Oxathiazinane derivatives display both antineoplastic and antibacterial activity: a structure activity study.

PURPOSE: The Oxathiazinane substance class is characterized by a high diversity of chemical structures yet to be fully investigated. Our research group recently proved that the 1.4.5-oxathiazine-4.4-dioxide, known as substance GP-2250, possesses antineoplastic properties as shown on pancreatic carcinoma. This current study aims to gain insights into the structure and activity relationship of a series of different Oxathiazinanes regarding their antineoplastic activity and the potential correlation with antibacterial activity. We investigated the newly synthesized Oxathiazinane derivatives: 2255, 2256, 2287, 2289, 2293 and 2296 in comparison to GP-2250. METHODS: The antineoplastic effect was evaluated in different cancer entities (breast, skin, pancreas and colon cancer cell lines) by viability, proliferation, and cell migration assays in vitro. Disc diffusion tests were performed on various bacteria strains to examine the antibacterial potential. Additionally, reactive oxygen species (ROS) assays were conducted to investigate mechanistic aspects. RESULTS: The substances GP-2250, 2293, 2289 and 2296 not only showed antineoplastic activity in four different cancer entities but also antibacterial effects, as tested on multiple bacteria strains including MRSA (Methicillin-resistant Staphylococcus aureus). Furthermore, these substances also induced high ROS levels up to 110% in the treated cancer cell lines compared to untreated control cells. These results indicate a correlation between an antineoplastic capacity and antibacterial properties of these derivatives. Both activities appear to be ROS driven. The Oxathiazinane derivatives 2255, 2256 and 2287 lacked both, antineoplastic and antibacterial activity. CONCLUSION: Thus, a comparable structure activity relationship became apparent for both the antineoplastic and antibacterial activity.

Cardiac challenges in patients with Fabry disease.

Fabry disease, an X-linked lysosomal storage disorder affecting both men and women, is a relatively prevalent cause of hypertrophic cardiomyopathy (HCM) and is associated with significant morbidity and early death due to heart failure or ventricular arrhythmias. Fabry cardiomyopathy results from progressive build-up of glycosphingolipids in cardiac structures, but the underlying complex pathophysiologic mechanisms remain poorly understood. Disease-specific enzyme replacement therapy (ERT) is available for Fabry disease and, therefore, attention should be focused on early diagnosis of this progressive, life-threatening disease. Selected cardiology patients at high risk for Fabry disease can be tested using simple enzymatic assays, and diagnosis is confirmed by demonstration of a Fabry mutation. Testing cardiology patients with HCM of unknown etiology may identify previously unrecognized Fabry patients and allow genetic mapping to be carried out to identify other affected family members at a relatively early stage of the disease. Timely intervention early on in the disease is a key, as the best responses to ERT are seen in patients with the lowest degree of cardiac hypertrophy and fibrosis at the start of treatment.

[Large left ventricular aneurysm after silent myocardial infarction. Documentation by serial non-invasive imaging]. / Grosses linksventrikuläres Aneurysma nach stummem Myokardinfarkt. Dokumentation mittels serieller nicht-invasiver Bildgebung.

HISTORY AND CLINICAL FINDINGS: A 60-year-old man had a workup for atypical angina. Noninvasive investigations, including computed tomography, showed no evidence for coronary artery disease. A few months later the patient was hospitalized because of severe epileptic seizures. Thyrotoxicosis was diagnosed and emergency thyroidectomy was performed. Two months after discharge the patient was again referred because of exercise-induced angina pectoris. INVESTIGATIONS AND DIAGNOSIS: Echocardiography and cardiac magnetic resonance imaging (MRI) showed a large aneurysm of the lateral wall of the left ventricle with a thrombus adhering to the wall. Coronary angiography and levocardiography confirmed the aneurysm and detected an occlusion of the distal part of the circumflex artery. TREATMENT AND COURSE: Surgical aneurysm resection with thrombectomy and endoventricular circular plasty (Dor procedure) was performed without postoperative complications. Six months after surgery the patient was in good general condition without any angina. Follow-up echocardiography as well as cardiac MRI gave proof of an excellent postoperative result. CONCLUSIONS: Noninvasive preoperative diagnosis and documentation as well as postoperative monitoring with modern imaging modalities, such as echocardiography and MRI are of great value in patients with left ventricular aneurysm.

Misleading terms in Anderson-Fabry disease.

