A case of Sj?gren''s syndrome associated with advanced hemolytic anemia caused by worsening autoimmune cholangiopathy

AIMS: Recent research suggests that people who become smokers may be more sensitive to the positive effects of nicotine than those who do not take up smoking. DESIGN AND SETTING: The present study was designed to investigate this hypothesis by querying initial experiences with cigarette smoking in smokers, ex-smokers and never-smokers recruited from the local community. PARTICIPANTS: Subjects were 80 women (23 highly-dependent smokers (Fagerstrom Tolerance Questionnaire score > or = 7), 30 less-dependent smokers (FTQ < or = 6), 12 ex-smokers and 15 never-smokers). MEASUREMENTS: Subjects were asked to rate pleasurable sensations and displeasurable sensations on a scale of 1 = none to 4 = intense, and to indicate the presence or absence of pleasurable rush or buzz, relaxation, dizziness, nausea and cough; social context was also queried. Pleasurable rush or buzz, relaxation, dizziness, nausea and cough were related to ratings of pleasurable and unpleasant sensations to establish their affective valence. FINDINGS: Pleasurable sensations, pleasurable rush or buzz and relaxation (pleasant effects) were significantly more likely to occur in the smoker categories than in never-smokers. The ratio of pleasurable to unpleasant sensations, computed as an index of overall hedonic impact of initial exposure, also significantly favored the smoker categories. By contrast, unpleasant sensations, nausea and cough (unpleasant effects) did not differ significantly among groups. Dizziness, which did not definitely emerge as either pleasurable or unpleasant, was significantly more likely to be reported among the smoker groups than among never-smokers. CONCLUSIONS: People who become highly dependent cigarette smokers appear to have more pleasurable sensations at their initial exposure to tobacco; unpleasant reactions to the first cigarette do not seem to protect against subsequent smoking.     

Quantitation of the fatty acid composition of phosphatidic acid by capillary gas chromatography electron-capture detection with picomole sensitivity

We describe a relatively simple and sensitive method to measure femtomole amounts of phosphatidic acid in cells. Phosphatidic acid was extracted from cells in the presence of 1-heptadecanoyl-2-heptadecanoyl-sn-glycero-3-phosphate as an internal standard, purified by two-dimensional thin-layer chromatography, and hydrolyzed to its constituent free fatty acids which were then derivatized to the corresponding pentafluorobenzyl esters. Pentafluorobenzyl esters of fatty acids were analyzed by gas chromatography with electron-capture detection. Long-chain fatty acids were resolved with excellent signal-to-noise ratios. Using heptadecanoic acid as an internal standard for quantitation, as little as 1 fmol of pentafluorobenzyl ester of stearic acid was detected with a linear response up to 10 pmol. Linear detector responses were obtained for all major classes of fatty acids. For phosphatidic acid measurement, the detection limit was at least 50 fmol thus achieving a 1000-fold increase in sensitivity compared to the most sensitive of the previously described methods. An example is provided of quantitating phosphatidic acid from minute amounts of biological samples such as islets of Langerhans.     

Diet-induced changes in the fatty acid composition of mouse hepatocyte plasma membranes

Hepatocyte plasma membranes were isolated from the livers of mice fed either a low fat diet or high fat diets containing polyunsaturated or saturated fat. The combined rate and isopycnic ultracentrifugation technique which was used produced highly purified hepatocyte plasma membrane fractions. The efficacy of the procedure was checked by electron microscopy and the assay to marker enzymes for the different subcellular organelles. Mice were maintained on a low fat diet until 60-70 days of age, when they were fed high fat diets containing polyunsaturated fat. The hepatocyte plasma membrane lipids of mice fed the polyunsaturated fat diet for 4 wk contained increased proportions of the major dietary unsaturated fatty acid, linoleic acid, and increased proportions of arachidonic acid. The proportion of linoleic and arachidonic acids decreased with continued feeding of the polyunsaturated fat diet. The hepatocyte plasma membrane lipids of mice fed the saturated fat diet contained increased proportions of oleic acid.     

