Lung-derived SSEA-1(+) stem/progenitor cells inhibit allergic airway inflammation in mice.

BACKGROUND: Asthma is characterized by chronic airway inflammation and airway hyperresponsiveness (AHR). Little is known about the role of pulmonary stem/progenitor cells (PSCs) in allergic airway inflammation. METHODS: To identify and investigate the role of PSCs in the bronchial epithelium of neonatal mice, we developed an enzyme-based digestion method to obtain single-cell suspension from lung tissues. Characterization of PSCs was performed using flow cytometry, real-time PCR, immunofluorescence staining, confocal microscopy, and scanning electron microscopy. The effects of SSEA-1(+) (stage-specific embryonic antigen-1) PSCs was studied in an in vivo model of ovalbumin-induced allergic inflammation and an in vitro model of cell-based regulation using flow cytometry, real-time PCR, and immune-blotting. RESULTS: Single-cell suspensions derived from neonatal lung tissue included populations that expressed either SSEA-1(+) or Sca-1(+) (stem cell antigen-1). The SSEA-1(+) PSCs were highly prevalent in neonatal mice, and they were rare in adult mice. Enriched neonatal SSEA-1(+) PSCs had the ability of self-renewal and differentiated into pneumocytes and tracheal epithelial cells. SSEA-1(+) PSCs reduced AHR and airway damage in asthmatic mice by decreasing eosinophil infiltration, inhibiting chemokines/cytokines production, and preserving the level of CCSP. CONCLUSIONS: Here, we demonstrated that neonatal SSEA-1(+) PSCs play an immunomodulatory role in the progression of asthma by reducing lung damage and inhibiting inflammatory responses. Further understanding the molecular mechanisms of neonatal SSEA-1(+) PSCs might shed light on exploring the novel therapeutic approaches for allergic airway inflammation.

Perceived challenges and priorities in co-morbidity management of older patients with Type 2 diabetes.

AIMS: To explore older patients' perceived impact of chronic co-morbid conditions on Type 2 diabetes self-management. METHODS: We used purposive sampling to select 32 mentally alert community-dwelling adults, aged 60 years or older, diagnosed with Type 2 diabetes and at least one other chronic health condition to participate in focus groups. We summarized the discussions following each focus group and identified codes to describe the overarching themes. RESULTS: We conducted eight 90-min focus groups, each consisting of two to six patients. Three themes emerged. (i) Diabetes complications as a motivator: managing co-morbid conditions made health an important focal point in the lives of older patients. Most patients acknowledged the positive effect complications had on their diabetes self-management by motivating them to pay greater attention to their diabetes to diminish the progression of these complications. (ii) Prioritizing health conditions: patients reported prioritizing health conditions and selectively attending to the management of those conditions based on perceived severity or importance. Further, many patients perceived some conditions as more serious than others and admitted to prioritizing another health condition over their diabetes. (iii) Emotional impact of co-morbidity management: patients described feeling frustrated, confused, and overwhelmed in response to conflicting treatment recommendations, particularly for diet, physical activity and medication regimens. CONCLUSIONS: Complications and co-morbidities may have differential impacts on the diabetes self-management of older patients. Addressing the perceived impact of co-morbidity on diabetes self-management may improve patients' outcomes; however, the most effective method of utilizing this information in clinical practice needs to be examined.

Selective arterialization of coronary veins for diffuse coronary occlusion. An experimental evaluation.

