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The purpose of the present investigation was to study the effect of delay in fixation on the mitotic activity in tumour tissue. A human osteogenic sarcoma, especially suitable for counting of mitoses, grown in athymic nude mice, was fixed... more
The purpose of the present investigation was to study the effect of delay in fixation on the mitotic activity in tumour tissue. A human osteogenic sarcoma, especially suitable for counting of mitoses, grown in athymic nude mice, was fixed with varying delay and the mitotic, prophase, metaphase and ana-telophase indices were determined. An almost exponential decline of the mitotic index was observed with a reduction to 49.4% and 15.0% after respectively 60 and 180 minutes. The proportional incidence of prophases, metaphases and ana-telophases changed so that a relative accummulation of advanced phases occured during the 180 minutes of observation. It is concluded that delay in fixation of a magnitude, which is not uncommon in routine surgical pathology, may allow the majority of mitoses to terminate, resulting in unreliable assessments of mitotic activity.
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In a follow-up study of 1 000 patients subjected to Billroth II resection for duodenal ulcer in the period 1948-1956, the late mortality up to the end of 1977 (522 patients) was analyzed. The observed mortality was compared with the... more
In a follow-up study of 1 000 patients subjected to Billroth II resection for duodenal ulcer in the period 1948-1956, the late mortality up to the end of 1977 (522 patients) was analyzed. The observed mortality was compared with the expected mortality calculated by the life-table method and indirectly standardized for age, sex, domicile and time and cause of death. The overall mortality rate was significantly increased, mainly due to suicide, which occurred at five times the expected rate and could be related to excessive alcohol consumption and psychiatric disturbances. Malignant neoplasms, including gastric carcinoma, were not more common than expected as causes of death. The same applied to pulmonary tuberculosis, other respiratory disorders, cardiovascular, gastro-intestinal and urogenital disease and to accidents. It is concluded that the main mortality risk factors were psychiatric disease and alcohol consumption.
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Effects of the tumor initiator 7,12-dimethylbenz(a)anthracene (DMBA) and of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on epidermis of human fetal and adult skin were studied in the nude mouse/human skin model. Human... more
Effects of the tumor initiator 7,12-dimethylbenz(a)anthracene (DMBA) and of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on epidermis of human fetal and adult skin were studied in the nude mouse/human skin model. Human skin grafts on NC nude mice were exposed to two topical applications of 1 mg of DMBA in 50 microliter of acetone with an interval of 3 days and/or to applications of 10 micrograms of TPA in 50 microliter of acetone twice weekly. In some animals, it was attempted to augment the susceptibility of the grafts to the tumor-initiating effect of DMBA by pretreatment with TPA or ultraviolet light. The mice were sacrificed 8-32 wk after the initial treatment. Tumors did not appear in the central portions of any of the grafts, but epidermal tumors were seen at the graft border in 34.9% of the DMBA-treated animals. To identify human epidermis on the grafts and to determine the species origin of the induced tumors, two independently working histological marker methods were applied. (a) The first is detection of a human Blood Group B-like antigen present in mouse epidermis and in chemically induced murine epidermal tumors. This antigen cannot be demonstrated in human epidermis and in epidermal tumors of human patients. (b) The second is histological staining with the DNA-specific fluorochrome, bisbenzimide, displaying a characteristic pattern of 5-10 intranuclear fluorescent bodies in murine nonneoplastic epidermal cells and in murine epidermal tumor cells. Such a pattern is not seen in human epidermis and in epidermal tumors of human patients. The studies showed that TPA treatment resulted in epidermal hyperplasia in both the human epidermis and the adjacent mouse epidermis and that the induced tumors were derived from murine tissue. The mechanisms behind the DMBA action in the nude mouse/human skin model are discussed, and suggestions for future carcinogenesis studies on the model are given.
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The purpose of the present investigation was to study the effect of delay in fixation on the mitotic activity in tumour tissue. A human osteogenic sarcoma, especially suitable for counting of mitoses, grown in athymic nude mice, was fixed... more
The purpose of the present investigation was to study the effect of delay in fixation on the mitotic activity in tumour tissue. A human osteogenic sarcoma, especially suitable for counting of mitoses, grown in athymic nude mice, was fixed with varying delay and the mitotic, prophase, metaphase and ana-telophase indices were determined. An almost exponential decline of the mitotic index was observed with a reduction to 49.4% and 15.0% after respectively 60 and 180 minutes. The proportional incidence of prophases, metaphases and ana-telophases changed so that a relative accummulation of advanced phases occured during the 180 minutes of observation. It is concluded that delay in fixation of a magnitude, which is not uncommon in routine surgical pathology, may allow the majority of mitoses to terminate, resulting in unreliable assessments of mitotic activity.
