By P. Yussuf. Champlain College. 2018.
Tatton WG quality 2.5 ml xalatan, Eastovan MJ generic xalatan 2.5 ml overnight delivery, Bedingham W cheap 2.5 ml xalatan mastercard, Verrier MC buy xalatan 2.5 ml cheap, Bruce IC. Defective utilization of sensory input as the basis for bradykinesia, rigidity and Copyright 2003 by Marcel Dekker, Inc. Perceptual motor dysfunction in Parkinson’s disease: a deficit in sequential and predictive voluntary movement. Reaction time of patients with Parkinson’s disease with reference to asymmetry of neurological signs. Differentiation of choice reaction time performance in Parkinson’s disease on the basis of motor symptoms. The Bereitschaftspotential, L-dopa and Parkinson’s disease. Electroencephalogr Clin Neurophysiol 1987; 66:263– 274. Methods for evaluating treatment in Parkinson’s disease. Tremor and rhythmical involuntary movements in Parkinson’s disease. Electrophysiology of mammalian thalamic neurons in vitro. Animal models of physiological, essential and parkinsonian-like tremors. Resetting of tremor by mechanical perturbations: a comparison of essential tremor and parkinsonian tremor. Computer-assisted stereotactic ventralis lateralis thalamatomy with microelectrode recording control in patients with Parkinson’s disease. Tremor, the cogwheel phenomenon and clonus in Parkinson’s disease. Bernheimer H, Birkmayer W, Horrnykiewicz O, Jellinger K, Seitelberger F. Brain dopamine and the syndromes of Parkinson and Huntington: clinical Copyright 2003 by Marcel Dekker, Inc. Parkinsonian akinesia, rigidity and tremor in the monkey. Permanent human parkinsonism due to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): seven cases. MPT: A neurotoxin relevant to the pathophysiology of Parkinson’s disease. Clinical symptoms of cerebellar disease and their interpretation. Studies on induced exacerbation of parkinsonian rigidity. Frozen shoulder and other disturbances in Parkinson’s disease. Askmark H, Edebol Eeg-Olofsson K, Johnsson A, et al. Camptocormia (bent spine) in patients with Parkinson’s disease—characterization and possible pathogenesis of an unusual phenomenon. Philadelphia: Lippincott Williams and Wilkins, 2002. Grimes JD, Hassan MN, Trent G, Halle D, Armstrong GW. Clinical and radiographic features of scoliosis in Parkinson’s disease.
C N N CH3 H2N 3+ Pernicious anemia purchase xalatan 2.5 ml fast delivery, a deficiency of Co intrinsic factor order xalatan 2.5 ml without prescription, is a relatively com- N N H mon problem caused by malab- O sorption of dietary cobalamin buy xalatan 2.5 ml with mastercard. It may result CH3 from an inherited defect that leads to a CH2 C NH2 decreased ability of gastric parietal cells to CH3 H synthesize intrinsic factor or from partial H CH3 resection of the stomach or of the ileum generic 2.5 ml xalatan amex. CH CH Production of intrinsic factor often declines O 2 CH3 2 CH2 with age and may be low in elderly individu- C CH2 als. An alternative circumstance that leads to H2N C the development of a B12 deficiency is pan- CH3 N NH creatic insufficiency or a high intestinal pH, CH which would result from too little acid being N 2 CH3 produced by the stomach. Both of these H 3 conditions prevent the degradation of the O R-binder-B12 complex; as a result, B12 will O O P O– not be released from the R-binder protein H O and, therefore, cannot bind to intrinsic factor. H OH CH2OH H H How should vitamin B12 be admin- istered to a patient with pernicious Fig. X 5 -deoxyadenosine in deoxyadenosylcobalamin; X CH3 in anemia? Once the B12 is released from its bound protein, it will bind to the haptocorrins. In the small intestine, the pancreatic proteases digest the hapto- corrins, and the released B12 then binds to intrinsic factor, a glycoprotein secreted by the parietal cells of the stomach when food enters the stomach. The intrinsic fac- tor–B12 complex attaches to specific receptors in the terminal segment of the small intestine known as the ileum, after which the complex is internalized. The B12 within the enterocyte complexes with transcobalamin II and then is released into circulation. The transcobalamin II–B12 complex delivers B12 to the tissues, which contain specific receptors for this complex. The liver takes up approximately 50% of the vitamin B12, and the remainder is transported to other tissues. The amount of the vitamin stored in the liver is large enough that 3 to 6 years pass before symptoms of a dietary deficiency occur. Functions of Vitamin B12 Vitamin B12 is involved in two reactions in the body: the transfer of a methyl group 5 from N -methyl FH4 to homocysteine to form methionine and the rearrangement of the methyl group of L-methylmalonyl CoA to form succinyl CoA (Fig. Tetrahydrofolate receives a one-carbon group from serine or from other sources. This carbon is reduced to the methyl level and transferred to vitamin B12, forming 740 SECTION SEVEN / NITROGEN METABOLISM Because the problem in pernicious Dietary B ( ) 12 anemia is a lack of intrinsic factor, which results in an inability to Stomach absorb vitamin B12 from the gastrointestinal tract, B12 cannot be administered orally to Gastric mucosa