Selective stimulation of jugular ganglion afferent neurons in guinea pig airways by hypertonic saline

We evaluated the ability of hyperosmolar stimuli to activate afferent nerves in the guinea pig trachea and main bronchi and investigated the neural pathways involved. By using electrophysiological techniques, studies in vitro examined the effect of hyperosmolar solutions of sodium chloride (hypertonic saline) on guinea pig airway afferent nerve endings arising from either vagal nodose or jugular ganglia. The data reveal a differential sensitivity of airway afferent neurons to activation with hypertonic saline. Afferent fibers (both A delta and C fibers) with cell bodies located in jugular ganglia were much more sensitive to stimulation with hypertonic saline, compared with afferent neurons with cell bodies located in nodose ganglia. Additional studies in vivo demonstrated that inhalation of aerosols of hypertonic saline induced plasma extravasation in guinea pig trachea that was mediated via tachykinin NK1 receptors. Identification of a differential sensitivity of guinea pig airway afferent nerves to hypertonic saline leads to the speculation that airway responses to hyperosmolar stimuli may result from activation of afferent neurons originating predominantly from the jugular ganglion.     

Comparison of rabbit and human corneas stored in Optisol-GS: changes in stromal sodium

PURPOSE: To evaluate the hydration, and the levels of free, total and bound sodium in fresh rabbit corneal stromas and also those preserved for up to 21 days in Optisol-GS. The effect of epithelial removal on stromal sodium and hydration parameters was also evaluated. Trends in stromal hydration and sodium environment were compared to results we previously obtained using human eyes stored under identical conditions. METHODS: Stromal hydration was evaluated thermogravimetrically. A sodium-specific electrode and an atomic absorption spectrophotometer were used to determine the amounts of free and total stromal sodium, respectively. In one cornea of each pair, the epithelium was removed prior to placement in the storage media. After 3, 7, 14 or 21 days at 4 degrees C, corneas were removed from the Optisol-GS, at which time sodium and hydration measurements were obtained. RESULTS: With an intact epithelium, the hydration of the rabbit stromas was elevated significantly at each day of storage compared to fresh corneas. Free and total sodium levels of rabbit stromas did not differ statistically from fresh values, however the bound sodium values did increase during storage. In the absence of the epithelium, the stromal hydration and sodium content (free, total and bound) were significantly elevated and the increase was much greater than in corneas stored with an intact epithelium. These findings differ from those we measured previously using human tissue. CONCLUSIONS: Rabbit corneas responded differently from human corneas to storage in Optisol-GS. The hydration levels increased to a greater level in rabbit than human corneas under both storage conditions. The trends in amounts of both free and total sodium were similar between the species, although the absolute amounts differed. The largest discrepancy was observed in the amount of bound sodium, with the rabbit corneas experiencing large increases not documented in the human tissue. These results suggest that direct comparisons of stromal hydration and ionic environment between the species should be approached with caution.     

Growth hormone-releasing factor mobilizes cytosolic free calcium through different mechanisms in two somatotrope subpopulations from porcine pituitary

Porcine somatotropes can be separated by Percoll density gradient centrifugation into low (LD) and high density (HD) subpopulations that differ ultrastructurally and functionally. Here, we report the effects of growth hormone-releasing factor (GRF) on the cytosolic free calcium concentration ([Ca2+]i) of single LD and HD somatotropes. Resting [Ca2+]i in LD somatotropes was 2-fold higher than in HD cells. GRF induced [Ca2+]i increases in a similar percentage of somatotropes from both subsets. However, amplitude and kinetics of the responses were markedly different. In all responsive LD somatotropes, GRF evoked a rapid initial peak followed by a sustained plateau (plateau-type response). Blockade of extracellular Ca2+ entry by 3 mM EDTA, 2 mM CoCl2, or 100 microM verapamil completely abolished the plateau phase without affecting the initial Ca2+ spike. Conversely, only the plateau phase was preserved in thapsigargin (TG)-treated LD cells. The vast majority of GRF-responsive HD somatotropes exhibited a transient [Ca2+]i peak that returned gradually to baseline (transient-type response). This response was completely blocked by removal of extracellular Ca2+, whereas TG treatment had no effect. Taken together, our results indicate that the response of LD somatotropes to GRF depends on mobilization of Ca2+ of both extra- and intracellular origin, whereas that of HD somatotropes seems to be exclusively dependent on extracellular Ca2+ entry through L-type voltage sensitive Ca2+ channels (VSCC). These findings are the first to demonstrate a differential effect of GRF on Ca2+ mobilization in two somatotrope subpopulations, and suggest the existence of differences in the GRF receptor(s) expressed in each subpopulation and/or in the intracellular signalling pathways activated upon GRF binding.     

