By W. Basir. Knox College.

The ability to released crude anthrax preparations in Tokyo on at least eight grow and disperse infectious microorganisms was once separate occasions in 1993 discount silagra 50mg amex lloyds pharmacy erectile dysfunction pills. However cheap silagra 50mg with amex erectile dysfunction drugs insurance coverage, the explosion of biotechnol- that anthrax was used as a weapon against a civilian popula- ogy in the 1980s and 1990s demonstrated that the many basic tion. In addition, state-sanctioned terrorism by the government microbiological techniques are fairly simple and attainable. A laboratory sufficient to grow tance—continues (despite United Nations’ efforts at inspec- and harvest the bacteria and to dry down the material to pow- tion and destruction) to develop biological weapons, including dered form could fit into the average sized household base- 21 Anti-adhesion methods WORLD OF MICROBIOLOGY AND IMMUNOLOGY Workers in biohazard protective suits respond to an anthrax incident in Florida. The more highly trained the terrorist, the more effective ANTI-ADHESION METHODS Anti-adhesion methods weapons could be expected to be produced. Even though Bacillus anthracis could be grown in such The adhesion of bacteria and other microorganisms to non- a makeshift laboratory, the preparation of the spores and the living and living surfaces is a crucial part of the contamination drying of the spores into a powder is not a trivial task. In fact, the growth of microorganisms example, even after a decade of dedicated effort, United on surfaces is the preferred mode of existence. The ability to Nations inspectors who toured Iraq bioweapons facilities after block adhesion would prevent surface growth. There are numerous examples of surface growth of the Gulf War found that Iraq had only managed to develop microorganisms. Still, the Iraq bioweapons program Escherichia coli on urinary catheters (synthetic tubes that are managed to produce 8,500 liters of concentrated anthrax. This small size and nonde- agent that causes meningitis, relies upon adhesion with host script nature of a bioweapons facility could make detection of cells. The adhesion of this and many other bacteria, including such a lab very difficult. Accordingly, the terrorist potential of disease causing Escherichia coli, is mediated by a surface anthrax will remain a threat for the foreseeable future. Other bacterial proteins are involved in adhesion, typi- See also Bacteria and bacterial infection; Biological warfare; cally by recognizing and biding to another protein on the sur- Bioterrorism, protective measures; Bioterrorism; Epidemics face of the host cell. Microorganism proteins that function in and pandemics; Vaccine adhesion are generically known as adhesins. Thus, the bac- The disadvantage of this approach is that the presence of resid- teria install their own receptor in the host tissue. The Pre-coating implant material with an antimicrobial compound chemistry of the surface can also drive adhesion. For example, that is permanently bonded has also been promising in lab the surface of the spores of bacillus and the capsule surround- studies. This hydropho- See also Biofilm formation and dynamic behavior; Infection bicity will drive the spore or bacterium to associate with a sur- and resistance; Probiotics face of similar chemistry. In order to block adhesion that is the result of the above mechanisms, the molecular details of these mechanisms must ANTIBIOTIC RESISTANCE, TESTS FOR Antibiotic resistance, tests for be unraveled. This is an on-going process, but advances are being made through research. Bacteria can sometimes adapt to the antibiotics used to kill Adhesion of Escherichia coli can depend on the pres- them. This adaptation, which can involve structural changes or ence of an adhesin called FimH. Antibodies to FimH can block the production of enzymes that render the antibiotic useless, adhesion, presumable by binding to the FimH protein, pre- can make the particular bacterial species resistant to the par- venting that protein from binding to the receptor on the surface ticular antibiotic. Furthermore, the three-dimensional structure usually display a spectrum of susceptibilities to antibiotics, of this adhesion is similar to that of adhesins from other bac- with some antibiotics being very effective and others totally teria. For another bacterial species, the pattern of antibi- protective effect against the adhesion of other bacteria. Thus, for diag- In the case of the capsule-mediated adhesion, such as nosis of an infection and for clinical decisions regarding the the example above, capsular antibodies may also thwart adhe- best treatment, tests of an organism’s response to antibiotics sion. A standard method of testing for antibiotic resistance For microorganisms that secrete their own receptor, involves growth of the target bacteria in the presence of vari- such as Escherichia coli, or which have receptor molecules ous concentrations of the antibiotic of interest. Typically, this protruding from their own surface (an example is the hemag- test is performed in a specially designed plastic dish that can glutinin protein on the surface of Bordetella pertussis), adhe- be filled with agar (a Petri plate). Contamination of the agar, sion could be eliminated by blocking the manufacture or the which would spoil the test results, is guaranteed by the steril- release of the receptor molecule. The type of agar used is essential for the validity of the a vaccine to the adhesin target of Escherichia coli O157:H7. This pathogen, which can be permanently debilitating and The hardened agar surface receives a suspension of the even lethal to humans who ingest contaminated food or water, test bacteria, which is then spread out evenly over the surface often lives in the intestinal tracts of cattle. The intention is to form a so-called lawn of organ- adhesion of the bacteria, they could be “flushed” out of the isms as growth occurs. Thus, a vital reservoir of infection would have been absorbent material. The vaccine could be ready for the market by as Each disc has been soaked in a known and different concen- early as 2003.

