Thematic review series: Lipid droplet synthesis and metabolism: from yeast to man. Lipid droplet-based storage fat metabolism in Drosophila

The fruit fly Drosophila melanogaster is an emerging model system in lipid metabolism research. Lipid droplets are omnipresent and dynamically regulated organelles found in various cell types throughout the complex life cycle of this insect. The vital importance of lipid droplets as energy resources and storage compartments for lipoanabolic components has recently attracted research attention to the basic enzymatic machinery, which controls the delicate balance between triacylglycerol deposition and mobilization in flies. This review aims to present current insights in experimentally supported and inferred biological functions of lipogenic and lipolytic enzymes as well as regulatory proteins, which control the lipid droplet-based storage fat turnover in Drosophila.     

Lipid storage myopathy: successful treatment with propranolol.

Lipid storage myopathies are a rare but serious cause of muscle weakness characterised by the accumulation of abnormal amounts of neutral fat in type 1 fibres. A case is reported in which the patient presented with weakness of the proximal limb muscles and greatly increased activities of creatine kinase and lactate dehydrogenase. After two years lipid myopathy was diagnosed when electron microscopy confirmed the presence of large numbers of lipid particles within muscle fibres. Twelve years after the initial presentation propranolol (40 mg thrice daily) was started. Strength gradually improved and enzyme activities returned to normal. The improvement in the patient''s condition was almost certainly due to the propranolol, although the mode of action of the drug remains unknown.     

Lipid metabolism in cartilage and its diseases:a concise review of the research progress

The homeostasis of the vertebrate body depends on anabolic and catabolic activities that are closely linked the inside and outside of the cell.Lipid metabolism ...     

The histochemical evaluation of the glycogen storage diseases. A review of techniques and their limitations

Synopsis Histochemical techniques have been applied to biopsies of liver and muscle in cases of glycogen storage disease in order to demonstrate the presence of glycogen and the various enzymes which are involved in the degradation and synthesis of glycogen. This review of techniques is based on the examination of tissues from a group of patients with glycogen storage disease, and the results have been correlated with biochemical assays on the same tissues. It is possible to differentiate between the various forms of glycogen storage disease with the exception of Types III and VI which, due to the vagaries of the phosphorylase reaction, have very similar staining characteristics. The techniques have also been applied successfully to blood films from which considerable information can be obtained.     

Psychological and social evaluation in cases of deliberate self-poisoning admitted to a general hospital.

In a prospective clinical trial 312 cases of self-poisoning (276 patients) consecutively admitted to hospital were randomly allocated to medical teams or to psychiatrists for an initial psychiatric assessment and a decision as to "disposal." Junior doctors and nurses received some instruction in this work. Both groups of assessors asked for help from social workers when necessary. Once the medical teams had completed their assessments, psychiatrists provided most of the hospital treatment. Follow-up at one year showed no significant difference between the two groups of patients in the numbers who repeated their self-poisoning or self-injury (or both), or committed suicide. Provided junior doctors and nurses are taught to assess self-poisoned patients, we think medical teams can evaluate the suicidal risk and identify patients requiring psychiatric treatment or help from social workers, or both. Contrary to the Department of Health''s recommendation that all cases of deliberate self-poisoning should be seen by psychiatrists, we have reached the conclusion that physicians should decide for each of their patients if specialist psychiatric advice is necessary.     

The molecular basis of the type 1 glycogen storage diseases.

Microsomal glucose-6-phosphatase catalyses the last step in liver glucose production. Glucose-6-phosphatase deficiency, now termed type 1 glycogen storage disease, was first described almost 40 years ago but until recently very little was known about the molecular basis of the various type 1 glycogen storage diseases. Recently we have shown that at least six different proteins are needed for normal glucose-6-phosphatase activity in liver. Four of the proteins have been purified and three cloned. Study of the type 1 glycogen storage diseases has stimulated investigations of the mechanisms of small molecule transport across the endoplasmic reticulum membrane and demonstrated the existence of novel endoplasmic reticulum transport proteins for glucose and phosphate.     

Endobronchial lipoma: two cases and review of the literature.

Endobronchial lipoma is a benign tumour of the large bronchi occurring in middle-aged men. To the 38 successfully treated cases in the English literature a further 2 are added. The symptoms are those of obstructive pneumonitis mimicking bronchogenic carcinoma, and the result of delayed therapy may be bronchiectasis. Treatment includes local resection through a bronchoscope or a bronchotomy incision, or removal, if necessary, of the obstructed lobe or lung at thoracotomy. Smoking may be important in the pathogenesis of this tumour.     

Antenatal diagnosis of sphingolipid and mucopolysaccharide storage diseases.

In 4 years of 24 fetuses at risk for various sphingolipid and mucopolysaccharide storage diseases were examined. Amniocentesis at 16 weeks'' gestation was followed in most cases by culture of amniotic fluid cells and measurement in the cells of the activity of the enzyme suspected to be deficient. Six fetuses were affected; five were examined morphologically and biochemically after abortion. Two fetuses had Tay-Sachs disease, two had GM1 gangliosidosis and one had Hurler''s syndrome. Although in each affected detus the specific enzyme activity was absent, we found in the placenta 5 to 50% of the normal activity.     

