Evidence for distinct signaling mechanisms in two mammalian olfactory sense organs

In mammals, olfactory stimuli are detected by sensory neurons at two distinct sites: the olfactory epithelium (OE) of the nasal cavity and the neuroepithelium of the vomeronasal organ (VNO). While the OE can detect volatile chemicals released from numerous sources, the VNO appears to be specialized to detect pheromones that are emitted by other animals and that convey information of behavioral or physiological importance. The mechanisms underlying sensory transduction in the OE have been well studied and a number of components of the transduction cascade have been cloned. Here, we investigated sensory transduction in the VNO by asking whether VNO neurons express molecules that have been implicated in sensory transduction in the OE. Using in situ hybridization and Northern blot analyses, we found that most of the olfactory transduction components examined, including the guanine nucleotide binding protein alpha subunit (G-alpha-olf), adenylyl cyclase type III, and an olfactory cyclic nucleotide-gated (CNG) channel subunit (oCNC1), are not expressed by VNO sensory neurons. In contrast, VNO neurons do express a second olfactory CNG channel subunit (oCNC2). These results indicate that VNO sensory transduction is distinct from that in the OE but raise the possibility that, like OE sensory transduction, sensory transduction in the VNO might involve cyclic nucleotide-gated ion channels.     

Decomposition of electromagnetic boundary conditions at planarinterfaces with applications to TE and TM field solutions

Electromagnetic fields in homogeneous source-free regions can be decomposed into fields that are TE and TM with respect to a particular reference direction (e.g., the z direction). If transverse sources exist, both TE and TM fields may be excited simultaneously. This paper considers the case of two infinite regions having a common planar interface and prescribed sources (surface currents) on the interface. The source currents are decomposed in a manner consistent with the decomposition of the fields. Accordingly, a procedure is established for describing the boundary conditions at the interface in terms of the longitudinal field components E_z, H_z and the surface currents J¯_s. The development is unique in that the continuity of the transverse field components at the boundary are not explicitly considered but interpreted in terms of z-directed fields. This boundary condition approach is shown to give results consistent with those obtained by matching the tangential fields at the interface using vector transforms. A simple example illustrating the procedure using a ring of current in free-space is presented     

Control of locomotion in the marine mollusc Clione limacina. XI. Effects of serotonin

The locomotor activity in the marine mollusc Clione limacina has been found to be strongly excited by serotonergic mechanisms. In the present study putative serotonergic cerebropedal neurons were recorded simultaneously with pedal locomotor motoneurons and interneurons. Stimulation of serotonergic neurons produced acceleration of the locomotor rhythm and strengthening of motoneuron discharges. These effects were accompanied by depolarization of motoneurons, while depolarization of the generator interneurons was considerably lower (if it occurred at all). Effects of serotonin application on isolated locomotor and non-locomotor pedal neurons were studied. Serotonin (5 x 10(-7) to 1 x 10(-6) M) affected most pedal neurons. All locomotor neurons were excited by serotonin. This suggests that serotonergic command neurons exert direct influence on locomotor neurons. Effects of serotonin on nonlocomotor neurons were diverse, most neurons being inhibited by serotonin. Some effects of serotonin on locomotor neurons could not be reproduced by neuron depolarization. This suggests that, along with depolarization, serotonin modulates voltage-sensitive membrane properties of the neurons. As a result, serotonin promotes the endogenous rhythmical activity in neurons of the C. limacina locomotor central pattern generator.     

Transgenic overproduction of islet amyloid polypeptide (amylin) is not sufficient for islet amyloid formation

Islet amyloid polypeptide forms islet amyloid deposits in non-insulin-dependent diabetes mellitus. We have generated transgenic mice which express human islet amyloid polypeptide in their pancreatic beta cells yet do not develop islet amyloid deposits despite producing levels of the amyloidogenic human peptide 2 - 3 fold higher than the native (mouse) peptide. To determine whether marked overproduction of islet amyloid polypeptide is a potential cause of islet amyloid formation, we increased expression of this transgene by producing homozygous transgenic animals and by making heterozygous mice experimentally insulin resistant with nicotinic acid. Pancreatic content of islet amyloid polypeptide-like immunoreactivity in homozygous and nicotinic acid-treated mice was 2-fold (25 +/- 7 fmol/microg; n = 6) and 3.5-fold (47 +/- 20 fmol/microg; n = 3) higher, respectively, than that of untreated heterozygous animals (13+/-2 fmol/microg; n = 11; both p < 0.05). Despite this marked increase in production of islet amyloid polypeptide, neither group of mice developed gross islet amyloid deposits even after 16 months of age. We conclude that overproduction of islet amyloid polypeptide, even as produced by extreme insulin resistance, is not in itself sufficient for islet amyloid formation.     