BACKGROUND: Signs and symptoms of classic Fabry disease manifest itself on the skin (angiokeratoma), the nervous system (acroparaesthesia), the heart (restrictive cardiomyopathy) and a variety of other organs. MATERIALS AND METHODS: Diagnosis of Fabry disease was confirmed by genetic tests in a cohort of 100 patients and a standardized examination programme was performed in all patients. We were puzzled when applying well-established and textbook-anchored signs and symptoms to our patients. RESULTS: Among the 47 male and 53 female patients (mean age 41 +/- 16 years) with genetically proven disease, the Fabry-type vascular skin lesions were without hyperkeratotic aspect and keratomas were virtually absent. The peripheral neuropathic pain found in all male patients was not compatible with the wording 'acro' and 'paraesthesia', suggesting a different pathophysiological mechanism. Upon echocardiographic examination, patients mainly revealed diastolic relaxation abnormalities of the heart and only one patient had a restrictive cardiac pattern. CONCLUSIONS: Our findings suggest that some terms used to describe signs and symptoms of Fabry disease are historically derived and do not comply with state-of-the-art examination. We propose to replace the term 'angiokeratoma' with 'angioma', the term 'acroparaesthesia' with 'neuropathic pain' and the term 'restrictive cardiomyopathy' with 'cardiac hypertrophic storage disease'. As most of the physicians are not familiar with Fabry disease, terms used in the past might prevent the correct diagnosis of a potentially treatable disease.

[Hypertensive crisis in infancy and childhood]. / Die hypertensive Krise im Kindes- und Jugendalter.

The extended physical examination of a patient includes measurement of blood pressure. In infancy and childhood the blood pressure measurement may be difficult due to an uncooperative and restless patient. In a 16-month-old girl apparently unmeasurable blood pressure was a hypertensive crisis with systolic blood pressure of more than 200 mmHg. The cause of the hypertension was found to be a nephroblastoma. In the case of rapidly progressive arterial hypertension in another 16-month-old girl with left ventricular dilatation and reduced function was a consequence of kidney dysplasia. Headache attacks lead to diagnosis of a subtotal coarctation of the aortic isthmus in a 17-year-old boy. Hypertensive crisis in infancy, childhood and adolescence is discussed based on these case reports. Special features of blood pressure measurement in the pediatric age group, pathogenesis of hypertensive crisis and the potential therapies are discussed incorporating a brief review of the literature.

Natriuretic peptides and myocardial oxygen supply-to-demand ratio in patients with aortic stenosis.

BACKGROUND: In severe aortic stenosis (AS), brain natriuretic peptide (BNP) and its precursor, the amino-terminal pro-hormone (NT-proBNP) are independent predictors of outcome. Deterioration of cardiac function in AS is currently assessed by symptomatology and echocardiography to determine the optimal time point for surgery. We investigated whether BNP or NT-proBNP may help to estimate the individual risk of patients for subendocardial ischaemia in patients with moderate and severe AS. DESIGN: In 71 patients with AS and 24 controls, the association of plasma natriuretic peptides with invasively measured haemodynamic parameters, including the myocardial oxygen supply-to-demand ratio [diastolic pressure time index/systolic pressure time index (DPTI/SPTI)] was cross-sectionally assessed. RESULTS: Levels of natriuretic peptides increased with severity of AS. In patients with moderate AS (n = 30), natriuretic peptides differentiated between symptomatic and asymptomatic status (P = 0.01). BNP and NT-proBNP values correlated negatively with DPTI/SPTI (r = -0.58 and -0.51, P < 0.001, respectively) and left ventricular (LV) ejection fraction (EF) (r = -0.52 and -0.59, P < 0.001, respectively). DPTI/SPTI correlated with aortic valve area (P < 0.0001) but not with EF. Receiver operating characteristic analysis determined cut-off values of > 450 pg mL(-1) for BNP and of > 1800 pg mL(-1) for NT-proBNP for those AS patients who were at highest risk for subendocardial ischaemia (i.e. DPTI/SPTI < 0.22) in combination with impaired LV systolic function (i.e. EF < 45%). CONCLUSIONS: Elevated natriuretic peptides show cardiac deterioration in AS and may help to identify those patients in need for early valve replacement.

Role of p38 mitogen-activated protein kinase in cardiac remodelling.