Hereditary lymphedema: evidence for linkage and genetic heterogeneity

Hereditary or primary lymphedema is a developmental disorder of the lymphatic system which leads to a disabling and disfiguring swelling of the extremities. Hereditary lymphedema generally shows an autosomal dominant pattern of inheritance with reduced penetrance, variable expression and variable age at onset. Three multigeneration families demonstrating the phenotype of hereditary lymphedema segregating as an autosomal dominant trait with incomplete penetrance were genotyped for 366 autosomal markers. Linkage analysis yielded a two-point LOD score of 6.1 at straight theta = 0. 0 for marker D5S1354 and a maximum multipoint LOD score of 8.8 at marker D5S1354 located at chromosome 5q34-q35. Linkage analysis in two additional families using markers from the linked region showed one family consistent for linkage to distal chromosome 5. In the second family, linkage to 5q was excluded for all markers in the region with LOD scores Z < -2.0. The vascular endothelial growth factor C receptor ( FLT4 ) was mapped to the linked region, and partial sequence analysis identified a G-->A transition at nucleotide position 3360 of the FLT4 cDNA, predicting a leucine for proline substitution at residue 1126 of the mature receptor in one nuclear family. This study localizes a gene for primary lymphedema to distal chromosome 5q, identifies a plausible candidate gene in the linked region, and provides evidence for a second, unlinked locus for primary lymphedema.     

Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1

BACKGROUND: Hereditary breast cancer has been associated with mutations in the BRCA1 and BRCA2 genes and has a natural history different from sporadic breast cancer. We investigated disease-free and overall survival for patients with a proven BRCA1 alteration. METHODS: We estimated disease-free and overall survival for 49 Dutch patients from 19 consecutive families with a proven specific BRCA1 mutation and one family with strong evidence for linkage to the BRCA1 gene. We compared clinical outcome and data on tumour size, histology, axillary nodal status, contralateral breast cancer, and oestrogen-receptor and progesterone-receptor status with those of 196 patients with sporadic breast cancer, matched for age and year of diagnosis. FINDINGS: Disease-free survival for BRCA1 and sporadic patients at 5 years was 49% (95% CI 33-64) and 51% (43-59), respectively (p=0.98). Overall survival at 5 years was 63% (47-76) and 69% (62-76), respectively (p=0.88). Recurrence and death rates did not differ significantly between groups. Hazard ratios for recurrence and death among BRCA1 patients were 1.00 (0.65-1.55) and 1.04 (0.63-1.71) relative to sporadic patients (p=0.88), and these did not differ significantly after adjustment for prognostic factors. Patients with BRCA1-associated breast cancer had twice as many progesterone-receptor-negative tumours (p<0.005) and development of contralateral breast cancer was four to five times as frequent as in the sporadic group (p<0.001). INTERPRETATION: We showed that disease-free and overall survival were similar for sporadic and hereditary breast cancer in the presence of different tumour characteristics, which has implications for screening prophylactic therapy, and different treatments of hereditary breast cancer.     

Associations between TGF-beta1 receptors in human bone marrow stromal cells

Bone marrow stromal cells are required for sustained haemopoiesis. Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine present in the bone marrow microenvironment which regulates the expression of several cytokines, cytokine receptors and cell adhesion elements. The TGF-beta receptors type I and II, and endoglin, mediate TGF-beta1 binding to the membrane of human bone marrow stromal cells. [125I]TGF-beta1-affinity labelling experiments showed that three different anti-endoglin monoclonal antibodies co-immunoprecipitated a 68 kD TGF-beta1-labelled polypeptide together with TGF-beta1/endoglin complexes. Here, we have shown that the 68 kD receptor corresponds to the type I receptor, indicating that endoglin and the type I receptor associate on the membrane of these cells upon ligand binding. The expression of endoglin by stromal cells was found to be up-regulated by TGF-beta1, but not by IL-1beta. The association of endoglin with signalling components of the TGF-beta receptor system on the membrane of bone marrow stromal cells might modulate TGF-beta1 access to the signalling pathways, and therefore it could regulate TGF-beta1-mediated stromal cellular responses.     