Lipid droplets as fat storage organelles in Caenorhabditis elegans: Thematic Review Series: Lipid Droplet Synthesis and Metabolism: from Yeast to Man

Lipid droplets are evolutionarily conserved organelles where cellular fat storage and mobilization are exquisitely regulated. Recent studies have defined lipid droplets in C. elegans and explored how they are regulated by genetic and dietary factors. C. elegans offers unique opportunities to visualize lipid droplets at single-cell resolution in live animals. The development of novel microscopy techniques and protein markers for lipid droplets will accelerate studies on how nutritional states and subcellular organization are linked in vivo. Together with powerful tools for genetic and biochemical analysis of metabolic pathways, alteration in lipid droplet abundance, size, and distribution in C. elegans can be readily connected to whole-animal energy homeostasis, behavior, and life span. Therefore, further studies on lipid droplets in C. elegans promise to yield valuable insights that complement our knowledge gained from yeast, Drosophila, and mammalian systems on cellular and organismal fat storage.     

Invasive external otitis: review of 12 cases.

Invasive external otitis is an infection caused by Pseudomonas aeruginosa that often occurs in elderly people with diabetes. Twelve cases that illustrate the problems associated with the clinical recognition and successful outcome of the condition were reviewed. The patients'' average age was 62.5 years, and they had been ill for an average of 1.8 months before admission to hospital. Predisposing factors included diabetes, swimming in a warm climate and the use of a hearing aid. Radionuclide bone scanning and surgical exploration revealed pathognomonic findings. Initial therapy was often suboptimal: one or more relapses occurred in seven of the patients. All of the patients were cured without relapse after a minimum of 4 weeks of therapy with tobramycin plus an anti-Pseudomonas penicillin. The average duration of the illness was 3.9 months. The outcome in invasive external otitis should be excellent if the condition is diagnosed early and appropriate therapy is instituted.     

Obstetric accidents: a review of 64 cases.

OBJECTIVE--To identify the causes of obstetric accidents. DESIGN AND SETTING--Analysis of case records at the Medical Protection Society''s London office covering the five years 1982-6. SUBJECTS--Cases that had come to litigation which had resulted in stillbirth, perinatal or neonatal death, central nervous system damage to the baby, or maternal death and in which there was an opinion from a senior obstetrician consulted by the society. Of 147 cases reviewed, 64 met the criteria for the study. MAIN OUTCOME MEASURES--The principal findings of the expert reviewers. RESULTS--Three major topics of concern emerged common to most of the 64 cases. These were inadequate fetal heart monitoring, mismanagement of forceps, and inadequate supervision by senior staff. In 11 of the 64 cases cardiotocography was omitted, in 19 cases the trace was missing, in six cases the trace was unreadable, and in 14 of the remaining 28 cases signs of fetal distress went unnoticed or were ignored. In 31 cases forceps were used to aid delivery or were tried and abandoned in favour of caesarean section. In 16 cases two or more attempts to use forceps were made. Five infant deaths were directly attributed to mismanaged forceps. In 20 cases senior staff were criticised by the expert reviewer for failure to come to the labour ward. In many of these cases they may have given advice over the telephone, but the inadequacy of records made it impossible to tell. In these cases the labour and birth were managed by junior staff, usually a senior house officer. In six cases when senior staff did come they suggested that no action was needed. CONCLUSION--These few cases should not be dismissed as isolated incidents in obstetric practice in Britain. They reflect more general problems--namely, concerning the ability of junior doctors to interpret fetal heart traces accurately, their ability to use forceps, and the participation of senior staff in running a labour ward and delivery suite.     

Lipid peroxidation-induced DNA damage in cancer-prone inflammatory diseases: a review of published adduct types and levels in humans

Persistent oxidative stress and excess lipid peroxidation (LPO), induced by inflammatory processes, impaired metal storage, and/or dietary imbalance, cause accumulations and massive DNA damage. This massive DNA damage, along with deregulation of cell homeostasis, leads to malignant diseases. Reactive aldehydes produced by LPO, such as 4-hydroxy-2-nonenal, malondialdehyde, acrolein, and crotonaldehyde, react directly with DNA bases or generate bifunctional intermediates which form exocyclic DNA adducts. Modification of DNA bases by these electrophiles, yielding promutagenic exocyclic adducts, is thought to contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. Ultrasensitive detection methods have facilitated studies of the concentrations of promutagenic DNA adducts in human tissues, white blood cells, and urine, where they are excreted as modified nucleosides and bases. Thus, immunoaffinity-(32)P-postlabeling, high-performance liquid chromatography-electrochemical detection, gas chromatography-mass spectrometry, liquid chromatography-tandem mass spectrometry, immunoslotblot assay, and immunohistochemistry have made it possible to detect background concentrations of adducts arising from endogenous LPO products in vivo and studies of their role in carcinogenesis. These background adduct levels in asymptomatic human tissues occur in the order of 1 adduct/10(8) and in organs affected by cancer-prone inflammatory diseases these can be 1 or 2 orders of magnitude higher. In this review, we critically discuss the accuracy of the available methods and their validation and summarize studies in which measurement of exocyclic adducts suggested new mechanisms of cancer causation, providing potential biomarkers for cancer risk assessment in humans with cancer-prone diseases.