BACKGROUND AND PURPOSE: Mitogen-activated protein kinases (MAPK) are centrally involved in several mechanisms important for heart failure such as apoptosis, activation of inflammatory responses and cell proliferation. We therefore evaluated the effect of the selective p38 MAPK inhibitor SB 239063 on progression of left ventricular remodelling after myocardial infarction (MI) in rats. EXPERIMENTAL APPROACH: Rats were treated for 9 weeks with placebo or SB 239063 by gavage (15 mg kg(-1)) twice daily starting 7 days after ligation of the left anterior descending artery. Serial transthoracic echocardiography was performed at days 7, 36 and 70. KEY RESULTS: Over the 9 weeks, mortality was not different between the groups. On echocardiography, animals after myocardial infarction exhibited significant left ventricular dilatation as expected (week 10, end-systolic diameter, placebo sham 5.21+/- 0.34 vs. placebo MI 8.44+/- 0.57 mm). However, there was no difference between placebo and SB 239063-treated rats (week 10, end-systolic diameter, SB MI 7.76+/- 0.74 mm, not significantly different from placebo MI). Haemodynamics changed accordingly. Moreover, SB 239063 had no effect on left ventricular hypertrophy. Treatment with SB 239063 significantly reduced cytokine expression of tumour necrosis factor and interleukin-1beta after myocardial infarction. However, collagen content was not influenced by the treatment. CONCLUSION: Despite a reduction of inflammation, treatment with the p38 inhibitor SB 239063 does not affect cardiac remodelling and cardiac function when treatment is started 7 days after myocardial infarction.

The sense of smell: multiple olfactory subsystems.

The mammalian olfactory system is not uniformly organized but consists of several subsystems each of which probably serves distinct functions. Not only are the two major nasal chemosensory systems, the vomeronasal organ and the main olfactory epithelium, structurally and functionally separate entities, but the latter is further subcompartimentalized into overlapping expression zones and projection-related subzones. Moreover, the populations of 'OR37' neurons not only express a unique type of olfactory receptors but also are segregated in a cluster-like manner and generally project to only one receptor-specific glomerulus. The septal organ is an island of sensory epithelium on the nasal septum positioned at the nasoplatine duct; it is considered as a 'mini-nose' with dual function. A specific chemosensory function of the most recently discovered subsystem, the so-called Grueneberg ganglion, is based on the expression of olfactory marker protein and the axonal projections to defined glomeruli within the olfactory bulb. This complexity of distinct olfactory subsystems may be one of the features determining the enormous chemosensory capacity of the sense of smell.

Clinical benefit of enzyme replacement therapy in Fabry disease.

Enzyme replacement therapy (ERT) with recombinant human alpha-galactosidase A (r-halphaGalA) enhances microvascular globotriaosylceramide clearance and improves clinical symptoms in patients with Fabry disease. We evaluated whether these effects are translated into a long-term benefit of kidney and heart function. We did a single center, prospective, open label study in 26 patients with Fabry disease (one early death, follow-up in 25 patients). r-Alpha-GalA was administered in a dosage of 1 mg/kg body weight every second week. The effect of therapy on clinical end points (death, cardiac and cerebrovascular event, renal failure), cardiac and renal function monitored by Doppler echocardiography, 99Tc-GFR, and proteinuria was investigated. After a mean treatment time of 23 +/- 8 months, nine patients experienced 12 end points, including two deaths. All end points occurred in patients with impaired renal function (n = 16; GFR 71 +/- 17 ml/min/1.73 m2). Despite ERT, renal function deteriorated to 60 +/- 23 ml/min/1.73 m2 (P = 0.04) and left ventricular posterior wall thickness (PWT) did not change (14.0 +/- 2.1 vs 13.4 +/- 2.3 mm). In contrast, patients without impairment of renal function (n = 9) had a more favorable outcome (no clinical events; GFR 115 +/- 18 vs 102 +/- 14 ml/min/1.73 m2, NS; PWT 11.7 +/- 1 and 10.7+/-0.7 mm, P = 0.04). Proteinuria remained unchanged (1.34 +/- 0.94 vs 1.01 +/- 0.97 g/day, n = 10). Patients with impaired renal function have a less favorable outcome and may develop cardiovascular and renal end points despite ERT.

Morbus Fabry of the heart. Why should cardiologists care?

