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Masses that rapidly increase in size heart attack mp3 purchase generic inderal on line, involve skin changes, facial nerve weakness, or regional lymphadenopathy should all be considered high risk for malignancy. Achieving a diagnostic biopsy in salivary tumours is controversial with many authors recommending no pre-op biopsy. As therapy for almost all lesions is surgery in the first instance, the impact on treatment approach is minimal whatever the biopsy result. All authors would agree that open biopsy is never indicated, as it leads to tumour seeding and might compromise the outcomes, whether the lesion is benign or malignant. It is in this region that the facial nerve leaves the stylomastoid foramen to pass to the muscles of facial expression. The substance of the gland envelops these fibres almost as if poured into the anatomical space. The vast majority (80%) of the gland lies superficial to the nerve, and, crucially, there is rarely if ever a lymph node in the deep lobe. The significance of this is that, unless the deep lobe is involved with tumour, no dissection deep to the nerve is required to remove potentially involved nodes. When raising the skin flap for parotid surgery, the great auricular nerve must be sacrificed. Occasionally the posterior branch might be spared, but patients should be warned that the earlobe will remain numb following surgery. Between the two lies the nerve, and it should be dissected 409 50: disorders of the salivary glands Table 50. This can make identification of the nerve challenging, particularly if bleeding is encountered. The surgeon must resist the temptation to use bipolar diathermy indiscriminately at this point, as nerve injury will result. It might be prevented by placing a barrier of muscle or facia between the remaining parotid and skin, although this has not gained universal acceptance. B, D, E Mumps is a viral infection of the parotid glands, and although it can present with symmetrical involvement, unilateral atypical viral parotiditis does occur and should be considered when assessing a unilateral painful parotid swelling. Classical patients at risk from bacterial parotid infections include elderly dehydrated patients, and those who have undergone recent surgery. Recurrent parotitis of childhood has a typical history of swelling and pain that responds to antibiotics and rarely results in abscess. A, D, E As stated previously, most parotid gland tumours are benign and the pleomorphic adenoma is the most common benign tumour. Pleomorphic adenomas have incomplete capsules and so-called pseudopodia (small extensions of disease under the microscope), which lead to high rates of recurrence unless formal excision with a cuff of tissue is undertaken. Even in malignant lesions, however, if the nerve can be dissected off the tumour, no survival advantage has been shown from nerve sacrifice. The majority of such tumours will be treated with postoperative radiation therapy to address microscopic residual disease. It is not uncommon for elderly patients in care homes to become dehydrated and present in this manner. Treatment generally consists of rehydration, taking care in patients who might have cardiac compromise and antibiotics. Incision and drainage might be complicated by facial nerve injury, so in most cases antibiotics are used with milking of secretions from the parotid duct. Most tumours of minor salivary glands are malignant, and if <1 cm they can be excised as both a diagnostic and therapeutic procedure. Investigation of lesions in this area should delineate the locoregional extent of disease, with particular attention to destruction of the bone of the hard palate and presence of regional lymph nodes. Attempts should be made to prevent a through-and-through defect allowing communication between the mouth and nose. If this is required given the extent of disease, reconstructive options include rotation palata or temporalis flaps, vascularised free flaps and simple obturation with a dental appliance. Although aspiration will lead to temporary resolution, excision with the affected minor gland should be undertaken to prevent recurrence. Lesions such as this on the upper lip can be seen but are more suspicious for malignancy. There can also be involvement of the pancreas and testicles, so care must be taken to examine and investigate the patient appropriately. Although less common in the developed world following vaccination programmes, mumps is still seen and even in those considered vaccinated the condition can present. It might also present with unilateral symptoms; therefore, the clinician should be aware of the possibility. Management is expectant, although most clinicians do provide antibiotics to avoid secondary bacterial infection. E Parotid gland cancer Warning signs here include age, rapid increase in size and facial nerve involvement. Although most parotid gland masses are benign, parotid cancers are not uncommon due to the overall incidence of parotid masses. In addition, cross-sectional imaging will outline the extent of locoregional disease and screen for distant metastases. Primary therapy is surgical, and the clinician should assess the extent of disease for resectability. Particular attention should be paid to the relationship of the mass to the facial nerve. Involvement of the mastoid bone will require a lateral temporal bone resection with resection of the facial nerve to achieve macroscopically clear margins. In addition, adenoid cystic carcinoma has a propensity for perineural invasion, so postoperative therapy that will include radiation should be planned to include the skull base, to try and control microscopic disease extension. The majority of masses such as this will be adequately managed with superficial parotidectomy. Many clinicians now order crosssectional imaging to confirm the position of the mass. The retromandibular vein can be seen on axial contrast-enhanced imaging and marks the junction of the superficial and deep lobes of the parotid. Although approaches are identical between total and superficial parotidectomy, the former puts the facial nerve at higher risk and the patient should be aware of this prior to surgery. Assuming surgery is successful and the mass is excised without rupture of the capsule, recurrence rates are low. In fact if recurrence occurs, it might not present for decades following surgery, so patients should be followed up over a long period. The rates of recurrence in this event are thought to be higher, although yet again clinical evidence of recurrence might not present for many years. Some authors advocate postoperative radiation to minimise the risk of recurrence, although side effects, including osteoradionecrosis of the temporal bone, are common. Many authors would consider close follow-up with revision surgery and postoperative radiation reserved only for those patient who do recur. C Salivary calculus Salivary calculi are most commonly seen in the submandibular duct. This is thought to be because the saliva is more viscous from this gland and that it drains against gravity. Also the duct crosses the lingual nerve, providing a potential area of compression, adding to salivary stasis. An intraoral incision with a suture placed behind the stone, around the duct to prevent posterior migration, is the classic description. Following removal, the duct should be marsuplialised to prevent stricture on healing. For stones more posterior than this, damage to the lingual nerve is a risk and many authors would advocate submandibulectomy with identification of the stone in the duct from behind and removal. Sialendoscopy and interventional radiology techniques have made previously inaccessible stones targets for procedures that prevent the need for surgical incisions. The equipment and expertise required to perform such procedures, however, has limited its widespread application.
