Development of the myocardium of the atrioventricular canal and the vestibular spine in the human heart.

To establish the morphogenetic mechanisms underlying formation and separation of the atrioventricular connections, we studied the remodeling of the myocardium of the atrioventricular canal and the extracardiac mesenchymal tissue of the vestibular spine in human embryonic hearts from 4.5 to 10 weeks of development. Septation of the atrioventricular junction is brought about by downgrowth of the primary atrial septum, fusion of the endocardial cushions, and forward expansion of the vestibular spine between atrial septum and cushions. The vestibular spine subsequently myocardializes to form the ventral rim of the oval fossa. The connection of the atrioventricular canal with the atria expands evenly. In contrast, the expression patterns of creatine kinase M and GlN2, markers for the atrioventricular and interventricular junctions, respectively, show that the junction of the canal with the right ventricle forms by local growth in the inner curvature of the heart. Growth of the caudal portion of the muscular ventricular septum to make contact with the inferior endocardial cushion occurs only after the canal has expanded rightward. The atrioventricular node develops from that part of the canal myocardium that retains its continuity with the ventricular myocardium.

Dystrophin expression in the developing conduction system of the human heart.

Duchenne muscular dystrophy (DMD) is frequently associated with myocardial involvement. Dystrophin, the DMD protein, is found at the plasmamembrane of striated muscle fibers. Although dystrophin is missing in most or all muscle fibers of DMD patients, cardiac muscle is not as severely affected as skeletal muscle. Therefore it is of great importance to study the expression of dystrophin in normal cardiac muscle. We performed immunohistochemical studies and examined cardiac muscle of fetuses of 8 to 13 weeks of development on dystrophin expression. At these stages dystrophin is observed in the myocytes of the developing ventricular conduction system and in the atrial cardiomyocytes. Dystrophin was absent from the heart of a 12-week-old DMD fetus.

Cell surface glycoconjugates and the extracellular matrix of the developing mouse embryo epicardium.

Cell surface glycoconjugates and the extracellular matrix (ECM) of the proepicardium and the developing epicardium were studied in early mouse embryos by light and electron microscopy with histochaemical and immunocytochaemical techniques. The extracardially located proepicardium consists of polarized mesothelial cells forming the proepicardial vesicles. These vesicles contain a fine proteoglycan network and an acellular ECM rich in hyaluronic acid. Membrane-bound glycoconjugates are shown with cuprolinic blue, alcian blue and ruthenium red on the apical (outer) cell surface, while fibronectin and laminin are present on the basal (luminal) cell surface. These membrane and matrix components of the proepicardium might be involved in specific attachment of proepicardial cells to the bare heart tube and might facilitate the initial migration of epicardial cells over the myocardial surface. In the cell coat of the cardiomyocytes of the bare heart tube the fibronectin and laminin are concentrated in patches. The formation of the epicardial covering is a rapid process, requiring only about 2 days (9-11 days) to ensheath the entire heart tube from the inflow to the outflow segment. The subepicardial matrix between the newly formed epicardial covering and myocardial layer is acellular at first, but contains a condensing proteoglycan network, membrane and matrix fibronectin, type IV collagen and laminin on the myocardial cell surface. The formation and the distribution of the subepicardial ECM show regional characteristics. The accumulating ECM forms wide subepicardial spaces and protuberances in the atrioventricular and interventricular sulci. The sulci of the heart seem to provide the optimum microenvironment for haematopoiesis and vasculogenesis. Haematopoietic islands and coronary vessel forerunners appear and concentrate in the regularly spaced surface protuberances. The vasculogenesis proceeds from the inflow to the outflow segment of the heart. The first blood capillaries appear in the sinoatrial sulcus of the 10-day embryo. By 11-13 days the subepicardial blood vessels form an interconnected network and establish the coronary artery orifices.

Early development of quail heart epicardium and associated vascular and glandular structures.

