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Light absorption determines a change in the configuration of the retinal chromophore from cis to trans treatment high blood pressure combivir 300 mg low cost. The isomerization of 11-cis-retinal to activated all-trans-retinal is identical in rods and cones treatment diverticulitis combivir 300mg on line. The retina is a stratified layer of nervous cells formed by two layers: (1) the outer retinal pigmented epithelium and (2) the inner sensory retina. The optic papilla lacks photoreceptors and represents the blind spot of the retina. Conducting neurons: Bipolar and ganglion cells (9-18) Bipolar cells receive information derived from the interaction of horizontal cells with cone or rod photoreceptors. Ganglion cells are the output neurons of the retina; their axons form the optic nerve. Rod and cone photoreceptors establish chemical synapses with different bipolar cells to separate signaling into parallel retinal streams. Dendrites of the diffuse cone bipolar cells branch within the outer plexiform layer and contact several cone pedicles. On the opposite pole, the axon of a diffuse bipolar cell projects into the inner plexiform layer and contacts the dendrites of ganglion cells. Midget cone bipolar cells synapse with a single cone pedicle and a single axon, which contacts a single ganglion cell. The layers of the retina observed in the photomicrograph are represented in the adjacent diagram. Radial branches from blood vessels (arteries and veins), located on the retinal surface, are interconnected by capillary beds present in the inner layers of the retina. Retinal capillary beds are lined by endothelial cells linked by tight junctions creating an internal blood-retinal barrier. An external retinal barrier is formed by tight junctions linking the cells of the pigmented epithelium. Choroid the axons of the cones and rods project into the outer plexiform layer and synapse with dendrites of the bipolar cells. Axons of the bipolar cells synapse with dendrites of the ganglion cells in the inner plexiform layer. Amacrine cells synapse with axons of bipolar cells and dendrites of ganglion cells. The nuclei of the bipolar cells form part of the inner nuclear layer of the retina. Ganglion cells extend their dendrites into the inner plexiform layer; the axons form part of the optic nerve. Midget ganglion cells, with their dendrites contacting a single midget bipolar cell. In Chapter 18, Neuroendocrine System, we discuss in the pineal gland section the presence of a subset of ganglion cells with a function independent of image formation. The intraciliary transport mechanism (see Cytoskeleton in Chapter 1, Epithelium Cell Biology) uses microtubule-based molecular motors (kinesins and cytoplasmic dyneins) to transport proteins, Dendrite of a rod bipolar cell vesicles and other materials from the inner segment to the outer segment. The modified cilium facilitates the delivery of molecules from a proximal site of synthesis to a distal site of assembly. The plus/minus polarity of the microtubules enables an anterograde and retrograde transport mechanism through molecular motors. Older disks of the rods are shed and phagocytosed by the pigmented epithelial cells of the retina. Regeneration of the photopigment consists of the enzymatic conversion within the pigmented epithelium of all-trans retinol back to 11-cis-retinal.

Subclasses of type A spermatogonia (with a dark nucleus treatment 5cm ovarian cyst cheapest combivir, called A dark spermatogonium medications in carry on luggage combivir 300 mg cheap, and with a lighter nucleus, called A pale spermatogonium) are observed in human testes. Type B spermatogonia have a round nucleus, masses of heterochromatin attached to the nuclear envelope and a central nucleolus (see 20-4). Acquired factors responsible for the loss of spermatogenic cells include radiation therapy, chemotherapy and severe trauma. Mitotically dividing spermatogonia, meiotically dividing spermatocytes and differentiating spermatids are sensitive to radiation and cancer chemotherapy. Failure of spermatogonia to undergo differentiation in humans results in a neoplastic transformation into carcinoma in situ, leading to testicular germ cell carcinoma in the adult. A primary spermatocyte undergoes the first meiotic division (or reductional division) to produce two secondary spermatocytes (see 20-8). The secondary spermatocytes rapidly undergo the second meiotic division (or equational division). Each secondary spermatocyte gives rise to two spermatids, which differentiate into sperm without further cell division. Now, spermatids are ready to initiate a complex differentiation process, called spermiogenesis, to become sperm. Because the first meiotic division is a long process (days) and the second meiotic division is very short (minutes), primary spermatocytes are the most abundant cells observed in the seminiferous epithelium. Turn your attention to 20-8 to review the highlights of the meiotic process of the male and female gametes. Keep in mind that female meiosis starts in the ovary during fetal development (see Chapter 