treat this condition. In the past, it was usu- R-binders ally given by injection. An effective nasal spray containing B12 has recently been mar- keted, however, and its use precludes the Parietal cells need for lifelong injections of this vitamin. Intrinsic factor Pancreas Proteases Liver B12 Transcobalamin II Blood Ileum Fig. Dietary B12 binds to R-binders (haptocorrins) in the stomach and travels to the intestine, where the R-binders are destroyed by pancreatic proteases. B12 is absorbed in the ileum and carried by called transcobalamins (TC) to the liver, where B12 is stored. Methylcobalamin transfers the methyl group to homocysteine, which is converted to methionine by the enzyme methionine syn- thase. Methionine can then be activated to SAM to transfer the methyl group to other compounds (Fig. Vitamin B12 also participates in the conversion of L-methylmalonyl CoA to suc- cinyl CoA. In this case, the active form of the coenzyme is 5 -deoxyadenosylcobal- amin. This reaction is part of the metabolic route for the conversion of carbons from valine, isoleucine, threonine, thymine, and the last three carbons of odd-chain fatty acids, all of which form propionyl CoA, to the TCA cycle intermediate succinyl CoA (see Chapter 39). There are two major clinical manifestations of cobalamin (B12) deficiency.
Regulatory Modifications Phosphorylation buy xalatan 2.5 ml lowest price, acetylation buy generic xalatan 2.5 ml on-line, and adenosine diphosphate (ADP)-ribosylation of specific amino acid residues in a polypeptide can alter bonding by that residue and change the activity of the protein (see Fig cheap xalatan 2.5 ml free shipping. Phosphorylation of an OH group on serine cheap xalatan 2.5 ml with amex, threonine, or tyrosine by a protein kinase (an enzyme that trans- fers a phosphate group from ATP to a protein) introduces a large, bulky, nega- tively charged group that can alter the activity of a protein. Reversible acetylation occurring on lysine residues of histone proteins in the chromosome changes their 86 SECTION TWO / CHEMICAL AND BIOLOGICAL FOUNDATIONS OF BIOCHEMISTRY Carbohydrate addition O-glycosylation: OH of ser, thr, tyr, N-glycosylation: NH2 of asn O H O CH2 CH2 R O R O ser asn N N AC AC Lipid addition Palmitoylation: Internal SH of cys Myristoylation: NH of N-terminal gly O O O H3C (CH2)14 C S CH2 H3C (CH2)12 C N CH2 C H cys gly Prenylation: SH of cys O Cys C OCH3 SH O CH3 CH3 Cys C OCH3 CH3 C (CH2 CH2)2 H Regulation Phosphorylation: OH of ser, thr, tyr Acetylation: NH2 of lys, terminus O O CH O P O– CH C N CH CH CH CH 2 3 2 2 2 2 H O– ser arg ADP-ribosylation: N of arg, gln; S of cys + O O NH2 H Adenine CH2 P CH2 N C CH2 CH2 CH2 O – – O O O arg H HO OH HO OH Modified amino acids Oxidation: pro, lys Carboxylation: glu O N CH C CH2 pro H2 2 glu C CH –COO COO– H 4-Hydroxyproline γ–Carboxyglutamate residue Fig. Posttranslational modifications of amino acids in proteins. Some of the com- mon amino acid modifications and the sites of attachment are illustrated. Because these modifications are enzyme-catalyzed, only a specific amino acid in the primary sequence is altered. In N-glycosylation, the attached sugar is usually N-acetylglucosamine (N-Ac). CHAPTER 6 / AMINO ACIDS IN PROTEINS 87 interaction with the negatively charged phosphate groups of DNA. ADP-ribosyla- A number of pathogenic bacteria tion is the transfer of an ADP-ribose from NAD to an arginine, glutamine, or a produce bacterial toxins that are ADP-ribosyl transferases (NAD - cysteine residue on a target protein in the membrane (primarily in leukocytes, glycohydrolases). These enzymes hydrolyze skeletal muscles, brain, and testes). This modification may regulate the activity of the N-glycosidic bond of NAD and transfer these proteins the ADP-ribose portion to a specific amino acid residue on a protein in the affected E. Other Amino Acid Posttranslational Modifications human cell. Cholera A-B toxin, a pertussis toxin, and a diptheria toxin are all ADP-ribo- A number of other posttranslational modifications of amino acid side chains alter syl transferases. Carboxylation of the carbon of glutamate (carbon 4) in certain blood clotting proteins is important for attaching the clot to a surface. Calcium ions mediate this attachment by binding to the two negatively charged carboxyl groups of –glutamate and two additional negatively charged groups provided by phospholipids in the cell membrane. Collagen, an abundant fibrous extracellular protein, contains the oxidized amino acid hydrox- yproline. The addition of the hydroxyl group to the proline side chain provides an extra polar group that can engage in hydrogen bonding between the polypeptide strands of the fibrous protein. Selenocysteine HSe CH CH COO– 2 +NH The unusual amino acid selenocysteine is found in a few enzymes and is required 3 for their activity (Fig. Its synthesis is not a posttranslational modification, Selenocysteine however, but a modification to serine that occurs while serine is bound to a unique Fig. The selenocysteine is then inserted into the protein as it is being synthesized. Will Sichel was treated for 3 days with parenteral (intravas- cular) narcotics, hydration, and nasal inhalation of oxygen for his vaso- occlusive crisis. The diffuse severe pains of sickle cell crises result from occlusion of small vessels in a variety of tissues, thereby causing damage to cells from ischemia (low blood flow) or hypoxia (low levels of oxygen). Vaso-occlusion occurs when HbS molecules in red blood cells polymerize in the capillaries, where the partial pressure of O2 ( pO2) is low. This polymerization causes the red blood cells to change from a biconcave disc to a sickle shape that cannot deform to pass through the narrow capillary lumen. The cells aggregate in the capillaries and occlude blood flow. In addition, Will Sichel was treated with hydroxyurea therapy, which increases the production of red blood cells containing fetal hemoglobin. Had his severe pain persisted, partial exchange blood transfusions would have been considered because no other effective therapy is currently available.
Central nervous system—where im- pulses are coordinated and a response is organized xalatan 2.5 ml discount. One or more interneu- Table 9•2 Components of a Reflex Arc rons may carry impulses to and from the brain purchase 2.5 ml xalatan with visa, may function within the COMPONENT FUNCTION brain purchase xalatan 2.5 ml with mastercard, or may distribute impulses to Receptor End of a dendrite or specialized cell that responds to different regions of the spinal cord proven 2.5 ml xalatan. Central nervous Coordinates sensory impulses and organizes a 4. Motor neuron, or efferent neuron— system response; usually requires interneurons a cell that carries impulses away Motor neuron Carries impulses away from the CNS toward the from the CNS. Motor impulses leave effector, a muscle, or a gland Effector A muscle or gland outside the CNS that carries out a the cord through the ventral horn of response the spinal cord gray matter. Injection of anesthetic into the epidural space in the lumbar region of the spine (an “epidural”) is 2 Sensory often used during labor and childbirth. The spinal route neuron also can be used to administer pain medication. This process of demyelination (quadriceps muscle) slows the speed of nerve impulse conduction and disrupts nervous system communication. Although the cause of MS is not completely understood, there is strong evidence that it involves an attack on the myelin sheath by a person’s own immune system, a situation described as autoimmunity. Genetic makeup, in combination with environmental fac- tors, may trigger MS. Some research suggests that a prior viral or bacterial infection, even one that occurred many Figure 9-14 The patellar (knee-jerk) reflex. Numbers indi- years before, may set off the disease. ZOOMING IN How many MS is the most common chronic CNS disease of young total neurons are involved in this spinal reflex? The disease affects women transmitter is released at the synapse shown by number 5? MS progresses at different rates depending on the contracting, is one example of a spinal reflex. If you tap individual, and it may be marked by episodes of relapse the tendon below the kneecap (the patellar tendon), the and remission. At this point, no cure has been found for muscle of the anterior thigh (quadriceps femoris) con- MS, but drugs that stop the autoimmune response and tracts, eliciting the knee-jerk reflex (Fig. Such stretch reflexes may be evoked by appropriate tap- Amyotrophic (ah-mi-o-TROF-ik) lateral sclerosis is a ping of most large muscles (such as the triceps brachii in the disorder of the nervous system in which motor neurons arm and the gastrocnemius in the calf of the leg). The progressive destruction causes muscle flexes are simple and predictable, they are used in physical atrophy and loss of motor control until finally the affected examinations to test the condition of the nervous system. Poliomyelitis (po-le-o-mi-eh-LI-tis) (“polio”) is a Medical Procedures Involving the viral disease of the nervous system that occurs most com- Spinal Cord monly in children. Polio is spread by ingestion of water contaminated with feces containing the virus. It is sometimes necessary to remove the gastrointestinal tract leads to passage of the virus into a small amount of cerebrospinal fluid (CSF) from the the blood, from which it spreads to the CNS. CSF is the fluid that circu- tends to multiply in motor neurons in the spinal cord, lates in and around the brain and spinal cord. This fluid leading to paralysis, including paralysis of the breathing is taken from the space below the spinal cord to avoid muscles. Because the spinal cord is Polio has been virtually eliminated in many countries only about 18 inches long and ends above the level of through the use of vaccines against the disease—first the the hip line, a lumbar puncture or spinal tap is usually injected Salk vaccine developed in 1954, followed by the done between the third and fourth lumbar vertebrae, at Sabin oral vaccine. A goal of the World Health Organiza- about the level of the top of the hipbone. The sample tion (WHO) is the total eradication of polio by worldwide that is removed can then be studied in the laboratory vaccination programs.
