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H Sariola

Publications and source records attributed to H Sariola.

126 records · Page 7Linked to original sources

Breast tumors with a solid and uniform carcinoid pattern. Ultrastructural and immunohistochemical study of two cases.

Two cases of breast tumors with a uniform solid carcinoid pattern and argyrophilic dense-core granules were analyzed by immunohistochemistry in order to compare their characteristics with known features of other carcinoid tumors and ordinary breast carcinomas. The tumors were positive for keratin-type intermediate filaments, neuron-specific enolase and alpha-chain of human chorion gonadotropin but negative for vimentin and S-100 protein. Laminin was found only in a rim between tumor cell islands and stroma but not among the cells. It is concluded that these tumors are histologically, ultrastructurally and immunohistochemically similar to other carcinoid tumors. The present results suggest that both breast carcinoids and carcinomas may have a common precursor in the mammary secretory unit.

Aged↗

Interspecies chimeras: an experimental approach for studies on embryonic angiogenesis.

Most studies on the growth of vessels have so far focused on the tumour vascularization or that occurring in the area of inflammation. The mechanisms of embryonic angiogenesis have not been characterized in such a detail and only relatively few experimental studies have been carried out to analyse the origin and development of the embryonic vasculature. It is not known if the vessels develop in situ in each organ rudiment or by invasion of earlier committed vascular cells. Because morphological analyses of in vivo tissues have proved to be unreliable for judging the origin of vascular cells, new methods have been presented. Nuclear differences between of some species can be used to trace the origin of cells in interspecies transplantation experiments. This review presents data on the biology of vasculogenesis and shows how interspecies chimeras can be used in studies on angiogenesis. For example, the transplantation experiments with embryonic kidneys are described in more detail.

Angiogenesis Inducing Agents↗

Extracellular matrix and epithelial differentiation of Wilms' tumor.

Different histologic types of 82 Wilms' tumors were graded on the basis of the histologic pattern. Representative tumors of each group were analyzed by the immunoperoxidase method for evaluation of the histogenesis of Wilms' tumor and the value of antibodies against extracellular matrix (ECM) components (collagens I and III, laminin, fibronectin) in differential diagnosis of different types of Wilms' tumors. The tubules of classic Wilms' tumor expressed laminin, which could be seen also in and around some blastemal cells. Blastema and tubules were negative for interstitial collagens, but Type I and III collagen were prominent in the fibrovascular stroma. The monomorphous tubular, psammomatous and rosetting tumors expressed laminin, but no interstitial collagens. In sarcomas, only the blastemal variant of spindle-cell sarcomas was negative for interstitial collagens, which were abundantly seen in all other sarcomas. While spindle-cell sarcomas were devoid of laminin, the highly malignant rhabdoid and clear-cell sarcomas expressed laminin in a characteristic dotted fashion. Staining for fibronectin gave varying results and had therefore only a limited value in distinguishing different types of Wilms' tumors. However, the antibodies against interstitial collagens and against the basement membrane glycoprotein laminin turned out to be a useful adjunct in differential diagnosis and classification, especially of sarcomatoid Wilms' tumors. The basement membrane of normal nephrons is similar to that in tubules of triphasic Wilms' tumor, but the ECM of blastemas is different. This transformed phenotype might represent a maturation arrest of the blastemal cell when compared with the expression of proteins during normal nephrogenesis.

Adenocarcinoma↗

Organogenesis.

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Animals↗

Dual origin of glomerular basement membrane.

The histogenesis of renal basement membranes was studied in grafts of avascular, 11-day-old mouse embryonic kidney rudiments grown on chick chorioallantoic membrane (CAM). Vessels of the chick CAM invade the mouse tissue during an incubation period of 7-10 days and eventually hybrid glomeruli composed of mouse epithelium and chick endothelium form. Formation of basement membranes during this development was followed by immunofluorescence and immunoperoxidase stainings using polyclonal and monoclonal antibodies against mouse and chick collagen type IV and against mouse laminin. These antibodies were species-specific as shown in immunochemical and immunohistologic analyses. The glomerular basement membrane contained both mouse and chick collagen type IV, demonstrating its dual cellular origin. All other basement membranes were either exclusively of chick origin (mesangium, vessels) or of mouse origin (tubuli, Bowman's capsule).