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We present a case of a previously healthy 14-month-old girl with malignant ventricular tachycardia, which developed in relation to acute gastroenteritis. Autopsy revealed histiocytoid cardiomyopathy.
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Membrane changes in keratinocytes were studied in a selected series of skin biopsies from 58 patients comprising cases of healing wounds, keratoachanthomas, actinic keratoses, Bowen's disease and squamous and basal cell carcinomas.... more
Membrane changes in keratinocytes were studied in a selected series of skin biopsies from 58 patients comprising cases of healing wounds, keratoachanthomas, actinic keratoses, Bowen's disease and squamous and basal cell carcinomas. The changes were demonstrated by means of a fluorescein-conjugated lectin ricinus communis agglutinin I, which specifically binds to beta-D-galactopyranosyl residues normally present on the keratinocyte surface. The RCA I binding equalled the binding of the normal epidermis in hyperplastic epidermis adjacent to healing wounds and in keratoachanthomas, but was slightly decreased in actinic keratoses and cases of Bowen's disease. In epidermal outgrowths from the edges of healing wounds and in squamous and basal cell carcinomas a heavy loss of RCA I binding was seen. The results are supported by previous in vivo and in vitro studies of normal and transformed cells, and it is suggested that the presented histochemical RCA I binding technique could be ...
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In order to characterize the pathomechanisms behind intraepidermal in vivo deposits of IgG, which are found in 68% of patients with primary Sjögren's syndrome (primary SS), skin biopsies and serum from patients with... more
In order to characterize the pathomechanisms behind intraepidermal in vivo deposits of IgG, which are found in 68% of patients with primary Sjögren's syndrome (primary SS), skin biopsies and serum from patients with epidermal IgG deposits were examined and compared to normal controls. Double-labelling experiments on skin biopsies, from 5 patients and 5 normal controls, showed that IgG deposits were predominantly located to surface membranes of OKT6 positive Langerhans cells. Only IgG1 and IgG3 were found deposited. Neither IgG2, IgG4, IgM, IgA, IgE, IgD, C1q, C3c, fibrinogen, albumin, beta-2 microglobulin nor C-reactive protein were found deposited in the epidermis of patients. Sera from 6 other patients with primary SS were examined for in vitro and in vivo binding of IgG to normal human epidermis. Using the athymic nude mouse/human skin model we were able to show that serum IgG from patients can be experimentally deposited in vivo in human skin transplants, but in vitro binding could not be demonstrated. The Fc-fragments of epidermal IgG were accessible to binding of anti-Fc-fragment antibodies and protein-A. We suggest that IgG-containing immune complexes constitute the intraepidermal IgG deposits seen in patients with primary SS, and that the binding possible is mediated by Fc-receptors of Langerhans cells and keratinocytes.
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Monofucosyl type 1 chain A (type 1 Aa) and difucosyl type 1 chain A (ALeb), but not other types of A antigens, have been detected by application of carrier type-specific monoclonal anti-A antibodies (AH21 and HH3) in colonic tumors of... more
Monofucosyl type 1 chain A (type 1 Aa) and difucosyl type 1 chain A (ALeb), but not other types of A antigens, have been detected by application of carrier type-specific monoclonal anti-A antibodies (AH21 and HH3) in colonic tumors of blood group O individuals. An A-transferase activity (UDP-Gal-NAc:H-alpha-GalNAc transferase) was demonstrated in the extract of one of the O tumors expressing A antigen. The incidence of A antigen expression in O tumors was found to be two out of 15 cases, based on TLC immunostaining of glycolipid extracts, and five out of 50 cases, based on immunofluorescent staining of tumors with AH21 and HH3 antibodies.