Fabry Disease is an X-linked lysosomal storage disorder leading to the accumulation of glycosphingolipids, mainly globotriaosylceramides in all tissues and solid organs of the body. The disease was described by Johannes Fabry and William Anderson coevally in 1898. Beside the involvement of the central nervous system, peripheral nerves, kidneys, skin and endovascular endothelium, the heart plays a major role in the disease. Left ventricular hypertrophy is one hallmark initially presenting with preserved ventricular function. However, with progression of the disease patients die due to heart failure. Though angina is often reported, the incidence of epicardial coronary stenosis is not a dominant feature, if at all small vessel disease can occur. In respect of arrhythmias a broad spectrum can be seen including shortened or prolonged PR-intervals, AV blocks of different degrees and sometimes malignant ventricular arrhythmias. In the past, women were considered to be carriers of the disease but hardly to develop clinical symptoms. In recent years there is evidence that female carriers may more often be affected with severe symptoms. In addition, a group of Fabry patients displaying mainly cardiac involvement were described as having a cardiac variant of the disease. This implied the hypothesis that some of those patients with unexplained myocardial hypertrophy do suffer from Fabry disease. Since 2002 enzyme replacement therapy is available and there is first evidence for its efficacy to reduce hypertrophy and increase myocardial function. If this is associated with a prognostic improvement has to be determined in future studies.

[Myocardial infarction after influenza vaccination]. / Myokardinfarkt nach Influenza-Schutzimpfung.

Influenza is a common disease in the population. Influenza vaccination is performed routinely and is usually well tolerated. Minor local or systemic side effects like fever and myalgia are described. Rarely there are more severe adverse events. Systemic vasculitis has been reported in some cases. In this case we report on a female patient with secondary vasculitis and myocardial infarction after influenza vaccination. The patient received cortisol and recovered. The literature about influenza vaccination, its side effects and recommendations about vaccination in patients with coronary artery disease is reviewed.

The feasibility of ultrasonic regional strain and strain rate imaging in quantifying dobutamine stress echocardiography.

BACKGROUND: Ultrasonic strain rate and strain can characterize regional one-dimensional myocardial deformation at rest. In theory, these deformation indices could be used to quantify normal or abnormal regional function during a dobutamine stress echo test. AIMS: The aims of our pilot study were threefold: (1) to determine the percentage of segments in which interpretable strain rate/strain data could be obtained during routine dobutamine stress echo, (2) to establish whether either the increase in heart rate or artefacts induced by respiration during dobutamine stress echo would influence analysis by degrading the data and (3) to determine the optimal frame rate vs image sector angle settings for data acquisition. Furthermore, although the detection of ischaemia was not to be addressed specifically in this study, we would describe the findings on the potential clinical role of regional deformation vs velocity imaging in detecting ischaemia-induced changes. METHODS: A standard dobutamine stress echo protocol was performed in 20 consecutive patients with a history of chest pain (16 with angiographic coronary artery disease and four with normal coronary angiograms). DMI velocities were acquired at baseline, low dose, peak dose, and recovery. To evaluate radial function (basal segment of the left ventricle posterior wall segment), parasternal LAX, SAX views were used. For long axis function data were acquired (4-CH, 2-CH views) from the septum; lateral, inferior and anterior left ventricle walls. Data was acquired using both 15 degrees (>150 frames per second (fps) and 45 degrees (115fps) sector angles. During post-processing each wall was divided into three segments: basal, mid and apical. Strain rate/strain values were averaged over three consecutive heart cycles. RESULTS: Data was obtained from 1936 segments, of which only 54 had to be excluded from subsequent analysis (2.8%) because of suboptimal quality. An increase in heart rates (up to 150/min) was not associated with a significant reduction in the number of interpretable segments. There was a significant correlation between maximal systolic strain rate/strain values obtained at narrow and at wide sector angles (e.g. a correlation for the septal segments: r=0.73,P <0.001 for strain rate, and r=0.71; P<0.001 for strain). The correlation for the timing of events obtained from narrow and wide sector angles was weaker. This would indicate that there was the insufficient temporal resolution for the latter acquisition method. Normal and abnormal regional strain rate/strain responses to an incremental dobutamine infusion were defined. In normal segments, maximal systolic strain rate values increased continuously from baseline, reaching the highest values at the peak dose of dobutamine. The segmental strain response was different. For strain, there was an initial slight increase at low dose of dobutamine (5, 10 microg/kg/min), but no further increase with increasing dose. A pattern representing an ischaemic response was identified and described. CONCLUSIONS: The feasibility study would suggest that with appropriate data collection and post-processing methodologies, strain rate/strain imaging can be applied to the quantification of dobutamine stress echo. However, appropriate post-processing algorithms must be introduced to reduce data analysis time in order to make this a practical clinical technique.

