Early alterations of actin in cultured human keratinocytes and fibroblasts exposed to long-wavelength radiations. Possible involvement in the UVA-induced perturbations of endocytotic processes.

Exposure of cultured MRC5 human fibroblasts or NCTC 2544 human keratinocytes to mild doses of ultraviolet A (UVA: 320-400 nm) radiations markedly decreased the actin reactivity with fluorescein-labeled phalloidin. This indicates a change in the degree of polymerization of actin and thus in the organization of actin filaments. Such a phenomenon might be involved in the previously reported UVA-induced inhibition of specific and nonspecific endocytotic processes.

[Severe hepatic steatosis: a cause of sudden death in the alcoholic patient]. / La stéatose hépatique massive: une cause de décès brutal chez le malade alcoolique.

The authors report the cases of 4 patients with heavy chronic alcoholic intake who presented with hepatomegaly and jaundice without obvious hepatic failure and who died rapidly. In all 4 cases, histological examination of the liver showed massive microvesicular and macrovesicular steatosis involving approximately 100% of hepatocytes and, in 2 cases, minimal lesions of alcoholic hepatitis. Histochemical study, performed in 3 cases, showed that steatosis was constituted of triglycerides only, and that hepatic glycogen was completely depleted in 2 of 3 cases. No obvious cause of death was found in these 4 patients. Shortly, before their death, the 4 patients had increased their ethanol and decreased their food intake. The authors suggest that death as well as microvesicular steatosis could have be due to acute mitochondrial dysfunction.

Niemann Pick c or storage by excessive blood cell destruction: a case presenting a diagnosis problem.

A case of storage disease followed up during 12 a was studied by morphological, histochemical, immunological, and biochemical techniques. Data were analysed in an attempt to differentiate an acquired storage by excessive cell degradation from a storage of genetic origin. If, as it is our belief, a conclusion of acquired storage can be made, this observation in which the same cholesterol metabolism abnormalities as in Niemann Pick type C were seen, leads to a rediscussion of their diagnostic significance.

An atypical ultrastructural pattern in Fabry's disease: a study on its nature and incidence in 7 cases.

This is a report on a stored lipid atypical ultrastructural pattern in skin samples of Fabry's disease expressed exclusively in the endothelium. The pattern consisted of intersecting short crescentic tightly packed membranes with a periodicity identical to that in classical ultrastructural variants. At low magnification the lysosomal aggregates of the material resembled "sunbursts" or aggregates of densely packed squirming villus-like structures. According to results of ultrastructural, lipid, and lectin histochemical analyses including analysis of the patients' blood groups, it could be concluded that it is just a variant physical state of the otherwise typical Fabry lipid. Its origin could be attributed to impeded formation (or maintenance) of larger lipid lamellae. It was found in great amounts in skin capillaries in 2 cases, and rarely in 5 additional cases. Knowledge of this atypical ultrastructural pattern is of practical significance because it could, if prevalent, cause diagnostic problems.

Diffuse storage of vegetal wax hydrocarbons of dietary origin. Pathologic and chemical findings in a case.

A 55-year-old man died suddenly, after presenting with unstable angina and an asymptomatic micronodular pulmonary pattern. Autopsy revealed storage of a crystallized fatty substance in the lymph nodes, liver, spleen, adrenal glands, and lungs. In the latter organ, the deposition formed foreign body granulomas, accounting for the radiographic appearance. Mass spectrometry identified the fatty substance as straight-chain saturated hydrocarbons (n-alkanes) of carbon-29 and carbon-31 atoms, which are naturally present in the cuticular wax of many vegetals. The case history and the elimination as causal agent of products manipulated in the patient's work led to the conclusion that the storage was due to excessive consumption of apples, and to a lesser degree of Brussels sprouts. We present the light-microscopic findings and the principal biochemical results. Pathogenic mechanisms are described. As far as we are aware, this is the only observation of vegetal alkane storage to be described to date.

[Hepatic lipid overload in 2 cases of cholestasis associated with parenteral feeding]. / Etude de la surcharge lipidique hépatique au cours de deux cas de cholestase associée à la nutrition parentérale.

The authors report 2 cases of patients with ileal stenosis who developed progressive jaundice while receiving total parenteral nutrition including lipids (Intralipid). In both cases the histologic and histochemical study of the liver demonstrated lipid overload in Kupffer cells and to a lesser extent hepatocytes. Biochemical study established that linoleic acid, a component of Intralipid, associated with a digalactosyl-diglyceride from vegetal origin were the main components of the hepatic overload. The authors hypothesize that two associated mechanisms were responsible for jaundice in their patients: Kupffer cell dysfunction due, at least in part, to lipid overload and intestinal bacterial overgrowth leading to endotoxinemia.