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The purpose of the present study was to investigate the axial skeleton related to the notochord in human anencephalic fetuses in order to elucidate the pathogenesis. Fifteen second trimester fetuses were examined. The spine and the... more
The purpose of the present study was to investigate the axial skeleton related to the notochord in human anencephalic fetuses in order to elucidate the pathogenesis. Fifteen second trimester fetuses were examined. The spine and the cranial base were dissected and radiographed. Comparison with normal fetuses was performed. Two patterns of abnormal ossification were seen. Anencephalic cases without cervical rachischisis (Groups I and II) differed markedly from cases with cervical rachischisis (Group III). Morphological characteristics, such as bilateral narrowing of the basilar part of the occipital bone combined with normal cranio-caudal dimension, were found in cases without cervical rachischisis. In these cases frontal clefting of vertebral corpora occurred. Caudocranial shortening of the basilar part of the occipital bone was found in cases with cervical rachischisis, where complete median clefting of vertebral corpora also occurred. Because the vertebral corpora and the basilar p...
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It has been hypothesized that carcinoma in situ of the testis (CIS), which is the precursor of invasive testicular germ cell tumours, may arise from fetal germ cells during fetal development rather than later in life. In order to... more
It has been hypothesized that carcinoma in situ of the testis (CIS), which is the precursor of invasive testicular germ cell tumours, may arise from fetal germ cells during fetal development rather than later in life. In order to corroborate this hypothesis, we undertook the present study. Normal human germ cells from 10 first-trimester fetuses and 76 second- and third-trimester testes were investigated for the immunohistochemical expression of the markers of testicular carcinoma in situ. The panel of markers included in the study consisted of placental-like alkaline phosphatase, the protooncogene c-kit protein product, and the antigens for the monoclonal antibodies TRA-1-60 and M2A. The relative numbers of fetal germ cells that demonstrated positive reaction with the markers were calculated. The vast majority of the germ cells (75-100%) in the first-trimester gonads were positive for placental-like alkaline phosphatase, TRA-1-60, and M2A. The c-kit protein was detected in three out...
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The development of the human neocortex is a complex and highly regulated process involving a time-related expression of many transcription factors including the homeobox genes Pax6 and Meis2. During early development, Pax6 is expressed in... more
The development of the human neocortex is a complex and highly regulated process involving a time-related expression of many transcription factors including the homeobox genes Pax6 and Meis2. During early development, Pax6 is expressed in nuclei of radial glia cells in the neocortical proliferative zones and controls the differentiation and neurogenetic fate of these cells in the dorsal telencephalon in rodents. Animal studies on the Meis2 gene have revealed expression in the developing telencephalon and Meis2 is known to regulate the expression of Pax6 in the eye and pancreas. Because of this functional relation between Pax6 and Meis2, we studied the spatial and temporal expression of PAX6, and MEIS2 using a developmental series of human fetal brains at 7-19 postconceptional weeks with emphasis on the forebrain to investigate whether the two genes are expressed in the same regions and zones in the same time window. We demonstrate by in situ hybridization and immunohistochemistry th...
Research Interests: Cognitive Science, Neuroanatomy, Animal Studies, Developmental neuroscience, Immunohistochemistry, and 14 moreTranscription Factors, Brain development, In Situ Hybridization, Pregnancy, Humans, Female, Animals, Early development, Transcription Factor, Single Cell, Radial Glia, Gestational Age, Homeobox genes, and Neurosciences
The aim of this radiographic study of human fetuses was to examine the pattern and sequence of ossification in the occipital bone and the spinal vertebrae. Together with previous studies of ossification of the human fetal basal cranium,... more
The aim of this radiographic study of human fetuses was to examine the pattern and sequence of ossification in the occipital bone and the spinal vertebrae. Together with previous studies of ossification of the human fetal basal cranium, this study can serve as a reference for normalcy in future studies of fetuses with neural tube defects and associated pathological development of the axial skeleton. Thirty-nine normal fetuses aborted between 9 and 14 weeks of gestation were examined. Based on the appearance of ossification centers in the bones under study, the fetuses could be grouped in four well-defined developmental stages, which were named occipito-spinal stages I-IV (OS I-IV). The OS stage was closely related to gestational age, crown-rump length, foot length, and degree of ossification in the hands and feet.