Precision of fit: the Procera AllCeram crown

STATEMENT OF PROBLEM: Strength, color stability, and precision of fit are requirements for all-ceramic restorations. The Procera AllCeram crown system, composed of a densely sintered high-purity alumina core combined with a low fusing surface porcelain, appears to satisfy most of these requirements. However, evaluation of marginal fit has not been reported. PURPOSE: This study measured the precision of fit of the Procera AllCeram crown fabricated with Procera CAD/CAM technology for the premolar and molar teeth fit to a die. MATERIAL AND METHODS: Five ivorine maxillary first premolars and first molars were prepared for full-coverage crowns. Preparations were standardized with a convergence angle of 10 degrees, chamfer margins of 1.3 to 1.5 mm circumferentially, and occlusal reduction of 2.0 mm. AllCeram crowns were fabricated for the dies, and the fit of the crown to the die was determined by using a standardized procedure with a silicone impression material that served a dual role: (1) as a retrievable luting agent, and (2) to replicate the internal aspects of the crown. Laser videography was used to measure the gap dimension between the crowns and the dies at the marginal opening, the axial wall, the cusp tip, and the occlusal adaptation measurement locations. Mean gap dimensions and standard deviations (SDs) were calculated for marginal opening, internal adaptation, and precision of fit. RESULTS: Mean gap dimensions and standard deviations at the marginal opening for the premolar and molar crowns were 56.0 microns SD +/- 21 and 63.0 microns SD +/- 13 microns, respectively. The mean gap dimensions and SDs of the internal adaptation were 69.0 microns SD +/- 17 microns for axial wall, 48.0 microns SD +/- 12 microns for cusp tip, and 36.0 microns SD +/- 7 microns for occlusal adaptation for the premolar crowns; and 49.0 microns SD +/- 3 microns axial wall, 67.0 microns SD +/- 21 microns cusp tip, and 74.0 microns SD +/- 29 microns occlusal adaptation for molar crowns. Precision of fit and SDs for premolar and molar crowns were 52.0 microns SD +/- 19 microns and 63.0 microns SD +/- 20 microns, respectively. Mean marginal openings and precision of fit gap dimensions for the crown groups were not significantly different at the .05 level. However, gap dimensions that defined the internal adaptation at the measurement locations were different (P < or = .05). CONCLUSION: Mean gap dimensions for marginal openings, internal adaptation, and precision of fit for the crown groups were below 70 microns. These findings show that the crowns studied can be prescribed with confidence knowing that the precision of fit will consistently be less than 70 microns.     

A mediational model of quality of life for individuals with severe mental health problems

BACKGROUND: Despite the increasing importance of quality of life in the mental health field, the theoretical conceptualization of the construct remains poorly developed. A proposed mediational model of quality of life, which links subjective quality of life with self-related constructs, is examined with a group of long-term psychiatric hostel residents. The present study aims to develop a measure of quality of life based on the proposed model, to explore the data and their implications for service development and finally to conduct a preliminary analysis of the model's predictions. METHODS: A cross-sectional research design was employed. Quality of life interviews, using a modified version of Lehman's Quality of Life Interview, were carried out with 54 psychiatric residents in Greece. The model's predictions were examined by using a series of regression analyses. RESULTS: The results indicate that perceived improvements in lifestyle, greater autonomy and positive self-concept are significantly and directly associated with better quality of life. In contrast, a direct relationship between objective indicators and subjective quality of life was not found. CONCLUSIONS: The traditional two-part quality of life model that includes objective indicators of life circumstances and subjective indicators is extended to included the constructs of self-concept and perceived autonomy. The present extended mediational model of quality of life for individuals with long-term mental health problems appears to have important implications for the planning and delivery of mental health programmes.     

Microvascular effects of atrial natriuretic peptide (ANP) in man: studies during high and low salt diet

OBJECTIVE: Infusion of ANP in anephric dogs causes a decrease in cardiac output and a rise in peripheral vascular resistance. This reduced cardiac output is possibly related to increased resistance to venous return generated in the microcirculation by venular constriction. The aim of the present study was to evaluate in healthy volunteers the effects of low-dose ANP infusion on both conjunctival and skin microcirculation during high or low salt diet. METHODS: ANP (7.5 ng/kg/min) and placebo were infused (i.v.) for 4 h, in random order on two separate days, in two groups of 10 healthy male volunteers each. One group was studied during high salt (ad libitum), and one group during low salt (55 mmol Na+/24 h) diet. Microvascular density and diameters of both conjunctiva and nailfold were studied using intravital videomicroscopy. Nailfold capillary red blood cell velocity (CBV) was studied using intravital videomicroscopy, and skin (thermoregulatory) blood flow (SBF) was studied using laser-Doppler fluximetry. RESULTS: In the high salt group ANP induced a 43% reduction in basal SBF as compared to an 18% reduction by placebo (P < 0.01). Parallel to SBF, ANP significantly reduced CBV (P < 0.02). Conjunctival capillary density decreased by 5% during ANP, while it increased by 28% during placebo (P < 0.05). No such effects of ANP were observed in the low salt group. Blood pressure and heart rate were not influenced by ANP infusion in neither group. CONCLUSION: Infusion of low doses of ANP into humans on an ad libitum salt diet results in vasoconstriction of the microcirculation, probably on the venular side. The lack of effect of ANP on the microcirculation during low salt diet may be related to a higher vascular tone prior to infusion.