Gregory Dale Kirk, M.D., M.P.H., Ph.D.
- Joint Appointment in Oncology
https://www.hopkinsmedicine.org/profiles/results/directory/profile/0017371/gregory-kirk
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Na+ Peptidases Na+ Na+ To the liver H2N the amino-terminal end of the protein; carboxypeptidases act at the carboxy-terminal end. The most necessary digestive exopeptidases are two isozymes of carboxypeptidase secreted by the pancreas. Once inside the epithelial cell, these oligopeptides oligos, little have two potential fates. Most are digested by cytoplasmic peptidases into individual amino acids, that are then transported throughout the basolateral membrane and into the circulation. The transport system that moves oligopeptides also is liable for intestinal uptake of certain medication, including some antibiotics, angiotensin-converting enzyme inhibitors, and thrombin inhibitors. Peptide Absorption the primary merchandise of protein digestion are free amino acids, dipeptides, and tripeptides, all of which may be absorbed. Amino acid construction is so variable that multiple amino acid transport systems occur within the intestine. Dipeptides and tripeptides are carried into enterocytes on the oligopeptide transporter PepT1 that makes use of H+@dependent cotransport Some Larger Peptides Can Be Absorbed Intact Some peptides bigger than three amino acids are absorbed by transcytosis [p. The discovery that ingested proteins could be absorbed as small peptides has implications in medication as a outcome of these peptides may act as antigens, substances that stimulate antibody formation and lead to allergic reactions. Consequently, the intestinal absorption of peptides could also be a significant factor within the growth of meals allergies and meals intolerances. Oral Rehydration Therapy Intestinal Na Transport Experiment the graph exhibits Na+ transport throughout the gut with out glucose and after glucose was added to the lumen of the intestinal sac. What did including glucose to a saline answer within the lumen do to water absorption by the gut Cholera, a water-borne diarrheal illness brought on by the micro organism Vibrio cholera, is one of these killers. In the late Fifties, nonetheless, researchers showed that the intestinal mucosa of sufferers with cholera was not broken.
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Genetic variability within the insertion point can have a dramatic effect on the pressure required to move or resist a load. Some research have shown a correlation between muscle insertion points and success in sure athletic events. What happens In physics, rotational drive is expressed as torque, and the drive of contraction is expressed in newtons (mass * acceleration because of gravity). For simplicity, we ignore the contribution of gravity in this discussion and use the mass unit "kilograms" for force of contraction. Because the insertion of the biceps is near the fulcrum, a small motion of the biceps becomes a much larger motion of the hand. Rotational forceup = Rotational forcedown Biceps pressure 3 5 cm = 2 kg three 15 cm Biceps force = 30 kg. One frequent muscle dysfunction is a "charley horse," or muscle cramp-a sustained painful contraction of skeletal muscles. Many muscle cramps are brought on by hyperexcitability of the somatic motor neurons controlling the muscle. As the neuron fires repeatedly, the muscle fibers of its motor unit go right into a state of painful sustained contraction. Apparently, stretching sends sensory data to the central nervous system that inhibits the somatic motor neuron, relieving the cramp. Most of us have exercised too long or too exhausting and suffered from fatigue or soreness in consequence. With more severe trauma, muscle fibers, the connective tissue sheath, or the union of muscle and tendon may tear. With extended inactivity, such as could occur when a limb is immobilized in a solid, the skeletal muscular tissues atrophy. If the atrophy outcomes from somatic motor neuron dysfunction, therapists now try to keep muscle perform by administering electrical impulses that instantly stimulate the muscle fibers. Acquired disorders that affect the skeletal muscle system embody infectious ailments, such as influenza, that result in weak spot and achiness, and poisoning by toxins, similar to these produced in botulism (Clostridium botulinus) and tetanus (Clostridium tetani).
