Heterogeneity of proteoglycans extracted before and after collagenase treatment of human articular cartilage. I. Physical properties related to age

Proteoglycans were isolated from young and mature human articular cartilage 4 different ways: by direct extraction with 4M guanidine hydrochloride (GuHCl); after digestion of the residue from this first extraction with collagenase, by extraction with 4M GuHCl; associatively with 0.5M GuHCl after digestion of the cartilage with collagenase; and dissociatively with 4M GuHCl after digestion of the cartilage with collagenase. The structural properties of these proteoglycans were compared. Proteoglycan aggregates and monomers isolated from second extractions and from young cartilage were of larger hydrodynamic size than proteoglycans isolated from first extractions and mature cartilage, respectively. The same applied to the chondroitin sulfate chain lengths of these proteoglycans. The proteoglycan fraction from second extractions of cartilage contained a larger proportion of monomers than the fraction from first extractions. Associative extraction of mature collagenase-digested cartilage yielded mainly proteoglycan monomers, whereas an appreciable amount of proteoglycan aggregate was also liberated from young collagenase-digested cartilage. Our results indicate that, because of their larger size, proteoglycans from second extractions of cartilage are more entrapped in the collagen network. These large proteoglycans can only be liberated from the matrix after extraction of the smaller proteoglycans, followed by digestion of the residue with collagenase. This indicates that proteoglycans overlap and entangle with the collagen and protect it from degradation by collagenase.     

Epithelioid hemangioendothelioma of the liver following contact with vinyl chloride. Recurrence after orthotopic liver transplantation

Malignant epithelioid hemangioendothelioma of the liver is a recently recognized and uncommon neoplasm of vascular origin. Few cases have been reported and the treatment remains therefore difficult to define. A relationship to oral contraceptive use has been suggested but no other toxic agents have been incriminated. We report here the first case occurring after a close contact with vinyl chloride. Because of wide hepatic destruction and serious portal hypertension with bleeding varices, the patient underwent orthotopic liver transplantation. After a disease-free interval of 20 months, he died from variceal hemorrhage and encephalopathy due to local tumor recurrence with portal thrombosis. Nevertheless, orthotopic liver transplantation remains the only hope of salvage when extensive liver destruction and life-threatening complications are present.     

Bilateral renal artery embolization in a case with severe proteinuria secondary to amyloidosis in a hemodialysis patient

Amyloid-associated protein (secondary, reactive) amyloidosis occurs most frequently as a complication of chronic inflammatory disease. Renal involvement with amyloidosis is common and proteinuria is often the first symptom. We submit a case with severe proteinuria and hypoalbuminemia, and end-stage renal disease secondary to bronchiectasis-related amyloidosis. Bilateral embolization of the renal arteries was performed to prevent loss of albumin.     

Apoptosis induced in neuronal cultures by either the phosphatase inhibitor okadaic acid or the kinase inhibitor staurosporine is attenuated by isoquinolinesulfonamides H-7, H-8, and H-9

Protein phosphorylation is kept in balance by an orchestrated action of kinases and phosphatases; when this balance is lost, neuronal apoptosis may occur. Okadaic acid (OKA), a marine toxin that inhibits specifically protein phosphatases 1 and 2A (EC 3.1.3.16), and staurosporine, an inhibitor of protein kinase C (PKC; EC 2.7.1.37), induced apoptosis in primary cultures of rat cerebellar granule neurons. We assayed apoptosis by the DNA gel electrophoresis, by thein situ TUNEL assay, and by morphological appearance following propidium iodide staining. Cell viability was assessed by the Trypan blue assay. Both OKA- and staurosporine-induced neuronal apoptosis were prevented by a macromolecular synthesis inhibitor actinomycin D and by a group of isoquinolinesulfonamide kinase inhibitors (H-7, 1-[5-isoquinolinesulfonyl]-2-methylpiperazine; H-8, N-{2-[methylamino]ethyl}-5-isoquinolinesulfonamide; H-9, N-(2-aminoethyl)-5-isoquinolinesulfonamide, but not by inhibitors of PKC, cyclic-GMP- and cyclic-AMP-dependent kinases, calcium/calmodulin-dependent kinases, tyrosine kinases, or by antioxidants. We postulate that a common mechanism, possibly an increased protein phosphorylation, is responsible for apoptosis triggered by an inhibition of phosphatases 1 and 2A and PKC. Elucidating the isoquinolinesulfonamide-sensitive mechanism may help us find new therapies for neurodegenerative diseases that involve apoptosis.     

Tumor-Simulating Thoracic Extramedullary Hematopoiesis

Two patients with massive, tumorsimulating extramedullary hematopoiesis are presented. In 1 patient with homozygous β-thalassemia, a progressive paraparesis developed because of a mass of ectopic marrow in the spinal epidural space. Surgical removal and radiotherapy were successful. The second patient, who died during surgical biopsy, had posterior mediastinal masses without any apparent cause. A correct preoperative diagnosis may avoid unnecessary surgical intervention. It is suggested that heterotopic marrow should be included in the differential diagnosis of a mass in the lower thoracic region.