Electrophoretic analysis of glycoprotein enzymes in the sialidoses and mucolipidoses

Ten enzymes, all known to be glycoproteins, were examined by electrophoresis or gel isoelectric focusing in 12 different patients with primary or secondary sialidase deficiency. Aberrant electrophoretic mobilities of many of the enzymes attributable to abnormal sialylation were found in all the patients. In ten of the patients seven of the enzymes were affected. The unaffected enzymes were β -galactosidase, alkaline phosphatase and β -glucuronidase. In the cells from the two patients with I cell disease (mucolipidosis II) in which sialidase is one of many deficient enzymes, β -galactosidase, α -galactosidase, α -fucosidase and α -mannosidase were undetectable, alkaline phosphatase showed a normal electrophoretic mobility and acid phosphatase, adenosine deaminase, α -glucosidase and β -D- N -acetylhexosaminidase showed aberrant mobilities.     

Decreased responsiveness to immune complexes of granulocytes from patients with acute leukemia in remission demonstrated by microcalorimetry

Functional activity of granulocytes from healthy individuals and from patients with acute leukemia in remission was studied. The increase of heat production rate (metabolic activity) after stimulation of the blood cells with in vitro formed immune complexes was measured by microcalorimeters of heat conduction type. It was demonstrated that increased heat production rate after exposure to immune complexes was significantly lower (p<0.0005) in 9 patients with acute leukemia with a remission duration of less than 6 months than in 25 healthy volunteers.     

Fc-Gamma receptor III shedding by polymorphonucIear cells in primary Sjögren's syndrome

Abstract. A sandwich enzyme-linked immunosorbent assay was developed to assess Fc-gamma receptor III (Fc γ RIII), based on a combination of two non-competing monoclonal antibodies. This receptor was detectable in the serum of eight out of 23 patients with primary Sjögren's syndrome and two out of 23 normal controls. The proportion of FcγRIII-carrying polymorphonuclear (PMN) cells was lower (P < 0.05) in the patients with cell-free Fc γ RIII (90·4 ± 7.5%) than in the remainder (84.8 ± 8.3%). The PMN cell functions were evaluated and the diminished adherence (71.7, geometric mean) and chemotaxis (1.23) paralleled the Fc γ RIII release. The relative inefficiency of PMN cells in SS might be due to phagocytosis of immune complexes.     

CASE REPORT: Steatonecrosis in the upper abdomen following transcatheter arterial embolization for hepatocellular carcinoma

A 66-year-old female with liver cirrhosis was treated by transcatheter arterial embolization (TAE) for a small hepatocellular carcinoma. She developed steatonecrosis with tenderness which occurred in the upper abdomen after TAE. The hepatic falciform artery from the middle hepatic artery was detected by arteriography. Necrosis in the upper abdomen was considered to be due to ischaemic changes caused by micromaterials for embolization of this artery, injuries of hepatic arterial endothelia slowly caused by carcinostatics, and chemotoxicity. It was considered that such complication as observed in this patient should be taken into consideration when performing TAE.     

Data on the HL-A linkage group

Lod scores from a study in 229 families of the linkage relations of HL-A-PGM3 to 19 marker loci and cystic fibrosis are reported. The data exclude that ADA belongs to this linkage group while they give weak support for the inclusion of P. There is weak evidence for linkage of cystic fibrosis to PGM3, but none for linkage to HL-A. No new suggestive linkages appeared.     

The Postmortem Changes of Pyramidal Neurons in the Hippocampus of Rats

The postmortem changes (0.5, 1, 2, 3, 5, 7 and 10 hours) in pyramidal neurons of the area CAI of the hippocampus of rats have been studied with the light and electron microscope. 1. (light microscopy) In the pyramidal neurons that have undergone 0.5- and 1-hour postmortem autolysis (postmortem autolysis for 0.5 and 1 hours), no remarkable changes were found. In the neurons which had undergone 2- or 3-hour postmortem autolysis, nuclei were slightly edematous and the perineuronal spaces were slightly disintegrated. In the neurons which had undergone more than 5-hour postmortem autolysis, these changes were more prominent. 2. (electron microscopy) The aggregation of the nuclear chromatin was already observed in the neurons which had undergone 0.5- or 1-hour postmortem autolysis. In the cytoplasm, the swelling of mitochondria, Golgi vesicles and the disintegration tion of myelin sheath were partly observed in the neurons which had undergone 0.5-hour postmortem autolysis. Within 1-hour postmortem period, the dilatation of the endoplasmic reticulum in the neurons and the swelling of the processes of astrocytes were distinguishable. These alterations proceeded gradually in the course of time. With regard to the postmortem changes, the autolysis and the other artefacts such as pH, osmolality and concentration of the fixative and hypoxic or ischaemic factor were discussed.     