Diseases
- Protein R deficiency
- Succinic semialdehyde dehydrogenase deficiency
- Brown syndrome
- Dystonia musculorum deformans
- Midline cleft of lower lip
- Argininosuccinic aciduria
- Vulvovaginitis
- Polychondritis
- Hemophagocytic reticulosis
- Purtilo syndrome
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Glucose excretion takes place only when the renal threshold for glucose reabsorption is exceeded [p. However, if glucose intake is low, amino acids may be transformed into glucose through the pathways known as gluconeogenesis. This word literally means "the delivery (genesis) of recent (neo) glucose" and refers to the synthesis of glucose from a noncarbohydrate precursor. Amino acids are the primary supply for glucose through the gluconeogenesis pathways, however glycerol from triglycerides may also be used. Both gluconeogenesis and glycogenolysis are necessary backup sources for glucose during periods of fasting. The reactions making up these pathways (1) extract vitality from vitamins, (2) use vitality for work, and (3) retailer extra energy so that it could be used later. Metabolic pathways that synthesize massive molecules from smaller ones are known as anabolic pathways ana-, completion + metabole, change. Those that break giant molecules into smaller ones are known as catabolic pathways cata-, down or again. The classification of a pathway is its net result, not what occurs in any particular person step of the pathway. This single reaction is anabolic, however by the end of glycolysis, the preliminary 6-carbon glucose molecule has been converted to two 3-carbon pyruvate molecules. The breakdown of 1 glucose to two pyruvate makes glycolysis a catabolic pathway. The period of time following a meal, when the merchandise of digestion are being absorbed, used, and stored, known as the fed state or the absorptive state. This is an anabolic state during which the power of nutrient biomolecules is transferred to high-energy compounds or saved in the chemical bonds of different molecules. Once vitamins from a latest meal are not in the bloodstream and available for use by the tissues, the body enters what is called the fasted state or the postabsorptive state.
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It has been suggested that paternal mitochondria within the creating embryo are focused by the proteolytic marker ubiquitin and are destroyed via a ubiquitindependent mechanism [72]. It has been also proposed that elimination of paternal mitochondrial materials is an evolutionary mechanism to avoid deadly genome conflict between these important organelles in the growing embryo [73]. As a result, sure sequence variants populate the maturing oocyte with potential transmission to future progenies. The synthesis of the opposite strand, the light strand (Lstrand), starts when the replication of the H-strand reaches two-thirds of the molecule size and uncovers the L-strand origin of replication. Mitochondrial replication and transcription depend on interaction between the nuclear and mitochondrial genomes. Thus, the mitochondrial content material of the mature oocyte should be enough to meet the power requirements of fertilization and early embryonic improvement till mitochondrial replication is reinitiated. It is clear, nevertheless, that genomic silencing in mitochondria concomitantly with the increased vitality requirements make the oocyte extra susceptible to mitochondrial dysfunction, significantly if mitochondria are abnormally distributed throughout cell division. Mitochondrial Distribution and Dynamics Mitochondria show a dynamic morphology and kind complicated interconnected networks [76]. Frequent fission and fusion events rework mitochondrial interconnections inside the cell, which appears to be necessary for the upkeep of mitochondrial bioenergetics and mitochondrial distribution [77]. Homogeneousness and heterogeneousness describe two completely different patterns of mitochondrial distribution in the oocyte cytoplasm. Homogeneous distribution of mitochondria is usually observed on the germinal vesicle stage [78]. Homogenously distributed mitochondria are dominate in the later phases of oocyte maturation, which signifies poor oocyte and embryo quality. This suggests that the distribution pattern of mitochondria could also be used to estimate cytoplasmic maturation [65, 68].