As in the other vertebrates the epicardium of the quail embryo develops from proepicardial tissue located between the sinus horns and the liver primordium. The cuboidal cells of the coelomic lining above the proepicardium are transformed into mesothelial cells which in cooperation with the underlying mesenchymal cells elaborate a large quantity of extracellular matrix, so producing the villous outgrowths of the proepicardium. The mesenchymal cells of this area are attached to each other with typical desmosomes and have anti-alpha cytokeratin-stained tonofilament bundles. These cells resemble keratinocytes and are designated as proepicardial matrix keratinocytes. The proepicardium proliferates first in the sulci of the U-shaped tubular heart, and within 2 days (between stages 15-25) establishes the visceral layer of the epicardium. The proliferating proepicardium consists of gland-like tubular strands, formed by the invaginations of the surface mesothelial cells, mesenchymal cells, fibroblasts, angioblasts, blood cells and capillaries. Because of its heterogeneous structure and multiple functions, the proepicardium is considered a transitory organ of the developing heart. In the quail embryo the forerunners of the coronary vessels grow from the perihepatic area into the proepicardial organ, and when the epicardial covering is completed, but before the coronary artery orifices open, these primordial vessels form a subepicardial and intramural vascular network in the ventricular myocardium. After the completion of the epicardial covering the proepicardium involutes and is not seem from stage 26 onward.

[Bacillary angiomatosis]. / Bacillaris angiomatosis.

In a 78 years old patient with chronic lymphoid leukemia, diabetes mellitus a cat scratch induced disseminated angiomatous papules were observed. In the lesions great number of bacilluses were observed with light -and electron microscope. As a result of antibiotic treatment the lesions regressed without trace. This opportunist infection resulting general symptoms as well, may be regarded as a cutaneous manifestation of immunodeficiency. The adequate antibiotic treatment depends on the exact diagnosis.

[Diagnostic problems of Wilson disease]. / A Wilson-kór diagnosztikájának problémái.

A family (three siblings) of Wilson's-disease is described. The authors review the pathogenesis, diagnostics, pathology and treatment of Wilson's-disease. The diagnostic difficulties are emphasised. The variety of liver lesions are demonstrated in the different grades of the disease. The importance of the early diagnosis is stressed.

[Development of the avian and mammalian heart prior to the onset of blood circulation, studied in chick and mouse embryos]. / Néhány adat a szárnyas és emlös embrió szívének eredetéröl és a vérkeringés elötti fejlödéséröl.

Heart development, its morphological and functional development prior the start of blood circulation were compared in chicken and mouse embryos. At beginning of neurula stage, when also somites appear, the cardiogenic mesoderm forms into tissue of epithelial type and cardiac plate is developed in wall of pleuroperitoneal cavity. In conjugated cardiac plate, primordial cardiac cavity fundaments appear in the about 30-hour old chicken embryo with 6-7 somites. First myoblasts (and spontaneous action potentials) can be observed in the ventricular part of embryos with 7 somites. Hence, muscular differentiation is expanded to atrial section. In embryo with 9-10 somites straight cardiac tube is developed, its ventricular section pulsates feebly, but it is unable for blood circulation yet. Pacemaker tissue of cardiac tube is in the atrium. At the end of second day the first curvature of heart appears and myocytes of venous sinus become pacemaker. At the end of neurula stage the blood circulation starts in two-day old embryo with 16 somites. Development of heart of mammalian embryos differs in several aspects from cardiac development of avian ambryos. In mammals transformation and differentiation of cells in cardiac plate and primordial cardiac fundaments have a cranio-caudal trend and in nearly same developmental stage as in chicken. In mouse circulation is started by curved cardiac tube of embryo with 10-12 somites (eight and half day old) at the end of neurala stage.

Histological investigations of the nasal mucosa in human fetuses.

The adult nasal mucosa has been exposed to various external agents and selected physiological conditions. Changes in intranasal airflow influenced the morphological appearance of the mucosa. Studies of agents on the fetal mucosa and its development may contribute to better understanding of the morphology of the nasal mucosa. The authors studied the nasal mucosa of 20- to 26-week-old fetuses using light microscopy and scanning and transmission electron microscopy. Findings showed that this developing nasal mucosa took part in the production and movement of mucus in the nasal cavity.