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The early-time ( 150fs) motions of the complex discount 50 mg silagra with visa erectile dysfunction treatment in unani, which is almost T-shaped silagra 100mg generic impotence used in a sentence, comprise a simultaneous length- ening of the I–Br distance and a slower transfer of vibrational energy from the intramolecular mode to the IBr–Ar coordinate. By 840fs, bursts of vibrational energy transfer to the atom–molecule degree of freedom give rise to a stream of population which eventually leads to expulsion of argon from the complex. To connect this dynamical picture with information available from experiments, calculations of the vibra- tional spectra of the cluster as a function of time after the femtosecond pump pulse show that relaxation of the nascent IBr vibrational content is at first sequential but at times longer than about 500fs becomes quasi-con- tinuous as a result of a complex interplay between intermode vibrational energy redistribution and molecular dissociation. A speculative prognosis Ultrafast laser spectroscopy is very much a science that, by its very nature, is driven by improvements in laser and optical technology. Dangerous though it is to make forecasts of scientific advances, what is clear at the time of writing (early 2000) is that at the cutting edge of this research field is the progress towards even faster laser pulses and the ability to design femtosecond laser pulses of a specified shape for optical control of individ- ual molecular motions. Quantum theory of IBr·Ar dissociation, showing a snapshot of the wavepacket states at 840fs after excitation of the I–Br mode by a 100fs laser pulse. The wavepacket maximum reveals predominant fragmentation of the IBr molecule along the r coordinate at short IBr–Ar distances (R coordinate), whilst a tail of amplitude stretches to longer R coordinates, indicating transfer of energy from the I–Br vibration to the IBr–Ar dimension, which propels the argon atom away from the intact IBr molecule. Laser pulses with durations in the attosecond regime would open up the possibility of observing the motions of electrons in atoms and molecules on their natural time scale and would enable phenomena such as atomic and molecular ionisation (Section 1. There are several proposals actively being pursued around the world to generate laser pulses that are significantly shorter than the shortest avail- able today (the current world record is 4. The physics of each scheme is well understood and the technology required to implement them in exis- tence; what is tricky is that the proposals are not so easy to apply in the laboratory. To reach the attosecond regime, laser pulses must be composed of very many different frequencies, as required by the time–energy uncer- tainty principle, and they must be coherent. A usable source of attosecond pulses must also be intense enough to result in experimentally detectable changes in light absorption or emission, and they must be separated in time by at least one millionth of a second so that the changes they induce can be recorded by modern electronic circuitry. One scheme which has generated considerable optimism is that sug- gested by Corkum and colleagues at the National Research Council in Ottawa, Canada, which takes advantage of the high harmonic frequencies simultaneously generated when an intense femtosecond laser pulse ionises a gas of helium or neon in a narrow waveguide to construct the broad spec- trum of colours necessary to support attosecond laser emission. These har- monics are just like the overtones of a musical note: they are generated by oscillations of the electrons liberated by ionisation in the laser field and are formed coherently, that is with their amplitudes in phase with one another. At the present time researchers have succeeded in generating up to the 297th harmonic in helium of the original 800 nm light from a 25fs titanium:sapphire laser by this approach, yielding a harmonic spectrum which extends into the X-ray region as far as 2. In addition to providing a possible source of attosecond light, high-order harmonic gen- Laser snapshots of molecular motions 19 eration also offers the chance to develop coherent, ultrafast X-ray laser devices. The reasoning was that by choosing the fre- quency of a monochromatic (long pulse duration) laser to match exactly that of a local vibrational mode between atoms in a polyatomic molecule, it ought to be possible to deposit sufficient energy in the mode in question to bring about a massively enhanced collision probability, and thereby gen- erate a selected set of target states. With the benefit of hindsight, it is clear that the approach failed to take into account the immediate and rapid loss of mode specificity due to intramolecular redistribution of energy over a femtosecond time scale, as described above. Eight years ago it was suggested by US researchers that in order to arrive at a particular molecular destination state, the electric field asso- ciated with an ultrafast laser pulse could be specially designed to guide a molecule during a collision at different points along its trajectory in such a way that the amplitudes