A case of failure of mitroflow pericardial valve with severe hemolytic anemia

A 49-year-old woman who underwent mitral valve replacement with 29 mm Mitroflow pericardial valve in 1985 started to have severe hematuria, anemia and icterus around May 1994. She was diagnosed to have mitral regurgitation with hemolytic anemia due to structural deterioration of the prosthetic valve. She underwent replacement of the prosthetic valve with 29 mm St. Jude medical mechanical valve, which alleviated the symptoms remarkably. The explanted valve showed an extensive cuspal tear and prolapse close to the commissure and poor endothelialization of the inflow surface of the frame. In our experience the rate of structural deterioration of the Mitroflow valve is so high that we discontinued using this bioprosthesis.     

Character of structural disturbances caused by chloroalkylamines in the model and erythrocyte membranes

beta, beta-Dichlorodiethylamine is proved not to induce structural disturbances in phosphatidylcholine liposomes and erythrocyte membranes which is registered by fluorescence methods. Methyl-beta, beta-dichlorodiethylamine and metaxylyl-beta, beta-dichlorodiethylamine cause the increase in microviscosity of lipid bilayer hydrophobic areas in both erythrocyte membranes and liposomes. Besides, polarity of the latter also decreases, and the metaxylyl derivative alkylates nucleophilic centers of phospholipid phosphate groups in liposomes. Erythrocyte membranes, being treated by beta, beta-dichlorodiethylamine derivatives, the increase in the membrane protein hydrophobicity is registered as well as the decrease in their immersion in the lipid bilayer.     

Fatty acid composition of the lipids in human blood plasma and erythrocyte membranes during simulation of extravehicular activities of cosmonauts

Dynamics of the lipoacidic content of total plasma lipids and erythtocyte membranes was studied in 32 experiments with ten apparently healthy male subjects aged 27 to 41 years who were exposed to repeated decompression from the normal ground down to 40-35 kPa. For two hours of exposure to lowered pressure the subjects were breathing pure oxygen in mask and performing incremental physical work mimicking loading of the upper extremities of cosmonauts doing extravehicular activities (EVA) at the energy cost of 3 kcal/min. Decompression sessions were repeated with intervals from 3 to 5 days. In seven experiments, the subjects developed symptoms of the decompression sickness (DCS). Penetration of gas bubbles (GB) into the pulmonary artery was registered in 27 cases (84.4%). In 24 cases maximal intensity of the US signals from GB reached 3 to 4 Spencer's points. No changes in the lipidoacidic content of blood plasma or erythrocyte membranes were determined following the first exposure to decompression. BY the onset of repeated decompression, total number of lipids in erythrocyte membranes decreased from 54.6 to 40.4 mg% in the group of subjects who had not displayed DCS symptoms (n = 5) and from 51.2 to 35.2 mg% (p < 0.05) in the group of subjects with DCS symptoms (n = 5). In the subjects with DCS, polyunsaturated linoleic acid (18:2) tended to decrease against the upward trend of saturated fatty acids (16:0, 18:0). In these subjects, arachidonic acid in erythrocyte membranes (20:4) decreased following each decompression exposure and significantly increased (p < 0.05) in-between. In both groups, blood plasma showed slight fluctuations in the lipoacidic contents. These data suggest that exposure to the variety of the EVA-simulating factors may entail quite distinct but reversible modifications in the lipid metabolism in blood and the structural/functional state of erythrocyte membranes. The most marked alterations were observed in the subjects with the DCS symptoms during high intensity of US signals from GB in the venous blood flow.     