A novel perfusion catheter for hybrid procedures in minimally invasive bypass surgery.

BACKGROUND: Combined off-pump bypass grafting and percutaneous coronary intervention (hybrid procedures) is supposed to be beneficial for high-risk patients. We developed a novel perfusion catheter to facilitate these hybrid interventions. METHODS: First, we tested coagulatory activation in vitro. Afterwards, 6 landrace pigs underwent active coronary perfusion of the LAD. In a second study, 15 pigs underwent off-pump bypass surgery (LIMA to LAD grafting) and the catheter was used to provide myocardial perfusion and prevent bleeding at the site of the coronary anastomosis. RESULTS: In the in vitro perfusion studies, no activation of coagulation or clotting occurred. Active coronary perfusion was feasible without signs of regional myocardial ischemia or coagulation over a 50-minute period. During off-pump bypass surgery, the catheter prevented bleeding in the operation field and facilitated the surgical procedure. CONCLUSION: The new perfusion catheter can optimize the conditions of off-pump bypass surgery by preventing bleeding in the operation field, maintaining myocardial perfusion and allowing direct angiographic control of the anastomosis. Therefore, this new technique could be an important tool to facilitate hybrid interventions.

Quantification of the spectrum of changes in regional myocardial function during acute ischemia in closed chest pigs: an ultrasonic strain rate and strain study.

The objectives of this study were to define the spectrum of regional myocardial function changes during acute ischemia in closed chest animals by using newly developed ultrasonic strain rate and strain indexes derived from regional color Doppler myocardial imaging (CDMI) velocity data. Myocardial ischemia was induced in 18 pigs either with acute total 20-second occlusions (group 1, n = 12) or graded hypoperfusion (40 to 0 mL/min, group 2, n = 6) of the circumflex coronary artery. In addition, a dobutamine challenge (5 to 10 microg/kg per minute) was performed during sustained subtotal ischemia (10 mL/min) in group 2. CDMI acquisitions with parasternal views monitored the myocardial posterior wall function. Regional radial strain rate and strain (epsilon(r)) were measured for systole, isovolumic relaxation, early diastole, and atrial filling, respectively. During total and graded ischemia, epsilon(r) profiles were consistently modified, showing a delayed onset and a decrease in regional systolic thickening as well as increased postsystolic thickening. Radial strain rate and epsilon(r) indexes decreased consistently during systole and early diastole and increased during isovolumic relaxation. End-systolic epsilon(r) could differentiate total ischemia from severe hypoperfusion (10 mL/min), decreasing from 32% +/- 8% to 16% +/- 5% (versus 60% +/- 10% at baseline). During dobutamine infusion (10 microg/kg per minute), end-systolic epsilon(r) tended to decrease from 27% +/- 5% to 18% +/- 11%, whereas postsystolic thickening increased by 2-fold (P <.05). The combined analysis of regional deformation characteristics and global cardiac event timing derived from CDMI data can identify and quantify regional function changes induced by experimental acute ischemia in closed chest pigs. This would appear to be a potentially promising new noninvasive approach to the clinical evaluation of ischemia-induced changes in segmental myocardial function.

Doppler myocardial imaging in the assessment of normal and ischemic myocardial function--past, present and future.

Myocardial ischemia is associated with impaired regional myocardial function. Echocardiography is a suitable technique for the assessment of regional myocardial function as it is easily applicable and commonly available. However, most of the currently used echo-techniques are based on 2D images or M-mode traces. Therefore, they are limited either to the assessment of myocardial segments that can be insonated at 90 degrees or are based on visually assessed wall motion scoring which is semiquantitative at best. Doppler myocardial imaging (DMI) is a new ultrasound technique which assesses the velocity of myocardial motion. Different parameters can be derived from this velocity information such as velocity time integrals, intramural velocity gradients and strain/strain-rate information. Moreover, DMI provides information of the timing of regional motion related to myocardial contraction and relaxation. These parameters are all assessed quantitatively, therefore, DMI is a promising technique to quantify myocardial function, avoiding the disadvantages of observer-dependant judgement of myocardial contraction.

