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These cells were also stained with two additional dyes: a mitochondria-selective dye topical antibiotics for acne in pregnancy buy zithromac 100mg lowest price. Their fast-growing end is referred to as the plus () or barbed end; the slow-growing end is referred to as the minus () or pointed end antibiotics for dogs after spaying purchase zithromac 250mg online. An example of this modification occurs inside the microvillus antibiotics for acne cipro purchase 250mg zithromac mastercard, where actin filaments are cross-linked by the actin-bundling proteins fascin and fimbrin antibiotic qt prolongation order cheapest zithromac. Actin-capping proteins block further addition of actin molecules by binding to the free end of an actin filament. An example is tropomodulin, which can be isolated from skeletal and cardiac muscle cells. Tropomodulin binds to the free end of actin myofilaments, regulating the length of the filaments in a sarcomere. Actin cross-linking proteins are responsible for cross-linking actin filaments with each other. Immunofluorescence micrograph of a chick cardiac myocyte stained for actin (green) to show the thin filaments and for tropomodulin (red) to show the location of the slow-growing () ends of the thin filaments. Tropomodulin appears as regular striations because of the uniform lengths and alignment of the thin filaments in sarcomeres. The polarity of the thin filament is indicated by the fast-growing () end and the slow-growing () end. The troponin complex binds to each tropomyosin molecule every seven actin monomers along the length of the thin filament. There are two types of filaments (myofilaments) present in muscle cells: 6- to 8-nm actin filaments (called thin filaments;. Extensive studies have revealed the presence of a variety of other nonmuscle myosin isoforms that are responsible for motor functions in many specialized cells, such as melanocytes, kidney and intestinal absorptive cells, nerve growth cones, and inner ear hair cells. As in lamellipodia, these protrusions contain loose aggregations of 10 to 20 actin filaments organized in the same direction, again with their plus ends directed toward the plasma membrane. In listeriosis, an infection caused by Listeria monocytogenes, the actin polymerization machinery of the cell can be hijacked by the invading pathogen and utilized for its intracellular movement and dissemination throughout the tissue. Actin polymerization allows bacteria to pass into a neighboring cell by forming protrusions in the host plasma membrane. Intermediate Filaments Intermediate filaments play a supporting or general structural role. These rope-like filaments are called intermediate because their diameter of 8 to 10 nm is between those of actin filaments and microtubules. Nearly all intermediate filaments consist of subunits with a molecular weight of about 50 kDa. Some evidence suggests that many of the stable structural proteins in intermediate filaments evolved from highly conserved enzymes, with only minor genetic modification. Intermediate filaments are formed from nonpolar and highly variable intermediate filament subunits. Locomotion is achieved by the force exerted by actin filaments by polymerization at their growing ends. This mechanism is used in many migrating cells-in particular, on transformed cells of invasive tumors. As a result of actin polymerization at their leading edge, cells extend processes from their surface by pushing the plasma membrane ahead of the growing actin filaments. The leading-edge extensions of a crawling cell are called lamellipodia; they contain elongating organized bundles of actin filaments with their plus ends directed toward the plasma membrane. These processes can be observed in many other cells that exhibit small protrusions Unlike those of microfilaments and microtubules, the protein subunits of intermediate filaments show considerable diversity and tissue specificity. Intermediate filaments also do not typically disappear and re-form in the continuous manner characteristic of most microtubules and actin filaments. For these reasons, intermediate filaments are believed to play a primarily structural role within the cell and to compose the cytoplasmic link of a tissue-wide continuum of cytoplasmic, nuclear, and extracellular filaments. The long, straight actin filament cores or rootlets (R) extending from the microvilli are cross-linked by a dense network of actin filaments containing numerous actin-binding proteins. The network of intermediate filaments can be seen beneath the terminal web anchoring the actin filaments of the microvilli. Mechanism of brush border contractility studied by the quick-freeze, deep-etch method. Although the various classes of intermediate filaments differ in the amino acid sequence of the rod-shaped domain and show some variation in molecular weight, they all share a homologous region that is important in filament self-assembly. Intermediate filaments are assembled from a pair of helical monomers that twist around each other to form coiled-coil dimers. Then, two coiled-coil dimers twist around each other in antiparallel fashion (parallel but pointing in opposite directions) to generate a staggered tetramer of two coiled-coil dimers, thus forming the nonpolarized unit of the intermediate filaments. Each tetramer, acting as an individual unit, is aligned along the axis of the filament. The ends of the tetramers are bound together to form the free ends of the filament. This assembly process provides a stable, staggered, helical array in which filaments are packed together and additionally stabilized by lateral binding interactions between adjacent tetramers. Intermediate filaments are a heterogeneous group of cytoskeletal elements found in various cell types. Intermediate filaments are self-assembled from a pair of monomers that twist around each other in parallel fashion to form a stable dimer. Two coiled-coil dimers then twist around each other in antiparallel fashion to generate a staggered tetramer of two coiled-coil dimers. Each tetramer, acting as an individual unit, aligns along the axis of the filament and binds to the free end of the elongating structure.
