongly support the theory that ameloblastomas are of odontogenic origin and not direct derivatives of basal cells of oral epithelium or epidermis.

Adolescent↗

Expression of intermediate filaments (IF) in tissues and cultured cells.

Intermediate filaments are found in most nucleated cells as part of their cytoskeleton. Intermediate filaments are formed by different proteins in cells of major tissues types. Therefore, antibodies against intermediate filaments can be used in tissue typing, in the analysis of cell lineages during development and in the elucidation of the origin of unknown tumors.

Animals↗

Introduction to immunocytochemistry.

Immunocytochemistry has opened a new era in research and diagnosis. The development of immunocytochemical methods has made it possible to identify in situ normal and pathological tissue constituents, which it has not been possible to detect using ordinary histological methods. However, immunocytochemical techniques involve several pitfalls, which without proper control protocols can easily lead to incorrect findings. When interpreting the results obtained, account must always be taken of the morphological findings from routine histological sections. In other words, it is essential to understand the principles of these methods as well as to have enough basic knowledge in the field of research interest for making correct conclusions of the immunocytochemical findings.

Humans↗