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Preoperative ureteric stenting helps to protect or instantly recognise damage should it occur during operations such as retroperitoneal lymph node dissection in testicular tumours blood pressure medication first line buy inderal american express, excision of retroperitoneal liposarcoma, or open repair of inflammatory abdominal aortic aneurysm. Damaged ureter manifests itself as a urinary fistula through the abdominal or vaginal wound. Sometimes loin pain and fever might be a presenting feature of an unrecognised 717 75: the kidneys and ureters and stone formation. Most of the time, however, they are an incidental finding and therefore best left alone. Polycystic kidneys are hereditary and transmitted by either parent as an autosomal dominant trait. The condition does not manifest itself clinically before the age of 30 years and therefore does not present in childhood as renal failure. The procedure chosen will depend upon the type of injury, time of diagnosis, and whether a segment of ureter is missing. The choices are end-to-end anastomosis with spatulation, ureteric re-implantation, Boari operation, and ileal ureteric replacement. Isotope renography is the best test to establish that dilatation is caused by obstruction. In hydronephrosis the isotope remains in the renal pelvis and does so in spite of frusemide. A procedure to preserve the kidney is carried out when a renogram shows that there is more than 20% (not 5%) of renal function. Hydronephrosis is defined as an aseptic dilatation of the pelvi-calyceal system from an obstruction. Staphylococci, streptococci, and Proteus species have the ability to split urea, causing alkaline urine that is conducive to the formation of stones. Primary hyperparathyroidism causing hypercalcaemia and hypercalciuria is found in 5% of patients who present with radio-opaque calculi. This metabolic disturbance must be excluded in patients who present with recurrent urinary calculi (see Chapter 51, dealing with section on hyperparathyroidism). If a parathyroid adenoma is found in the presence of renal calculi, it must be removed first before treating the kidney stones. Because of its composition it is smooth and dirty white growing in alkaline urine, is radio-opaque, and grows to occupy the entire renal pelvis. When symptomatic it might cause haematuria, infection, and renal failure in bilateral calculi. Some might cast a faint shadow on plain x-ray by virtue of containing some calcium. The pain is agonising, typically passing from the loin to the groin and then to the genitalia with the patient writhing and unable to find a comfortable position. A, B, C, D Plain radiography has a limited place as opacities from calcified mesenteric lymph nodes, gallstones, foreign bodies, phleboliths and calcified adrenal gland might cause confusion. A kidney stone will be seen superimposed on the vertebral body while the others would be in front. It would show delayed excretion from the affected kidney; repeated pictures at delayed intervals might show the exact site of stone in the ureter. Retrograde pyelography has no role as the information obtained from it would be available from the above methods; moreover it can introduce infection. Presence of infection in an obstructed upper urinary tract requires urgent surgical intervention under antibiotic cover. The exception is that the kidney with pain or pyonephrosis is treated first by decompression through a nephrostomy. Clinically the condition might present as loin pain exacerbated by excessive fluid intake. Minimal-access surgical techniques such as endoscopic pyelotomy with balloon dilatation and temporary stenting are the alternative procedures. The vast majority of stones in the genito-urinary tract are treated by minimal access surgery. A cannula is placed in the renal pelvis; a balloon catheter is passed to stop stone fragments migrating into the ureter. The stone is then fragmented by contact lithotripsy; the fragments are then removed by forceps or washed out. Finally a nephrostogram is done to make sure of the integrity of the renal pelvis. In the rare instance when an open procedure is to be done, the approach is extraperitoneal through the loin. A, D the vast majority of ureteric stones pass spontaneously as they are <5 mm in diameter. Stones that require surgical intervention (those > 5mm or presence of infection) are treated by minimal access surgical methods in the vast majority. The most common method is electrohydraulic fragmentation, washout +/- stent insertion through an ureteroscope. In the ureter, stones are commonly arrested at one of the folowing five (not two) anatomical sites of narrowing: pelviureteric junction, crossing of the iliac vessels, proximity of vas deferens or broad ligament, entrance to the bladder wall, and ureteric orifice. Severe renal pain subsiding after 1 day or so is a sinister symptom and denotes complete ureteric obstruction, a situation that requires immediate decompression by percutaneous nephrostomy followed by definitive treatment. They are urea-splitting organisms and form ammonia, which makes the urine alkaline, predisposing to stone formation. Patients might present either as an emergency with acute pyelonephritis or electively as chronic pyelonephritis. Acute pyelonephritis is more common in females at all ages and presents with lassitude, nausea and vomiting, loin pain with rigors and high temperature and scalding micturition. The elective patient with chronic pyelonephritis is usually a woman who presents with dull lumbar non-specific pain and generally feeling unwell over a period of time. When it occurs in children, 50% have an underlying abnormality such as vesicoureteric reflux or obstruction. In 35% of them vesicoureteric reflux is the cause and in extreme cases reflux nephropathy might result in end-stage renal failure. A, B, C, D, E Sterile pyuria, when there are abundant white cells in the urine without any growth of organisms, is typical in renal tuberculosis. Frequency of micturition is often the only symptom; suprapubic pain might be present with minimal loin ache. The diagnosis should be suspected when symptoms of cystitis persist in spite of prolonged antibiotic therapy. Vesico-ureteric reflux is often the cause of chronic pyelonephritis that results in renal scarring in the long term ultimately causing end-stage renal failure. Pyonephrosis is infected hydronephrosis and is caused by a stone obstructing the ureter. Once the patient has recovered, the function of the kidney is determined and appropriate definitive treatment instituted. Renal carbuncle is an abscess within the renal parenchyma that results from blood-borne infection. It is commonly seen in the immunocompromised-diabetic, drug abusers, chronic debilitating diseases, and acquired immunodeficiency. The abscess is drained by open surgery, as the pus is usually too thick for percutaneous aspiration. Perinephric abscess might result from a retrocaecal appendix abscess, extension from a cortical abscess or by haematogenous spread. The patient presents as a surgical emergency with swinging pyrexia and tender loin mass. B the most common presentation is an abdominal mass noticed by the mother when bathing the child. Haematuria is a late symptom and denotes extension of the tumour into the renal pelvis and therefore a poor prognosis. Besides a lump, on examination there might be hemihypertrophy of the body and absence of the iris. Once suspected, the patient should be referred to the paediatric surgeon with special interest in oncology. Depending upon the staging the management is discussed in a multidisciplinary team meeting followed by treatment that would consist of a combination of surgery, chemotherapy, and radiotherapy.