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A low-compliance lung requires extra pressure from the inspiratory muscle tissue to stretch it. Compliance is the reciprocal of elastance (elastic recoil), the power to resist being deformed. Elastance additionally refers to the ability of a physique to return to its authentic form when a deforming force is eliminated. After many washings the elastic waistband is simple to stretch (high compliance) but missing in elastance, making it inconceivable for the shorts to keep up round your waist. For example, as famous within the Running Problem, emphysema is a illness during which elastin fibers normally present in lung tissue are 17. Destruction of elastin leads to lungs that exhibit excessive compliance and stretch simply during inspiration. To understand the significance of elastic recoil to expiration, consider an inflated balloon and an inflated plastic bag. Its elastic walls squeeze on the air inside the balloon, thereby rising the internal air stress. When the neck of the balloon is opened to the environment, elastic recoil causes air to circulate out of the balloon. The inflated plastic bag, on the opposite hand, is like the lung of an individual with emphysema. If the inflated plastic bag is opened to the atmosphere, a lot of the air stays inside the bag. Surfactant Decreases the Work of Breathing For years, physiologists assumed that elastin and different elastic fibers had been the primary source of resistance to stretch within the lung. However, studies comparing the work required to expand air-filled and saline-filled lungs confirmed that air-filled lungs are a lot more durable to inflate. From this outcome, researchers concluded that lung tissue itself contributes much less to resistance than once thought. Some other property of the normal air-filled lung, a property not present in the saline-filled lung, must create most of the resistance to stretch. At any air-fluid interface, the floor of the fluid is beneath tension, like a thin membrane being stretched. When the fluid is water, surface pressure arises because of the hydrogen bonds between water molecules.
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Maternally recruited aurora C kinase is extra secure than aurora B to help mouse oocyte maturation and early improvement. Mad2 prevents aneuploidy and premature proteolysis of cyclin B and securin throughout meiosis I in mouse oocytes. Changing Mad2 levels affects chromosome segregation and spindle assembly checkpoint management in feminine mouse meiosis-I. Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice. Complete kinetochore tracking reveals error-prone homologous chromosome biorientation in mammalian oocytes. Bi-orientation of achiasmatic chromosomes in meiosis I oocytes contributes to aneuploidy in mice. Oocyte-specific variations in cell-cycle control create an innate susceptibility to meiotic errors. Evidence of a excessive proportion of untimely unbalanced separation of sister chromatids within the first polar bodies of ladies of advanced age. Age-associated improve in aneuploidy and changes in gene expression in mouse eggs. Evidence that weakened centromere cohesion is a leading explanation for age-related aneuploidy in oocytes. Age-related meiotic segregation errors in mammalian oocytes are preceded by depletion of Cohesin and Sgo2. Shugoshin-2 is essential for the completion of meiosis however not for mitotic cell division in mice. Unified mode of centromeric protection by shugoshin in mammalian oocytes and somatic cells. Inadequate histone deacetylation throughout oocyte meiosis causes aneuploidy and embryo demise in mice.
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At one end of every canal is an enlarged chamber, the ampulla 5 bottle6, which contains a sensory structure known as 10. Sensory info from the inner ear mixed with indicators from joint and muscle proprioceptors tell our mind the place body parts are in relation to each other and to the setting. Visual info additionally performs an necessary role in equilibrium, as you understand when you have ever gone to one of the 360� film theaters the place the scene tilts abruptly to one facet and the viewers tilts with it! Our sense of equilibrium is mediated by hair cells lining the fluid-filled vestibular apparatus of the inner ear. These nonneural receptors respond to changes in rotational, vertical, and horizontal acceleration and positioning. The hair cells operate just like these of the cochlea, however gravity and acceleration rather than sound waves provide the pressure that strikes the stereocilia. Vestibular hair cells have a single lengthy cilium called a kinocilium 5 kinein, to move6 situated at one facet of the ciliary bundle. Movement in one direction causes the hair cells to depolarize; with movement in the opposite direction, they hyperpolarize. Starting from the ear canal, name the auditory structures by which issues may arise. Left right the superior canal senses rotation of the top from entrance to again, corresponding to that which happens when nodding "sure. Semicircular canals Superior Horizontal Posterior Cochlea the horizontal canal senses rotation of the top because it turns left or right, such as that which occurs when shaking the pinnacle "no. Gelatinous otolith membrane Hair cells (b) Crista Movement of the endolymph pushes on the gelatinous cupula and prompts the hair cells. Nerve fibers Endolymph Cupula Hair cells Supporting cells Nerve Head in neutral position Macula Gravity Brush strikes proper. Hair cells Endolymph Head tilted posteriorly Bone Gravity Otolith Direction of rotation of the head When the top turns right, endolymph pushes the cupula to the left. In the ampullae, the drag of endolymph bends the cupula and its hair cells within the path opposite to the direction in which the head is turning. For an analogy, consider pulling a paintbrush (a cupula attached to the wall of a semicircular canal) via sticky moist paint (the endolymph) on a board.
