Molecular and functional analysis of the human prothrombinase gene (HFGL2) and its role in viral hepatitis

In the present studies, we report the cloning and structural characterization of the HFGL2 gene and its functional role in human fulminant hepatitis. The HFGL2 gene is approximately 7 kb in length with 2 exons. The putative promoter contains cis element consensus sequences that strongly suggest the inducibility of its expression. From the nucleotide sequence of the human gene, a 439-amino acid long protein is predicted. The overall identity between the murine fgl2 and hfgl2 coded proteins is over 70%. About 225 amino acids at the carboxyl end of these molecules are almost 90% identical, and correspond to a well-conserved fibrinogen-related domain. Both HFGL2 and FGL2 encode a type II transmembrane protein with a predicted catalytic domain toward the amino terminus of the protein. Transient transfection of Chinese hamster ovary (CHO) cells with a full-length cDNA of HFGL2 coding region resulted in high levels of prothrombinase activity. Livers from 8 patients transplanted for fulminant viral hepatitis were examined for extent of necrosis, inflammation, fibrin deposition, and HFGL2 induction. In situ hybridization showed positive staining of macrophages in areas of active hepatocellular necrosis. Fibrin stained positively in these areas and was confirmed by electron microscopy. These studies define a unique prothrombinase gene (HFGL2) and implicate its importance in the pathogenesis of fulminant viral hepatitis.     

Investigation of the idiotypic determinants of IgM monoclonal proteins associated with neuropathy

Occasionally IgM monoclonal proteins (MP) from benign gammopathies bind neural antigens and have been associated with demyelinating peripheral neuropathy. A monoclonal antibody (McAb) has been raised against a cross-reactive idiotypic determinant expressed by three out of 12 MP with specificity for neural antigens. The determinant recognised by this MoAb is only expressed when both H and L chain are properly associated. The idiotypic determinant was not expressed by 130 MP randomly selected from patients without neuropathy nor in polyclonal immunoglobulin preparations obtained from healthy individuals.     

Delayed cutaneous hypersensitivity reaction: complication of lymphangiography

An unusual delayed hypersensitivity skin reaction developed after lymphangiography to stage the patient's adenocarcinoma of the prostate.     

Exaggerated phosphaturic response to volume expansion in patients with essential hypertension.

1. Tubular handling of sodium in hypertensive patients has been evaluated with urinary phosphate excretion used as a marker for proximal tubular reabsorptive capacity. 2. Nine hypertensive patients and nine normal control subjects were studied during sustained water diuresis and the intravenous infusion of isotonic sodium chloride solution to produce volume expansion. 3. In the hypertensive patients there was exaggerated phosphaturia, natriuresis and enhanced distal delivery of sodium. Sodium reabsorption in the diluting segment was normal. 4. The enhanced distal delivery and augmented phosphaturia suggest that a decreased reabsorption of sodium in the proximal tubule is the most likely explanation for the exaggerated natriuretic response to volume expansion in hypertensive patients.     

Effects of para-chlorophenylalanine and 5-hydroxytryptophan on mouse killing behavior in killer rats.

The effects of para-chlorophenylalanine (PCPA) on mouse killing behavior were examined in natural killer rats. Forty-eight hr after injection, this serotonin synthesis inhibitor, at relatively low doses of 75 and 150 mg/kg, facilitated mouse killing, as indicated by a decrease in latency to attack the mouse. This effect was revealed in a test of satiation, in which five successive mice were presented to the rat, and also in a novel cage situation. Other than the shorter latencies to attack and kill mice, the killing response was similar in topography to the natural kill. The increase in killing after PCPA injection was associated with a reliable reduction in brain serotonin and in 5-hydroxyindoleacetic acid, and the time courses of the behavioral and biochemical changes were generally similar. In contrast to PCPA, injection of the serotonin precursor 5-hydroxytryptophan (5-HTP, 100 mg/kg) reliably lengthened attack and kill latencies in killer rats. In rats pretreated with PCPA, 5-HTP not only reversed this drug's facilitation of killing, but completely blocked killing in 67% of the rats tested. These results strengthen the hypothesis that brain serotonergic neurons are involved in the inhibition of mouse killing.