23, Fertilization, Placentation and Lactation). Meiosis (Primers 20-B, 20-C and 20-D) Meiosis is focused on chromosomal events and on establishing the conditions appropriate for sex determination. The homologous chromosomes pair together and exchange segments by a process known as crossing over, or recombination. The end products of meiosis are four haploid spermatids with only one set of chromosomes. When the chromosomes of haploid egg and sperm combine at fertilization, the embryo regains the normal diploid number. The first meiotic division is characterized by a long prophase, lasting about 10 days. A coordinated chain of events in the extended meiotic prophase I results in pairing and synapsis (Greek syn, together; hapto, to connect) of homologous chromosomes, creating bivalent chromosomes. Each bivalent consists of four chromatids, two sister chromatids for each member of the bivalent structure. If we count the number of chromatids per bivalent, we have a tetrad (Greek tetras, the number four). Genetic recombination takes place between the non-sister chromatids of each bivalent. During meiotic anaphase I, the chromosome number is reduced by one-half, when homologous chromosomes, each consisting of sister chromatids, separate. Meiosis in the female Primary oocyte (at diplotene, prophase of meiosis I, at the time of birth) First polar body In the female: (1) the proliferation of oogonia by mitosis, equivalent to spermatogonia in the male, occurs in the fetal ovary. Fertilizing sperm 4C Second polar body Secondary oocyte Meiosis I is completed at ovulation. Homologous chromosomes Non-sister chromatids Initiation of pairing and synapsis of the homologous chromosomes. X chromosome Y chromosome 1 1 1 Chromosomal disjunction 2 Chiasma terminalization 2 2 3 Electron microscopy Light microscopy 2 Chiasma Disjunction X chromosome Y chromosome Centrioles duplicate.

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Defects in the processing of procollagen and tropocollagen and the assembly of collagen fibrils give rise to variations of the Ehlers-Danlos syndrome medications for migraines cheap combivir online visa, characterized by hyperelasticity of the skin and hypermobility of the joints medicine pills cheap combivir master card. Elastin, the precursor of elastic fibers, is also synthesized and processed sequentially. Fibroblasts or smooth muscle cells secrete desmosine- and isodesmosine-containing proelastin, which is partially cleaved to give rise to tropoelastin. Tropoelastin, fibrillins and fibulin 1 assemble into elastic fibers that aggregate to form bundles of elastic fibers. A defect in fibrillin 1 affects the assembly of mature elastic fibers, a characteristic of Marfan syndrome. Macrophages derive mainly from monocytes, produced in the bone marrow and, during embryogenesis, from cell precursors in the yolk sac. Their function in connective tissue is the turnover of fibers and extracellular matrix and, most important, the presentation of antigens to lymphocytes as an essential step of immune and inflammatory reactions. Mast cells acquire metachromatic granules in the connective tissue and mucosa, which stain with a color that is different from the color of the dye. The granules contain vasoactive mediators (histamine, heparin and chemotactic mediators), chymases and other proteases. Like most vasoactive agents, they induce an increase in vascular permeability leading to edema. Mast cells and basophils circulating in blood derive from the same progenitor in the bone marrow. Mast cells play a role in allergic hypersensitivity reactions associated with asthma, hay fever and eczema. Mastocytosis is a disorder consisting of the systemic and local increases in the number of morphologically altered mast cells. Three structural characteristics of a plasma cell are: (1) a well-developed rough endoplasmic reticulum; (2) an extensive Golgi apparatus; and (3) a prominent nucleolus. These features define the plasma cell as an actively protein-producing cell, whose main product is a single class of immunoglobulin for each plasma cell. Each proteoglycan consists of a core protein attached to a hyaluronan molecule by a linker protein. Attached to the core protein are glycosaminoglycan chains (keratan sulfate, dermatan sulfate and chondroitin sulfate). Malignant cells originated in a lining epithelium (carcinoma) or a glandular epithelium (adenocarcinoma) can break down the basement membrane and invade the underlying connective tissue. The histologic sequence of epithelial tumor invasion starts with dysplasia (increased cell proliferation and incomplete cell maturation), followed by carcinoma in situ (loss of epithelial normal organization within the limits of the basement membrane), microinvasive carcinoma (decreased expression of cadherins and breakdown of the basement membrane) and invasive carcinoma. Cessation in the expression of cadherins weakens the cohesive nature of the epithelial tumor. The production of proteinases allows the tumor cells to invade and attach to components of the connective tissue. Then, tumor cells produce autocrine motility factors, to enable tumor cell motility; vascular