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Several species of gadY with sizes 105 nt pulse pressure deficit trusted inderal 80mg, 90 nt, and 59 nt were observed and are believed to be the result of endonucleolytic processing, the mechanistic details of which are not known. The novel transcription factor SgrR coordinates the response to glucose-phosphate stress. Padalon-Brauch G, Hershberg R, ElgrablyWeiss M, Baruch K, Rosenshine I, Margalit H, Altuvia S. Fozo E, Kawano M, Fontaine F, Kaya Y, Mendieta K, Jones K, Ocampo A, Rudd K, Storz G. Abundance of type I toxin-antitoxin systems in bacteria: searches for new candidates and discovery of novel families. Mutations that increase expression of the rpoS gene and decrease its dependence on hfq function in Salmonella typhimurium. Promoter substitution and deletion analysis of upstream region required for rpoS translational regulation. Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity. Transcriptional interference between convergent promoters caused by elongation over the promoter. Andre G, Even S, Putzer H, Burguiere P, Croux C, Danchin A, Martin-Verstraete I, Soutourina O. The SsrA-SmpB system for protein tagging, directed degradation and ribosome rescue. Intracellular location, quantitation, and purification by polyadenylate-cellulose chromatography. Regulation of the Escherichia coli hfq gene encoding the host factor for phage Q beta. Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid. Characterization of broadly pleiotropic phenotypes caused by an hfq insertion mutation in Escherichia coli K-12. Impact of hfq on the intrinsic drug resistance of Salmonella enterica serovar typhimurium. Negative regulation of mutS and mutH repair gene expression by the Hfq and RpoS global regulators of Escherichia coli K-12. Host factor Hfq of Escherichia coli stimulates elongation of poly(A) tails by poly(A) polymerase I. A highly conserved protein of unknown function is required by Sinorhizobium meliloti for symbiosis and environmental stress protection. L-Arabinose-sensitive, L-ribulose 5phosphate 4-epimerase-deficient mutants of Escherichia coli. Structural relationships in the OmpR family of winged-helix transcription factors. Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria. Isolation and characterization of Xenorhabdus nematophila transposon insertion mutants defective in lipase activity against Tween. The related effector proteins SopD and SopD2 from Salmonella enterica serovar Typhimurium contribute to virulence during systemic infection of mice. Regulation and function of Escherichia coli sugar efflux transporter A (SetA) during glucose-phosphate stress. Functional and biochemical characterization of Escherichia coli sugar efflux transporters. Genetics and regulation of the major enzymes of alanine synthesis in Escherichia coli. Induction of the Pho regulon suppresses the growth defect of an Escherichia coli sgrS mutant, connecting phosphate metabolism to the glucose-phosphate stress response. Depletion of glycolytic intermediates plays a key role in glucose-phosphate stress in Escherichia coli. Regulation of galactose operon expression: glucose effects and role of cyclic adenosine 3,5-monophosphate. Differential translation efficiency explains discoordinate expression of the galactose operon. Catabolite repression of Pseudomonas aeruginosa amidase: the effect of carbon source on amidase synthesis. The nucleotide sequence of the Pseudomonas aeruginosa pyrEcrc-rph region and the purification of the crc gene product. Carbon catabolite repression in Pseudomonas: optimizing metabolic versatility and interactions with the environment. The Pseudomonas putida Crc global regulator controls the hierarchical assimilation of amino acids in a complete medium: evidence from proteomic and genomic analyses. The target for the Pseudomonas putida Crc global regulator in the benzoate degradation pathway is the BenR transcriptional regulator. The global carbon metabolism regulator Crc is a component of a signal transduction pathway required for biofilm development by Pseudomonas aeruginosa. Regulation of ferric iron transport in Escherichia coli K12: isolation of a constitutive mutant. GeneChip expression analysis of the iron starvation response in Pseudomonas aeruginosa: identification of novel pyoverdine biosynthesis genes. Post-transcriptional regulation on a global scale: form and function of Csr/Rsm systems. Depolymerization of beta-1,6-N-acetyl-D-glucosamine disrupts the integrity of diverse bacterial biofilms. Biofilm formation and dispersal under the influence of the global regulator CsrA of Escherichia coli. Complex regulation of the global regulatory gene csrA: CsrA-mediated translational repression, transcription from five promoters by Esigma (7)(0) and Esigma(S), and indirect transcriptional activation by CsrA. Campylobacter jejuni CsrA mediates oxidative stress responses, biofilm formation, and host cell invasion. Global control in Pseudomonas fluorescens mediating antibiotic synthesis and suppression of black root rot of tobacco. Zuber S, Carruthers F, Keel C, Mattart A, Blumer C, Pessi G, Gigot-Bonnefoy C, Schnider-Keel U, Heeb S, Reimmann C, Haas D. Expression of two csg operons is required for production of fibronectin- and congo red-binding curli polymers in Escherichia coli K-12. Inverse regulatory coordination of motility and curli-mediated adhesion in Escherichia coli. The multicellular morphotypes of Salmonella typhimurium and Escherichia coli produce cellulose as the second component of the extracellular matrix. Role of the biofilm master regulator CsgD in cross-regulation between biofilm formation and flagellar synthesis. Bacterial quorum sensing: its role in virulence and possibilities for its control. Requirements for Vibrio cholerae HapR binding and transcriptional repression at the hapR promoter are distinct from those at the aphA promoter. So similar, yet so different: uncovering distinctive features in the genomes of Salmonella enterica serovars Typhimurium and Typhi. A two-component regulatory system (phoP phoQ) controls Salmonella typhimurium virulence. GadX/GadW-dependent regulation of the Escherichia coli acid fitness island: transcriptional control at the gadY-gadW divergent promoters and identification of four novel 42 bp GadX/GadW-specific binding sites. Gastric acid barrier to ingested microorganisms in man: studies in vivo and in vitro. Starvation- and stationary-phase-induced acid tolerance in Escherichia coli O157:H7.