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Synonym: goblet cell (Ch 21), 661, 673 mucous membrane, sixty one, 766f mucous secretion, 79. Synonym: fibrinolysin (Ch sixteen, 26), 523, 524f, 525, 527f, 528t, 823 plasminogen, 525, 527f, 528t plasticity Ability of grownup stem cells to turn into a quantity of cell sorts (Ch three, 9), 87, 272 plateau part Intermediate section of the human sexual response (Ch 26), 823, 824 platelet Cell fragments that take part in coagulation. Modern name Cu Fe K Na Latin name Copper Iron Potassium Sodium Cuprium Ferrum Kalium Natrium. The Sry gene expression induces the event of Sertoli cells, which set off the signaling both for the rest of the testicular organization and the regression of the Mullerian duct. There are key genes involved in the early growth and survival of the gonads, a few of that are Nr51, Lhx9, Wt1, Cbx2, and Igf1r. The chromatin modification and remodeling factor Cbx2 [8] (also generally identified as M33) also performs a key position. Embryos lacking this gene have lowered expression of Nr51 and Lhx9, resulting in gonadal development defects. Mice missing these two genes have lowered proliferation charges of the somatic progenitor, agenesis of the adrenal gland, and failure of testis growth. The Y chromosome has a specific region, the Sry or sex-determining region, that shifts the bipotential gonad to differentiate into the testis by inducing the differentiation of the Sertoli cells [10, 11]. Sry upregulates Sox9 to stimulate the expression of fibroblast progress factor 9 (Fgf9) [12]. Sox9 and Nr5a1 activate expression of the Anti-Mullerian hormone/Mullerian inhibiting substance (Amh/Mis) [13]. Sertoli cells secrete Amh into the embryonic genital ridge, inflicting regression of the Mullerian ducts in males. In mouse models, ectopic expression of Sox9 introduced in feminine mice results in female-to-male intercourse reversal, suggesting that Sox9 can induce male development in feminine mice [14].
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The commonest sensation carried by these pathways is perceived as pain, but when histamine or another stimulus activates a subtype of C fiber, we perceive the sensation we call itch. Posterior view the quantity of space on the somatosensory cortex dedicated to each physique half is proportional to the sensitivity of that half. They are found in the subcutaneous layers of skin and in muscle tissue, joints, and inner organs. The concentric layers of connective tissue in the corpuscles create large receptive fields. Pacinian corpuscles reply greatest to high-frequency vibrations, whose energy is transferred through the connective tissue capsule to the nerve ending, where the power opens mechanically gated ion channels [p. Recent research using knockout mice signifies that one other sensory receptor, the Merkel receptor, also makes use of mechanically gated ion channels to respond to contact. Pacinian corpuscles are quickly adapting phasic receptors, and this property permits them to respond to a change in contact however then ignore it. For instance, you discover your shirt whenever you first put it on, but the touch receptors quickly adapt. Slow pain, described as duller and more diffuse, is carried on small, unmyelinated C fibers. You first expertise a quick stabbing sensation (fast pain), followed shortly by a uninteresting throbbing (slow pain). Itch (pruritus) comes only from nociceptors within the skin and is characteristic of many rashes and other skin conditions. When one thing itches, we scratch it, creating a mildly painful sensation that seems to interrupt the itch sensation. Many of the opioid painkillers, such as morphine, relieve ache, but in some individuals they also induce the side effect of itching.
