The role of lipids in pulmonary surfactant

Pulmonary surfactant is composed of approx. 90% lipids and 10% protein. This review article focusses on the lipid components of surfactant. The first sections will describe the lipid composition of mammalian surfactant and the techniques that have been utilized to study the involvement of these lipids in reducing the surface tension at an air-liquid interface, the main function of pulmonary surfactant. Subsequently, the roles of specific lipids in surfactant will be discussed. For the two main surfactant phospholipids, phosphatidylcholine and phosphatidylglycerol, specific contributions to the overall surface tension reducing properties of surfactant have been indicated. In contrast, the role of the minor phospholipid components and the neutral lipid fraction of surfactant is less clear and requires further study. Recent technical advances, such as fluorescent microscopic techniques, hold great potential for expanding our knowledge of how surfactant lipids, including some of the minor components, function. Interesting information regarding surfactant lipids has also been obtained in studies evaluating the surfactant system in non-mammalian species. In certain non-mammalian species (and at least one marsupial), surfactant lipid composition, most notably disaturated phosphatidylcholine and cholesterol, changes drastically under different conditions such as an alteration in body temperature. The impact of these changes on surfactant function provide insight into the function of these lipids, not only in non-mammalian lungs but also in the surfactant from mammalian species.     

The role of lipids in plastid protein transport

The elaborate compartmentalization of plant cells requires multiple mechanisms of protein targeting and trafficking. In addition to the organelles found in all eukaryotes, the plant cell contains a semi-autonomous organelle, the plastid. The plastid is not only the most active site of protein transport in the cell, but with its three membranes and three aqueous compartments, it also represents the most topologically complex organelle in the cell. The chloroplast contains both a protein import system in the envelope and multiple protein export systems in the thylakoid. Although significant advances have identified several proteinaceous components of the protein import and export apparatuses, the lipids found within plastid membranes are also emerging as important players in the targeting, insertion, and assembly of proteins in plastid membranes. The apparent affinity of chloroplast transit peptides for chloroplast lipids and the tendency for unsaturated MGDG to adopt a hexagonal II phase organization are discussed as possible mechanisms for initiating the binding and/or translocation of precursors to plastid membranes. Other important roles for lipids in plastid biogenesis are addressed, including the spontaneous insertion of proteins into the outer envelope and thylakoid, the role of cubic lipid structures in targeting and assembly of proteins to the prolamellar body, and the repair process of D1 after photoinhibition. The current progress in the identification of the genes and their associated mutations in galactolipid biosynthesis is discussed. Finally, the potential role of plastid-derived tubules in facilitating macromolecular transport between plastids and other cellular organelles is discussed.     

The role of magnetic resonance angiography in the assessment of intracranial vascular disease

Magnetic resonance techniques have a significant role in the evaluation of intracranial vascular diseases; however, to achieve an appropriate diagnosis, a combination of both magnetic resonance imaging and angiography are needed. It is extremely important for the interpreting physician to be aware of the potential limitations of the techniques being used. With this knowledge, magnetic resonance techniques can eliminate the need for more invasive procedures. An overview of the current methods and their applications and limitations is provided.     

Re-evaluating the role of vascular changes in the differential diagnosis of Alzheimer's disease and vascular dementia

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common causes of dementia, and much effort has been devoted to their differential diagnosis. However, current epidemiological, clinical and neuropathological evidence points to a substantial overlap between AD and VaD and suggests that vascular pathology, the traditional cornerstone of the differential diagnosis between the two entities, may not represent as clear a line of demarcation as originally believed. It may be time to reevaluate the dichotomy between AD and VaD.     

The role of leukocyte adhesion molecules in acute transplant rejection

The specific adhesion of cells to other cells or to particular tissues or tissue components is a basic function of cell migration and recognition and underlies many biologic processes including embryogenesis, repair, and immunity. Adhesion molecules are involved in and mediate most cell to cell interactions, implement migration of leukocytes to inflammatory or alloantigenic sites, and costimulate well activation and transformation. Because of these functions, the subject of adhesion molecules is gaining broader interest in the field of transplantation, particularly in the conceptualization and development of future treatment strategies. These molecules influence not only the first interaction between host leukocytes and vascular endothelial cells of the graft but also their migration through the grafted tissues. These contacts seem to be based initially on antigen-independent events of adhesion, which then progress to the antigen-dependent events of antigen recognition and host cell activation. This review evaluates current studies concerning the role of adhesion molecules in the context of the multifaceted processes of allograft rejection.     