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The association of endotoxin in Gram-negative bacteria is a result of the presence of: (a) Peptidoglycan (d) Steroids (b) Lipopolysaccharide (e) Calcified proteins (c) Polypeptide 7 prehypertension quiz purchase inderal 80mg on line. Match the following bacterial locomotion and external structure terms to their descriptions: Phototaxis (a) Spirochete endoflagella causing Flagellum corkscrew motion Conjugation pilus (b) Tiny, hollow projection that Slime layer attaches two cells, providing a Chemotaxis conduit for exchange of Glycocalyx genetic material Axial filaments (c) Term used to describe all Capsule polysaccharide-containing substances external to the cell wall (d) A response of some bacteria to move toward or away from light (e) A thick, protective polysaccharide containing structure located outside of the cell wall (f) Long, thin, helical appendage used for movement (g) Thin glycocalyx that prevents dehydration, traps nutrients, and allows for attachment to other cells and objects in the environment (h) Nonrandom response of movement toward or away from chemical concentration gradients in the environment 9. Draw a diagram describing what will happen to a bacterial cell when it is placed in: (a) Hypotonic solution (b) Isotonic solution (c) Hypertonic solution 10. Bacterial fimbriae present on the outer cell surface are used for: (a) Cellular motility (b) Sexual reproduction (c) Cell wall synthesis (d) Adherence to surfaces (e) Adherence and exchange of genetic information 11. Polyphosphate and sulfur are stored in bacterial cells in structures called: (a) Endospores (d) Glycocalyx (b) Mesosomes (e) Nucleoids (c) Inclusions 12. Glucose is often present in very low concentrations in environments populated by microorganisms. To import the maximum amount of available glucose, cells use: (a) Simple diffusion (d) Osmosis (b) Facilitated diffusion (e) Receptor-mediated (c) Active transport endocytosis 14. Peptidoglycan digested from Gram- bacteria retain their cell membrane but lose their cell walls, making them protoplasts, whereas cell wall digests of Gramnegative bacteria retain their cell and outer membranes intact, making them. Other genera of bacteria normally have cell walls but can lose their ability to form cell walls; such bacteria are called. Match each following organelle with its function: Cytoskeleton (a) Contains enzymes for lipid Lysosomes synthesis Smooth endoplasmic (b) Vacuole that contains reticulum digestive enzymes Rough endoplasmic (c) Has sites for protein reticulum synthesis Nucleus (d) Site of ribosome synthesis (e) Network of microtubules and microfilaments 17. For each of the lettered regions identified on this figure, give its name and function. And that the mitochondria and chloroplast probably originated from bacteria that were engulfed by larger bacteria Did you know that the components of the cell membrane can move side to side and flip-flop We lack the enzymes needed for the metabolic pathways that digest grass-as does the cow. However, she has billions of microbes, a different mix in each of the four "stomachs, " that do metabolize the grass for her. It includes anabolism, reactions that require energy to synthesize complex molecules from simpler ones, and catabolism, reactions that release energy by breaking complex molecules into simpler ones that can then be reused as building blocks. Catabolism provides an organism with energy for its life processes, including movement, transport, and the synthesis of complex molecules-that is, anabolism. Large, complex molecules are generally richer in energy than are small, simple ones. Catabolic reactions break down large molecules into smaller ones, releasing energy. The molecules synthesized in this way are used for growth, reproduction, and repair. Although many substances combine with oxygen and transfer electrons to oxygen, oxygen need not be present if another electron acceptor is available. When a substance loses electrons, or is oxidized, energy is released, but another substance must gain the electrons, or be reduced, at the same time. In this reaction, hydrogen is an electron donor, or reducing agent, and oxygen is an electron acceptor, or oxidizing agent. Because oxidation and reduction must occur simultaneously, the reactions in which they occur are sometimes called redox reactions. Among all living things, microorganisms are particularly versatile in the ways in which they obtain energy. They include photoautotrophs, which obtain energy from light, and chemoautotrophs, which obtain energy from oxidizing simple inorganic substances such as sulfides and nitrites. Heterotrophs get their carbon from ready-made organic molecules, which they obtain from other organisms, living or dead. There are photoheterotrophs, which obtain chemical energy from light, and chemoheterotrophs, which obtain chemical energy from breaking down ready-made organic compounds. Autotrophic metabolism (especially photosynthesis) is important as a means of energy capture in many free-living microorganisms. We emphasize metabolic processes that occur in chemoheterotrophs because many microorganisms, including nearly all infectious ones, are chemoheterotrophs. These processes include glycolysis (oxidation of glucose to pyruvic acid), fermentation (conversion of pyruvic acid to ethyl alcohol, lactic acid, or other organic compounds), and aerobic respiration (oxidation of pyruvic acid to carbon dioxide and water). The overall synthesis of glucose by photosynthesis in cyanobacteria (Other photosynthetic bacteria, as we shall see later, use a different version of this process. In this pathway, A is the initial substrate, E is the final product, and B, C, and D are intermediates. Anabolic pathways make the complex molecules that form the structure of cells, enzymes, and other molecules that control cells. In photosynthesis, light energy is used to reduce carbon dioxide, forming energy-rich compounds such as glucose and other carbohydrates. In aerobic respiration, energy-rich compounds are oxidized to carbon dioxide and water, and some of the energy released is captured for use in life processes. Yields are higher in aerobic processes because their end products are highly oxidized, whereas end products of anaerobic processes are only partially oxidized. The only bacterial enzymes, other way to speed up the reaction rate which break down would be to increase the temperature: In hair and grease. To explain how enzymes do these things, we must consider their properties (Chapter 2, p. In fact, most cells contain hundreds of enzymes, and cells are constantly synthesizing proteins, many of which are enzymes. Enzymes act as catalysts-substances In general, chemical reactions that release energy can occur without input of energy from the surroundings. Nevertheless, such reactions often occur at unmeasurably low rates because the molecules lack the energy to start the reaction. For example, although the oxidation of glucose releases energy, that reaction does not occur unless energy to start it is available. Activation energy can be thought of as a hurdle over which molecules must be raised to get a reaction started. By analogy, a rock resting in a depression at the top of a hill would easily roll down the hill if pushed out of the depression. Activation energy is like the energy required to lift the rock out of the depression. A common way to activate a reaction is to raise the temperature, thereby increasing molecular movement, as you do when you strike a match. A chemical reaction cannot take place unless a certain amount of activation energy is available to start it. They thus make it possible for biologically important reactions to occur at the relatively low temperatures that living organisms can tolerate. Such a reaction in cells would raise the temperature enough to denature proteins and evaporate liquids. Enzymes lower the activation energy so reactions can occur at mild temperatures in living cells. Each enzyme has a certain area on its surface called the active site, a binding site. Like all molecules, a substrate molecule has kinetic energy, and it collides with various molecules within a cell. As a result of binding to the enzyme, some of the chemical bonds in the substrate are weakened. The substrate then undergoes chemical change, the product or products are formed, and the enzyme detaches. Enzymes generally have a high degree of specificity; they catalyze only one type of reaction, and most act on only one particular substrate. When an enzyme acts on more than one substrate, it usually acts on substrates with the same functional group or the same kind of chemical bond. For example, proteolytic, or protein-splitting, enzymes act on different proteins but always act on the peptide bonds in those proteins. Enzymes are usually named by adding the suffix -ase to the name of the substrate on which they act. For example, phosphatases act on phosphates, sucrase breaks down the sugar sucrose, lipases break down lipids, and peptidases break peptide bonds.