Outbreak of serogroup C meningococcal disease associated with campus bar patronage

Between February 1991 and April 1992, eight undergraduates at a US residential university and one at a nearby 2-year college contracted serogroup C meningococcal disease. A case-control investigation with 20 controls per case, oropharyngeal carriage surveys, and multilocus enzyme electrophoresis (MEE) of serogroup C isolates were used to identify factors contributing to the outbreak. All eight sterile-site isolates from cases were closely related by MEE and were similar (though not identical) to the strain associated with the 1991-1992 epidemic of meningococcal disease in eastern Canada. Disease was associated with cigarette smoking (p = 0.012), recent patronage of campus-area bars (p = 0.034), estimated amount of time spent in campus-area bars (p = 0.0003), and, especially, recent patronage of one specific bar, bar A (p = 0.0006; odds ratio = 23.1, 95% confidence interval 3.0-571.5). In carriage surveys, 1,528 throat cultures taken from (primarily student) noncases yielded only five (0.3%) strains that were identical by MEE to those from cases. Two of these were found among 22 cultures obtained from bar A employees in spring 1992. Some cases in this outbreak may have followed transmission of the epidemic strain in bar A. Campus bar environments may facilitate the spread of meningococcal disease among teenagers and young adults.     

In vivo effects of activated H-ras oncogene expressed in the liver and in urogenital tissues

PURPOSE: The clinical significance of isolated calf vein thrombosis (CVT), particularly with respect to development of the postthrombotic syndrome, remains controversial. The purpose of this study was to define the early natural history of CVT in relation to persistent lower extremity symptoms, propagation, recanalization, and the development of valvular incompetence. METHODS: Over a 116-month period, 499 patients with acute deep venous thrombosis (DVT) were referred to our research laboratory, of whom 58 (12%) had thrombosis confined to the calf veins of at least one extremity. The lower extremities of 268 patients (29 with isolated CVT) were followed-up clinically and with duplex ultrasonography at intervals of 1 day, 7 days, 1 month, every 3 months for the first year, and yearly thereafter. RESULTS: Seventy percent of extremities with CVT were symptomatic at presentation. Although the prevalence of clinical signs and symptoms decreased to 29% by 1 month, 23% of patients had persistent pain, edema, or both at 12 months. In contrast, 9% of uninvolved extremities contralateral to a CVT and 54% of extremities with proximal DVT remained symptomatic at 1 year (p = 0.004). Recanalization proceeded rapidly such that the mean thrombus load was reduced by 50% at 1 month and to zero at 1 year. The prevalence of valvular incompetence progressively increased such that reflux was present in 24% of extremities at 1 year. Although its investigation was not a primary goal of this study, pulmonary embolism was diagnosed at presentation and during follow-up in 11% and 3% of patients, respectively. CONCLUSIONS: The natural history of CVT is complicated by persistent symptoms and the development of valvular incompetence in approximately one-quarter of patients. This potential for persistent lower extremity symptoms should be considered in evaluating the clinical relevance of isolated calf vein DVT.     

Myeloma stem cells in autografting in multiple myeloma

Autologous transplantation has been used increasingly over the last 10 years for the treatment of multiple myeloma. As is the case in other cancers treated by high-dose therapy and stem cell rescue, the contribution of occult tumor cells in the graft to relapse posttransplant remains to be resolved. In this report, we review the biology and differentiation of plasma cells in the context of their significance as an origin of relapse in multiple myeloma.     

Ornithine-delta-aminotransferase expression and ornithine metabolism in cultured epidermal keratinocytes: toward metabolic sink therapy for gyrate atrophy

There is now strong evidence that the chorioretinal degeneration associated with ornithine-delta-aminotransferase (OAT) deficiency is a consequence of hyperornithinemia. Therefore development of a metabolic system for clearing ornithine from the circulation is being pursued as a potential treatment. The skin is considered an attractive location for such a metabolic system because autologous cells can be safely and easily utilized. This study was undertaken to determine the ornithine metabolizing capacity of epidermal keratinocytes expressing normal and superphysiologic amounts of OAT. The data show that overexpression of OAT in keratinocytes cultured from a gyrate atrophy patient restores ornithine metabolism and results in a rate of ornithine disappearance from the medium that is significantly higher than the rate of disappearance from the medium bathing normal keratinocytes. In addition, OAT activity determined in soluble protein prepared from sonicates suggests that the capacity to maintain plasma ornithine within the normal range is contained within an accomplishable graft of keratinocytes overexpressing OAT. However, the actual rate of ornithine disappearance from the media was significantly less than predicted from enzyme activity assays. Following ornithine metabolite production by intact cells suggests that ornithine metabolism is limited primarily by clearance of downstream metabolites, as opposed to substrate delivery.     

Characterization of resol resins modified by the addition of PVC plastisols

Plastisols, which are a blend of poly(vinyl chloride) resin and a plasticizer (DEHP), were used as a toughening agent of a resol resin in order to improve the mechanical properties. It was not possible to formulate resol blends by adding more than 10 % of plastisol owing to a lack of apparent homogeneity in the systems, which also showed many air bubbles. The relationship between dynamic mechanical, mechanical and thermal properties and the amount of plastisol added was studied. It was determined from the infrared spectroscopy and dynamic mechanical results that the resol–plastisol blends seem to be formed by a reaction between the phenol and PVC giving a higher crosslinked structure. An improvement in the thermal resistance of the blends at lower temperatures was observed with an increase in the percentage of plastisol. Flexural analysis showed the elastic behaviour of the systems. However, it was not possible to observe the effect of the plasticizer (DEHP) owing to the low quantity of plastisol that was added to the resol. Copyright © 2004 Society of Chemical Industry