A dynamic relationship between mucosal T helper type 17 and regulatory T-cell populations in nasopharynx evolves with age and associates with the clearance of pneumococcal carriage in humans.

Pneumococcal carriage is common in young children, which may account for the high incidence of disease in this age group. Host factors determining the clearance of carriage in humans remain unclear. We aimed to study the relationships between T helper type 17 (Th17) and Foxp3(+) regulatory T (Treg) cells in nasopharynx-associated lymphoid tissue (NALT) and carriage in children and adults.

ENT manifestations of alkaptonuria: report on a case series.

Background: Alkaptonuria is an inborn error of metabolism. It is a multisystem disease with characteristic ENT manifestations. This paper reports, for the first time, the ENT findings in a cohort of alkaptonuria patients.

Activation of memory Th17 cells by domain 4 pneumolysin in human nasopharynx-associated lymphoid tissue and its association with pneumococcal carriage.

Pneumococcal carriage is common in children that may account for the high incidence of disease in this age group. Recent studies in animals suggest an important role for CD4+ T cells, T helper type 17 (Th17) cells in particular, in pneumococcal clearance. Whether this Th17-mediated mechanism operates in humans and what pneumococcal components activate Th17 are unknown.

Rational design of fatty acid amide hydrolase inhibitors that act by covalently bonding to two active site residues.

The design and characterization of α-ketoheterocycle fatty acid amide hydrolase (FAAH) inhibitors are disclosed that additionally and irreversibly target a cysteine (Cys269) found in the enzyme cytosolic port while maintaining the reversible covalent Ser241 attachment responsible for their rapid and initially reversible enzyme inhibition. Two α-ketooxazoles (3 and 4) containing strategically placed electrophiles at the C5 position of the pyridyl substituent of 2 (OL-135) were prepared and examined as inhibitors of FAAH. Consistent with the observed time-dependent noncompetitive inhibition, the cocrystal X-ray structure of 3 bound to a humanized variant of rat FAAH revealed that 3 was not only covalently bound to the active site catalytic nucleophile Ser241 as a deprotonated hemiketal, but also to Cys269 through the pyridyl C5-substituent, thus providing an inhibitor with dual covalent attachment in the enzyme active site.

Infection with 2009 H1N1 influenza virus primes for immunological memory in human nose-associated lymphoid tissue, offering cross-reactive immunity to H1N1 and avian H5N1 viruses.

Influenza is a highly contagious mucosal infection in the respiratory tract. The 2009 pandemic H1N1 (pH1N1) influenza virus infection resulted in substantial morbidity and mortality in humans. Little is known on whether immunological memory develops following pH1N1 infection and whether it provides protection against other virus subtypes.

Control of substrate access to the active site in methane monooxygenase.

Methanotrophs consume methane as their major carbon source and have an essential role in the global carbon cycle by limiting escape of this greenhouse gas to the atmosphere. These bacteria oxidize methane to methanol by soluble and particulate methane monooxygenases (MMOs). Soluble MMO contains three protein components, a 251-kilodalton hydroxylase (MMOH), a 38.

Analysis of substrate access to active sites in bacterial multicomponent monooxygenase hydroxylases: X-ray crystal structure of xenon-pressurized phenol hydroxylase from Pseudomonas sp. OX1.

In all structurally characterized bacterial multicomponent monooxygenase (BMM) hydroxylase proteins, a series of hydrophobic cavities in the α-subunit trace a conserved path from the protein exterior to the carboxylate-bridged diiron active site. This study examines these cavities as a potential route for transport of dioxygen to the active site by crystallographic characterization of a xenon-pressurized sample of the hydroxylase component of phenol hydroxylase from Pseudomonas sp. OX1.

Active site threonine facilitates proton transfer during dioxygen activation at the diiron center of toluene/o-xylene monooxygenase hydroxylase.

Toluene/o-xylene monooxygenase hydroxylase (ToMOH), a diiron-containing enzyme, can activate dioxygen to oxidize aromatic substrates. To elucidate the role of a strictly conserved T201 residue during dioxygen activation of the enzyme, T201S, T201G, T201C, and T201V variants of ToMOH were prepared by site-directed mutagenesis. X-ray crystal structures of all the variants were obtained.

Percutaneous chemical myotomy using botulium neurtoxin A under local anaesthesia in the treatment of cricopharyngeal dysphagia following laryngectomy.

Objective: The purpose of this study was to evaluate the outcome of the use of percutaneous injection of botulinum neurotoxin A under local anaesthesia in the management of cricophayngeus dysphagia in post-laryngectomy patients.

Methods: Fifteen post-laryngectomy patients (6 males, 9 females, age range 48-72 years) with surgery performed not less than five years with post-operative radiotherapy were recruited. Under video-fluoroscopic control and the attachment of a metal safety pin to the neck as a topographical marker for the cricopharyngeus muscle, botulinum neurotoxin was injected after local anaesthesia infiltration.

cis-Diammine(pyridine)chloroplatinum(II), a monofunctional platinum(II) antitumor agent: Uptake, structure, function, and prospects.

We have identified unique chemical and biological properties of a cationic monofunctional platinum(II) complex, cis-diammine(pyridine)chloroplatinum(II), cis-[Pt(NH(3))(2)(py)Cl](+) or cDPCP, a coordination compound previously identified to have significant anticancer activity in a mouse tumor model. This compound is an excellent substrate for organic cation transporters 1 and 2, also designated SLC22A1 and SLC22A2, respectively. These transporters are abundantly expressed in human colorectal cancers, where they mediate uptake of oxaliplatin, cis-[Pt(DACH)(oxalate)] (DACH = trans-R,R-1,2-diaminocyclohexane), an FDA-approved first-line therapy for colorectal cancer.