Generalized peroxisomal disorder in male twins: fatty acid composition of serum lipids and response to n-3 fatty acids

Ischemia leads to intracellular acidification which can be counteracted by the Na+/H+-exchange mechanism. A blockade of this exchanger has been hypothesized to cause stronger intracellular acidification in the course of ischemia thereby protecting the heart from ischemic damage. The aim of our study was to find out (1) whether in the course of ischemia areas become electrically silent, (2) whether this is enhanced by the Na+/H+-exchange inhibitor cariporide (4-Isopropyl-3-methylsulfonylbenzoyl-guanidine; Hoe 642) and whether cariporide has protective effects. Therefore, we submitted isolated rabbit hearts, perfused according to the Langendorff technique to regional ischemia (LAD occlusion) for 30 min followed by 30 min reperfusion with (n=7) or without (n=7) pre-treatment with 1 microM cariporide. Under these conditions 256-channel epicardial potential mapping was carried out. Under non-ischemic conditions cariporide did not alter any of the parameters under observation. We found that ischemia led to marked alterations of the activation pattern, to action potential shortening and a marked increase in the dispersion of refractoriness. In the ischemic region there was a significant ST deviation from the isoelectrical line (control 32+/-10; 30 min ischemia: 290+/-35 arbitrary units [a.u.]). This was markedly reduced by cariporide (control 39+/-10; 30 min ischemia: 170+/-25 a.u.). The increase in dispersion by ischemia (by 50+/-5 ms) was significantly counteracted by cariporide (increased dispersion by 20+/-4 ms). In a similar way the alteration of the activation pattern was antagonized. Under the influence of cariporide we found a lower increase in the left ventricular enddiastolic pressure, and a significantly slower recovery of the action potential duration. After 30 min of ischemia 24+/-5 (control series) 24.5+/-5 mm2 (cariporide) became electrically silent. In a second series of experiments the incidence of arrhythmia was assessed: we found ventricular fibrillation in 6/7 untreated control hearts and in 4/7 cariporide treated hearts. In a third series of experiments we determined the intracellular [ATP] after 30 min of LAD occlusion using a histochemical method. We observed a decrease in [ATP] in the ischemic region as compared to the non-ischemic right ventricular wall, which was less pronounced in cariporide-treated hearts. Thus, we conclude that (1) cariporide protects the heart from ischemic damage and (2) at least under these conditions an enlargement of the electrically silent area did not occur.     

A case of herpetiform pemphigus associated with autoimmune hemolytic anemia: detection of autoantibodies against multiple epidermal antigens

We report a case who was clinically and histopathologically diagnosed as herpetiform pemphigus (HP) and associated with autoimmune hemolytic anemia (AIHA). However, immunofluorescence studies demonstrated concurrent anti-cell-surface and anti-basement-membrane-zone antibodies in the patient's serum. Immunochemical studies showed that the patient's serum reacted with both the pemphigus foliaceus antigen and the two bullous pemphigoid antigens. Subsequently, the patient developed AIHA. Both anemia and skin lesions were successfully treated with oral prednisolone. We believe that this is the first case with HP in association with AIHA. The presence of autoantibodies against multiple antigens suggests an abnormal immunologic tolerance in the antibody production system in this patient.     

Selective modifications of the phospholipid fatty acid composition in human platelet membranes using nonspecific and specific lipid transfer proteins

In the framework of an earlier constructed model [N.S. Ananikyan et al. (1990) Biopolymers, Vol. 30, pp. 357-367], some analytical estimates for the correlation length and degree of helicity near the transition point were obtained in the case of an arbitrary topology of hydrogen bond closing (delta). It was shown that the Zimm-Bragg cooperativity parameter sigma is determined by the set of (delta-1) amino acid residues and so is nonlocal. An analytic expression for cooperativity parameters in a heteropolypeptide chain was obtained and numerical calculations showed that in case of heteropolypeptide with random primary structure the nonlocality of cooperativity parameter influenced the temperature dependence of helicity degree.     

