Reversibility of organic anion-induced cholestasis: Association with compensatory hypersecretion of biliary phospholipid and protein in the dog

Abstract The effect of a concomitant infusion of organic anions, structurally related phthaleins, on bile flow was studied in anaesthetized dogs. A combination of rose bengal and sulfobromophthalein was found to uniquely and synergistically produce an acute, reversible form of intrahepatic cholestasis (< 10% of control level). This phenomenon was not observed with the administration of those individual organic anions at concentrations previously associated with the induction of intrahepatic cholestasis. The infusion of either a micelle forming bile salt, sodium taurocholate, or a non-micelle forming bile salt, sodium dehydrocholate, rapidly reversed the intrahepatic cholestasis (within 20 min after bile salt infusion). During the choleretic phase immediately following the bile salt infusion, a transient but marked hypersecretion, a disproportionately increased output in relation to that of bile acids, of biliary phospholipid (176% of control level by taurocholate and 138% of control level by dehydrocholate), and an even more striking amount of biliary protein hypersecretion were observed (392% of control level by taurocholate and 357% of control leverl by dehydrocholate). Although the significance of these new post-cholestatic observations requires clarification, it is suggested that the intrahepatic cholestasis induced by organic anions reflects a reversible defect in the mechanism(s) involved in transcellular transport.     

Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on respiratory burst activity of neutrophiis in patients with myelodysplastic syndromes

The superoxide (O₂-releasing capacity in response lo N-fomiyl-methionyl-leucyl-phenylalanine (FMLP)and the priming effects ofrecombinant human granuloeyte colony-stimulating factor (rhG-CSF) and granulocyte-macrophage colony-stimulating faclor (rhGM-CSF) on FMLP-induced O₂ release were investigated in neutrophils from 14 patients with myelodysplastic syndromes (MDS). The O₂ -releasing capacity in MDS neutrophils varied from patient to patient. As compared with normal neutJ-ophils. theO₂-releasing capacity in MDS neutrophils was increased in 9/14 patients, nonnal in three patients and decreased in two patients. There was no close relationship between the 02-reIeasing capacity and the peripheral blood neutrophil count or the plasma concentration of C-reactive protein. The priming of neutrophils by rhG-CSF was not observed in five patients, whereas rhGM-CSF primed neutrophils from all patients. The priming eflect of rhGM-CSF was consistently greater than that of rhG-CSF in each patient. The intravenous administration of rhG-CSF (300 μg/body) to two MDS patients showed an increase in the peripheral blood neutrophil count and enhancement of neutrophil O₂ release. These findings demonstrate that the neutrophil O₂-releasing capacity in MDS varies from patient to patient and is not always impaired, and that rhGM-CSF is able to prime neutrophils which never respond to rhG-CSF.     

An estimation of human bile metastability: Clinical application of a sensitive cholesterol crystal growth assay

The formation of cholesterol monohydrate crystal initiates cholesterol gallstone formation. The nucleation time (NT), a light microscopy method, is used currently to estimate human bile metastability. Recently, a cholesterol crystal growth (CCG) assay utilizing photometric turbidity to quantitate cholesterol crystallization was developed using model bile systems. The object of this study was to determine whether this novel CCG assay was applicable to the quantitative assessment of native human bile metastability. Human gall-bladder bile samples were collected from patients undergoing cholecystectomy. There were five patients with cholesterol gallstone and five stone-free patients. A significant correlation between the onset time measured by the CCG assay and the NT observed by light microscopy was found in our modified assay condition where interference by bilirubin was negligible (P < 0.01). Also, the growth rate measured by the CCG assay significantly correlated with the NT (P < 0.05). These results indicate that the CCG assay is applicable to quantitative assessment of human bile metastability reflected by cholesterol crystal nucleation and that the cholesterol crystal growth is also conveniently estimated by this method.     

Immunological studies on aphthous ulcer and erythema nodosum-like eruptions in Behcet''s disease

Patients with Behcet's disease show an intense delayed hypersensitivity (DH) reaction to a group of streptococcal bacteria. We have attempted to detect deposits of immune complexes and to analyse cytological reactions in the aphthous ulcers and erythema nodosum (EN)-like eruptions. Deposits of IgM and positive fluorescence of anti-streptococcal group D serum were found in vessel walls and sites infiltrated by inflammatory cells. Cytological analysis has revealed that the inflammatory infiltrating cells are mainly composed of activated T-cells and macrophages in association with natural killer cells. These results suggest that DH reactions with antigen-antibody mediated cytotoxicity may play an important role in causing the lesions of Behcet's disease.     