The selective arterialization of coronary veins as a surgical therapy for diffuse coronary arteriosclerosis was studied in canine and sheep experiments. The arterialized blood can be delivered promptly to the selected region of the myocardium and an adequate runoff exists for this mode of revascularization, so that myocardial edema and hemorrhage do not occur. The retrograde blood flow through an anastomosis between the internal mammary artery (IMA) and great cardiac vein (GCV) is excellent, with a predominantly diastolic flow pattern. Follow-up studies indicate significant but partial protection of the myocardium against diffuse LAD occlusion. The size of infarcts is decreased. However, the focal or small transmural infarcts observed are usually located near the apex of the heart. The studies with radioactive microspheres (15 plus or minus 5 mu diameter) revealed that the degree of capillary trapping of microspheres is very much less when the microspheres are injected retrograde into the vein than when injected into the artery. This may indicate that significant "shunt" blood flow exists when the coronary vein is arterialized. Thus this study demonstrates both the potential and the limitation of the selective arterialization of coronary veins in revascularizing patients suffering from diffuse coronary arteriosclerosis.

The roles of ventilation and perfusion in lung metabolism.

The lung, like other viable organs, requires the adequate supply of oxygen and metabolic substrates for its functional and structural integrity. Therefore, we studied the metabolic and ultrastructural consequences in the canine lung following bronchial and/or pulmonary arterial occlusions. The results indicate that the lung can maintain its bioenergetic levels for 5 hours with either the ventilation or perfusion alone. Ultrastructural changes appear to precede metabolic alterations measured. When both the ventilation and perfusion were interrupted, rapid biochemical and structural deteriorations occurred, whereas the combinations of alveolar obliteration and hypoxemia, induced with low F102, produced intermediate damage. The implications of these findings on the pathogenesis and evolution of acute respiratory distress syndrome, on the lung preservation for transplantation, and on the rationale for membrane oxygenator support are discussed.

Effects of exogenous cyclic adenosine monophosphate in hemorrhagic shock.

Hemorrhageic shock produces potentially damaging alterations in the metabolism of cyclic adenosine 3',5'-monophosphate (cAMP), which is an intracellular second messenger for many hormones. The hypothesis that the administration of exogenous cAMP might have salutary effects on cardiovascular hemodynamics in shock was tested in canine experimetns. Intravenous bolus injection of dibutyryl cAMP (2 mg. per kilogram) produced hyperglycemia, but no changes occurred in heart rate, arerial pressure cardiac output, or in the first derivative of left ventricualr pressure (dp/dt). The findings were similar in conscious and anesthetized (Nembutal) normotensive dogs, in dogs after 3 hours of shock (at blood pressure of 40 mm. Hg) and after the reinfusion of shed blood. The only hemodynamic change noted was a transient hypotensionupon injection of massive doses of dibutyryl-(db-) cAMP or cAMP (greater than 10 mg. per kilogram). The implication of these findings in light of earlier reported hemodynamic effects of cAMP is discussed.

Cyclic AMP response to epinephrine and shock.

Hormonal regulation is fundamental to homeostasis, and the response in tissues is mediated by adenosine 3':5' equals cyclic phosphate (cyclic AMP). Since circulating levels of catecholamines are elevated during hemorrhagic shock, experiments were carried out to study the effects of epinephrine and of shock on cyclic AMP levels of plasma and of the intestine, a particularly vulnerable organ in canine hemorrhagic shock. Epinephrine was given to normotensive dogs as a constant infusion (group 1) or as a single pulse (group 2). Sequential blood samples showed a marked increase in circulating cyclic AMP, especially in portal and hepatic venous blood. Little change was noted in the tissues. Hemorrhagic shock (group 3) induced a marked increase in plasma cyclic AMP, with a depletion of mucosal cyclic AMP and adenosine triphosphate (ATP). Pretreatment before shock with alpha-blockade (group 4) abolished the decrease in mucosal cyclic AMP and ATP, and reduced the increase in plasma cyclic AMP.

Why do radial artery grafts for aortocoronary bypass fail? A reappraisal.