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Closure of the palatal shelves during normal prenatal palate formation is commonly supposed to be the result of a complex interaction between tissue growth processes and functional factors such as mandibular and tongue movements. The... more
Closure of the palatal shelves during normal prenatal palate formation is commonly supposed to be the result of a complex interaction between tissue growth processes and functional factors such as mandibular and tongue movements. The purpose of the present study was to analyze tongue and palatine bone positions during palatal shelf closure. The material consisted of 40 normal human fetuses (CRL 26-57 mm). The series covers the developmental stages in which palatal shelf closure takes place. The spatial relation between the tip of the tongue and the lips was examined by visual inspection, and radiographic/cephalometric methods were used for analyzing palatine bone positions. On axial radiographs of the upper jaws, the angle in the horizontal plane between the vertical plates of the palatine bones was measured. The study revealed that the vertical plates of the palatine bones rotate on their vertical axes during palatal closure, the mean interpalatine angle changing from 23.7 degrees ...
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A series of lectins were examined in order to find suitable epidermal species markers for the human skin/nude mouse model. In histological sections of formalin-fixed and paraffin-embedded material it was found that the lectins GSA I and... more
A series of lectins were examined in order to find suitable epidermal species markers for the human skin/nude mouse model. In histological sections of formalin-fixed and paraffin-embedded material it was found that the lectins GSA I and PNA could serve as suitable markers for murine and human epidermis, respectively.
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ABSTRACT A new radiography technique for examining second trimester abortions permits an accurate analysis of growth and maturation of the fetal skull. Reference material for normal development has been previously published. The potential... more
ABSTRACT A new radiography technique for examining second trimester abortions permits an accurate analysis of growth and maturation of the fetal skull. Reference material for normal development has been previously published. The potential of the method is demonstrated with three examples: thanatophoric dysplasia, Arnold-Chiari malformation, and anencephaly.
The present study reveals new data concerning the prenatal interrelationship between maturation of teeth and basicranial bones. By using radiographs of the mid-sagittal tissue segment of 43 human craniums, the developmental relationship... more
The present study reveals new data concerning the prenatal interrelationship between maturation of teeth and basicranial bones. By using radiographs of the mid-sagittal tissue segment of 43 human craniums, the developmental relationship between a well-defined stage of the central maxillary incisor development and the development of the basicranium was determined. Histological controls were performed to verify the radiographic findings. The study shows a close connection between the incisor development and the cranial development. Furthermore, comparisons are performed to the generally used parameters for prenatal growth, i.e. the crown-rump length (CRL) and the gestational age (GA). A thorough understanding of developmental interactions between the teeth and cranium is important for the understanding of normal, as well as pathological craniofacial development, including tooth development.
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Grafts of human skin on nude mice were subjected to a single dose of either 2 1/2 min or 4 min of radiation from two different commercial dental light curing units with emission mainly in the visible light spectrum but also with a small... more
Grafts of human skin on nude mice were subjected to a single dose of either 2 1/2 min or 4 min of radiation from two different commercial dental light curing units with emission mainly in the visible light spectrum but also with a small fraction of UV-A light. Seventy-two hours after exposure the tissue was examined for presence of Langerhans cells using monoclonal antibody OKT6 double layer immunofluorescence staining. Epithelial hyperplasia and reduced reactivities for OKT6 were seen after 2 1/2 min exposure. After 4 min of exposure OKT6 positive cells were completely absent from the epithelium. The results indicate that emission from dental light curing units can affect Langerhans cells in human epithelium and could thus modify the local immunologic response.
Research Interests: Dentistry, Humans, Mice, Animals, Light, and 4 moreSkin, Epithelium, Langerhans cells, and Dental Equipment
The development of the human neocortex is a complex and highly regulated process involving a time-related expression of many transcription factors including the homeobox genes Pax6 and Meis2. During early development, Pax6 is expressed in... more
The development of the human neocortex is a complex and highly regulated process involving a time-related expression of many transcription factors including the homeobox genes Pax6 and Meis2. During early development, Pax6 is expressed in nuclei of radial glia cells in the neocortical proliferative zones and controls the differentiation and neurogenetic fate of these cells in the dorsal telencephalon in rodents. Animal studies on the Meis2 gene have revealed expression in the developing telencephalon and Meis2 is known to regulate the expression of Pax6 in the eye and pancreas. Because of this functional relation between Pax6 and Meis2, we studied the spatial and temporal expression of PAX6, and MEIS2 using a developmental series of human fetal brains at 7-19 postconceptional weeks with emphasis on the forebrain to investigate whether the two genes are expressed in the same regions and zones in the same time window. We demonstrate by in situ hybridization and immunohistochemistry that the two homeobox genes are expressed during early fetal brain development in humans. PAX6 mRNA and protein were located in the proliferative zones of the neocortex and in single cells in the cortical preplate at 7 fetal weeks and in the developing cortical plate from 8 or 9 to 19 fetal weeks. The expression of PAX6 expanded into the ganglionic eminence just prior to the stage at which a stereological estimation showed an exponential rise in total cell number in this area. The MEIS2 gene was also present in the proliferative zones of the human fetal neocortex and a higher expression of MEIS2 than PAX6 was observed in these areas at 9 fetal weeks. Further, MEIS2 was expressed at a very high level in the developing ganglionic eminence and at a more moderate level in the cortical plate.