A new human pathology with visceral accumulation of long-chain n-alkanes; tissue distribution of the stored compounds and pathophysiological hypotheses.

This report deals with a new human disorder characterized by the accumulation of plant long-chain n-alkanes in viscera of a human patient. Lipid analysis of tissues from an adult male after sudden death (affected with diffuse visceral granuloma containing lipophilic crystallized material) showed the presence of abnormal compounds identified as long-chain n-alkanes with 29 (n-nonacosane), 31 (n-hentriacontane) and 33 carbons (n-tritriacontane). Study of n-alkane distribution in patient tissues showed a major accumulation in lumbo-aortic lymph nodes, adrenal glands, lung (the highest levels were found in lung granulomas) and liver; significantly lower amounts were detected in myocardium and kidney, whereas no detectable level was found in brain. On the basis of the structural composition and of the tissue distribution of the accumulated n-alkanes, their dietary (plant) origin and the pathophysiological mechanism of the storage are discussed.

The effects of perhexiline maleate on low density lipoprotein processing and cholesterol metabolism in cultured human fibroblasts.

The effects of perhexiline maleate (PM, Pexid) on low density lipoprotein (LDL) processing and cholesterol metabolism were investigated after a 24 h pretreatment with the drug. Perhexiline maleate increased LDL uptake in the range 10(-6) to 10(-5) M (180% of control for 10(-5) M), whereas LDL binding and degradation were not affected. Sterol synthesis from sodium acetate was enhanced by perhexiline maleate (X 2.2 for 10(-5) M), while cholesterol esterification with oleic acid was decreased (40% of control for 10(-5) M). These effects of perhexiline on cholesterol metabolism are specific, since the synthesis of triacylglycerols from sodium acetate is not affected and since the incorporation of oleic acid into triacylglycerols is much less impaired. The decreased cholesterol esterification is accompanied by a reduction of acylcoenzyme A-cholesterol-O-acyltransferase (ACAT) activity measured in vitro on cell extracts.

Abnormal n-nonacosane storage in humans: detection by gas chromatography/mass spectrometry of tissue extracts.

We report a case of n-nonacosane storage disease, which went undiagnosed until the death of a 55-year-old farmer. Clinical, histological, and biochemical features are discussed. n-Nonacosane storage was identified by gas chromatographic-mass spectrometric analysis of different tissue extracts, n-nonacosane concentration reaching 1.2 mg g-1 of lung tissue and 0.32 mg g-1 of liver tissue. It was possible to rule out a work-induced intoxication, and n-nonacosane storage appeared to be accounted for by a lifelong, heavy consumption of unpeeled apples and Brussels sprouts.

Characterization by lectin binding of the sugar moiety of glycocompounds stored in inherited diseases.

Kidney and liver samples from two cases of Fabry's disease and spleen and liver samples from Gaucher and Niemann-Pick diseases were tested for binding to lectins such as peanut agglutinin (PNA), Bandeiraea simplicifolia, (BSA), canavalia ensiformis (Con A), soybean agglutinin (SBA) and wheat germ agglutinin (WGA) labelled with horseradish peroxidase using histochemical techniques. These techniques allowed the localization of compounds with alpha-galactosyl residues in tissues from Fabry's disease. In tissues from the Gaucher and Niemann-Pick cases, the storage material was found to be more complex than expected, and some problems regarding the significance of lectin binding are discussed.

[Lesions of coronary atherosclerosis in drug users. Preliminary studies]. / Lésions d'athérosclérose coronariennes chez les usagers de drogues. Etudes préliminaires.

A study of hearts removed during medicolegal autopsy of drug addicts after their sudden death demonstrated the constant presence of coronary lesions very similar to common atherosclerosis but remarkable by their magnitude, especially in patients dying at an age when atheromatous disease is relatively rare. Coronary circulation was studied in 10 cases by histoenzymatic, immunologic, histologic and ultrastructural examination of fresh and fixed tissues. The parietal thickening, noted in all cases to variable degrees, had provoked stenosis in several cases, preferentially in the proximal portion of the anterior interventricular vessel. On light and ultrastructural microscopy, the lesions observed were similar to atherosclerotic lesions, but differed in several respects and notably the absence of antiglobulin and the lack of increase of glycosaminoglycans. Although the relations between the drug and atheroma are undeniable, their mechanism is at present unknown.