A possible mechanism of toxicity by the antidepressant amoxapine based on its effects in three in vitro models

When the antidepressant amoxapine is taken in overdose, it can cause metabolic acidosis, brain damage and sometimes death. In previous studies, biochemical evidence has been presented that amoxapine disrupts reactions of membrane-associated multi-enzyme complexes, and mitochondrial energy conservation may be one of the first systems affected. Three in vitro systems were investigated to determine whether general membrane disruption or more specific mitochondrial effects of amoxapine could be responsible for toxicity and for lactic acid accumulation. In Saccharomyces cerevisiae, increased amoxapine concentrations led to decreased oxygen uptake associated with decreased survival of cells. In Chinese hamster ovary cells in culture, an initial increase in oxygen uptake was observed up to 10 μg amoxapine/ml and a decrease thereafter. At drug levels that caused an increased oxygen uptake, there was increased lactic acid output by cells, but no observable toxicity. At higher drug levels, the decreased oxygen uptake was accompanied by cell death, reduced lactic acid output and a change in the mitochondrial cristae configuration. Cell death in both of the above systems was attributed to interference with energy conservation. Isolated, beating guinea-pig hearts perfused with 5 μg amoxapine/ml stopped after 13 min, but no lactic acid accumulated. This may be explained by the membrane-stabilizing activity of the drug. In an arrested perfused heart, increased concentrations of amoxapine stimulated oxygen consumption and lactic acid production. Hence, membrane-stabilizing activity alone is not adequate to explain the action of amoxapine on isolated cells, and on the perfused arrested heart, or the clinical pattern of overdose, and disruption of energy conservation in cells is likely to be involved also.     

Antibodies to human T-cell lymphotropic virus type III in promiscuous healthy homosexual men. Relation to immunological and clinical findings

Antibodies to human T-cell lymphotropic virus type III (HTLV-III Ab) were present in twenty-one out of sixty-four asymptomatic promiscuous homosexual men from Copenhagen. The presence of HTLV-III Ab was associated with lymphadenopathy (P less than 0.0005), cytomegalovirus isolation (P less than 0.01), low skin test reactivity (P less than 0.01) and episodes of fever within the 2 month period prior to investigation (P less than 0.05). No significant differences occurred in the total number of T-cells, T-suppressor cytotoxic cells, T-helper cells or helper to suppressor ratio (H/S ratio) between HTLV-III Ab positive and negative homosexuals. An H/S ratio less than or equal to 1.0 was significantly more frequent in homosexual men who both had HTLV-III Ab and excreted cytomegalovirus (P less than 0.01). The H/S ratio of HTLV-III negative homosexuals were significantly lower than that of the controls suggesting that a non-HTLV-III related immunosuppression occurs among homosexuals. Within 2 years after the investigation AIDS or the AIDS related complex developed in three of the men, who at the first investigation all had HTLV-III Ab, alterations in T-lymphocyte subsets and cutaneous anergy. It is suggested that a combination of T-cell subset determination and determination of HTLV-III Ab may provide more valuable prognostic information than isolated determination of HTLV-III Ab.     

RE-EVALUATION OF THE SA GENE IN SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

1. To investigate whether the difference in the SA gene expression in the kidneys is causally related to the pathogenesis of hypertension, we reassessed the expression of the SA gene in the kidneys of the spontaneously hypertensive rat (SHR), its stroke-prone substrain (SHRSP) and Wistar-Kyoto (WKY) rat from different sources (SHR/Izm, SHRSP/Izm and WKY/ Izm from Izumo colony; SHR/Crj and WKY/Crj from Charles River Laboratories). 2. At the age of 5 weeks, high levels of the SA mRNA were expressed in the kidneys of SHRSP/Izm, SHR/Izm, SHR/Crj and WKY/Izm, while very low levels of the SA mRNA were observed in those of WKY/Crj. At the age of 8 weeks, the expression of the SA mRNA in the kidneys of WKY/Izm was at the same level as in those of SHRSP/Izm and two SHR strains. 3. Four genetic markers at the SA locus, an StuI restriction fragment length polymorphism and three microsatellite markers, were not polymorphic among Izumo strains of SHR, SHRSP and WKY rats. 4. In situ hybridization showed strong signals of the SA mRNA in the renal proximal tubules, while no positive signals were detected in the glomeruli. 5. Because WKY/Izm has normal blood pressure, our observations indicate that a simple difference of the SA gene expression in the kidney cannot be an explanation for the difference of blood pressure between SHR(SP)/Izm and WKY/Izm.     

EXPERIMENTAL BILATERAL CAROTID ARTERY OCCLUSION: A STUDY OF THE OPTIC NERVE IN THE RAT

The presence of marked changes in the neural retina and retinal vessels of Long-Evans pigmented rat following bilateral carotid ligation has been previously documented by serial ophthalmologic examinations. Light and electron microscopic studies of the optic nerve in this experimental animal model revealed advanced optic nerve atrophy in ten of twelve rats examined. There was no significant pathology in either the retina or optic nerve in the remaining two rats after carotid ligation or in the sham-operated controls.