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Stress, reproduction, and growth are additionally mediated by the hypothalamus by means of a number of hormones. You will be taught more about these reflexes in later chapters as we talk about the varied techniques of the body. The behavioral state system can modulate reflex pathways, and the cognitive system exerts each voluntary and involuntary management over motor capabilities. The diffuse modulatory systems regulate brain operate by influencing attention, motivation, wakefulness, memory, motor control, temper, and metabolic homeostasis. As talked about earlier, dopamine is unable to cross the bloodbrain barrier so medication to complement dopamine should be given as precursors that can be transported. Experimental evidence shows that the reticular activating system, a diffuse collection of neurons in the reticular formation, performs an essential role in preserving the "conscious mind" awake. If connections between the reticular formation and the cerebral cortex are disrupted surgically, an animal becomes comatose. Other proof for the importance of the reticular formation in states of arousal comes from studies exhibiting that basic anesthetics depress synaptic transmission in that region of the brain. Presumably, blocking ascending pathways between the reticular formation and the cerebral cortex creates a state of unconsciousness. One approach to outline arousal states is by the pattern of electrical exercise created by the cortical neurons. The measurement of brain activity is recorded by a process generally recognized as electroencephalography (see Table 9. Surface electrodes positioned on or in the scalp detect depolarizations of the cortical neurons within the area slightly below the electrode. The full cessation of brain waves is likely considered one of the scientific criteria for determining dying. In people, our major relaxation period is marked by a behavior generally recognized as sleep, outlined as an simply reversible state of inactivity characterised by lack of interplay with the exterior environment. Most mammals and birds present the identical stages of sleep as humans, telling us that sleep is a very ancient property of vertebrate brains.
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Tom, 53 years: Airways Connect Lungs to the External Environment Air enters the higher respiratory tract via the mouth and nostril and passes into the pharynx, a common passageway for food, liquids, and air pharynx, throat. In advanced atherosclerosis, calcified plaques trigger the normally elastic aorta and arteries to become stiff and noncompliant. Cyclin-dependent kinase 2 is crucial for meiosis but not for mitotic cell division in mice.
Muntasir, 51 years: Enzymes in the smooth endoplasmic reticulum and cytosol of cells are responsible for most lipid synthesis. This response reduces glucose uptake by most cells, making more glucose obtainable for exercising muscle. The warmth released is a direct measure of the power content material of the burned food and is usually measured in kilocalories (kcal).
Chenor, 62 years: Arterial strain is a steadiness between cardiac output and peripheral resistance, the resistance to blood circulate provided by the arterioles. Even so, growing regular train habits is one way of life change that many people discover difficult to make. How does an action potential in a muscle fiber set off a Ca2+ signal inside the fiber
Zuben, 52 years: Secretion selectively removes molecules from the blood and adds them to the filtrate within the tubule lumen. Viscosity also modifications barely with atmospheric pressure, reducing as stress decreases. Coal miners who spend years inhaling nice coal dust have much of their alveolar surface area covered with scarlike tissue.
Sanuyem, 64 years: The antibody molecule is Y formed, with antigen-binding websites on the arms and a stem that can bind to immune cell receptors. Immediate and fast cooling of those sufferers is essential, as enzymes and different proteins begin to denature at temperatures above 41 �C (106 �F). Increased intraocular stress is one threat factor for the eye disease glaucoma, characterised by degeneration of the optic nerve.
Dennis, 58 years: Objects seen with just one eye fall outdoors the binocular zone and are perceived in solely two dimensions. Mutation of Eif4g3, encoding a eukaryotic translation initiation factor, causes male infertility and meiotic arrest of mouse spermatocytes. Taste receptor cells are nonneural cells with membrane channels or receptors that work together with style ligands.
Owen, 25 years: Active bone marrow is red as a result of it accommodates hemoglobin, the oxygen-binding protein of red blood cells. A third principle relies on the postulated existence of muscle chemoreceptors which are delicate to metabolites (probably H+) produced during strenuous exercise. Light waves are focused by the lens, whose form is adjusted by contracting or enjoyable the ciliary muscle.
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References
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- Alston TA, Abeles RH. Enzymatic conversion of the antibiotic metronidazole to an analog of thiamine. Arch Biochem Biophys. 1987;257:357-362.
- Fullerton DA, McIntyre RCJ, Mitchell MB, et al: Lung transplantation with cardiopulmonary bypass exaggerates pulmonary vasomotor dysfunction in the transplanted lung, J Thorac Cardiovasc Surg 109:212, 1995.
- Lee AY, Levine MN, Baker RI, et al: Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer, N Engl J Med 349:146-153, 2003.