The reasons for the high failure rate of radial artery grafts for aortocoronary bypass (ACB) are appraised. Each of 11 dogs received four types of grafts: femoral arteries were grafted to carotid arteries, and jugular veins were grafted to femoral arteries bilaterally. One of each pair of grafts was wrapped in a plastic sheet in order to interfere with the regeneration of vasa vasorum. The grafts were examined 2 months later. The results suggest that although operative trauma and intraluminal pressure change play important roles, the thick-walled artery appears to depend more on vasa vasorum for its integrity than does the thin-walled vein. A free radical artery graft, with vasa vasorum disrupted at both ends, cannot regenerate readily from the adjacent tissue, as is the case at the ACB position, and is therefore more vulnerable to subintimal hyperplasia and occlusion than either the vein graft or the internal mammary artery graft; both of these grafts are thinner, and the internal mammary artery graft remains undisrupted at one end.

Association between genetic polymorphism of tumor necrosis factor-alpha and risk of oral submucous fibrosis, a pre-cancerous condition of oral cancer.

Many cytokines have been thought to play important roles in the pathogenesis of oral submucous fibrosis (OSF), an areca nut chewing-specific pre-cancerous condition characterized by the deposition of collagen in oral submucosa. Tumor necrosis factor-alpha (TNF-alpha), situated in the class III region of human leukocyte antigen (HLA), is a mediator with multiple functions, including the regulation of inflammatory reaction and transcriptions of collagen and collagenase. In total, 809 male subjects were recruited for assessment of the association of OSF with a bi-allelic promoter-region (-308) polymorphism on the TNFA gene. The high production allele, TNF2, was significantly lower among OSF subjects (n = 166) than in areca-chewing controls (n = 284). This association was independent of oral cancer status. The multivariate-adjusted odds ratio for the TNFA 11 genotype was 2.6 (95% confidence interval = 1.4-4.9; p = 0.004). The finding may imply a multifunctional etiological factor of TNF-alpha in OSF pathogenesis.

Myopia and contrast sensitivity function.

PURPOSE: to measure the contrast sensitivity function of varying degrees of myopia with two types of optical correction (spectacle lens and contact lens). METHODS: One hundred and five myopic eyes and twenty-eight emmetropic eyes were collected. The myopic group included 105 eyes corrected with spectacle lenses and 71 eyes of them corrected with contact lenses, too; all had corrected vision acuity of 20/20 or better. The myopic eyes were divided into four groups: group 1 (-1D to -3D), low myopia; group 2 (-3.25D to -6D), medium myopia; group 3 (-6.25D to -12D), high myopia; and group 4 (> -12D), severe myopia. Spatial contrast sensitivity was measured using the OPTEC 2000 Contrast Sensitivity System. RESULTS: In groups 1 and 2, no statistically significant difference was found between myopes and emmetropes. In group 3, statistically significant loss of contrast sensitivity at higher spatial frequencies was found for myopic subjects corrected with spectacle lens, but not for myopes corrected with contact lens. In group 4, myopic subjects corrected with spectacle lenses showed significantly reduced contrast sensitivity function at all spatial frequencies; subjects corrected with contact lenses showed statistical sensitivity losses at 6, 12, 18 cycle/degree spatial frequencies. CONCLUSIONS: 1. We may suppose that low and medium myopes (groups 1 and 2), who showed normal contrast sensitivity functions, had no retinal dysfunction. 2. For high myopes, contact lens correction could reduce optical defocus and improve contrast sensitivity function in high spatial frequencies. 3. As retinal function disturbances occurred in severe myopes, the diminished contrast sensitivity was not fully compensated by contact lens correction. 4. Loss of contrast sensitivity might be interpreted as evidence for early retinal function disruption before retinal pathological events occur in severe myopes.

Epithelial lesions in low flow states: a unifying concept.

Several epithelium-lined organs are highly vulnerable in low flow states, and may lead to lesions such as hemorrhagic enteritis, stress ulcer, renal tubular necrosis, acalculous cholecystitis and "shock lung". A hypothesis is presented which postulated that the redistribution of the subepithelial microcirculatory blood flow and the subsequent damage to the epithelial barrier are the crucial processes in their pathogenesis. Presently available evidence in support of this thesis is summarized.