permeability factors, to ensure a supply of nutrients; and angiogenic factors, to increase the vascular support of the growing tumors. Finally, tumor cells can produce chemokine molecules on their surface that facilitate their transendothelial migration to metastasize. Fat can accumulate into a single lipid-strorage droplet (unilocular) or multiple small lipid droplets (multilocular). Leptin binds to the leptin receptor (LepR) present in several neuronal nuclei of the hypothalamus. Leptin-deficient mice are obese and infertile, conditions that are reversible when leptin is administered to the mutants. Cartilage lacks blood vessels and is surrounded by the perichondrium (except in fibrocartilage and articular hyaline cartilage, which lack a perichondrium). The perichondrium consists of two layers: an outermost fibrous layer, consisting of elongated fibroblast-like cells and blood vessels and the innermost chondrogenic cell layer. Chondrogenesis (cartilage growth) takes place by two mechanisms: (1) Interstitial growth (within the cartilage). During interstitial growth, centers of chondrogenesis, consisting of chondroblasts located in lacunae and surrounded by a territorial matrix, divide by mitosis without leaving the lacunae and form isogenous groups. During appositional growth, the cells of the perichondrial chondrogenic layer differentiate into chondroblasts following activation of the gene encoding the transcription factor Sox9.

Electron microscopy Electron microscopy has provided a powerful tool for examining the size medications online safe combivir 300 mg, distribution medicine misuse definition best 300 mg combivir, content and mode of synthesis and secretion of the various hormones stored in secretory granules in the cytoplasm of endocrine cells of the adenohypophysis. Chromophobes include cells that have depleted their hormone content and lost the staining affinity typical of acidophils and basophils. The precise identification of the endocrine cells of the adenohypophysis is by immunohistochemistry, which demonstrates their hormone content using specific antibodies. Prolactin-secreting cells, or lactotrophs, represent 15% to 20% of the cell population of the adenohypophysis. Growth hormone (18-6) Acidophils secrete growth hormone, also called somatotropin. These acidophilic cells, called somatotrophs, represent a large proportion (40% to 50%) of the cell population of the adenohy612 Growth hormone is a peptide of 191 amino acids in length (22 kd). Growth hormone has structural homology similar to prolactin and human placental lactogen. It is released into the blood circulation in the form of pulses throughout a 24-hour sleep-wake period, with peak secretion occurring during the first two hours of sleep. In most cases, an adenoma of the anterior hypophysis is responsible for growth hormone hypersecretion. An inhibitory effect is produced by somatostatin (a peptide of 14 amino acids) and by elevated blood glucose levels. If excessive growth hormone secretion occurs in the adult, when the epiphyseal plates are inactive, acromegaly (Greek akron, end or extremity; megas, large) develops. Long bones do not grow in length, but cartilage (nose, ears) and membranous bones (mandible and calvarium) continue to grow, leading to gross deformities. A decrease in the secretion of growth hormone in children results in short stature (dwarfism). Prolactin (18-7) Excessive secretion of growth hormone can occur in the presence of a benign tumor called an adenoma. Prolactin, growth hormone and human placental lactogen share some amino acid homology and overlapping activity, the predominant action of prolactin is to stimulate the initiation and maintenance of lactation. Mammogenesis, the growth and development of the mammary gland, is stimulated primarily by estrogen and progesterone in coordination with prolactin and human placental lactogen. The secretion of prolactin by acidophils is regulated primarily by inhibition rather than by stimulation. Prolactin Lactation Lactation involves (1) Mammogenesis, stimulated during pregnancy by estrogen and progesterone, acting together with prolactin. Lactation is inhibited during pregnancy by high levels of estrogen and progesterone, which decline at delivery. Galactopoiesis, the maintenance of milk production, requires both prolactin and oxytocin. The effects of prolactin, placental lactogen and steroids on the development of the lactating mammary gland are discussed in Chapter 23, Fertilization, Placentation and Lactation. Excessive prolactin in blood (hyperprolactinemia) alters the hypothalamohypophyseal-gonadal axis, leading to gonadotropin deficiency (called hypogonadism). The major effect is decreased levels of estrogen in women and testosterone in men. This condition results in decreased bone density and an increased risk of osteoporosis. Hypersecretion of prolactin in women can be associated with infertility, caused by the lack of ovulation and oligomenorrhea (irregular menstrual periods) or amenorrhea (dysfunctional uterine bleeding). Galactorrhea (non-puerperal milk secretion) is a common problem in hyperprolactinemia and can also occur in males.