Atherosclerotic vascular complications in diabetic transplant candidates

Serious vascular complications limit the success of renal transplantation in diabetic patients. Nearly half of diabetic transplant recipients die within 3 years after transplantation from a vascular complication. However, it has been difficult to determine before transplantation which patients are likely to do poorly. Because atherosclerosis is a systemic disease, we hypothesized that diabetic transplant candidates with pretransplant coronary artery disease would be at high risk for vascular complications even if asymptomatic at the time of pretransplant evaluation. Our hypothesis was that insulin-dependent (IDDM) transplant candidates with coronary artery disease identified with pretransplant coronary angiography would have an increased number of vascular events (amputation, cerebral vascular accident [CVA], or myocardial infarction [MI]) within 3 years of follow-up. We prospectively studied 198 consecutive diabetic transplant candidates grouped on the basis of coronary artery disease. Group 1 patients had no stenosis that was 50% or greater, group 2 patients had one or more stenoses between 50% and 74%, and group 3 patients had one or more stenoses of 75% or greater. During median follow-up of 41 months, 64 patients experienced 98 amputations, 28 MIs, and seven CVAs. At 36 months of follow-up, 55% of group 3 patients, 30% of group 2 patients, and 11% of group 1 patients had experienced a vascular event (P < 0.001). Cox regression confirmed the association of coronary artery disease with subsequent vascular events. Patients with coronary artery disease had a sevenfold increased risk of amputation and a fourfold increased risk of myocardial infarction. Six of seven CVAs occurred in patients with coronary artery disease. We conclude that coronary artery disease identified at pretransplant evaluation is associated with an increased risk of noncoronary vascular complications within 3 years after evaluation.     

Genetic therapy for transplant vascular sclerosis

Red blood cells are still transfused inappropriately in spite of recent media attention and public awareness about the risks of blood products. A prospective audit was conducted to determine the avoidable blood transfusion rates in the elective perioperative setting utilising the guidelines issued by the American College of Physicians (ACP). Of 82 consecutive adult patients who were admitted for major elective surgery over a 3-month period, 28 were transfused a total of 94 units of homologous SAG-M blood, of which 50 (53%) were inappropriate as recommended by the ACP guidelines. Violations of the guidelines were perioperative transfusion in bleeding patients who were haemodynamically stable (31%) and transfusion in asymptomatic, stable patients solely to attain a haemoglobin level above 10 g% (22%). There is a need for objective, easily adaptable and widely disseminated consensus guidelines to the indications for red blood cell transfusion.     

Vascular disease and lipids in diabetes

Atherosclerosis kills more patients with diabetes than all other causes combined. Aggressive reversal and treatment of dyslipidemias is the only proven prevention for coronary events in the patient with type 2 diabetes. Glycemic control with diet, oral hypoglycemic agents, and insulin, when necessary, is often only partially effective in normalizing lipid values in type 2 diabetes. Intensive treatment with lipid-regulating agents, particularly HMG-CoA reductase inhibitors, is often necessary to normalize diabetes-associated dyslipidemias. HMG-CoA reductase inhibitors are also the only agents thus far shown in prospective multicenter trials to reduce the risk of coronary events in diabetic patients.     

The role of nitric oxide in vascular biology and pathobiology

Brain natriuretic peptide (BNP) is a novel cardiac hormone secreted predominantly from the ventricle. We examined the plasma levels of BNP and atrial natriuretic peptide (ANP) in 13 patients with aortic stenosis undergoing corrective surgery. Preoperative plasma BNP and ANP levels correlated highly with preoperative left ventricular end-systolic wall stress (ESS) (r = 0.96, p < 0.0001 and r = 0.95, p < 0.0001, respectively). Moreover, between preoperative and late postoperative states, the difference of the plasma levels of BNP and ANP correlated with the difference of ESS. In two patients with elevated ESS and quite high preoperative plasma BNP (> 1000 pg/ml), rapid decrease of the plasma level after operation was observed. These results suggest that synthesis and secretion of BNP and ANP are stimulated by the increase of left ventricular end-systolic wall stress in patients with aortic stenosis.     

The role of intraglomerular hypertension and lipids in the development of diabetic nephropathy

To determine the mechanisms underlying diabetic nephropathy (DN) onset, a clinical and morphological study was initiated of 14 diabetics with insulin-dependent disease free of clinical renal manifestations. The patients were examined for intraglomerular hypertension, blood lipid spectrum and renal tissue morphology. In high intraglomerular hypertension, i. e. in renal functional reserve depletion, there is dyslipidemia with a characteristic significant rise in the levels of very low density lipoprotein cholesterol and low density lipoprotein cholesterol, in the value of atherogenic index. Morphologically, renal tissue of the hypertensive and dyslipidemic patients experienced hyperperfusion and massive lipid infiltration in glomerular cells. In contrast, renal tissue underwent only minimal nonspecific changes when intraglomerular hemodynamics and lipidemia were normal. The findings suggest that associated effects of intraglomerular hypertension and dyslipidemia may promote DN onset.     

The role of exercise in neuromuscular disease

Persons with hereditary neuromuscular diseases generally lead a sedentary lifestyle, placing them at risk for diseases associated with inactivity and causing weakness, which compounds their primary disease. Although research is lacking in this area, evidence to date suggests that this population may benefit from both strengthening and aerobic fitness training programs. Overwork weakness has not been demonstrated in controlled trials of exercise, but clinicians need to be prudent in their recommendations, encouraging alternating periods of physical activity with scheduled rest. Future investigations should focus on the primary symptom of fatigue, and quantify changes in the ability to work and participate in physical activities as outcome measures of an exercise program.     