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Regulation of the Bacillus subtilis GlcT antiterminator protein by components of the phosphotransferase system arteria umbilical percentil 95 buy inderal 40mg on-line. Regulation of the lic operon of Bacillus subtilis and characterization of potential phosphorylation sites of the LicR regulator protein by sitedirected mutagenesis. Control of Bacillus subtilis mtl operon expression by complex phosphorylation-dependent regulation of the transcriptional activator MtlR. A novel regulatory role of glucose transporter of Escherichia coli: membrane sequestration of a global repressor Mlc. The membrane-integrated transcriptional activator CadC of Escherichia coli senses lysine indirectly via the interaction with the lysine permease LysP. Escherichia coli dihydroxyacetone kinase controls gene expression by binding to transcription factor DhaR. Role of GlnR in acid-mediated repression of genes encoding proteins involved glutamine and glutamate metabolism in Streptococcus mutans. Identification of Bacillus subtilis SipW as a bifunctional signal peptidase that controls surface-adhered biofilm formation. ThnY is a ferredoxin reductaselike iron-sulfur flavoprotein that has evolved to function as a regulator of tetralin biodegradation gene expression. In essence, hosts serve as a reservoir for metabolites that overcome deficiencies in central and intermediary metabolism. Metabolic deficiencies are not created by only reductive evolution; they are also created when bacteria encounter stressful environments. The 13 biosynthetic intermediates discussed in this chapter are all derived from the three metabolic pathways of central metabolism. Alterations in the availability of these biosynthetic intermediates always affect virulence factor synthesis. In the first portion of this chapter, we discuss how genetic, environmental, and nutritional conditions alter the metabolome, primarily central metabolism, and in the second part, how these metabolic changes influence the activity of metabolite-responsive regulators. Finally, we discuss how metabolism and metaboliteresponsive global regulators influence the outcomes of host-pathogen interactions. The importance of these enzymatic reactions is evident from the complex feedback and feedforward allosteric regulation that controls their activity. Because the activity of enzymes like phosphofructokinase is modulated by allosteric effectors, changes in the intracellular concentrations of these effectors will alter carbon flow through glycolysis. In other words, anything that can alter the concentration of an allosteric effector will alter glycolysis. Free iron in a eukaryotic cell is present at a concentration of 10-18 M, meaning that free iron is unavailable to invading pathogens. Whereas the activity of phosphofructokinase is independent of iron, phosphofructokinase activity and carbon flux through glycolysis are nonetheless affected by growth in ironlimited conditions. Two possible explanations can be considered: First, variations in the availability of iron alter transcription of the phosphofructokinase gene in Mycobacterium smegmatis, Enterococcus faecalis, and S. Because citrate is an allosteric inhibitor of phosphofructokinase, the accumulation of citrate should lead to an increased concentration of fructose-6-phosphate or metabolites derived from fructose-6-phosphate. When the Krebs cycle in Staphylococcus epidermidis is genetically inactivated or the bacteria are cultivated in iron-limited medium, glucose-6-phosphate and amino sugars accumulate, which is indicative of reduced phosphofructokinase activity (1, 2, 12). The allosteric and genetic regulation of phosphofructokinase provides an excellent example of the interconnection between metabolism and the bacterial environment, but these connections also rely on metabolite-responsive regulators to control the adaptive response to environmental changes (discussed section 2). Two of these biosynthetic intermediates, ribose-5-phosphate and erythrose-4-phosphate, are essential for the synthesis of purines, histidine, and aromatic amino acids. This process starts with the oxidation of glucose6-phosphate to 6-phosphogluconolactone catalyzed by glucose-6-phosphate dehydrogenase. The metabolic consequences of the loss of glucose-6-phosphate dehydrogenase are a decreased ability to generate pentose sugars and reducing potential, while the loss of transaldolase prevents regeneration of fructose-6phosphate from sedoheptulose-7-phosphate. Reduced thioredoxin, in concert with other low-molecular-weight thiols, is critical for reducing protein disulfides and providing electrons to ribonucleotide reductase, methionine sulfoxide reductase, mycothiol disulfide reductase, and other enzymes (31). Fructose-6-phosphate is a precursor for N-acetylglucosamine, which is required for bacillithiol and mycothiol biosynthesis (26, 32). Interferon-activated macrophages increase synthesis of indoleamine 2,3-dioxygenase, which cleaves the 2,3-double bond in the indole ring of tryptophan, effectively depleting the cell of tryptophan and depriving bacteria of an important amino acid (35). To counter the host-mediated depletion of tryptophan, intracellular bacteria like L. While the ability to synthesize tryptophan can rescue some intracellular bacteria, bacteria that synthesize tryptophan but live predominantly extracellularly, such as S. These three biosynthetic intermediates are critical for the de novo synthesis of many amino acids and porphyrins; for example, oxaloacetate is a precursor for biosynthesis of aspartate, asparagine, lysine, cysteine, threonine, isoleucine, and methionine; ketoglutarate is a precursor of glutamate, glutamine, arginine, and proline; and succinate is used in porphyrin biosynthesis. It is hypothesized that the Krebs cycle evolved from two amino acid biosynthetic pathways: one oxidative pathway and one reductive pathway (45). This metabolic arrangement allows the formation of a bifurcated pathway starting at pyruvate, with branches leading to succinate/succinyl-CoA and ketoglutarate. This bifurcated configuration is found in several Gram-positive pathogens; for example, L. In these examples, bacteria have maintained the Krebs cycle in an incomplete format but one that still allows the generation of oxaloacetate, -ketoglutarate, and succinate. The use of anaerobic respiration also underscores the fact that most Grampositive pathogens using this bifurcated Krebs cycle are anaerobes, L. Though an incomplete Krebs cycle is common in Gram-positive bacteria, two of the most prevalent Gram-positive pathogens worldwide have complete Krebs cycles: namely, M. In Gram-positive bacteria, the glyoxylate cycle is primarily restricted to Actinobacteria. Doing so prevents the formation of a futile cycle in which two carbons enter the Krebs cycle and two carbons are lost through decarboxylation reactions. For the remainder of this chapter, discussion of the Krebs cycle will be kept to the Firmicutes. This catabolite repression leads to the accumulation of incompletely oxidized metabolites/fermentation products in the culture media, most commonly acetic acid and lactic acid (61, 64). Once carbohydrates are depleted from the medium, these metabolites can be re-imported and used to fuel the Krebs cycle and generate the three biosynthetic intermediates. At this point, acetyl-CoA can enter into the Krebs cycle via a condensation reaction with oxaloacetate that is catalyzed by citrate synthase, a process using the energy of thioester hydrolysis to drive carbon-carbon bond formation to form citric acid. For this reason, when biosynthetic intermediates are withdrawn from the Krebs cycle for biosynthesis, anaplerotic reactions are required to maintain carbon flow through the Krebs cycle. The most commonly used substrates for the anaplerotic reactions are amino acids (50). For instance, conversion of aspartate to oxaloacetate can start a new round of the Krebs cycle, allowing continued drawing off of intermediates. In total, catabolism of incompletely oxidized metabolites through the Krebs cycle provides biosynthetic intermediates. Of importance, the activity of metaboliteresponsive regulators is controlled by intracellular concentrations of biosynthetic intermediates (68), amino acids (69), nucleic acids (70), and cofactors. In other words, altering metabolism provides a means to transduce external environmental changes into internal metabolic signals that alter the activity of metabolite-responsive regulators, which facilitate adaptation to the altered environment (72). The function of metabolite-responsive regulators will be discussed in the second part of this chapter. These amino acids are important because they serve as the nitrogen donors in most biosynthetic processes (73).
