A distinctive composite lymphoma consisting of clonally related mantle cell lymphoma and follicle center cell lymphoma.

Although follicle center cell lymphoma and mantle cell lymphoma are both B cell non-Hodgkin's lymphomas (NHL), they are regarded as separate entities with distinct clinical, morphological, immunophenotypic and molecular characteristics. To our knowledge, the coexistence of these 2 lymphomas in the same patient has never been reported. We describe a 70-year-old woman with a long-standing history of follicle center cell lymphoma, cytological grade I, who subsequently developed a composite lymphoma consisting of well-demarcated foci of persistent follicle center cell lymphoma surrounded by mantle cell lymphoma. This morphological interpretation was supported by the presence of both bcl-1 and bcl-2 gene rearrangements, which are molecular genetic hallmarks of mantle cell lymphoma and follicle center cell lymphoma, respectively. Polymerase chain reaction (PCR) analysis for rearranged immunoglobulin heavy chain (IgH) genes showed a dominant band identical in size in microdissected tumor cells of the follicle center cell and mantle cell lymphomas. Cloning and sequence analysis of the PCR products revealed a common clone-specific IgH gene rearrangement in these 2 lymphomas. These findings suggest that this composite lymphoma represents the unusual evolution of a malignant B-cell clone that resulted in the development of 2 morphologically distinct but clonally related B-cell NHLs. These findings also show the importance of integrating morphological, immunophenotypic, and molecular data to enhance our understanding of the complex pathogenic interrelationships in lymphomagenesis.

Acquired protein S and antithrombin III deficiency caused by nephrotic syndrome: an unusual cause of graft thrombosis.

Thrombotic phenomena are well-recognized complications of nephrotic syndrome attributable to loss of intermediate-sized antithrombotic proteins in the urine, resulting in a hypercoaguable state. As such, nephrotic syndrome may be associated with a reduction in circulating antithrombin III and free protein S levels. Associated spontaneous thrombotic complications are generally venous in nature, with arterial thrombosis occurring less frequently. Hypercoagulability caused by acquired nephrotic syndrome has not generally been recognized as a cause of acute thrombosis of arterial bypass grafts. We report two patients who after having nephrotic syndrome sustained acute thrombosis of their arterial bypass grafts. Pathogenesis and management are discussed.

Cellular attachment to thrombospondin. Cooperative interactions between receptor systems.

Tumor cell attachment to thrombospondin (TSP) in the extracellular matrix may be of critical importance in the processes of invasion and hematogenous dissemination. To determine the specific receptor systems that mediate the interaction of tumor cells with insoluble TSP, the attachment of HT1080 fibrosarcoma and C32 and G361 melanoma cells to TSP-coated discs was studied in the presence of heparin, Arg-Gly-Asp-Ser, or antibodies to glycoprotein (GP) IV (CD36, GPIIIb), a TSP receptor. HT1080 and C32 cell attachment to TSP was inhibited by the combination of heparin and a monoclonal (or polyclonal) antibody to GPIV but not by either alone. Heparin alone inhibited cell spreading. Neither control monoclonal antibodies nor the cell attachment peptide Arg-Gly-Asp-Ser inhibited tumor cell attachment to TSP, alone or in the presence of heparin. HT1080 cells attached equally as well to a 140-kDa proteolytic TSP fragment lacking the heparin-binding domain as to intact TSP. A monoclonal antibody to GPIV alone inhibited tumor cell attachment to the heparin-domainless 140-kDa TSP fragment. No attachment to the heparin-binding fragment was observed, but the addition of the heparin fragment to 140-kDa heparin-domainless TSP restored the heparin sensitivity of binding. G361 cells that lack GPIV attached well to TSP but were not inhibited by heparin or anti-GPIV alone or in combination. The combination of heparin and Arg-Gly-Asp-Ser inhibited G361 attachment to TSP. These studies suggest that tumor cells may utilize separate receptor systems in a cooperative manner to adhere to TSP. HT1080 fibrosarcoma and C32 melanoma cells utilize GPIV in concert with a heparin-modulated binding systems to attach and spread on TSP. G361 cells, which lack GPIV expression, attach and spread on TSP using an integrin system as well as a heparin-modulated system.

Splanchnic amino acid and glucose metabolism during amino acid infusion in dogs.

With the organ-balance technique, we studied amino acid and glucose metabolism by hepatic and extrahepatic splanchnic tissues in awake dogs in the postabsorptive state and during a 3-h intravenous amino acid infusion. Dogs received a high (1.4 g/kg body wt, n = 5) or low (0.7 g/kg body wt, n = 8) dose of amino acids. In four of the latter dogs, the dose was delivered into a mesenteric vein. During the basal period there was a net removal of gluconeogenic amino acids (particularly alanine), but not branched-chain amino acids, and a net production of glucose by the liver in all dogs. During this time there was a net removal of glucose and production of alanine by the extrahepatic splanchnic tissues. During either high- or low-dose amino acid infusion, net hepatic glucose release increased; despite this, arterial plasma glucose declined due to an increase in tissue glucose uptake at extrasplanchnic sites. The net amount of glucogenic amino acids removed by the liver during high-dose (9.1 +/- 1.0 mmol.kg-1.3 h-1) and low-dose (4.8 +/- 0.6 mmol.kg-1.3 h-1) infusion equaled or exceeded the infused load of these amino acids. In addition, the liver contributed to the net disposal of branched-chain amino acids during high-dose (536 +/- 147 mumol.kg-1.3 h-1) and low-dose (341 +/- 70 mumol.kg-1.3 h-1) infusion. During high-dose infusion, extrahepatic splanchnic tissues participated in the net removal of branched-chain amino acids (436 +/- 162 mumol.kg-1.3 h-1) but not glucogenic amino acids, and net alanine production continued (410 +/- 91 mumol.kg-1.3 h-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino acid and glucose metabolism in the postabsorptive state and following amino acid ingestion in the dog.

Amino acid and glucose metabolism was studied in nine awake 18-hour fasted dogs with chronic portal, arterial, and hepatic venous catheters before and for three hours after oral ingestion of amino acids. The meal was composed of a crystalline mixture of free amino acid, containing neither carbohydrate nor lipid. Following the amino acid meal, plasma glucose concentration declined slowly and this occurred despite a rise in hepatic glucose release. Portal plasma insulin rose transiently (30 +/- 7 to 50 +/- 11 microU/mL, P less than 0.05) while the increase in portal glucagon was more striking and persisted throughout the study (162 +/- 40 to 412 +/- 166 pg/mL). Over the three hours following amino acid ingestion, the entire ingested load of glycine, serine, phenylalanine, proline, and threonine was recovered in portal blood as was 80% of the ingested branched chain amino acids (BCAA). The subsequent uptake of these glucogenic amino acids by the liver was equivalent to the amount ingested, while hepatic removal of BCAA could account for disposal of 44% of the BCAA absorbed; the remainder was released by the splanchnic bed. During this time, ongoing gut production of alanine was observed and the liver removed 1,740 +/- 170 mumol/kg of alanine, which was twofold greater than combined gut output of absorbed and synthesized alanine. In the postcibal state, the total net flux of alanine and five other glucogenic amino acids from peripheral to splanchnic tissues (1,480 mumol/kg 3 h) exceeded the net movement of branched chain amino acids from splanchnic to peripheral tissues (590 mumol/kg/3 h).(ABSTRACT TRUNCATED AT 250 WORDS)