Technetium pyrophosphate nuclear imaging is sensitive for detection of transthyretin amyloidosis medications definitions discount combivir 300 mg with mastercard. Anticoagulation often indicated medicine clip art order combivir with a mastercard, particularly in pts with eosinophilic endomyocarditis. Typically results from mutations in sarcomeric proteins (autosomal dominant transmission). Digoxin, other inotropes, diuretics, and vasodilators should generally be avoided. Antiarrhythmic agents, especially amiodarone, may suppress atrial and ventricular arrhythmias. Rare etiologies include eosinophil myocarditis, hypersensitivity myocarditis, and systemic inflammatory diseases. Pain is usually retrosternal or left precordial, radiating to neck, left shoulder, trapezius ridge, and/or arms; fever and palpitations are common. Intractable, prolonged pain or frequently recurrent episodes may require pericardiectomy. Anticoagulants are relatively contraindicated in acute pericarditis because of risk of pericardial hemorrhage. If tamponade develops subacutely, peripheral edema, hepatomegaly, and ascites may be present. Viral, tuberculosis (mostly in developing nations), previous cardiac surgery, collagen vascular disorders, uremia, neoplastic, and radiation-associated pericarditis are potential causes. Dramatic effects of respiration: During inspiration the ventricular septum shifts to the left with prominent reduction of blood flow velocity across mitral valve; pattern reverses during expiration (opposite pattern across the tricuspid valve with respiration). Always consider a secondary correctable form of hypertension, especially in pts aged 30 or those who become hypertensive after 55. Isolated systolic hypertension (systolic 140, diastolic <90) most common in elderly pts, due to reduced vascular compliance. Presents with recent onset of hypertension, refractory to usual antihypertensive therapy. Abdominal bruit is present in 50% of cases; hypokalemia due to activation of the renin-angiotensin-aldosterone system may be present. Renal Parenchymal Disease Elevated serum creatinine and/or abnormal urinalysis, containing protein, cells, or casts. Coarctation of Aorta Presents in children or young adults (including 35% of pts with Turner syndrome); constriction is usually present in aorta at origin of left subclavian artery. Examination shows diminished, delayed femoral pulsations; systolic murmur loudest at left infrascapular region. Doppler echocardiography identifies region of constriction and measures associated pressure gradient. Pheochromocytoma A catecholamine-secreting tumor, typically of the adrenal medulla or extraadrenal paraganglion tissue. Associated findings include chronic weight loss, orthostatic hypotension, and impaired glucose tolerance. Pheochromocytomas may be localized to the bladder wall and may present with micturition-associated symptoms of catecholamine excess. In pts with systolic hypertension and wide pulse pressure, consider thyrotoxicosis, aortic regurgitation (Chap. Physical examination: Measure bp with appropriate-sized cuff (large cuff for large arm). Signs of hypertension include retinal arteriolar changes (narrowing/nicking); left ventricular lift, loud A2, S4. Clues to secondary forms of hypertension include cushingoid appearance, thyromegaly, abdominal bruit (renal artery stenosis), delayed femoral pulses (coarctation of aorta). Diuretics Thiazides preferred over loop diuretics because of longer duration of action; however, the latter are more potent when serum creatinine >2. Major side effects include hypokalemia, hyperglycemia, and hyperuricemia, which can be minimized by using low dosage. May be used as monotherapy or in combination with a diuretic, calcium antagonist, or beta blocker.