of all possible pathways added up coherently just along one, specific pathway at successive times after the initial photoab- sorption event. To calculate the optimal pulse shapes required by this scheme dictates the use of a so-called ‘evolutionary’ or ‘genetic’ computer algorithm to optimise, by natural selection, the electric field pattern of the laser applied to the colliding molecule at successive stages, or ‘genera- tions’, during its dynamical progress from the original progenitor state until the sought-after daughter state is maximally attained. In order that this proposal can be made to work, what is required is a device which can make rapid changes to the temporal pattern of the elec- tric field associated with a femtosecond laser pulse. The recent develop- ment of liquid-crystal spatial light modulators to act as pulse shapers fulfils this task, and may open the gateway to a plethora of experimental realisations of coherent control of molecular dynamics. There has been much theoretical work on the types of laser pulse shapes required to bring about specific molecular goals. In the laboratory, successful optical control of molecular events has been demonstrated for strategic positioning of wavepackets, enhancement of molecular ionisation probabilities, and optimisation of different photodissociation pathways. ROBERTS femtosecond laser technology, the potential for control of molecular colli- sion dynamics with laser beams is becoming a reality. Scrutton2 1 Department of Chemistry, University of Leicester, Leicester LE17RH, UK 2 Department of Biochemistry, University of Leicester, Leicester LE17RH, UK 2. Not only do they sustain life – they are also involved in a myriad of processes that affect our everyday lives. These include applications in medicine, household detergents, fine chemical synthesis, the food industry, bioelec- tronics and the degradation of chemical waste. Since the discovery of enzymes just over a century ago, we have witnessed an explosion in our understanding of enzyme catalysis, leading to a more detailed appreciation of how they work. Over many years, much effort has been expended in the quest to create enzymes for specific biotechnological roles. Prior to the early 1980s, the only methods available for changing enzyme structure were those of chemical modification of functional groups (so-called ‘forced evolution’). The genetic engineering revolution has provided tools for dis- secting enzyme structure and enabling design of novel function. More recently, gene-shuffling techniques have been used to generate novel enzymes. Rational redesign of enzymes is a logical approach to producing better enzymes. However, with a few notable exceptions, rational approaches have been generally unsuccessful, reiterating our poor level of understanding of how enzymes work. This has led to a more ‘shot-gun’ approach to redesign, involving 21 22 M.

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Cross References Seizures Joint Position Sense - see PROPRIOCEPTION Jugular Foramen Syndrome The glossopharyngeal (IX) buy 50mg silagra free shipping erectile dysfunction doctor in nashville tn, vagus (X) order silagra 50mg with mastercard erectile dysfunction medications cost, and accessory (XI) cranial nerves may be damaged by lesions at or around the jugular foramen, producing a jugular foramen (or Vernet’s) syndrome. This produces: ● Dysphagia, dysphonia, palatal droop, impaired gag reflex; ipsilat- eral reduced taste sensation on the posterior one third of the tongue, and anesthesia of the posterior one third of the tongue, soft palate, pharynx, larynx and uvula, due to glossopharyngeal and vagus nerve involvement. The differential diagnosis includes retropharyngeal or retroparotid space occupying lesions, which may in addition involve the hypoglos- sal nerve (XII; Collet-Sicard syndrome) and the sympathetic chain with or without the facial nerve (VII; Villaret’s syndrome). Cross References Dysphagia; Dysphonia; Gag reflex Junctional Scotoma, Junctional Scotoma of Traquair Despite the similarity of these terms, they are used to refer to different types of scotoma: ● Junctional scotoma: Unilateral central scotoma with contralateral superior tem- poral defect, seen with lesions at the anterior angle of the chi- asm; this is said to damage the ipsilateral optic nerve plus the crossing loop of fibers (Wilbrand’s knee) originating from the inferonasal portion of the contralateral eye (it may be noted that some authors have questioned whether such a loop in fact exists). Postgraduate Medical Journal 2002; 78: 106, 112-113 Cross References Scotoma; Visual field defects - 177 - K Kayser-Fleischer Rings Kayser-Fleischer rings are deposits of copper, seen as a brownish dis- coloration, in Descemet’s membrane. Although often visible to the naked eye (difficult in people with a brown iris), they are best seen with slit-lamp examination. Since they are a highly reliable sign of intra- cerebral copper deposition in Wilson’s disease (hepatolenticular degen- eration), any patient suspected of this diagnosis (i. Very occasionally cases of neuro- logical Wilson’s disease without Kayser-Fleischer rings have been reported. Kayser-Fleischer