It stains the granules intensely and metachromatically because they contain heparin treatment for dogs eating poop purchase zithromac 100 mg on-line, a highly sulfated proteoglycan antibiotics for inflamed acne purchase 100mg zithromac overnight delivery. When macrophages encounter large foreign bodies antimicrobial yeast discount zithromac 100mg amex, they may fuse to form a large cell with as many as 100 nuclei that engulfs the foreign body antibiotics xanax interaction order zithromac online pills. These types of cells are called alternatively activated macrophages or M2 macrophages and in general are anti-inflammatory. They promote wound repair due to their anti-inflammatory, proliferative, and angiogenic activities. In addition to their beneficial activities, M2 macrophages are involved in pathogenesis of allergy and asthma. The granules stain intensely and, because of their numbers, tend to appear as a solid mass in some areas. This electron micrograph shows the cytoplasm of a mast cell that is virtually filled with granules. Mast Cells Mast cells develop in bone marrow and differentiate in connective tissue. A clean surgical skin incision begins the healing process when a blood clot containing fibrin and blood cells fills the narrow space between the edges of the incision. During the initial phases of inflammation, neutrophils and monocytes infiltrate the injury (maximum infiltration by neutrophils occurs in the first 1 to 2 days after injury). Monocytes transform into macrophages (they usually replace neutrophils by day 3 after injury; page 177). At the same time, in response to local growth factors, fibroblasts and vascular endothelial cells begin to proliferate and migrate into the delicate fibrin matrix of the blood clot, forming the granulation tissue, a specialized type of tissue characteristic of the repair process. Usually by day 5 after injury, the fully developed granulation tissue bridges the incision gap. It is composed mainly of large numbers of small vessels, fibroblasts, and myofibroblasts, and variable numbers of other inflammatory cells. The myofibroblasts generate and maintain steady contractile force (similar to that of smooth muscle cells) that causes shortening of the connective tissue fibers and wound closure. During the second week of wound healing, the amount of cells in tissue undergoing repair decreases; most of the myofibroblasts undergo apoptosis and disappear, resulting in a connective tissue scar that has very few cellular elements. In some pathologic conditions, myofibroblasts persist and continue the process of remodeling. This continued remodeling causes hypertrophic scar formation, resulting in excessive connective tissue contracture. Extensive numbers of myofibroblasts are found in most contractive diseases of connective tissue (fibromatoses). If scar tissue grows beyond boundaries of the original wound and does not regress, it is called a keloid. This immunofluorescence image shows wild-type 3T3 fibroblasts cultured on the collagen lattice. Note that some cells have completed their differentiation, and others are in the early stages. The most commonly affected areas near the crease of the hand close to the base of the ring and small fingers form contracted fibrous cords, which are infiltrated by an extensive number of myofibroblasts. Most patients report problems when they try to place the affected hand on the flat surface. In more severe cases, the fingers are permanently flexed and interfere with everyday activities such as washing hands or placing the hand into a pocket. Mast cells initially circulate in the peripheral blood as agranular cells of monocytic appearance. After migrating into the connective tissue, immature mast cells differentiate and produce their characteristic granules. Some functionally important phagocytic cells are not derived directly from monocytes. For example, microglia are small, stellate cells located primarily along capillaries of the central nervous system that function as phagocytic cells. Also, fibroblasts of the subepithelial sheath of the lamina propria of the intestine and uterine endometrium have been shown to differentiate into cells with morphologic, enzymatic, and functional characteristics of connective tissue macrophages. These cells are able to phagocytose avidly vital dyes such as trypan blue and India ink, which makes them visible and easy to identify in the light microscope. Mast cells can also be activated by the IgE-independent mechanism during complement protein activation. Two types of human mast cells have been identified based on morphologic and biochemical properties. Most mast cells in the connective tissue of the skin, intestinal submucosa, and breast and axillary lymph nodes contain cytoplasmic granules with a lattice-like internal structure. In contrast, mast cells in the lungs and intestinal mucosa have granules with a scroll-like internal structure. Mast cells are especially numerous in the connective tissues of skin and mucous membranes but are not present in the brain and spinal cord. On the basis of its anticoagulant properties, heparin is useful for treatment of thrombosis. Tryptase is selectively concentrated in the secretory granules of human mast cells (but not basophils). It is released by mast cells together with histamine and serves as a marker of mast cell activation.