Research Interests: Cognitive Science, Neuroanatomy, Animal Studies, Developmental neuroscience, Immunohistochemistry, and 15 moreTranscription Factors, Brain development, In Situ Hybridization, Pregnancy, Humans, Female, Animals, Early development, Transcription Factor, Developmental, Single Cell, Radial Glia, Gestational Age, Homeobox genes, and Neurosciences
The purpose of this study was to describe the midline maxillofacial skeleton (the axial skeleton anterior to the sella turcica) in 15 human anencephalic fetuses (14-19 weeks of gestation) by radiography and histology, and to relate the... more
The purpose of this study was to describe the midline maxillofacial skeleton (the axial skeleton anterior to the sella turcica) in 15 human anencephalic fetuses (14-19 weeks of gestation) by radiography and histology, and to relate the findings to skeletal patterns in the remaining part of the axial skeleton. Four patterns in the maxillofacial skeleton were recognized: normal structures, slightly deformed (6 cases); cleft palate (3 cases); incomplete nasal septum (3 cases); multilocular ethmoid cartilage (3 cases). No association was found between skeletal patterns in the different parts of the axial skeleton. The study demonstrates the existence of a developmental borderline in the anencephalic axial skeleton in the region of the sella turcica. It is presumed that this borderline indicates the boundary between skeletal tissue developed around the notochord (posterior axial skeleton) and the anterior skeletal components derived from neural crest cells.
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Testicular cancer is preceded by the noninvasive stage of carcinoma in situ (CIS). According to a recent hypothesis, testicular CIA cells are germ cells transformed in fetal life. The idea of an embryonal origin of testicular germ cell... more
Testicular cancer is preceded by the noninvasive stage of carcinoma in situ (CIS). According to a recent hypothesis, testicular CIA cells are germ cells transformed in fetal life. The idea of an embryonal origin of testicular germ cell neoplasia would be strengthened by the finding of antigenic similarity between fetal germ cells, CIS cells, and invasive testicular germ cell tumors. Monoclonal antibody (MoAb) TRA-1-60 raised against a human embryonal carcinoma cell line was immunohistochemically tested on 21 fetal gonads (11 male gonads and 10 female gonads; 11th-24th week of gestation). In addition, TRA-1-60 was tested on tissue from 27 testes with CIS, 11 testes with invasive testicular cancer, and 24 adult and 4 infant testicular control specimens. Expression of TRA-1-60 was found in germ cells of six female and two male fetal gonads. In addition, 26 of 27 adult human testes with CIS, 7 of 8 seminomas, and 3 of 3 embryonal carcinomas were TRA-1-60 positive. The study demonstrated an antigenic link between fetal germ cells, cells of CIS and seminomas, and embryonal carcinomas. The results provided additional evidence for the hypothesis that testicular neoplasia arises during early fetal life and CIS cells are malignant fetal gonocytes.
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Research Interests: Cancer, Humans, Child, Castration, Male, and 5 moreCryptorchidism, Precancerous Conditions, Adult, Spermatozoa, and Germ Cell
Placental insufficiency has been considered the cause of increased morbidity in infants delivered postmaturely. Former quantitative studies have indicated a decrease in some placental structures just before term. In this study we describe... more
Placental insufficiency has been considered the cause of increased morbidity in infants delivered postmaturely. Former quantitative studies have indicated a decrease in some placental structures just before term. In this study we describe a method of dual perfusion fixation to provide tissue for stereologic examination. Postmature placentas were examined with this method. Eleven postmature placentas and 14 placentas delivered at term were fixed by dual perfusion. The volume and the surface area of villi, the trophoblast volume, and the volume, surface area, and length of villous capillaries were estimated by stereologic examination. The Mann-Whitney test (p < or = 0.05) was used for statistical analysis. Morphologic features were normal in all placentas. No significant differences were disclosed in the stereologic estimates of placentas delivered at term and postmature placentas. No morphologic or significant quantitative changes were found in postmature placentas.