Alterations in cholesterol metabolism in cultured fibroblasts from patients with Niemann-Pick disease type C.

Cholesterol synthesis, esterification and efflux were investigated in cultured fibroblasts from patients with Niemann-Pick disease type C. Sterol synthesis from sodium acetate was markedly increased in the two Niemann-Pick disease type C strains as compared to controls, either in the presence or absence of exogenous cholesterol supply by low-density lipoproteins. By contrast, cholesterol esterification was about 2-3-fold reduced when measured by oleic acid incorporation into cholesteryl esters and 10-15-fold reduced when measured with labelled free cholesterol as precursor, although acylcoenzyme-A:cholesterol acyltransferase activity was normal when studied in vitro on cell homogenates. Chase experiments with 14C-cholesterol demonstrated that the rate of cholesterol efflux was decreased by about 3-4-fold in fibroblasts from patients with Niemann-Pick disease type C. These results provide further evidence for alterations of sterol metabolism in Niemann-Pick disease type C and support the hypothesis of a trapping of exogenous cholesterol, which cannot enter the regulatory intracellular pools.

Pulmonary lipogranulomatosis due to excessive consumption of apples.

A 55-year-old man was admitted for treatment of unstable angina. Chest x-ray films showed a micronodular pattern, but there were no respiratory symptoms. Autopsy, carried out following sudden death, revealed pulmonary granulomas surrounding lipid crystals. The same crystals were found elsewhere: lymph nodes, spleen, liver, adrenal glands, and were composed of aliphatic hydrocarbons of vegetal origin, mainly C29H60. Investigation of the case history revealed excessive consumption of apples, to which the hydrocarbon deposition could be attributed, since C29H60 is a natural constituent of the cuticular wax in apple peel. This is a unique example of pulmonary granulomatosis due to storage of vegetal hydrocarbons of dietary origin.

[Changes in the biosynthesis, esterification and efflux of cholesterol in fibroblasts in culture from patients with Niemann-Pick disease type C]. / Altérations de la biosynthèse, de l'estérification et de l'efflux du cholestérol dans les fibroblastes en culture de sujets atteints de maladie de Niemann-Pick type C.

Cholesterol synthesis, esterification and efflux have been comparatively studied in control fibroblasts and in fibroblasts from patients with Niemann-Pick disease type C (NPC). Sterol synthesis was markedly increased in NPC cells as compared to controls, either in whole medium or in medium devoid of lipoproteins. 14C-oleic acid incorporation into cholesteryl-esters was 2 to 3 fold reduced in NPC cells, and esterification of 14C-exogenous cholesterol was dramatically (15-30 fold) decreased. ACAT activity, measured in vitro, was not significantly altered in NPC cells. Finally, cholesterol efflux appeared to be decreased in NPC fibroblasts as compared to controls. The hypothesis of a defect in exogenous cholesterol access to intracellular regulatory pools is proposed.

[Clinical and histoenzymological peculiarities of cholesterol storage in 2 children of the same family]. / Particularités cliniques et histoenzymologiques de la polycorie cholestérolique chez deux enfants d'une même fratrie.

Two sisters, aged 6 and 9 years, presented with similar episodes of acute illness. Clinical, biological, pathological, ultrastructural, histochemical and biochemical investigations led to a diagnosis of cholesterol ester storage disease. The two have been followed for 7 years and during that time a number of features atypical of cholesterol ester storage disease have been observed. Severe jaundice, advanced fibrosis and decreased liver glycogen stored. Examination of liver and cultured fibroblasts showed excess esterified cholesterol storage and acid lipase deficiency as seen in Wolman disease.

Continuous subcutaneous infusion of glucagon by portable pump in non beta cell tumor hypoglycemia.

Subcutaneous infusion of glucagon by portable pump appears to give very effective symptomatic relief from non beta cell tumor hypoglycemia when surgery, radiotherapy and chemotherapy are impossible or ineffective. This mode of glucagon administration was proposed in a patient who had severe nocturnal hypoglycemic attacks. The aim of the study was to specify the modes of utilization and to test the efficiency and the tolerance of this treatment. Glucagon was infused at 400 micrograms/h during every 12 hour night. Because of the hepatic action of glucagon it is very important to use this treatment with an adequate diet and to stop the infusion during the day to reconstitute the glycogen overload. This mode of glucagon administration was very effective in over 6 months of use and well tolerated.