Heterotopic striated muscle on the surface of the brain.

Heterotopic tissue, identified by both light and electron microscopy as cardiac muscle, was detected at autopsy on the surface of the right superior temporal gyrus of a 73-year old female patient. The cells of the heterotopic tissue were interconnected by intercalated discs and the fibres contained regularly cross-striated, contracted, or relaxed myofibrils indicating a continuing contractile activity until the time of death.

Structure of cutaneous lymphatics propelling lymph.

In serial sections from the oedematous skin of hind limb of rats the lymph vessel walls were studied for structures active in propelling the lymph. To dilate the lymphatics lymph formation and transport were increased by dextran-oedema. A special type of sack-like structure lined almost exclusively by endothelial cells was observed at the postcapillary segment between the lymph capillaries and lymph vessels proper. The lymph flow from the capillaries into these postcapillary sack-like sinuses is regulated by valves. The postcapillary sacks joined the lymph vessels proper the media of which was built up of a muscle cell sheath. In these artery-type lymph vessels proper the lumen was found to be varying in diameter; some vessels seemed to have practically no lumen while other segments were open. Under the electron microscope thin, actin-type and thick, myosin-type myofilaments were seen in the muscle cells of lymphatic post-capillaries and lymph vessels proper. The lymph is accumulated in the postcapillary sack-like sinuses and from there is transported towards the centre by the contractions of artery-type lymph vessels. Thus, these structures may function as "lymph hearts" in the oedematous skin.

Effect of rehydration of rat liver tissue after water deprivation.

Male albino rats were deprived of water for 6 days, then they were allowed to drink tap water ad libitim. The structure of the liver was examined by light and electron microscopy, and the protein and dry matter contents, oxygen consumption and glucose-6-phosphatase activity of the liver were determined after rehydration. At 10 minutes, the mitochondria showed signs of division and a peculiar transformation of the cristae. At 60 minutes, the membranes of the rough endoplasmic reticulum were found to have proliferated. At 12 hours, the smooth-surfaced membranes showed hypertrophy and the bile canaliculi were distended. At 24 hours all rehydration induced organelle alterations were declining. The biochemical findings agreed well with the fine structural changes and both were indicative of an enchanced functional capacity of liver cells during rehydration.

The development of the early atrioventricular conduction system in the embryonic heart.

Recent electrophysiological evidence indicates that periodic spontaneous depolarizations occur in the primordial heart of the bird (and presumably mammal) even before the myocardial cells can contract, and these are initiated in the primordial sinoatrial region. As contractions are generated, these then establish a peristaltic wave. From that time on, during ontogenesis, the contractile sequence follows a regular pattern of development. As chambers form they contract sequentially in the direction of blood flow, even though, in the twisted configuration, myocardial continuities suggest the possibility of short-circuiting the electrical conduction pathways from atrium to bulbus. This implies that, even at these early stages, the electrical properties of the myocardium are not isotropic, and that specialized conduction pathways must exist. To the present time, electrophysiological techniques have limited the direct evidence that can be obtained on these delicate electrically specialized pathways. However, microscopical techniques have permitted studies on the morphological development of the tissue and of the cells in the various regions of the myocardium. The present paper traces the development of cell morphology in these regions, including the development of structural nodes and proximal ventricular fibre pathways, and from these observations, the manner in which the electrical conduction pathways are believed to develop is suggested.

The origin of the epicardium and the embryonic myocardial circulation in the mouse.