Voltage-gated Ca2+ channels in the axon terminals open asthma medications 7 letters order combivir amex, leading to transient Ca2+ influx and fusion of the neurosecretory granules with the nerve terminal membrane symptoms bacterial vaginosis cheap combivir 300 mg overnight delivery. As discussed in Chapter 23, Fertilization, Placentation and Lactation, oxytocin regulates lactation, parturition and reproductive behavior. Oxytocin stimulates the contraction of the myoepithelial cells surrounding the secretory acini and lactiferous ducts of the mammary glands to facilitate milk ejection (or letdown of milk) during lactation. Oxytocin increases uterine responsiveness during parturition (initiation and progression of labor), with help of prostaglandins. Each consists of nine amino acids Tyr Cys Tyr Cys 9 9 arranged as a ring formed by the linkage of two molecules Phe Cys Pro Arg Gly N Ile Cys Pro Leu Gly of cysteine (a disulfide linkage) and a short side chain. Gln Asn Glu Asn the structure of the two hormones differs only at amino Side chain Side chain acids 3 and 8. Estrogens increase the response of Arteriole the myometrium to oxytocin; progesterone decreases the response. Myoepithelial cell During lactation, oxytocin release is Nephron mediated by a neurohumoral reflex Capillary bed triggered by suckling. Sensory fibers are Collecting linked to the hypothalamic neurons tubule producing oxytocin. When the stimulus Alveolus arrives, an action potential transmitted along the axons of the paraventricular Contraction of neurons extending into the pars Arteriolar Contraction of the Increase of water myoepithelial cells of nervosa causes the release of vasoconstriction increases myometrium during permeability of the lactating mammary oxytocin into the blood. Most patients can maintain water balance through polydipsia (excessive thirst and water intake). Instead, postganglionic sympathetic nerve fibers derived from the superior cervical ganglia supply the pineal gland. Preganglionic fibers to the superior cervical ganglia derive from the lateral column of the spinal cord. In brief, the mammalian pineal gland is a neuroendocrine transducer handling photic information sent from the retina. Development of the pineal gland (18-16) the pineal gland, or epiphysis, is an endocrine organ formed by cells with a neurosecretory function. It lies in the center of the brain, behind the third ventricle and is connected to the brain by a stalk. Continued diverticulation and infolding result in a solid parenchymal mass of cords and clusters of pinealocytes and glial-like interstitial cells supported by a meninges-derived connective tissue (pia mater) that carries blood vessels and nerves to the pineal gland. The lumen is occluded, except at the base of the outpocketing, where the pineal recess persists and communicates with the third ventricle in the adult. Meninges envelop and invade the developing pineal gland, forming connective tissue septa. A typical feature of the histology of the pineal gland is the presence of calcium deposits, called corpora arenacea (brain sand), found in the extracellular space. The nerve input to the pineal gland is from the postganglionic sympathetic nerve fibers, derived from the superior cervical ganglion. Multiple ribbon synapses Synaptic cleft Synaptic ribbon L-type Ca2+ channel Postsynaptic plasma membrane Presynaptic releasing vesicle Presynaptic plasma membrane Free vesicle Tethered vesicle 1 the cytoplasm contains abundant mitochondria Axon Melatonin transport 3 Gap junctions link adjacent pinealocytes 2 Sympathetic nerve fibers originating in the superior cervical ganglia enter the pineal gland with the blood vessels supplying the brain. When the nerve fibers enter the gland, the myelin sheath is lost and bare axons are seen among the pinealocytes. In reptiles and birds, the photosensory function has been replaced by a secretory function. The pinealocytes are neuroepithelial secretory cells organized into cords and clusters resting on a basal lamina. Cords and clusters are surrounded by connective tissue, blood vessels lined by fenestrated endothelial cells, and nerves. The pinealocyte lacks an axon; it has two or more cell processes ending in bulbous expansions. The cytoplasm contains abundant mitochondria and randomly distributed multiple synaptic ribbons.