Allantois↗

Extracellular matrix and capillary ingrowth in interspecies chimeric kidneys.

The migration of capillaries into mouse embryonic kidneys grafted on quail chorioallantoic membrane (CAM) was analyzed by two monoclonal antibodies against quail endothelial and haematopoietic cells. As shown by immunohistochemistry, the quail chorioallantoic vessels invaded the kidney explant. Initially, the capillaries were detected in the interstitial stroma and, soon thereafter, tightly adjacent to the branches of the ureteric bud. The induced mesenchymal cell condensates, the prospective nephric vesicles, were avascular, but when the early S-shaped body was formed, the capillaries invaded its lower crevice. Finally chimeric glomeruli consisting of mouse podocytes and quail endothelial cells, were formed and, contemporarily, the capillaries ceased to migrate. Within the endothelial-mesangial area of the chimeric glomeruli, all cells expressed the quail-type nuclear structure and were stained by the quail endothelial-specific antibodies. The pattern of migrating capillaries was compared to the distribution of the extracellular matrix (ECM) molecules by double staining with polyclonal antibodies against laminin or fibronectin, and monoclonal quail endothelial-specific antibodies. Initially, the capillaries migrated in a fibronectin-rich matrix, devoid of laminin, but when the epithelial kidney tubules formed, some capillaries attached to the newly formed epithelial basement membrane. At no stage were the capillaries seen to penetrate the epithelial basement membrane. The orderly branching of the ureteric bud, followed by the formation of nephrons and the shift in the ECM, might create pathways for an oriented capillary migration. The fibronectin-rich areas could be a scaffold for the capillary migration, and the attachment to the basement membranes a means for their cessation.

Animals↗

Incomplete fusion of the epithelial and endothelial basement membranes in interspecies hybrid glomeruli.

Avascular, undifferentiated mouse kidneys transplanted onto quail chorioallantoic membrane differentiate and become vascularized by quail vessels. The glomeruli which form under these conditions consist of mouse podocytes and quail endothelial cells. Immunohistochemistry has shown that the glomerular basement membrane (GBM) has a dual origin, as integral basement membrane components are produced by both podocytes and endothelial cells. In electron microscopy this GBM is composed of two partially separated layers, an epithelial and an endothelial basal lamina which both have a lamina densa and a lamina rara. These two basal laminas are partially fused, but there are large areas where this fusion does not occur. In some places of incomplete fusion, fibrillar extracellular material is seen between and beneath the GBM. It is concluded that basement membrane components derived from the different species can interact partially, but the fusion is incomplete. The abnormal assembly of the epithelial and the endothelial basal laminas might be due to molecular differences between the components produced by the two cell lineages. In spite of the incomplete fusion, the system used serves as a good model-system to study basement membrane formation, since the cells organize in a histiotypic fashion and form true vascularized glomeruli.

Animals↗

Pathology of fetal congenital nephrosis: immunohistochemical and ultrastructural studies.

The kidneys of four human fetuses aged 18 to 20 weeks of gestation with congenital nephrosis of the Finnish type (CNF) were studied by immunohistochemistry and electron microscopy to elucidate the pathogenesis of the disease. The immunohistochemical stainings for laminin, type IV collagen, fibronectin, brushborder antigens (BBA), Tamm-Horsfall protein (TH), and binding of wheat germ agglutinin (WGA) did not reveal changes as compared to the age-matched control kidneys. Proximal tubules of the CNF kidneys showed excessive accumulation of coarse granular alpha fetoprotein (AFP) and large absorption droplets with paracrystalline and membraneous structures were seen in electron microscopy. The dilated tubules were both of proximal and distal origin as judged from the BBA and TH stainings. It is suggested that the formation of the dilated tubules results from degeneration caused by obstruction and excessive protein loading of the tubular epithelium. Demonstration of the coarse granular AFP in the proximal tubular epithelium and lumina indicates heavy fetal proteinuria and serves as an additional diagnostic marker for prenatal CNF.

Female↗

Cellular origin of fibronectin in interspecies hybrid kidneys.