The origin of the epicardium and the formation of the early blood vessels of the heart prior to the opening of the coronary arteries from the aorta have been studied in the 9-13.5 day post coitum (dpc) mouse embryo heart. The epicardium begins to appear by 9 dpc. The majority of the epicardial cells derive from the somatopleural investment of the septum transversum, from where they migrate, associated to form vesicles, to the dorsal aspect of the ventricles and atria. The epicardial cells then migrate over the lateral surfaces and the AV sulcus to the ventral aspect of the heart. In the subepicardial space around the sulci, the proliferating epithelial tissue is found, also in vesicular form, for a time. The ventrally migrating primordial epicardial tissue ensheaths lastly the truncus arteriosus, while the sinus venosus is coated with epicardium ab initio, where (and also in the SA sulcus) the epicardial cells derive in part from the cuboidal cells of the pleuroperitoneal canal and in part from the somatopleural cells. The early blood vessel formation follows in space and time the development of the epicardium. The first blood vessels appear by dpc by the invagination of the endocardium into the early sinus muscle, and at the same time in the ventricular chamber by the encasing of the endocardium, as the trabeculae become consolidated into the myocardial walls. By this process sinusoids are formed, some of which penetrate through the myocardium and which, by rapid proliferation, form an interconnected subepicardial plexus. These capillaries proliferate ventrally in the wide subepicardial space, reaching the septating truncus, in which the aorta and pulmonary artery are developing. The definitive coronary artery openings appear by 13 dpc, allowing the high pressure blood from the aorta to flow into a preexisting vascular bed.

The hepatic tissue spaces.

In a controlled study concerned with the site of intrahepatic lymph formation, liver tissue from normal dogs, cats, rats and from cats with ligated hepatic lymph vessels, was subjected to light and electron microscopy. It was found that the periportal space named after Mall by whom it had been described, represents an interstitial gap of submicroscopic size. It is bordered on the one side by the hepatocytes of the limiting plate and on the other by the connective tissue fibres and processes of the connective tissue cells of the portal canal. The relationships between the perisinusoidal (Disse) space and the periportal tissue-gap have been clarifed and their role in the formation of hepatic lymph is discussed.

Ultrastructure of the hepatic perisinusoidal cells in man and other mammalian species.

Perisinusoidal (P.S.) cells occurring in the spaces of Disse in the livers of normal cats, dogs, miniature pigs, albino rats, human adults and children were examined by electron microscopy. The ultrastructural details of the P.S. cells and their topographic relationships with hepatocytes, sinusoidal lining cells and reticulum fibers are described. Species differences between P.S. cells were primarily a dissimilarity in lipid content: the main ultrastructural features were the same in all species studied. The P.S. cells of the rat liver displayed only low endocytotic activity, and no phagosome formation following intravenous administration of horseradish peroxidase. The close topographic relationship of the P.S. cells with the intralobular reticulum fibers was reminiscent of the intimate connection between fibroblasts and collagen fibers, or, in cat liver, of the reticulum cell--reticulum fiber association seen in lymphoid organs. Fibroblasts were not found inside the hepatic lobules. These findings support the conclusion that the reticulum fibers of hepatic lobules are produced by perisinusoidal cells which, however, display also other functions.

Formation of the primitive myo- and endocardial tubes in the chicken embryo.

The morphogenesis of the mesenchymal cardiogenic plate, the formation of the bilateral heart primordia leading to the primitive heart tube, and also the genesis of the endocardial tube, have been studied in 1 to 13 somite chick embryos. The morphological data were compared with those obtained in electrophysiological studies of the development of the cardiac action potentials (Fujii et al., 1981a). The primordia of the consecutive heart chambers are definable before the appearance of myosin-type filaments and primitive Z bands, which occurs simultaneously with the first spontaneous action potentials in the 7 somite embryo. At the 8 to 9 somite stage, fusion of the lateral heart primordia proceeds to include the outflow tract and atrial primordia; the pacemaker site migrates into the atrial wall and subsequently into the sinus venosus, this process occurring simultaneously with the progressive transformation of mesenchymal cells into cardiomyocytes. Proendocardial cells are first detected detaching individually or in small groups from the cardiogenic plate to become attached by fine filamentous material to the basal surface of the foregut endoderm, on which they "stream", establishing an anastomosing V-shaped array with respect to the ventral mesoderm. This array coalesces first at the atrioventricular groove to form double endocardial tubes, which in turn fuse into a single tube with the establishment of the single myocardial tube. Evidence suggests a key role for the ventral mesocardium and its transient attachment zone with the foregut, in providing a line focus for migration of proendocardial cells and primitive capillaries from the lateral splanchnic mesoderm, from which they derive.