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The objective here is to have the secondary oocyte pronucleus reach a haploid state at the time when the haploid male pronucleus penetrates the egg symptoms xanax purchase generic combivir. If we take into account that each chromosome of the pair has two chromatids medications overactive bladder order combivir overnight delivery, the bivalent is called tetrad. Meiotic prophase I consists of well-defined substages: (1) Leptotene, in which each chromosome becomes visible as a thin thread; it consists of two sister chromatids. Crossing over between non-sister chromatids of the paired chromosomes takes place. The points of genetic exchange between non-sister chromatids are called chiasmata. Chiasmata move toward the ends of the chromosomes by a process referred to as terminalization. Each lateral element represents the remnant of the axial chromosomal core of each paired chromosome. There are two major morphologic types of spermatid: (1) Round or early spermatids. They are involved in a process called spermiogenesis, the last phase of spermatogenesis. The Golgi-associated centrosome (a pair of centrioles) initiates its migration to the opposite nuclear pole to develop the spermatid tail. The acrsosome sac forms a cap to the elongating spermatid nucleus and initiates, anchored to the acroplaxome, its caudal descent. The marginal ring of the acroplaxome has a desmosomelike structure that fastens the descending acrosome sac recess to the spermatid nuclear envelope. The manchette initiates its development, just below the marginal ring of the acroplaxome, by assembling a perinuclear ring, the insertion site of manchette microtubules. Spermatid nuclear condensation and elongation take place as somatic-type of nucleosomecontaining chromatin is replaced by smooth chromatin fibers. The manchette disassembles as mitochondria migrate and surround the proximal segment of the developing spermatid tail. These four phases describe the morphogenesis of the acrosome and the spermatid nucleus. Defective gene expression results in abnormal sperm development, a condition known as teratozoospermia, which affects male fertility. During spermiogenesis, spermatids undergo significant structural and biochemical changes in preparation for fertilization. We need to emphasize the following: (1) the acrosome is a sac consisting of an outer acrosomal membrane and an inner acrosomal membrane and contains hydrolytic enzymes to be released following the acrosome reaction during fertilization. The inner acrosome membrane is attached to a subjacent cytoskeletal plate called the acroplaxome. The acroplaxome, consisting of F-actin and keratin 5, is anchored to the nuclear envelope of the spermatid nucleus. The manchette participates in: (i) Nucleocytoplasmic transport, an important event during the somatic histone-protamine shift during nuclear condensation. The defective structure and function of the acrosomeacroplaxome-manchette complex results in sperm with round-shaped heads (globospermia), unable to fertilize the egg. Decapitation, abnormal separation of the sperm head from the tail at their attachment site, represents a sub-clinical form of male infertility. Spermatids develop a tail, a structure that contains the axoneme surrounded, along specific tail segments, by mitochondria, outer dense fibers and a fibrous sheath. Non-motile mature spermatids are released into the seminiferous tubular lumen and transported to the rete testis. Transport depends on fluid flowing along the lumen of the seminiferous tubules and the contractile activity of myoid cells present in the seminiferous peritubular wall. The acroplaxome, a cytoskeletal plate, links the acrosome to the nuclear envelope. The annulus, containing the protein septin 4, represents a limiting ring-shaped region between the middle piece and the principal piece. This temperature is achieved in the scrotum by the pampiniform plexus and spermatid artery participating in countercurrent heat exchange. Varicocele (dilation of the veins of the pampiniform plexus) hampers heat exchange and may lead to a decrease in sperm production.

In the absence of imatinib medicine 81 purchase 300mg combivir otc, a protein substrate will be phosphorylated on tyrosine and initiate a downstream signaling cascade symptoms 2 dpo combivir 300mg discount. Autophosphorylated c-kit receptor is the docking site of specific signaling molecules. Reduced migration, survival and proliferation of primordial germinal cells in the developing ovaries and testes (see Chapter 21, Sperm Transport and Maturation). They are characterized by the neoplastic proliferation of one or more cell lineages in bone marrow, frequent circulation of neoplastic cells in peripheral blood and reduction in the development of normal red blood cells and platelets. Acute leukemias consist of the massive proliferation of immature cells with respect to bone marrow cells and rapid progression of the disease. Anemia (caused by a depletion of red blood cell formation), infections (determined by a decline in the formation of normal leukocytes) and bleeding (a reduction in the number of platelets) are