No abstract

The processes leading to morphological changes of the chromatin in cells that undergo apoptosis are presently unclear. We have recently shown that chromatin fragmentation and the nuclear morphological changes typically seen in apoptosis were reproduced in an in itro system comprised of isolated rat thymocyte nuclei incubated in the presence of a lysate from Fas\APO-1-stimulated JURKAT cells [Chow, Weis, Kass, Holmstro$ m, Eriksson and Orrenius (1995) FEBS Lett. 364, [134][135][136][137][138]. Using this in itro system, we now report that the presence of ATP is necessary for chromatin condensation, its movement to the nuclear periphery and apoptotic body formation. In clear contrast, chromatin cleavage into high-molecular-mass and oligo-

The effects, over periods from 3 days to 9 months of administration, of diets containing di-2-ethylhexyl phthalate are very similar to those observed in rats administered diets containing hypolipidemic drugs such as clofibrate. Changes occur in a characteristic order commencing with alterations in the distribution of lipid within the liver, quickly followed by proliferation of hepatic peroxisomes and induction of the specialized P450 isoenzyme(s) catalyzing w oxidation of fatty acids. There follows a phase of mild liver damage indicated by induction of glucose-6-phosphatase activity and a loss of glycogen, eventually leading to the formation of enlarged lysosomes through autophagy and the accumulation of lipofuscin. Associated changes are found in the kidney and thyroid. The renal changes are limited to the proximal convoluted tubules and are generally similar to changes found in the liver. The effects on the thyroid are more marked. Although the levels of thyroxine in plasma fall to about half normal values, serum triiodothyronine remains close to normal values while the appearance of the thyroid varies, very marked hyperactivity being noted 7 days after commencement of treatment, this is less marked at 14 days, but even after 9 months treatment there is clear cut evidence for hyperactivity with colloid changes which indicate this has persisted for some time. Straight chain analogs of di-2-ethylhexyl phthalate, di-n-hexyl phthalate and di-n-oxtyl phthalate differ entirely in their short-term effects on the liver and kidney but have similar effects on the thyroid.The short-term in vivo hepatic effects of the three phthalate esters can be reproduced in hepatocytes in tissue culture. All three phthalate esters, as well as clofibrate, have early marked effects on the metabolism of fatty acids in isolated hepatocytes. The nature of these changes is such as to increase storage of lipid in the liver. A hypothesis is presented to explain the progress from these initial metabolic effects to the final formation of liver tumors.

The mechanism of Fas antigen-induced hepatocyte apoptosis was investigated. Using a monoclonal antibody directed against the Fas antigen, apoptosis was induced in freshly isolated murine hepatocytes within 90 minutes of antibody addition as assessed by plasma membrane bleb formation, chromatin condensation, and DNA fragmenta-

A 59-year-old man with no known past medical history presented to the emergency department with dyspnea, abdominal pain and malaise.Clinical assessment revealed hypoxia with bibasal crepitations on chest auscultation. A chest radiograph showed extensive bilateral air space opacification involving all zones. He was hospitalized with suspicion of infection with the novel coronavirus, SARS-CoV-2, later proven by positive RT-PCR. Blood tests showed multi-organ failure with deranged liver function tests (alkaline phosphatase 611 IU/L, alanine aminotransferase 208 IU/L, gamma-glutamyl transferase 435 IU/L), acute kidney injury (serum creatinine 197 μmol/L), and raised inflammatory markers (C-reactive protein 137 mg/L, ferritin 3303 μg/L). His blood count showed a hemoglobin concentration of 109 g/L, platelet count of 921 × 10 9 /L and total white cell count of 9.8 × 10 9 /L with a neutrophil count of 8.5 × 10 9 /L, and a lymphopenia of 0.9 × 10 9 /L. His blood film showed atypical lymphocytes that appeared reactive. Prominent among these were lymphoplasmacytoid lymphocytes with an eccentric nucleus, deeply basophilic cytoplasm and a prominent paranuclear hof (top and bottom left, ×100 objective). Lymphocytes with prominent cytoplasmic inclusions (Mott cells) were also seen (bottom right). The patient was treated with supplementary high-flow oxygen, intravenous antibiotics and intravenous fluids. He recovered and became oxygen-independent on day 9 post-admission, and was discharged on day 10. The newly emerged pandemic caused by this novel coronavirus presents a challenge to health services across the world. In studies reported from China, lymphopenia was observed in 72 and 85% of patients 1,2 with reduced numbers of T cells (CD4-positive and CD8-positive), B cells and natural killer (NK) cells. 1 A favorable clinical course correlated with an increasing lymphocyte count and improvements in B cell numbers and CD8-positive T cell numbers; multivariate analysis showed an adverse significance of reduced B cells, reduced CD8-positive T cells and an increased CD4/CD8 ratio during the course of the illness. 1