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Neural tube defects (NTDs) are congenital malformations of the central nervous system (CNS) secondary to abnormal closure of the neural tube during embryonic development. This study provides information on NTD rate, distribution,... more
Neural tube defects (NTDs) are congenital malformations of the central nervous system (CNS) secondary to abnormal closure of the neural tube during embryonic development. This study provides information on NTD rate, distribution, associated morphologic anomalies and organ weights in a Danish fetal and perinatal autopsy series during a 16 year period. The data were extracted from the autopsy reports of a consecutive series of 1984 fetal and perinatal autopsies from the Copenhagen area performed in the period 1989-2004. Registered parameters included: The location and morphology of the NTD, associated morphological anomalies, and organ weights. Organ weights were evaluated according to new fetal autopsy standards and grouped as low, normal or high. Ninety-seven NTD cases were found (4.9%): Spina bifida (38 cases), cephalocele (17 cases) and anencephaly (42 cases). 63% of NTD cases had associated morphologic anomalies. Among the most common were hydrocephalus, NTD in another region, and anomalies in the urogenital system. 58% of the NTD cases had abnormal weight of one or more organs. Most notable was low adrenal weight not only in anencephalic fetuses but also in cases with cephalocele, suggesting a possible association.
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The glycosylation of epithelial cell surface antigens follows cellular differentiation, and changes in the pattern of expression are seen in various premalignant and malignant epithelial lesions. The distribution of type-2 chain... more
The glycosylation of epithelial cell surface antigens follows cellular differentiation, and changes in the pattern of expression are seen in various premalignant and malignant epithelial lesions. The distribution of type-2 chain ABH-carbohydrate structures (N-acetyl-lactosamine, H-type 2 chain, Le-y, Le-x and sialyl-Le-x) of the ABO-histo-blood group system was investigated in 19 normal fetal thymuses (gestational age 16 to 39 weeks) and in 19 thymomas in order to study possible tumor-associated changes in the glycosylation pattern. The material was investigated by immunochemical stainings of formalin-fixed paraffin-imbedded tissue using monoclonal antibodies with defined specificity. In fetal thymus the epithelial cells of the medulla and the Hassal's bodies strongly expressed elongated carbohydrate structures (Le-y, Le-x and sialyl-Le-x). In a few cases the cortical epithelial cells weakly expressed Le-x and sialyl-Le-x. Compared with fetal thymus 16 of the thymomas showed a total loss, or a very much reduced expression of elongated carbohydrate structures. Three thymomas, which histologically had been reclassified according to Kirchner & Müller-Hermelink (14) as high grade thymic carcinomas, revealed strong expression of Le-y, moderate expression of Le-x and weak expression of sialyl-Le-x. This is of interest as in other tumors Le-y is correlated with increased cell motility and with poor prognosis.
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Research Interests: Methods, Humans, Infant, Clinical Sciences, Newborn Infant, and 3 moreAge Factors, Scalp, and Skin Neoplasms
Histological samples from 60 invasive ductal breast carcinomas were investigated for immunoreactivity for the receptor for urokinase-type plasminogen activator (uPAR) with the use of two monoclonal antibodies recognizing different... more
Histological samples from 60 invasive ductal breast carcinomas were investigated for immunoreactivity for the receptor for urokinase-type plasminogen activator (uPAR) with the use of two monoclonal antibodies recognizing different epitopes. In 51 cases, uPAR immunoreactivity was observed, and in 49 of these specimens, a population of periductal tissue macrophages showed pronounced uPAR immunoreactivity in areas with infiltrating and intraductal carcinoma. In the 2 remaining positive specimens no stromal immunoreactivity was seen. The carcinoma cells were found to contain uPAR immunoreactivity in 8 of the 51 positive cases, including the two specimens that did not show stromal immunostaining. Immunoactivity was not found in the epithelial cells of carcinoma in situ components occasionally seen in the specimens, but stromal macrophage-like cells which had invaded such lesions were positive. In most specimens a subpopulation of tissue neutrophils was also positive. Normally appearing e...