T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.      

Arylsulfatase A in urine of patients with urothelial tumors

A significant increase in urine arylsulfatase A activity (p less than 0.01) was found in patients with urothelial tumors. Arylsulfatase A activity was 1.36 +/- 1.10 U/24-h urine in control specimens, 1.90 +/- 1.66 U/24-h urine in various genitourinary tract disorders, and 3.90 +/- 1.98 U/24-h urine in transitional cell carcinoma specimens. Surgical treatment of the neoplastic patients lowered the arylsulfatase A activity found in urine to within reference values. The arylsulfatase A excreted by patients with these tumors was highly sensitive to thermal inactivation while the enzyme activity in the control urines was less affected by the heat treatment. The time course of the arylsulfatase A reaction with 4-nitrocatechol sulfate was not linear in normal individuals, while it was linear in 90% of patients with urothelial tumors. This difference in the kinetic pattern of the enzyme could be used to increase the diagnostic specificity of the determination.     

Detection of a vascular permeability factor in the extracellular products of Renibacterium salmoninarum.

The presence of vascular permeability factors in the extracellular products (ECP) of 10 strains of Renibacterium salmoninarum with different geographical origin and serological characteristics are reported. All the ECP produced haemorrhagic and/or oedematous zones at the injection site with a diameter ranging from 10-30 mm. However, the ECP samples did not display toxic effect in fish at the same dose as inoculated in rabbit (180-400 micrograms protein/0.1 ml). No differences were observed in the production of this dermatotoxic factor between the two antigenic groups found in this microorganism. Whereas heating (80 and 100 degrees C/15 min) the ECP samples resulted in a complete loss of their proteolytic activity, only a decrease (but not total inactivation) of the dermatotoxic effects was detected. Therefore, although proteases could be implicated in the permeability factor, they are not totally responsible for this activity.     

Hereditary protein C deficiency and portal-vein thrombosis

Inherited defects of the natural coagulation inhibitors predispose patients to thrombosis. These disorders have similar clinical presentations with a strong family history of thrombosis, episodes of recurrent venous thromboembolism, beginning in early adulthood. We report a case of upper gastrointestinal bleeding in a patient with portal hypertension due to portal-vein thrombosis secondary to hereditary protein C deficiency, an association that has seldom been reported.     

Choledochoenterostomy with an anti-reflux mechanism

A new technique of choledochoenterostomy was devised to solve some of the problems of enterobiliary anastomosis with a normal calibre. The distal extremity of the common bile duct is completely surrounded by the bowel mucosa to a length of 3 cm after seromyectomy of a bowel wall rectangle of 4 × 1 cm. Experimental studies in rats and dogs demonstrated that this procedure prevents the risks of anastomotic disruption and functions like a mechanical unidirectional valve, which has great efficacy in stopping enterobiliary reflux. Studies in ten patients with obstructive jaundice with an extrahepatic biliary dilation less than 1.2 cm diameter submitted to this procedure Confirmed the experimental results. All patients were asymptomatic, without jaundice and with normalization of the liver enzymes after 2 months. The permeability of the valvular anastomosis studied by cholangiography, the HIDA ^99mTc test and manometry was quite similar to other classical biliary-enteric anastomosis. In contrast, anti-reflux efficacy was only demonstrated in patients with a valvular anastomosis.     

Intraoperative radiotherapy in the multidisciplinary treatment of bone sarcomas in children and adolescents

From September 1984 to December 1989, 38 patients of pediatric age with localized bone sarcomas received intraoperative radiotherapy (IORT) as part of a multidisci plinary treatment program. The age ranged from 6 to 21 years. The tumor histologies were 22 osteosarcomas and 16 Ewing's sarcomas. Thirty-four had initial primary disease (90%) and 4 were treated for local recurrence (10%). IORT was used on 32 untreated patients and in 6 previously treated with external beam radiotherapy (EBR). The IORT field included the surgically exposed tumor bed area. Single radiation doses ranging from 10 to 20 Gy were delivered, using 6–20 MeV electron beams. The median follow-up time for the entire group is 25 months (2–65+ months). The projected 5-year disease-free and overall survival rates are 65% and 69%, respectively. One patient developed a local recurrence in each histological group: one chondroblastic osteosarcoma and one cervical Ewing's sarcoma. Six patients died from metastatic progression: 3 initially recurrent tumors and three primary disease cases. Severe neuropathy and soft tissue necrosis were seen in some patients as IORT related complications. IORT is a feasible technique to be integrated in multidisciplinary programs that may promote local control in pediatric and adolescent patients with bone sarcomas. Peripheral nerves are dose-limiting tissue structures for IORT.