A nonsense mutation in the erythrocyte band 3 gene associated with decreased mRNA accumulation in a kindred with dominant hereditary spherocytosis

We studied a French kindred with typical hereditary spherocytosis (HS). Studies of erythrocytes and erythrocyte membranes from HS individuals revealed abnormal erythrocyte membrane mechanical stability as well as 15-20% deficiency of band 3, the anion transporter. Anion transport studies of red cells from two affected individuals revealed decreased sulfate flux. Nucleotide sequence of cDNA encoding the distal third of the cytoplasmic domain and the entire transmembrane domain of band 3 obtained by RT-PCR of reticulocyte RNA of an affected family member was normal. Sequence analysis of genomic DNA from an HS individual identified a nonsense mutation of the band 3 gene, Q330X, near the end of the band 3 cytoplasmic domain. This mutation was present in genomic DNA of all HS family members and absent in DNA of unaffected family members. Using an RT-PCR-based assay, a marked quantitative decrease in accumulation of the mutant band 3 RNA was detected. Thus the codon 330 nonsense mutation is responsible for the decreased accumulation of mutant band 3 RNA and the deficiency of band 3 protein in this kindred. These results have important implications for the role of band 3 defects in the membrane pathobiology of HS as well as for the techniques used in detection of HS mutations.     

The cellular fatty acid composition of bacteria in the family Vibrionaceae

It is shown that strains of Vibrio cholerae of serovar O1, biovar eltor, subtype Ogawa, museum strains V. cholerae of serovar O1 and NAG-vibrios (isolated from various sources: sea, river and sewage water, canal water and people) possess identical composition of cell fatty acids with prevailing hexadecenoic, hexadecanoic and octadecenoic acids. Being identical, fatty acid profiles of V. parahaemolyticus and V. alginolyticus, are close to that of V. cholerae differing from the latter mainly by the higher content of dodecanoic acid. Similarity of Aeromonas sp. and Vibrio strains in the fatty acid composition proves phylogenetic relation-ship of these bacteria. Fatty acid composition of Plesiomonas shigelloides cells characterized by the presence of methylenhexadecanoic acid as well as by similarity with Vibrio and Aeromonas by the content of most fatty acids confirms a supposition of R. R. Colwell on the intermediate status of genus Plesiomonas between the families Enterobacteriaceae and Vibrionaceae. Independent of the growth medium, the strains Vibrio. Aeromonas and Plesiomonas preserved a fatty-acid profile, inherent in them, with variations mainly in the content of fatty acids with the odd number of carbon atoms. Allowing for relative stability of fatty acid composition and its peculiarity in certain taxonomic groups of the studied bacteria, the above test may be used as additional objective criterion to identify the representatives of Vibrionaceae family.     

Modification of ceftibuten transport by changes in lipid fluidity caused by fatty acid glycerol esters

The authors previously observed that schizophrenic patients generated fewer fixations of < or = 50.1 ms in response to faces than did a clinical control group. This study examined whether deficits in short-duration eye movements were related to patients' problems in gestalt perception of faces. Faces were presented in upright and inverted orientations to examine the effects of distorting facial gestalts on eye movements. Normal subjects generated more saccades of < or = 50.1 ms to upright than to inverted faces. Patients' saccades of < or = 50.1 ms did not differ between orientations. Patterns of fixations and of saccades > 50.1 ms did not differ between groups. The results may indicate deficits in these patients in search strategies that underlie perception of facial gestalts.     

Association of serum hemolytic complement levels with the major histocompatibility complex in chickens

The total hemolytic complement (C) levels in inbred line 7 chicks and adults were lower than C levels in inbred lines 2 and 3 and in outbred chickens of the same age. In all birds, adult levels of C were obtained in 5- to 6-wk-old chickens. Analysis of F1 and F3 generations clearly showed that the C level in chickens was determined by a dominant gene(s) associated with the major histocompatibility complex. Finding this association in a nonmammal strengthens the importance of the relationship between closely linked genes controlling histocompatibility, immune responsiveness, mixed leukocyte reaction, and C activity.