The role of glycosylation in autoimmune disease

Lack of knowledge concerning latex allergy may lead to a life-threatening adverse reaction to natural rubber latex. Registered nurses need a latex allergy knowledge base to provide latex-safe health care to clients and to create a latex-safe environment. This research explored the current knowledge base of registered nurses as related to (1) the care of clients at risk for latex allergy, or diagnosed with latex allergy, and (2) the provision of a latex-safe environment for all populations. This article describes this research and its implications for nurses. A copy of the Latex Allergy Knowledge Base Self-Assessment Questionnaire is included at the conclusion of the article.     

The role of ultrasonography in thyroid disease

Ultrasound examination of the thyroid gland is widely used in the diagnosis of thyroid disease. This test is easy and rapid to perform, widely available and the results are readily interpreted. Using ultrasound the image of foci of disease within the gland are easily identified, especially using high frequency probes which enable solid nodules up to approx 3 mm to be revealed with 10 MHz probes. In non-nodular thyroid disease the ultrasonic structure guides the diagnosis (thyroiditis, Graves' disease). During the follow-up of thyroidectomised patients ultrasound can easily reveal postoperative anatomic variations and an early diagnosis can be obtained of any signs of local recurrence of the primary disease. Only hemiagenesia and hypoplasia can be accurately evaluated in congenital disease, whereas in the event of the persistence of the thyroglossal duct the latter can only be diagnosed if it presents a cystic evolution. Thyroid ectopia cannot be identified and must be studied using thyroscintigraphy, preferably performed using 131I as the isotope. The acquired pathology is classified into phlogistic processes, diffuse or nodular hyperplasia, benign and malignant neoplasia. This classification is widely accepted by virtually all authors. In thyroiditis, ultrasound may facilitate the diagnosis of De Quervain's non-suppurative sub-acute thyroiditis (TANS) and Hashimoto's chronic thyroiditis, although always in association with clinical and laboratory tests. The most frequent thyroid pathology is without doubt goitre. This disorder may occur in a non-nodular (widespread goitre with an endemic or sporadic pattern) or nodular form which may be single or multiple. The term goitre is used to indicate the increased volume of the thyroid gland independently of the causes which have provoked it. Common goitre is defined as being endemic when in some geographic area 10% of the general population or 20% of the school-aged population suffers from thyroid hyperplasia (areas of goitrogenic endemic disease). Graves' disease may be included in the group of thyroid hyperplasia diseases, although it is distinguished from the simple versions by the marked glandular hyperactivity which creates manifest hyperthyroidism. In this pathology ultrasonography must be supplemented by colour-Doppler wherever possible. Thyroid nodules are subdivided in terms of their echostructure into 5 types: liquid, mixed (prevalently solid or prevalently liquid), hyperechogenic solid, isoechogenic solid and hypoechogenic solid. The characteristics of benign nodules are: hypoechogenic structure, regular edges, complete and uniform hypoechogenic peripheral halo.(ABSTRACT TRUNCATED AT 400 WORDS)     

The role of allergy in Meniere's disease

There is considerable clinical and immunologic evidence for a probable role of allergy in the production of the symptoms of Meniere's disease. The endolymphatic sac is the seat of immune reactivity in the inner ear. Inhalant and food allergies have been linked with symptoms of Meniere's disease, and many of the clinical characteristics of Meniere's disease suggest an underlying autoimmune etiology. A significant percentage of patients with Meniere's disease and allergy show improvement in their symptoms of tinnitus and vertigo when receiving specific allergy therapy.     

Malingering in vascular disease

BACKGROUND: Antioxidant enzymes (AEs), which catalyze the conversion of reactive oxygen species (ROS) to water, include catalase (CAT), manganese-containing superoxide dismutase (MnSOD), and copper and zinc-containing superoxide dismutase (CuZnSOD). Previous work has indicated that MnSOD, CAT, and CuZnSOD levels are nearly always low in cancer cells. METHODS: Formalin-fixed, paraffin-embedded tissue from 31 radical prostatectomy specimens was immunohistochemically stained with polyclonal antibodies to CAT, MnSOD, and CuZnSOD. RESULTS: Malignant glands are typically stained with less intensity than benign/ hyperplastic glands. Marked heterogeneity of staining intensity was seen in the malignant glands for each of the three enzymes. A similar, though less marked, spectrum of heterogeneity of staining intensity was observed in the benign/hyperplastic epithelium contained in the specimens. No statistically significant correlation was found between intensity of staining for any of the three antioxidant enzymes and Gleason score, tumor stage, or preoperative prostate-specific antigen (PSA). CONCLUSIONS: Cellular levels of CAT, MnSOD, and CuZnSOD in prostatic adenocarcinoma reveal that many tumors appear to have decreased levels of expression. The finding that malignant prostate epithelium may have lowered expression of AEs suggests that further study of the role of AEs in malignant transformation in the prostate is warranted.     

Liver transplant in adult Still's disease

Adult Still's disease (ASD) is an uncommon form of polyarthritis associated with numerous systemic manifestations, including hepatic involvement. Rarely, liver involvement can be fatal. We describe the case of a young man with ASD with terminal liver failure who required a life saving liver transplant.