relevant features. They are characterized by a lesser proliferation of immature cells and slow progression of the disease. Dense core granule Invaginated membrane system During the cytoplasmic maturation of a megakaryocyte, the cell membrane invaginates to form channels separating cytoplasmic islands about 3 to 4 m in diameter. Megakaryocytes typically rest next to bone marrow sinusoids (vascular niche) and extend multiple cytoplasmic protrusions into the sinusoid lumen. Fragmented protrusions, released by blood fluid shear, give rise first to proplatelets and then to platelets within the sinusoid lumen. A predominant proliferation of B cells and a large number of abnormal lymphocytes in peripheral blood are predominant features. Patients develop hepatosplenomegaly and leukocytosis (excessive myelocytes, metamyelocytes and neutrophils in peripheral blood). After a chronic phase of about five years, the disease can change into an acute leukemia, requiring stem cell bone marrow transplantation. A fusion gene is created by placing the abl gene on chromosome 9 (region q34) to a part of the bcr (breakpoint cluster region) gene on chromosome 22 (region q11). The fusion gene (abl/bcr) encodes a tyrosine kinase involved in cell transformation leading to a neoplastic phenotype. We come back to imatinib and tyrosine kinases inhibition at the end of this chapter. Megakaryocytes and platelets (6-26; see 6-12 and 6-15) Platelets are small anucleated cytoplasmic fragments with roles in hemostasis and thrombosis. Platelets bind and degrade thrombopoietin, a process that autoregulates platelet production. The megakaryoblast (15 to 50 m in diameter) displays a single kidney-shaped nucleus with several nucleoli. The megakaryoblast enlarges to give rise to the promegakaryocyte (20 to 80 m in diameter) with an irregularly shaped nucleus and a cytoplasm rich in azurophilic granules. The promegakaryocyte forms the mature megakaryocyte located in the vascular niche, adjacent to a sinusoid. The megakaryocyte can be mistaken for the osteoclast, another large cell in bone that is multinucleated instead of multilobed. The cytoplasm of the megakaryocyte shows a network of demarcation zones formed by the invagination of the plasma membrane. Multiple cytoplasmic protrusions extend into the marrow sinusoid space and are sheared off into free fragments. Within the vascular space, the fragmented protrusions give rise to proplatelets after coalescence of the demarcation zones. The entire cytoplasm of the megakaryocyte is gradually converted into proplatelets and platelets and its multilobed nucleus is extruded and phagocytosed by macrophages. Recall the sequential steps of hemostasis following platelet activation (see 6-12). Hepcidin binds to ferroportin and triggers its internalization and lysosomal degradation. Removal of ferroportin from the plasma membrane prevents iron export, leading to increasing levels of iron in the cytoplasm, stored in ferritin. This negative regulatory mechanism can be modulated during anemia, hypoxia and inflammation.

Remember the segmental distribution of the 712 male urethra because it will become useful when performing urethral catheterization to drain urine from patients unable to micturate treatment laryngitis buy combivir canada. The prostate gland is histologically arranged in three zones of clinical significance (see 21-9): 1 medicine cabinets with lights combivir 300mg lowest price. Benign prostatic hyperplasia Lower illustrations from Damjanov I, Linder J: Pathology: A Color Atlas. It consists of three groups of glands: (1) periurethral mucosal glands (in the central zone); (2) periurethral submucosal glands, linked to the urethra by short ducts (in the transition zone); and (3) main prostatic glands (in the peripheral zone). About 30 to 50 tubuloalveolar glands open directly into the prostatic urethra through 15 to 30 long ducts ending at the sides of the urethral crest. The epithelium of the main prostatic glands is simple columnar or pseudostratified and arranged into folds supported by a lamina propria. The lumen may contain corpora amylacea, a condensed structure rich in glycoproteins and cell fragments, with a tendency to calcify in older men. The secretion of the prostate contains fibrinolysin, with a role in the liquefaction of semen. Citric acid, zinc, amylase, prostate-specific antigen and acid phosphatase are present in high concentrations in prostate fluid secreted in the semen. The prostate glands are lined by simple columnar or pseudostratified columnar epithelium. The lumen contains concretions (corpora amylacea) rich in glycoproteins and, sometimes, a site of calcium deposition (see 21-10). The prostate produces a zinc-rich alkaline fluid, which neutralizes the acidic vaginal content, provides nutrients and transports sperm and liquefies semen. The periurethral mucosal (central zone) and submucosal (transition zone) prostate glands and cells of the stroma undergo nodular hyperplasia in older men. Difficulty in urination and urinary obstruction caused by partial or complete compression of the prostatic urethra by the nodular growth. Retention of urine in the bladder or inability to empty the