The cellular origin of fibronectin in the kidney was studied in three experimental models. Immunohistochemical techniques that use cross-reacting or species-specific antibodies against mouse or chicken fibronectin were employed. In the first model studied, initially avascular mouse kidneys cultured on avian chorioallantoic membranes differentiate into epithelial kidney tubules and become vascularized by chorioallantoic vessels. Subsequently, hybrid glomeruli composed of mouse podocytes and avian endothelial-mesangial cells form. In immunohistochemical studies, cross-reacting antibodies to fibronectin stained vascular walls, tubular basement membranes, interstitium, and glomeruli of mouse kidney grafts. The species-specific antibodies reacting only with mouse fibronectin stained interstitial areas and tubular basement membranes, but showed no reaction with hybrid glomeruli and avian vascular walls. In contrast, species-specific antibodies against chicken fibronectin stained both the interstitial areas and the vascular walls as well as the endothelial-mesangial areas of the hybrid glomeruli, but did not stain the mouse-derived epithelial structures of the kidneys. In the second model, embryonic kidneys cultured under avascular conditions in vitro develop glomerular tufts, which are devoid of endothelial cells. These explants showed fluorescence staining for fibronectin only in tubular basement membranes and in interstitium. The avascular, purely epithelial glomerular bodies remained unstained. Finally, in outgrowths of separated embryonic glomeruli, the cross-reacting fibronectin antibodies revealed two populations of cells: one devoid of fibronectin and another expressing fibronectin in strong fibrillar and granular patterns. These results favor the idea that the main endogenous cellular sources for fibronectin in the embryonic kidney are the interstitial and vascular cells. All experiments presented here suggest that fibronectin is not synthesized by glomerular epithelial cells in vivo.

Allantois↗

Differentiation and vascularization of the metanephric kidney grafted on the chorioallantoic membrane.

The origin and development of mouse kidney vasculature were examined in chorioallantoic grafts of early kidney rudiments and of experimentally induced explants of separated metanephric mesenchymes. Whole kidney rudiments developed into advanced stages, expressed the segment-specific antigenic markers of tubules and the polyanionic coat of the glomeruli. In contrast to development in vitro, these grafts regularly showed glomeruli with an endothelial component and a basement membrane expressing type IV collagen and laminin. The glomerular endothelial cells in these grafts were shown to carry the nuclear structure of the host. This confirms the outside origin of these cells and the true hybrid nature of the glomeruli. When in vitro induced mesenchymes were grafted on chorioallantoic membranes, abundant vascular invasion was regularly found but properly vascularized glomeruli were exceptional. Uninduced, similarly grafted mesenchymal explants remained avascular as did the undifferentiated portions of partially induced mesenchymal blastemas. It is concluded that the stimulation of the host endothelial cells to invade into the differentiating mesenchyme requires the morphogenetic tissue interaction between the ureter bud and the mesenchyme. The induced metanephric cells presumably start to produce chemoattractants for endothelial cells at an early stage of differentiation. Kidney development thus seems to require an orderly, synchronized development of the three cell lineages: the branching ureter, the induced, tubule-forming mesenchyme, and the invading endothelial cells of outside origin.

Allantois↗

The origin of the glomerular endothelium.

The origin of the glomerular endothelium has remained unsettled, although it has mostly been assumed that it is derived from the metanephric mesenchyme, like, the other parts of the nephron. Since our recent observations did not support this concept, the development of the vasculature of the kidney and of the glomerular endothelium was studied using both mouse/quail and quail/chick interspecies grafts. Undifferentiated 11-day mouse kidney anlagen were transplanted onto quail chorioallantoic membrane and allowed to develop for 7-10 days. Upon examination, grafts were well-vascularized, and both the glomerular and the vessel endothelium expressed the quail nuclear marker. Similar results were obtained in quail/chick transplantation experiments. Hence, we suggest that the endothelium of the glomeruli is derived from outside vasculature rather than by conversion of cells in the nephrogenic mesenchyme.

Animals↗

Other neurotrophic factors: glial cell line-derived neurotrophic factor (GDNF).