The exercises took around 30 minutes three times a week to complete and participants were also expected to walk at least twice a week during the trial cheap 2.5 ml xalatan. The exercise programme was effective in reducing falls in those aged 80 years and older but not in those aged 75 to 79 years generic xalatan 2.5 ml overnight delivery. The authors suggested that the programme may be more effective in frailer rather than fitter older people cheap xalatan 2.5 ml, because the exercises increase strength and balance above the critical threshold necessary for stability generic 2.5 ml xalatan with visa. The risk factors were lower extremity weakness, impaired gait, impaired balance, and more than one fall in the previous six months. Exercise physiology graduate students led the group sessions of progressive strength, endurance, and balance training exercises. Elastic bands, a 12-inch rubber ball, and ankle (up to 5·4 kg) and waist weights (up to 11·3 kg) were used for strength training. After 12 weeks those in the exercise group showed significant improvements in some of the strength, endurance, gait, and health status measures. There were 13 falls in 38·7% of the exercise group and 14 falls in 32·1% of the control group. When the authors adjusted for activity level during the 12 weeks to assess whether greater activity levels were associated with an increased risk of falls, those in the exercise group had a lower fall rate. The effects of two different exercise approaches on physical functioning and falls were studied by Wolf et al29 at the Atlanta FICSIT trial site. Men and women aged 70 years and older living in the community were randomised to one of three arms: Tai Chi classes (n = 72, mean [SD] age 76·9 [4·8] years), computerised balance training (n = 64, mean [SD] age 76·3 [5·1] years) or an education control group (n = 64, mean [SD] age 75·4 [4·1] years). Tai Chi classes concentrated on components of movement that often become limited with aging, including the standing base of support, body and trunk rotations, and reciprocal arm movements. The participants were encouraged to practise the movements at least twice a day at home for 15 minutes. Computerised balance training took place on a moveable platform and under one on one supervision. Participants practised moving their centre of mass without moving their feet with their eyes open and then closed and also during floor movement. Tai Chi was most effective in reducing falls in people who fell recurrently, and, compared with controls, Tai Chi participants were less afraid of falling. Multiple intervention trials with an exercise component In a large community trial reported by Hornbrook et al,17 participants were randomised by household to an intervention group (n = 1611) or minimal treatment control group (n = 1571). Nearly a third of participants (32%) were 70–74 years of age. The intervention emphasised removal of home hazards, reducing risk taking behaviour, and improving physical fitness. The exercises selected for the intervention were designed to involve all body parts, maintain range 138 Prevention of falls in older people of movement, provide strengthening, and improve posture and balance. After one supervised group session, the participants were given a manual and instructed to carry out the exercises at home. At one year the odds of being a faller was significantly less in the intervention group. Statistical analysis did not address the fact that participants were randomised by household but the unit of analysis was the individual. However 75% of the households had only one participant. McMurdo et al20 randomised a volunteer sample of 118 women, mean age 64·5 (range 60–73) years to a calcium supplementation or calcium supplementation plus exercise group. The exercise component of this two-year trial involved weight bearing exercises to music in a centre and was led by a person trained in physical education. Bone mineral density showed a significant increase at one of three sites in the exercise plus calcium supplementation group.