urinary bladder completely. The possibility of infection leads to inflammation of the urinary bladder (cystitis) and urinary tract infection (pyelonephritis). Acute and persistent urinary retention requires emergency urethral catheterization. Like prostate epithelial cells, prostate stromal cells can also produce growth factors with paracrine and autocrine effects (not shown). Androgen-deprivation therapy can lead to prostate cancer regression because cancer cells die or cease to progress in the absence of androgen-mediated cell signalling. This enzyme is localized predominantly in the stromal cells, the predominant androgen conversion site. Rectal examination (palpation of the prostate through the rectum) may reveal a markedly enlarged prostate. The androgen receptor (see 21-11) We consider now in detail the mechanism by which prostate stromal cells interact with prostate epithelial glandular cells. Trans-perineal or trans-rectal biopsy, if required, confirms a clinical diagnosis. Surgery (radical prostatectomy by retropubic or perineal surgery) and radiotherapy (external beam radiation therapy or radioactive seed implants in the prostate) are appropriate when the tumor is localized, as determined by computer imaging techniques. The pro-metastatic effect is suppressed with the administration of fatostatin, a blocker of adipogenesis. Male and female urethra (21-12; see 21-8) Prostate cancer originates from the main prostate glands of the peripheral zone, farthest from the urethra. Urethral glands produce a glycosaminoglycancontaining secretion, which protects and lubricates the surface of the urethral epithelium. The three cylindrical masses are surrounded by elastic connective tissue, the fascia, covered by skin. Each cylinder is surrounded by a dense connective tissue capsule, the tunica albuginea.

Pts experience an acute onset of severe eye pain medications for depression generic combivir 300mg on line, blurred vision treatment erectile dysfunction buy combivir 300mg with amex, photophobia, and watery eye discharge; edema, chemosis, and subconjunctival hemorrhage are evident. Wild-type poliovirus types 2 and 3 are no longer circulating anywhere in the world. During most of this period, rabies virus is present at or close to the site of the bite. This disease, which usually leads to death despite aggressive therapy, has three phases. Autonomic dysfunction is common and includes hypersalivation, gooseflesh, cardiac arrhythmia, and/or priapism. Muscle weakness usually begins in the bitten extremity and proceeds to quadriparesis. Only 15 pts have survived infection with rabies virus, and only one of these pts had not received rabies vaccine before disease onset. Yes Is rabies known or suspected to be present in the species and the geographic area No Does laboratory examination of the brain by fluorescent antibody staining confirm rabies Fever and Myalgia this is the most common syndrome associated with zoonotic viruses. Typically, pts have an acute onset of fever, chills, severe myalgia, malaise, and headache; true arthritis is not found. About one-fourth of infected pts have a 3- to 6-day febrile phase, a brief remission, and then recurrent fever, severe headache, nausea, vomiting, and meningeal signs lasting 1 week. The four serotypes of dengue virus are all transmitted by the mosquito Aedes aegypti, which is also a vector for yellow fever. Virus is easily isolated from blood during the acute phase by inoculation of mosquitoes or mosquito cell culture. Leukopenia, thrombocytopenia, and increased serum aminotransferase levels may be documented. Since then, there have been several outbreaks throughout Southeast Asia and the South Pacific as well as a larger worldwide epidemic that started in Brazil in 2015. Human infections are typically asymptomatic or benign and self-resolving, with characteristic low-grade fever, headache, malaise, nonpurulent conjunctivitis, myalgia, and arthralgia. Although most human infections are transmitted by infected female mosquitoes, transmission also occurs perinatally or via sexual intercourse, breastfeeding, or transfusion of blood products. Encephalitis Depending on the causative virus, the ratio of clinical to subclinical disease, the mortality rate, and residua vary widely. An effective vaccine (ideally given on days 0 and 28, with the second dose administered 1 week prior to travel) is available and is indicated for summer travelers to rural Asia, where the risk can be as high as 1 case per 5000 travelers per week. Unusual clinical features include chorioretinitis, flaccid paralysis, and initial presentation with focal neurologic deficits. Arthritis and Rash Alphaviruses are common causes of arthritis accompanied by a febrile illness and maculopapular rash, usually during the summer in temperate climates. The arthritis of this condition is multiarticular, migratory, and incapacitating, with resolution of the acute phase in a few days; joint pain may persist for months or years. Because of joint pain, only 50% and 90% of pts can resume normal activities at 4 weeks and 3 months, respectively. Pts surviving the first 2 days of hospitalization usually recover with no residua.