Noninvasive quantification of the contractile reserve of stunned myocardium by ultrasonic strain rate and strain.

BACKGROUND: We sought to investigate ultrasonic strain rate and strain as new indices to quantify the contractile reserve of stunned myocardium during dobutamine infusion. METHODS AND RESULTS: Stunning of the left ventricular posterior wall was induced in 9 closed-chest pigs after 30 minutes of severe hypoperfusion followed by 60 minutes of reperfusion of the left circumflex coronary artery territory. A second group of 7 animals had no coronary occlusion and served as normal controls. An incremental dobutamine infusion protocol was used in both groups. Changes in regional radial function were monitored by use of ultrasound-derived maximal systolic radial strain rate (SR) and systolic strain (epsilon). In the control group, dobutamine induced an increase in both SR and maximal dP/dt, which correlated linearly (r=0.85). Conversely, epsilon values increased at low doses of dobutamine (2.5 to 5 microg. kg(-1). min(-1)) but decreased during higher infusion rates (10 to 20 microg. kg(-1). min(-1)). During circumflex hypoperfusion, SR and epsilon of the posterior wall decreased from 5.0+/-0.3 s(-1) and 63+/-6% to 2.9+/-0.3 s(-1) and 27+/-4%, respectively (P<0.01). After 60 minutes of reperfusion, SR and epsilon failed to fully resume because of stunning, averaging 3.6+/-0.2 s(-1) and 35+/-3%, respectively (P=0.12 versus ischemia, P<0.05 versus baseline). During dobutamine infusion, SR increased at 5 microg. kg(-1). min(-1) and exceeded baseline values at 20 microg. kg(-1). min(-1) (P<0.05), whereas epsilon increased only at high doses and remained below baseline levels (P<0.05). CONCLUSIONS: The changes in regional function of stunned myocardium during inotropic stimulation could be characterized by use of ultrasonic deformation parameters. During dobutamine infusion, strain-rate values quantified the contractile reserve better than strain values.

Identification of a third rat odorant-binding protein (OBP3).

From a rat olfactory epithelium cDNA library clones encoding a lipocalin were isolated with sequence identity to the previously described salivary-specific alpha-2u globulin and the N-terminal region of mouse odorant-binding proteins OBP-III and OBP-IV. In situ hybridization showed strong expression in nasal glands displaying a pattern equivalent to rat OBP1. Heterologously expressed protein was evaluated for its binding properties using spectroscopic approaches. The recombinant protein interacted with two fluorescent probes, 1-aminoanthracene (1-AMA) and 1,1'-bis(4-anilino-5-naphthalene)-sulfonic acid. 1-AMA binding was competed by several odorants with high affinity. The thermodynamic parameters of the protein-odorant interaction were determined using isothermal titration calorimetry. Due to its nasal expression and odorant-binding characteristics this protein was designated OBP3.

Persistence of the eustachian valve in secundum atrial septal defects: possible implications for cerebral embolism and transcatheter closure procedures.

Transcatheter closure of large secundum atrial septal defects is now accepted clinical practice. With the introduction of easily applicable closure devices the indications for this procedure have been expanded to include the closure of patent foramen ovale after cerebral stroke of unknown origin. In some of these patients a persistent eustachian valve is present. The clinical relevance of this finding is still unclear. A 36 year old patient with a brainstem stroke of unknown origin and a secundum atrial septal defect in combination with a persisting prominent eustachian valve is reported. The potential role of the eustachian valve in the genesis of the stroke and the difficulties during transcatheter closure of the defect because of the persisting valve are discussed.

Targeting of olfactory neurons.

Olfactory sensory neurons detect an enormous variety of small volatile molecules with extremely high sensitivity and specificity. The actual recognition and discrimination of odorous compounds is accomplished by specific receptor proteins located in the ciliary membrane of the sensory neurons. Axonal connections into the olfactory bulb, the first relay station for odor processing in the brain, are organized such that all neurons expressing the same odorant receptor converge their axons onto common glomeruli which are located at similar positions in all individuals from one species. For the establishment of this precise targeting of olfactory axons to their appropriate glomeruli, combinatorial functions of axon-associated cell adhesion molecules and odorant receptor proteins appear to be required. Odorants that stimulate distinct receptor cell populations will thereby activate a specific combination of glomeruli in the bulb; this characteristic activity pattern may be used by the system to encode the quality of a particular odorant.