Glial cell line-derived neurotrophic factor (GDNF) was first discovered as a potent survival factor for midbrain dopaminergic neurons and was then shown to rescue these neurons in animal models of Parkinson's disease. GDNF is a more potent survival factor for dopaminergic neurons and the noradrenergic neurons of the locus coeruleus than other neurotrophic factors, and an almost 100 times more efficient survival factor for spinal motor neurons than the neurotrophins. The members of the GDNF family, GDNF, neurturin (NTN), persephin (PSP), and artemin (ART), have seven conserved cysteine residues with similar spacing, making them distant members of the transforming growth factor-beta (TGF-beta) superfamily. Like the members of the neurotrophin family, the GDNF-like growth factors belong structurally to the cysteine knot proteins. Like neurotrophins, GDNF family proteins are responsible for the development and maintenance of various sets of sensory and sympathetic neurons but, in addition, GDNF and NTN are also responsible for the development and survival of the enteric neurons, and NTN for parasympathetic neurons. All neurotrophins bind to the p75 low-affinity receptor, but their ligand specificity is determined by trk receptor tyrosine kinases. GDNF, NTN, PSP, and ART mediate their signals via a common receptor tyrosine kinase, Ret, but their ligand specificity is determined by a novel class of glycosylphosphatidylinositol (GPI)-anchored proteins called the GDNF family receptor alpha (GFR alpha). GDNF binds preferentially to GFR alpha1, NTN GFR alpha2, ART GRF alpha3, and PSP GFR alpha4 as a co-receptor to activate Ret. GFR alpha4 has until now been described only from chicken. Although the GDNF family members signal mainly via Ret receptor tyrosine kinase, there is recent evidence that they can also mediate their signals via GFR alpha receptors independently of Ret. The GDNF family of growth factors, unlike neurotrophins, has a well-defined function outside the nervous system. Recent transgenic and organ culture experiments have clearly demonstrated that GDNF is a mesenchyme-derived signaling molecule for the promotion of ureteric branching in kidney development. NTN, ART, and PSP are also expressed in the developing kidney, and NTN and PSP induce ureteric branching in vitro, but their true in vivo role in kidney morphogenesis is still unclear.

Animals↗

The prevalence and context of family violence against children in Finland.

The prevalence and context of violence against children in their families was surveyed as part of a study on the sexual abuse of children. A random sample of 409 comprehensive school classes with approximately 9,000 15-year-olds was asked to anonymously fill out questionnaires. The majority filled out the questionnaires in the privacy of the school nurse's office, the rest in their classrooms. Of the selected classes, 88.8% participated in the survey, and the response rate of the students in those classes was 96%. Mild violence (slapping, pushing, etc.) was reported by 72% of the respondents, and severe violence (hitting with a fist, kicking, use of weapons) was reported by 8%. Violence was committed by the parents sometime before the children reached age 14. Incidents of violence during the year preceding the survey were reported by 19% and 5%, mild and severe, respectively. Mild violence was committed slightly more often by mothers than fathers. Severe violence was perpetrated more frequently by fathers. Girls reported mild abuse more often than boys. Severe violence was experienced equally often by both sexes. Children living with single mothers reported less-than-average mild violence, but more frequent severe violence. The highest incidence of severe violence was found among youth living in families with a stepfather. Unemployment in a family tended to increase both mild and severe violence. Violence was reported least often by children living in farming families or Swedish speaking families (which make up about 6% of Finnish population). Overall the frequency of violence toward children in Finland is significantly lower than in the U.S. Comparison to Sweden seems to show an identical level of child abuse, although different study methods make comparisons difficult.

Adolescent↗

Myocardial function and postmortem myocardial histology in children given anthracycline therapy for cancer.

In an autopsy series of children with cancer, histopathologic myocardial changes caused by anthracyclines (A) were evaluated. The series comprised three groups: group A, 9 patients given A whose myocardial function had been evaluated before death; group B, 10 patients given A, but no lifetime echocardiographic evaluation; group C, 8 patients treated with chemotherapy regimens not including A. Both the cumulative A dose (P < 0.01) and the age of the patient at death (P < 0.001) were correlated with the pathologic changes in the myocardium. In echocardiography of group A patients, left ventricular (LV) contractility was subnormal in 5 (56%) patients, and the afterload was elevated in 3 (33%); the morphologic changes correlated with the LV wall stress (= afterload) (P < 0.05) and with LV fractional shortening (P < 0.04). We conclude that clinical decisions about A therapy should be based on cumulative A dose and myocardial function tests. Myocardial biopsies should be restricted to selected cases.

Adolescent↗