Interferon therapy for Japanese hemophiliacs with chronic hepatitis C

Eight Japanese hemophiliacs with chronic hepatitis C (CHC) received interferon (IFN) therapy and four of them (50%) responded completely. Non-responders included 3 double-infected patients: I with hepatitis B virus (HBV) and 2 with human immunodeficiency virus-1 (HIV-1). In one of the patients with HIV-1 double infection, the absolute number of CD4* lymphocytes decreased during IFN therapy. These findings suggest that hemophiliac patients with CHC can respond well to IFN therapy, but in patients who are double-infected with HBV and HIV-1, the indication of IFN therapy should be considered seriously.     

Bile acid-induced depolarization of mitochondrial membrane potential preceding cell injury in cultured gastric mucosal cells

Changes in energy metabolism elicited by sodium taurocholate and their relation to cell viability were determined in gastric mucosal cells. Cultured mucosal cells were labelled with rhodamine-123, a mitochondrial energization-sensitive fluorescence probe, or by propidium iodide, a fluorochrome which labels the nuclei of non-viable cells. The cells were observed under a fluorescence microscope with a laser scanning confocal imaging system. After the addition of sodium taurocholate at concentrations > 5 mol/L, mucosal cells showed a rapid and significant decrease in rhodamine-123 fluorescence. A decrease to 40% of the pretreated values at 30 min was seen with a concentration of sodium taurocholate of 7.5mmol/L. A marked increase in the percentage of propidium iodide-positive cells was noted when the concentration of sodium taurocholate exceeded 5mmol/L. However, the extent of the decrease in rhodamine-123 fluorescence was always greater than the increase in the percentage of propidium iodide-positive cells, suggesting that most of these gastric mucosal cells remained viable. It is therefore suggested that the decrease in rhodamine-123 fluorescence is largely due to the disturbed oxidative phosphorylation of mitochondria. Pretreatment of gastric mucosal cells with low concentrations of ethanol resulted in a significant cytoprotective effect against sodium taurocholate injury with significant prevention of a decrease in rhodamine-123 fluoresence. It is concluded that sodium taurocholate induces a depolarization of the mitochondrial membrane potential preceding cell injury and that the cytoprotective effect of ethanol relates to its attenuation of the uncoupling effect.     

Correlation of the hypo-osmotic swelling test, semen score and the zona-free hamster egg penetration assay in humans

The correlation between the hypo-osmotic swelling test, the modified Eliasson score for human semen analysis and the hamster egg penetration assay was examined. The results showed a weak but significant correlation between the group of subjects with swelling rates below 50% and the above 80% group. These groups showed hamster egg penetration assay rates of 9 +/- 14% and 39 +/- 29%, respectively (P less than 0.035). A significant correlation was also found between modified Eliasson scores (17 +/- 10 and 5 +/- 7, respectively) and swelling rates below 50% and above 70% (P less than 0.001). These results suggest that spermatozoa showing a low swelling rate have a poor fertilizing capacity. Therefore, the swelling tests and analysis of the patients semen can be used to discriminate sperm quality.     

Triphalangeal Thumb in the Typical Cleft Hand

Abstract Ten hands of six patients with only a single digit retained on the radial side of the cleft were observed from a group of 63 patients with typical cleft hand. All patients were bilaterally involved, and five were complicated with cleft foot. There were two types of retained thumb: a triphalangeal thumb with characteristic metacarpal bone(s), six hands of four patients; and a normal diphalangeal thumb, four hands of two patients. The metacarpal and distal phalangeal bone(s) of the triphalangeal thumb in typical cleft hand had signs of digital ray union: double epiphysis, deltametacarpal, bifurcated or perforated distal phalanx.     

Hyperactivation of Human Spermatozoa: Measurement of Motility before and after Incubation

The motility rate of sperm during capacitation process was determined by calculating a sperm motile efficiency index (SMEI) using a hemocytometer. The SMEI values for the sperm from 100% of normal fertile men and 64% of infertile patients increased significantly by the fourth hour of incubation, while for 36% of infertile patients there was no increase. A correlation between the increase of SMEI and original motility, original SMEI and original semen amount was not possible. In addition, a decrease of the SMEI value was observed after sperm incubated for 3 hours were added to the seminal plasma of the donor. It is concluded that in human spermatozoa "hyperactivation and dehyperactivation" can be measured by SMEI.