Dioxygen activation at non-heme diiron centers: oxidation of a proximal residue in the I100W variant of toluene/o-xylene monooxygenase hydroxylase.

At its carboxylate-bridged diiron active site, the hydroxylase component of toluene/o-xylene monooxygenase activates dioxygen for subsequent arene hydroxylation. In an I100W variant of this enzyme, we characterized the formation and decay of two species formed by addition of dioxygen to the reduced, diiron(II) state by rapid-freeze quench (RFQ) EPR, Mössbauer, and ENDOR spectroscopy. The dependence of the formation and decay rates of this mixed-valent transient on pH and the presence of phenol, propylene, or acetylene was investigated by double-mixing stopped-flow optical spectroscopy.

Laryngocoele presenting as acute airway obstruction.

A laryngocoele is an abnormal dilatation of the laryngeal saccule. Symptomatic laryngocoeles can present as rapidly developing airway obstruction. In this case report of a 37-year-old man with a laryngocoele, we discuss the management dilemma presented by his repeated flight from the hospital prior to definitive treatment.

X-ray structure of a hydroxylase-regulatory protein complex from a hydrocarbon-oxidizing multicomponent monooxygenase, Pseudomonas sp. OX1 phenol hydroxylase.

Phenol hydroxylase (PH) belongs to a family of bacterial multicomponent monooxygenases (BMMs) with carboxylate-bridged diiron active sites. Included are toluene/o-xylene (ToMO) and soluble methane (sMMO) monooxygenase. PH hydroxylates aromatic compounds, but unlike sMMO, it cannot oxidize alkanes despite having a similar dinuclear iron active site.

Nontuberculous mycobacterial adenitis: effectiveness of chemotherapy following incomplete excision.

Background: Management of lymphadenopathy caused by nontuberculous mycobacteria (NTM) is primarily surgical. Where this cannot achieve sufficient clearance of infected nodes, chemotherapy is often given.

Aim: This study compared results of surgery alone with surgery followed by chemotherapy in instances where there was incomplete surgical removal of diseased tissue.

Congenital cholesteatoma tract presenting as a postaural swelling.

The authors report a case of a three-year old boy, who presented with discharge from the site of a previously excised postaural lesion reported to have been an epidermoid cyst. It was found at operation that he had a fistulous connection between the site of the excised lesion and a congenital cholesteatoma sac in the mastoid bone. This case demonstrates the rare occurrence of congenital cholesteatoma eroding through the mastoid bone to the subcutaneous tissues and mimicking an epidermoid cyst.

A simple and reliable predictor for an adequate laryngeal view with rigid endoscopic laryngoscopy.

Objectives: It is sometimes impossible to obtain an adequate laryngeal view during rigid endoscopic laryngoscopy. This may be due to a high tongue base. Our study seeks to determine a correlation between tongue base level and the adequacy of laryngeal view obtained with a 70-degree rigid endoscope.

Aspirated stoma button: an unusual complication.

The larynx functions as a protective valve of the upper airway. An end-tracheostomy represents a risk factor for foreign body aspiration. We describe a case of tracheostomy stoma button aspiration, leading to recurrent chest infection and irreversible lung damage, necessitating a pneumonectomy.

Complicated otitis media caused by Fusobacterium necrophorum.

Fusobacterium necrophorum is implicated as an aetiological agent in a variety of necrotic diseases, such as Lemièrre's syndrome (LS) in humans. LS was initially described as septic thrombophlebitis of the internal jugular vein secondary to an acute oropharyngeal infection. Other primary sources of infection include parotitis, otitis media, sinusitis, odontogenic infection and mastoiditis.

Depressive symptoms in children after tonsillectomy.

Objective: Several cases of severe depression after tonsillectomy have been described in children, indicating psychological trauma after surgery and hospitalization. The actual prevalence of depressive symptoms after tonsillectomy is unknown and possibly underestimated. This study aims to quantify this problem by employing current diagnostic methods.

Paediatric epistaxis: Alder Hey experience.

Referrals for epistaxis management constitute a significant proportion of paediatric ENT consultations. A prospective audit of all new referrals to our paediatric ENT department for epistaxis management yielded 88 patients over four months. Parents completed a questionnaire with particular reference to the duration of history and frequency of epistaxis.

Cranial nerve dysfunction following carotid endarterectomy.

Background: Carotid endarterectomy (CEA) is the most common surgical procedure performed for the treatment of symptomatic carotid stenosis greater than 70%. Among the recognised complications, such as stroke and myocardial infarction, is injury to cranial nerves.

Methods: We report the incidence and follow-up of cranial nerve injury in 269 patients who underwent carotid endarterectomy between January 1994 and December 1997 at the Royal Liverpool University Hospital.

Globus pharyngeus: a postal questionnaire survey of UK ENT consultants.

Globus pharyngeus is a common complaint often referred to the ENT outpatient department. The precise nature of globus pharyngeus and its aetiology remains something of a mystery. There is no uniform policy of management of this condition.

Glossopharyngeal neuralgia following foreign body impaction in the neck.

Glossopharyngeal neuralgia is rare, typically idiopathic and treated with carbamazepine. Surgery to decompress or transect the glossopharyngeal nerve root may be performed if conservative management fails. We present a case following trauma to the neck with foreign body impaction.