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E Pulmonary function tests To determine the fitness of patients for lung resection arrhythmia practice strips cheap 10mg inderal, and the extent of resection they can tolerate, pulmonary function tests are necessary. Patients with borderline fitness based on pulmonary function test can be subjected to cardiopulmonary exercise testing or shuttle walk testing. B Thoracotomy Thoracotomy involves muscle cutting, rib-spreading and parietal pleura breeching. Sometimes rib fractures occur, and the intercostal nerves are bruised during rib-spreading. In the early postoperative period, therefore, thoracotomy pain can be severe and difficult to control. The functional consequence of post-thoracotomy pain leads to other complications such as impairment of mobilisation and normal breathing and gas exchange. D Severity of symptoms depends upon the size of the vessel and if the onset is acute or chronic. E Amputation of the affected limb should be done in all cases at the earliest to prevent the spread of life-threatening sepsis. A Intervention (surgical or radiological) should be considered at the first consultation before the obstruction gets worse. B When acute thrombosis is diagnosed, thrombolysis should always be the first line of treatment. C When an embolus is the cause of arterial occlusion, a left ventricular mural thrombus is the usual source. E Berry aneurysms occur along the trunks of the vessels that form the Circle of Willis. He has a systolic blood pressure of 90 mmHg, pulse rate of 120 per minute and is cold and clammy with a tender distended abdomen and a pulsatile mass. B A 52-year-old man complains of a weak grip in his left hand with tingling and numbness along the inner side of his arm and palm. When using his arm he has pain, and his palm has a dusky discoloration of the fingertips. C A 73-year-old woman complains of attacks of sudden blindness in her right eye that last for a few minutes. D A 68-year-old man, who is a heavy smoker, complains of pain in his right thigh and buttocks on walking about 400 metres. Once he stops, the pain disappears and returns when he walks a similar distance again. E A 60-year-old woman, who is a heavy smoker and works as a domestic, gets syncopal attacks when she is working scrubbing floors using her right upper limb vigorously. F A 68-year-old woman complains of sudden onset of severe pain in her right thigh, calf and leg of 6 hours duration. She has lost sensations from the mid-thigh distally, cannot move her foot or knee, her skin feels very cold and she looks pale. G A 32-year-old woman complains of episodes of pain in the fingers of both her hands when it is cold. The fingers go white, swollen and dusky when she is unable to make any fine movements. H A 28-year-old man, who is a heavy smoker, complains of pain in his right lower limb on walking. He has developed a tender cord-like structure along his long saphenous vein with some tenderness and a generally swollen leg. I A 74-year-old man complains of epigastric discomfort and throbbing backache for 4 months. On examination he has a mass in his epigastrium extending on to umbilical region, which shows expansile pulsation. J A 64-year-old man, who is a postman, complains of intermittent claudication in his calf for 8 months. K A 70-year-old man, who is a long-term heavy smoker, complains of onset of severe pain in his left calf and thigh of 2 days duration. Prior to this he had suffered from intermittent claudication, with a claudication distance of 50 metres. L A 45-year-old woman complains of a lump on the left side of her forehead for many years. M A 55-year-old woman who has been an insulin-dependent diabetic for 35 years has developed necrotic skin patches in her right forefoot following a fall from a bicycle. The lump was there a couple of years, but only over the last couple of days it has become extremely tender, the leg has become cold and he is unable to walk. P A 65-year-old woman with atrial fibrillation underwent a successful lower limb embolectomy under local anaesthetic. A couple of days later she developed in the same limb severe throbbing pain over a period of 4 hours; the limb looked pink. N A 66-year-old man presented with a tender lump over his right popliteal fossa and severe pain Answers to multiple choice questions 1. This fact clinically differentiates it from arthritic pain, which comes on after taking the first step and is not relieved by rest. The pain-free distance that a patient can walk is called the claudication distance. The pain is relieved by keeping the foot dependent and hanging it by the bedside or sleeping in a chair. In aortoiliac disease, the patient complains of thigh and buttock claudication whilst calf claudication indicates superficial femoral artery obstruction. The severity of symptoms depends upon the size of the original vessel and duration of onset. In acute onset the presentation would be sudden and severe, whereas in chronic disease the presentation will be gradual because there would have been time for collaterals to develop. C, E Duplex scanning is a major noninvasive technique that uses B-mode ultrasound to obtain an image of the vessels. It is done only when the decision has been made on clinical grounds to intervene, either radiologically or surgically. In all patients with arterial occlusive disease, intercurrent illnesses must be excluded. Haematological and biochemical investigations are done to exclude anaemia, diabetes, renal impairment and polycythaemia or thrombocythaemia. A cardiac echo and pulmonary function tests would be necessary in more severe disease for anaesthetic assessment, particularly when major arterial surgery is contemplated. The claudication distance is best measured by the treadmill in the vascular laboratory. C, D, E Drug treatment is required for concomitant diseases such as diabetes and hypertension. Intervention is necessary when the symptoms of the patient are threatening the limb (critical ischaemia), livelihood and lifestyle. Depending upon the site of obstruction the procedures are aortofemoral or aorto-bi-femoral bypass, femoro-popliteal, or femoro-distal bypass. In patients with severe comorbid disease who have aortoiliac obstruction, extra-anatomic bypass graft in the form of axillo-femoral or femoro-femoral should be considered as a limbsalvage procedure. D, E Renovascular hypertension from renal artery stenosis is not always due to atherosclerotic stenosis. In the latter all other vessels would be normal, while the narrowing would be smooth and confined to the main trunk of the artery without involvement of the origin; when atherosclerosis is the cause the neighbouring vessels would be involved, including the origin from the aorta. Ischaemic colitis occurs due to atherosclerosis of the inferior mesenteric artery, causing post-prandial pain and rectal bleeding. In addition, patients may present with amaurosis fugax, sudden episodic blindness and reversible intermittent neurological deficit, and a systolic bruit in the neck. Subclavian steal syndrome occurs when there is atherosclerotic obstruction of the first part of the subclavian artery. Thoracic inlet syndrome may cause compression of the subclavian artery from a cervical rib or fibrous band.