ring: Hepatolenticular degeneration (Wilson’s disease). Neurology 1995; 45: 1261-1262 Cross References Dystonia; Parkinsonism Kernig’s Sign Kernig’s sign is pain in the lower back (and also sometimes the neck) and resistance to movement with passive extension of the knee on the flexed thigh in a recumbent patient. It is indicative of meningeal mechanosensitivity due to inflammation, either infective (meningitis) or chemical (subarachnoid hemorrhage), in which case it may coexist with nuchal rigidity and Brudzinski’s (neck) sign. If unilateral it may indicate irritation of the lumbosacral nerve roots from a ruptured intervertebral disc (in which case Lasègue’s sign may also be present). London: Imperial College Press, 2003: 365-366 Cross References Brudzinski’s (neck) sign; Lasègue’s sign; Nuchal rigidity Kernohan’s Notch Syndrome Raised intracranial pressure as a result of an expanding supratentorial lesion (e. If the midbrain is shifted against the contralateral margin (free edge) of the tentorium, the cerebral peduncle on that side may be compressed, resulting in a hemiparesis which is ipsilateral to the supratentorial lesion (and hence may be considered “false-localizing”). There may also be an oculomotor nerve palsy ipsilateral to the lesion, which may be partial (unilateral pupil dilatation). Neurology 2000; 55: 1751 Cross References “False-localizing signs”; Hemiparesis; Hutchinson’s pupil Kinesis Paradoxica Kinesis paradoxica is the brief but remarkably rapid and effective movement sometimes observed in patients with Parkinson’s disease or post-encephalitic parkinsonism, despite the poverty and slowness of spontaneous movement (akinesia, hypokinesia; bradykinesia) seen in these conditions. Cross References Akinesia; Bradykinesia; Hypokinesia; Parkinsonism Klazomania Klazomania was the term applied to the motor and vocal tics seen as a sequel to encephalitis lethargica (von Economo’s disease), along with parkinsonism and oculogyric crises. This observation helped to pro- mote the idea that tics were due to neurological disease rather than being psychogenic, for example in Gilles de la Tourette syndrome. Compulsory shouting (Benedek’s “klazomania”) associated with oculogyric spasm in chronic epidemic encephalitis. Acta Psychiatrica Scandinavica 1961; 36: 369-377 Cross References Coprolalia; Echolalia; Parakinesia, Parakinesis; Tic Kleptomania Kleptomania, a morbid impulse to steal, has been related to the obses- sive-compulsive spectrum of behaviors in patients with frontal lobe dysfunction. Journal of Neurology, Neurosurgery and Psychiatry 2001; 70: 279 (abstract) Cross References Frontal lobe syndromes Klüver-Bucy Syndrome The Klüver-Bucy syndrome consists of a variety of neurobehavioral changes, originally observed following bilateral temporal lobectomy (especially anterior tip) in monkeys, but subsequently described - 179 - K Knee Tremor in man. The characteristic features, some or all of which may be present, are: Visual agnosia (e. Journal of Neurology, Neurosurgery and Psychiatry 1993; 56: 311-313 Klüver H, Bucy P. Cross References Apathy; Hypermetamorphosis; Hyperorality; Hyperphagia; Hyper- sexuality; Visual agnosia Knee Tremor A characteristic tremor of the patellae, sometimes known as knee bob- bing, juddering, or quivering, may be seen in primary orthostatic tremor (POT; “shaky legs syndrome”). It is due to rapid rhythmic con- tractions of the leg muscles on standing, which dampen or subside on walking, leaning against a wall, or being lifted off the ground, with dis- appearance of the knee tremor; hence this is a task-specific tremor. Auscultation with the diaphragm of a stethoscope over the lower limb muscles reveals a regular thumping sound, likened to the sound of a distant helicopter. EMG studies show pathognomonic synchronous activity in the leg muscles with a frequency of 14-18Hz, thought to be generated by a central oscillator (peripheral loading does not alter tremor frequency). A number of drugs may be helpful in POT, including phenobarbi- tone, primidone, clonazepam, and levodopa, but not propranolol (cf. Archives of Neurology 1984; 41: 880-881 - 180 - Kyphoscoliosis K Brown P. Lancet 1995; 346: 306-307 Cross References Tremor Körber-Salus-Elschnig Syndrome - see NYSTAGMUS Kyphoscoliosis Kyphoscoliosis is twisting of the spinal column in both the anteropos- terior (kyphosis) and lateral (scoliosis) planes. Although such defor- mity is often primary or idiopathic, thus falling within the orthopedic field of expertise, it may also be a consequence of neurological disease which causes weakness of paraspinal muscles. Recognized neurological associations of kyphoscoliosis and scol- iosis include: Chiari I malformation, syringomyelia Myelopathy (cause or effect? Skeletal disease, such as achon- droplasia, is more likely to be associated with myelopathy than idiopathic scoliosis) Cerebral palsy Friedreich’s ataxia Neurofibromatosis Hereditary motor and sensory neuropathies Spinal muscular atrophies Myopathies, e. Some degree of scoliosis occurs in virtually all patients suffering from paralytic poliomyelitis before the pubertal growth spurt.

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