The lightly stained basophilic area reveals immature chondrocytes (arrows) within the perichondrium (P) antibiotics for esbl uti buy zithromac 500 mg visa. These cells are formative chondrocytes that are just beginning to vyrus 987 c3 2v discount generic zithromac canada, or will shortly virus families cheap 500 mg zithromac fast delivery, produce matrix material antibiotics for bordetella dogs buy zithromac 100 mg free shipping. In contrast, the nuclei near the bottom edge of the micrograph are fibroblast nuclei (Fib); they belong to the outer layer of the perichondrium. Note how attenuated their nuclei are compared with the formative chondroblast nuclei of the inner perichondrial layer. This cartilage is replaced by bone tissue except where one bone contacts another, as in a movable joint. In these locations, cartilage persists and covers the end of each bone as articular cartilage, providing a smooth, well-lubricated surface against which the end of one bone moves on the other in the joint. In addition, cartilage, being capable of interstitial growth, persists in weight-supporting bones and other long bones as a growth plate as long as growth in length occurs. The role of hyaline cartilage in bone growth is considered briefly below and in more detail in Plates 13 and 14. This section shows the cartilages that will ultimately become the bones of the foot. In several places, developing ligaments (L) can be seen where they join the cartilages. They are aligned in rows and are separated from other rows of fibroblasts by collagenous material. The hue and intensity of color of the cartilage matrix, except at the periphery, are due to the combined uptake of the H&E. The collagen of the matrix stains with eosin; however, the presence of sulfated glycosaminoglycans results in staining by hematoxylin. The matrix of cartilage that is about to be replaced by bone, such as that shown here, becomes impregnated with calcium salts, and the calcium is also receptive to staining with hematoxylin. The many enlarged lacunae (seen as light spaces within the matrix where the chondrocytes have fallen out of the lacunae) are due to hypertrophy of the chondrocytes, an event associated with calcification of the matrix. Thus, where these large lacunae are present, that is, in the center region of the cartilage, the matrix is heavily stained. It will constitute the synovial membrane in the adult and contribute to the formation of a lubricating fluid (synovial fluid) that is present in the joint cavity. Therefore, all the surfaces that will enclose the adult joint cavity are derived originally from the mesenchyme. Synovial fluid is a viscous substance containing, among other things, hyaluronan and glycosaminoglycans; it can be considered an exudate of interstitial fluid. The synovial fluid could be considered an extension of the extracellular matrix, as the joint cavity is not lined by an epithelium. The newly formed metaphyseal bone, which is admixed with this degenerating calcified cartilage and is difficult to define at this low magnification, has the same yellow-brown color as the diaphyseal bone. Later, the cartilage becomes calcified; bone is then produced and occupies the site of the resorbed cartilage. With the cessation of cartilage proliferation and its replacement by bone, growth of the bone stops, and only the cartilage at the articular surface remains. The details of this process are explained under endochondral bone formation (Plates 13 and 14). This photomicrograph shows a developing long bone of the finger and its articulation with the distal and proximal bones. Before the stage shown here, each bone consisted entirely of a hyaline cartilaginous structure similar to the cartilages seen in the figure above but shaped like the long bones into which they would develop. Here, only the ends, or epiphyses, of the bone remain as cartilage, the epiphyseal cartilage (C). It is found in the auricle of the external ear, in the auditory tube, in the epiglottis, and in part of the larynx. The elastic material imparts properties of elasticity, as distinguished from resiliency, which are not shared by hyaline cartilage. Elastic cartilage is surrounded by perichondrium, and it, too, increases in size by both appositional and interstitial growth. Unlike hyaline cartilage, however, elastic cartilage does not normally undergo the calcification process. The essential components of the cartilage, namely, the matrix containing elastic fibers, which stains purple, and the light, unstained lacunae surrounded by matrix, are evident in this low-magnification micrograph. Adipose tissue in this micrograph is visible within the boundaries of the elastic cartilage. They are most evident at the edges of the cartilage, but they are obscured in some deeper parts of the matrix, where they blend with the elastic material that forms a honeycomb about the lacunae. Some of the lacunae in the cartilage are arranged in pairs separated by a thin plate of matrix. This is a reflection of interstitial growth by the cartilage, in that the adjacent cartilage cells are derived from the same parent cell. They have moved away from each other and secreted a plate of cartilage matrix between them to form two lacunae. This is, in part, due to shrinkage, but it is also due to the fact that older chondrocytes contain large lipid droplets that are lost during tissue preparation. The shrinkage of chondrocytes within the lacunae or their loss due to dropping out of the section during preparation causes the lacunae to stand out as light, unstained areas against the darkly stained matrix. Here, the elastic fibers (E) are again evident as elongate profiles, chiefly at the edges of the cartilage.