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Population-based screening for prostate cancer is carried out within clinical trials and it remains unclear whether national screening programmes should be established arteriovenous graft buy discount inderal 40mg. E Skeletal metastases from prostate cancer are mostly osteosclerotic (osteoblastic) where they form new bone. A scoring system devised by Donald Gleason is based on the degree of glandular de-differentiation and its relationship to stroma. The score ranges from 2 to 10 and correlates well with the prognosis and possibility of spread. Haematogenous spread occurs to the skeleton, the prostate being the most common site for such metastases. In prostate carcinoma the rectal mucosa will be adherent to the prostate or nodules might be felt within the gland. Obliteration of the median sulcus with irregular, stony hard induration is a typical feature. In advanced cases extension beyond the capsule infiltrating the bladder base and the seminal vesicles might occur, while in extreme cases the rectum is known to be stenosed from external compression. Radical prostatectomy might be considered in this group in patients below the age of 70 years although some will elect to pursue a conservative approach. In T3 disease where the cancer has extended through the capsule, surgery, radiotherapy and androgen ablation or a combination are used. Following radical prostatectomy, carried out by the expert, stress incontinence is <2%. A Acute prostatitis this young male has features of acute prostatitis where the general features are far more predominant than the local. After urine has been sent for culture, the patient must be started on trimethoprim or ciprofloxacin. Rarely this might proceed on to an abscess when the patient has constant perineal and rectal pain with tenesmus. The prostate will be felt as an enlarged, hot, very tender and fluctuant mass; acute urinary retention might occur when suprapubic catheterisation would be the ideal approach. Under antibiotic cover the abscess should be drained by transurethral resection and unroofing of the cavity. Urethroscopy might reveal inflamed prostatic urethra with an enlarged oedematous verumontanum. Long-term treatment with trimethoprim and metronidazole for 1 week helps when anaerobes are involved. Pain relief might be such a challenge that a referral to the pain clinic might be warranted. C Acute retention of urine this patient has acute urinary retention almost certainly precipitated by the use of proprietary cough and flu medicines. The patient, who will be in agony, needs strong analgesia followed by immediate decompression of his bladder by the passage of a Foley catheter. Even when urine comes out, the catheter should be pushed further into the bladder before inflating the balloon so as not to inflate the balloon within the prostatic urethra, which might be elongated and distorted. Once the urine has been drained into a close system of catheter drainage and the patient is comfortable, a detailed history and examination is undertaken. The patient should be fully examined, although there will be very little to find on clinical examination except for a benign enlarged prostate on rectal examination. Special investigation would be pressure-flow urodynamic studies and imaging of the upper tract if indicated because of infection or haematuria. Expectant management consists of fluid and caffeine restriction in the evening or at night. Drug treatment would consist of -blockers or 5-reductase inhibitors (for large prostates). The findings on rectal examination are very suggestive of a carcinoma of the prostate. After thorough clinical examination, the diagnosis should be confirmed followed by staging and then instituting definitive treatment. Radical prostatectomy is suitable for T1 and T2 disease and carried out in men with a life expectancy of >10 years. The procedure should be a nerve-sparing operation, the choice of approaches being the traditional open procedure, laparoscopic procedure or robotic procedure depending upon the available expertise. An alternative is radical radiotherapy bearing in mind that in 30% of treated patients persistent tumour is found within the prostate. Brachytherapy is another form of radiation treatment in which radioisotopes iodine-125 and palladium-103 are implanted as seeds directly into the prostate through the transperineal route. Patients with bone secondaries are offered bilateral subcapsular orchidectomy (or zoladex) + local radiotherapy to the bones. E Chronic urinary retention with overflow this patient has chronic retention with overflow, an aftermath of neglected retention. This might result in the following: (i) haematuria as the distended bladder veins collapse as the pressure is released and (ii) post-obstructive diuresis, which needs to be monitored carefully with fluid replacement by intravenous saline. D the posterior urethra comprises of preprostatic, prostatic and membranous segments. E the major portion of the female urethra is lined by stratified squamous epithelium. In rupture of the membranous urethra, the following statements are true except: A It is almost always associated with a pelvic fracture. The following statements are true except: A Urinary flow trace will show a prolonged flow with a plateau-shaped curve. The following statements are true except: A the most common indication for circumcision is cultural reasons. B In children circumcision is the treatment for non-retractile foreskin due to adhesions. A 45-year-old man complains of progressive deformity of his penis, which is very pronounced during erection; this has been going on for the past 2 years. A 60-year-old man who is under treatment for leukaemia recently started developing penile erection without any reason. G A 24-year-old man while performing on a Pommel Horse in a gymnastics competition, slipped and fell astride on the Pommel Horse. He complains of severe perineal pain in the penoscrotal junction where there is a haematoma. H A 52-year-old man complains of thickening of his foreskin over a period of 2 years. During this period he has had difficulty in retracting his foreskin, as a result of which he has been having difficulty in maintaining good hygiene. F A 32-year-old man was involved in a road-traffic accident in which he sustained polytrauma, Answers to multiple choice questions Anatomy 1. The urethral sphincter mechanism consists of the intrinsic striated and smooth muscle of the urethra and the pubourethralis component of the levator ani, which surrounds the membranous urethra in the male and the middle and lower thirds of the female urethra. In the female, it blends proximally with the smooth muscle of the bladder neck and distally with the lower urethra and vagina. The posterior urethra is constituted by the preprostatic, prostatic and membranous segments. The female urethra, about 4 cm long, is lined proximally by transitional epithelium whereas the major portion is lined by stratified squamous epithelium distally. The verumontanum (colliculus seminalis) is an important endoscopic landmark situated in the prostatic urethra that is 3 to 4 cm long; this is much elongated in benign prostatic hypertrophy when there is a considerable intravesical projection of the prostate. The verumontanum is a midline-rounded eminence that marks the proximal extent of the external urethral sphincter and is a very important landmark for the urologist performing transurethral resection of the prostate; all resection must be proximal to this vital landmark. D Glandular hypospadias does not need surgical treatment unless the meatus is stenosed, in which case a meatotomy is performed. Treatment is endoscopic valve destruction and treatment of any concomitant infection or renal impairment.
