Cross-reactive T-cell receptors in tumor and paraneoplastic target tissue.

BACKGROUND: According to established criteria, paraneoplastic encephalomyelitis with adrenal neuroblastoma comprises a definite paraneoplastic neurologic syndrome. OBJECTIVE: To detect T-cell clones that cross-react against antigens shared between tumor and nervous system. DESIGN: Case study. SETTING: Academic research. Patient A 22-year-old woman having paraneoplastic encephalomyelitis with adrenal neuroblastoma. MAIN OUTCOME MEASURES: We compared the T-cell receptor repertoires expressed in blood, cerebrospinal fluid, and neuroblastoma tumor tissue using complementary determining region 3 (CDR3) spectratyping and clone-specific polymerase chain reaction. RESULTS: The T-cell receptor repertoire in cerebrospinal fluid was narrow compared with that in tumor and blood. Four T-cell clones from different tissues had identical T-cell receptor beta chains. Remarkably, the chains showed identical amino acid sequences but different nucleotide sequences. CONCLUSIONS: These T cells represent ontogenetically distinct clones but share functionally identical receptors. They recognize the same antigen in nervous system and tumor tissue and represent an attractive target for selective therapy.

Relation between plasma and cerebrospinal fluid levels of 3-methoxy-4-hydroxyphenylglycol.

Concentrations of free 3-methoxy-4-hydroxyphenylglycol in the plasma and cerebrospinal fluid are highly correlated, but concentrations in the cerebrospinal fluid are always higher than those in plasma, even when large amounts of the catecholamine metabolite are derived from a tumor of the adrenal medulla. This is explained by considering the plasma and cerebrospinal fluid as a two-compartment system in which the rate constants for entry into and exit from the cerebrospinal fluid compartment are similar. 3-Methoxy-4-hydroxyphenylglycol that is synthesized, but not catabolized, in the central nervous system maintains cerebrospinal fluid levels at an increment over those in plasma. This increment can be used to provide the best available index of formation of 3-methoxy-4-hydroxyphenylglycol in the central nervous system.

Central and regional normetadrenaline in evaluation of neurogenic aspects of hypertension: aid to diagnosis of phaeochromocytoma.

1. Free normetadrenaline concentrations in plasma of patients with phaeochromocytoma were elevated 20-1000-fold as compared with values in primary hypertensive subjects. 2. Spinal fluid normetadrenaline was 1.8-16% of the simultaneous plasma values in patients with phaeochromocytoma, whereas levels in spinal fluid exceeded those of plasma in primary hypertension. 3. Spinal fluid noradrenaline was 7.9-58% of simultaneous values of plasma noradrenaline in patients with phaeochromocytoma, whereas values in plasma and cerebrospinal fluid were similar in primary hypertension. 4. Plasma noradrenaline and normetadrenaline levels were both elevated in veins from regions subsequently found to harbour chromaffin tumours. 5. The excessive amounts of normetadrenaline produced in phaeochromocytoma enters plasma but not spinal fluid and can be used for diagnosis and localization of phaeochromocytoma.