In contrast antibiotic resistance worksheet zithromac 100 mg with visa, the lower right side of the micrograph displays numerous lymphocytes that have invaded the epithelium infection the game order zithromac 100 mg overnight delivery. More striking is the presence of what appear as isolated islands of epithelial cells (Ep) within the periphery antibiotics mnemonics buy cheap zithromac 250mg line. The thin band of collagen (C) lying at the interface of the epithelium is so disrupted in this area that it appears as small fragments antibiotics for menopausal acne buy discount zithromac 100 mg. They serve as filters of the lymph and as the principal site in which T and B lymphocytes undergo antigen-dependent proliferation and differentiation into effector lymphocytes (plasma cells and T cells) and memory B cells and T cells. A low-magnification (14) micrograph of a section through a human lymph node is shown on this page for orientation. The parenchyma of the node is composed of a mass of lymphatic tissue, arranged as a cortex (C) that surrounds a less dense area, the medulla (M). The cortex is interrupted at the hilum of the organ (H), where there is a recognizable concavity. It is at this site that blood vessels enter and leave the lymph node; the efferent lymphatic vessels also leave the node at the hilum. Afferent lymphatic vessels penetrate the capsule at multiple sites to empty into an endothelium-lined space, the cortical or subcapsular sinus. This sinus drains into the trabecular sinuses that extend through the cortex alongside the trabeculae and then supply the medullary sinuses. These, in turn, drain to the efferent lymphatic vessels that leave the node at the hilum. The capsule (Cap) is composed of dense connective tissue from which trabeculae (T) penetrate into the organ. Whereas lymph nodules and their lighter staining germinal centers characterize the outer cortex, a more dense mass of lymphocytes, which impart a distinct basophilia, characterize the deep cortex. The medullary sinuses receive lymph from the trabecular sinuses and lymph filtered through the cortical tissue. Dividing lymphocytes are shown at slightly higher magnification in the inset (arrows), which corresponds to the area in the circle in this figure. The ovoid reticular cell has a large pale-staining nucleus, and its cytoplasm forms long processes that surround the reticular fibers. In H&E preparations, the reticular fibers and the surrounding cytoplasm are difficult to identify. Reticular cells are best seen in the sinuses, where they extend across the lymphatic space and are relatively unobscured by other cells. These vessels have an endothelium composed of tall cells between which lymphocytes migrate from the vessel lumen into the parenchyma. They proliferate further in superficial cortex into a clone of lymphocytes that differentiate into antibody-secreting plasma cells and memory cells. B-cell proliferation and differentiation take place in germinal centers in the superficial cortex of the lymph node. Newly differentiated plasma cells migrate to the medulla, where they release antibodies into the lymph leaving the node. They may also leave the node, enter the blood vascular system at the thoracic duct, and travel to localized sites in the connective tissue where they may continue to produce antibodies. As noted in the previous plate, it lies below the region containing the lymph nodules and consists of closely packed lymphocytes. A small vessel that can be identified as a venule (Ven), based on lumen size and wall thickness, is seen at a point of transition to become a high endothelial venule (arrowheads). The high endothelial venule is identified by its endothelium, which is composed of cells that are cuboidal. A cross-sectioned profile of a postcapillary venule is shown in the inset at higher magnification (700). The endothelial cell nuclei are round and are lightly stained, in contrast to the nuclei of the surrounding lymphocytes, which are of similar size and shape but are densely stained. This vessel also shows three lymphocytes (arrows) that are in the process of migrating through the wall of the vessel. The lower right corner of this figure reveals a region where there is a considerably lesser concentration of lymphocytes. These cells wrap around the collagen bundles that form the supporting trabecular framework of the node. In H&E preparations, these characteristics allow for the distinction between the reticular cell and the lymphocyte. The openings in the vessel wall (arrows) are sites in which the medullary sinuses are emptying their contents into the lymphatic vessel. The substance of the spleen, the splenic pulp, consists of red pulp and white pulp, so named because of their appearance in fresh tissue. The red pulp contains large numbers of red blood cells that it filters and degrades. Aged, damaged, or abnormal red blood cells are trapped by macrophages associated with unusual vascular sinuses in the red pulp. These macrophages break down the red cells, begin the metabolic breakdown of hemoglobin, and retrieve and store the iron from the heme for reutilization in the formation of new red blood cells in the bone marrow. In life, the red pulp has pulp-like texture; it is red as a result of the natural coloration of the numerous red blood cells present, hence its name. The white pulp, on the other hand, is so named because its content of lymphocytes appears in life as whitish areas.
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