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The ciliated pseudostratified columnar epithelium extends throughout the respiratory tract heart attack get me going 10mg inderal sale, but not to the smallest bronchioles and alveoli. These regions of the upper respiratory tract provide a moist, warm environment for microbial growth, but to effectively interact with those host cells, organisms attempting to colonize the airway must encounter the appropriate epithelial cells for which its adhesins and colonization factors have evolved. The mammalian respiratory tract contains local respiratory lymphoid tissues such as the nasopharynx-associated and bronchusassociated lymphoid tissues (3). Other airway mucosal cells include macrophages and dendritic cells, some of which are resident intraepithelial dendritic cells that are positioned for luminal antigen sampling. T cells can also localize to intraepithelial spaces and to the lamina propria, along with IgA-producing plasma cells, mast cells, and B cells (3). Resident memory T cells may also be present in the mucosa after their migration from local lymphoid tissues (4), and the nasal mucosa may harbor M cells that are involved in antigen sampling at localized lymphoid tissues (4, 5). Inflammation of the airway increases vascular permeability, promoting immune-cell migration and transudation of plasma components onto the respiratory epithelial surface (6, 7). Components of this mucus blanket contribute to its high osmolarity, but also constitute potential food sources for pathogens. Mucins have characteristic Pro-Thr-Ser repeats as well as Cys-rich domains that provide key disulfidebonding capability, important for mucin multimerization and mucus function. In the mouse respiratory tract, very little Muc5ac is made, whereas secretory cells produce Muc5b (1). Within the secretory cell, newly synthesized mucin is dehydrated and then enclosed within membrane-bound secretory granules. Beneath this highly viscous layer and in direct contact with the epithelium, is the periciliary layer, with a depth of approximately 7 m. This periciliary layer, often referred to as the sol phase, has traditionally been thought to be the less viscous watery layer of the mucus blanket, allowing free movement of the cilia to achieve mucus clearance. Recent ex vivo studies using human airway tissue have provided detailed compositional analyses of the mucus layers, revealing that the periciliary layer is not "watery", but filled with a mesh network of membrane-bound mucins and mucopolysaccharides (14). These network molecules fill the interciliary spaces and are also connected to the cilia and microvilli of airway epithelial cells. This complex periciliary layer is proposed to function as a brush and stabilize the two mucus layers, in part by prevention of soluble mucins in the luminal gel layer from extending into the periciliary layer and disrupting ciliary movement. Human Upper Respiratory Tract Microbiota Microbial inhabitants of the nasopharynx and other regions of the respiratory tract are likely to not only modify that environment, but may also produce metabolites and other factors that influence the growth of pathogenic microbes. Sampling of specific regions of the human respiratory tract can be challenging, since obtaining specimens can involve invasive procedures and certain sampling methods are prone to cross contamination of samples from differing sites. Recently, Yan and colleagues characterized the bacterial biota from three distinct regions of the human nasal cavity, comparing persistent carriers of Staphylococcus aureus with non-persistent carriers (22). Genera, including those from the Firmicutes, Actinobacteria, - and - Proteobacteria, and other Staphylococcus species, were variably prevalent in the sample set from non-carriers. Of note, the microbiota from the middle meatus and sphenoethmoidal recess nasal sites of individuals from both subject groups exhibited more taxonomic diversity compared with the nasal vestibule site. Since the sphenoethmoidal recess is the closest geographically of the three sampled regions to the nasopharynx, these results may inform our understanding of the nasopharyngeal and tracheal microbiota. In a different study, Charlson and colleagues performed a comprehensive biogeographical analysis of the healthy human respiratory tract, using methods designed to minimize cross-contamination of epithelial site samples (19). For the nasopharynx, they reported that Staphylococcaceae and Propionibacteriaceae were predominant, and noted significant relative abundance of members of families listed in Table 1. Populations found in the left upper lobe of all of the adult donors were similar and included taxa listed in Table 1. Compared with controls, patients with chronic obstructive pulmonary disease had significantly fewer Prevotella species and more Haemophilus and other Proteobacteria species. Huang and colleagues examined bronchial epithelial brushings from healthy controls and patients with asthma (20). Importantly, a diverse microbiota was identified in both subject groups, but several taxa, in particular, members of the Comamonadaceae, Oxalobacteraceae, and Sphingomonadaceae, were associated with asthma patients experiencing bronchial hyperresponsiveness. Although these analyses have yielded useful information about the human respiratory microbiota, the majority of the identified bacterial taxa have not been studied to any extent that would allow predictions of their metabolites or compounds that could be produced or excreted in vivo to promote the growth of infecting pathogens. The aforementioned study of the human microbiota from three nasal sites revealed that in per sistent carriers of S. In noncarriers, there was instead, colonization by Corynebacterium pseudodiphtheriticum. Bacteria that have evolved to be obligate pathogens may be auxotrophic for vitamins and cofactors that other bacterial species can produce endogenously. Secreted enzymes such as proteases, mucinases, lipases, and nucleases from resident microflora would be predicted to degrade host resources to yield soluble nutrients. Streptococcus species can produce hemolysins, cytolytic toxins, and pyrogenic toxins (29). Since these enzymes and toxins may lyse host cells, making their cytosolic contents available for microbial degradation and consumption, commensal Staphylococcus and Streptococcus species may play important roles in modulating airway nutrient sources available to invading pathogens. Nutrients in Airway Mucus Respiratory mucus contains a number of host molecules that contribute to resistance to infection, but may also be degraded and utilized by microbes as nutrient sources. Within the mucus, debris from sloughed and dead respiratory cells (1, 2) may provide additional sources of nutrition such as lipids, nucleic acids, and proteins. The respiratory microbiota, including pathogens, are also likely to use small, readily assimilated metabolites that are in the airway surface liquid. These authors also identified the metabolites palmitic acid, phosphatidylcholines, and stearic acid in both healthy and diseased subjects. In patients diagnosed with acute respiratory disease, elevated levels of branched-chain amino acids arginine, glutamate, glycine, aspartate, acetate, taurine, threonine, lactate, and succinate were observed and the proline concentration was reduced, compared with control samples. In sum, these mouse and human studies indicate that in the respiratory tract of healthy animals there exists a baseline level of metabolites available for microbial consumption. This would serve to further increase the levels of potential nutrients for pathogens. Potential sulfur sources would include taurine, cysteine, and sulfate derived from mucins, and inorganic sulfur compounds. Phosphorus requirements could be met by host phospholipids, phosphocholine, glycerophosphocholine, nucleic acids, and other phosphate sources. Airway surface liquid is known to contain ascorbic acid (38) as well as high concentrations of glutathione that are critical for defense against oxidative damage (39); therefore, microbes may use these as carbon, nitrogen, and sulfur sources. Iron and Its Acquisition by Microbes Most living cells, including prokaryotes, require nutritional iron. Hepcidin inhibits iron transport to plasma and tissues by binding the cellular ferroportin iron exporter and inducing its breakdown within the lysosome. The bone morphogenetic protein pathway transcriptionally regulates hepcidin production, and iron abundance and inflammation also upregulate expression of the hepcidin gene (45). Another arm of the host iron-withholding defense is that exerted by the iron-binding glycoproteins transferrin and lactoferrin, each of which can coordinate two atoms of ferric iron (43, 44). Transferrin is found primarily in plasma and is the primary means by which the cells of the body receive nutritional iron. Lactoferrin exists on mucosal surfaces and is also stored within neutrophil granules that can be deployed upon encounter with microbes (43, 46). The N-terminal region of lactoferrin (termed lactoferricin) has been shown in vitro to have antimicrobial activities that are distinct from its iron-scavenging functions. Pathogenic bacteria must overcome host iron restriction for successful in vivo growth, and when starved for iron, they employ several general mechanisms for retrieval of iron from host sources. Under conditions of iron-replete growth (a rare circumstance in vivo), expression of iron-acquisition genes is usually repressed by Fur (or an analogous regulator) that requires ferrous iron as a corepressor (47). Iron starvation leads to decreased intracellular iron corepressor concentrations and subsequent derepression of genes involved in iron uptake. For numerous pathogens, the predominant classes of in vivo-expressed genes are involved in nutrient acquisition, and of those, iron-acquisition genes dominate the transcription profile (48).
