Requirement for autologous cancer extracts and lipoxygenation of arachidonic acid for human T-cell responses in leukocyte adherence inhibition and transmembrane potential change assays

Assays of leukocyte adherence inhibition (LAI) and transmembrane potential (delta psi) change were used to examine the responses of T-cells from control subjects and breast cancer patients when incubated with extracts of breast cancer and other tissues. Of T-cells from 25 patients with breast cancer, 21 exhibited delta psi changes or inhibition of adherence to glass when they were incubated with extracts of autologous but not allogeneic breast cancer; extracts of autologous normal breast tissue did not induce delta psi changes or LAI in T-cells from patients with breast cancer. Supernatants were collected after incubating 1 X 10(7) T-cells from patients with breast cancer or from control subjects with extracts of the autologous cancer. When the supernatants were added to either peripheral blood leukocytes or mononuclear cells from normal donors, neither delta psi changes nor LAI were detected. To still determine whether the nonadherence was mediated by chemoattractant lymphokines, the effect of inhibiting T-cell arachidonic acid metabolism was examined. The lipoxygenase pathway antagonist, 5,8,11,14-eicosatetraynoic acid, or a leukotriene antagonist, FPL 55712, inhibited T-cell LAI, but a cyclooxygenase pathway antagonist, indomethacin, did not. Moreover, authentic leukotriene B4 induced delta psi changes and LAI in T-cells. The results indicated that T-cells from patients with breast cancer recognized and bound a tumor-specific antigen in the autologous neoplastic breast tissue that transduced a transmembrane signal to trigger a series of biochemical changes, releasing lipoxygenase products of arachidonate. The lipoxygenase products, which may be important in the inflammatory response to cancer, induced a loss of T-cell adherence to glass.     

Hippocampal-dentate Θ disturbance after selective CA1 pyramidal cell damage in the rat

The contribution of the CA1 area of the dorsal hippocampus to both superficial and deep theta recorded from the dorsal hippocampal formation was assessed in rats anesthetized with ether. CA1 area cells were destroyed unilaterally by local injection of 2 micrograms of ibotenic acid dissolved in 0.1 microliters of phosphate buffer. Limited destruction of CA1 resulted in partial suppression of both superficial and deep theta, whereas extensive destruction resulted in almost total suppression of both theta's. A good correlation was found between the extent of the lesion and the theta disruption. Control preparations involving destructions by means of this neurotoxin of the hippocampal CA3 area or lower blade of the dentate gyrus failed to alter either superficial or deep theta. These data suggest that neuroanatomical integrity of the CA1 area of the dorsal hippocampus is a necessary condition for the normal appearance and maintenance of both superficial and deep theta as recorded from the dorsal hippocampal formation of the ether-anesthetized rat.     

Circulating form of beta-2-microglobulin in dialysis patients

The circulating profile of beta-2-microglobulin (beta 2M) was determined in 8 end-stage renal disease patients on long-term dialysis (6 on hemodialysis, 2 on CAPD) by measuring beta 2M in different fraction after molecular sieve separation of their sera. Four patients had carpal tunnel syndrome with demonstrated amyloid in excised wrist tissues of which 2 were positive for beta 2M. In all patients despite very high blood levels (34.3-63.1 mg/l), beta 2M eluted exclusively as a single peak in the molecular weight region of about 12,000 daltons on a calibrated Sephacryl S-200 column. Recoveries from within the peak accounted for 96% of the applied beta 2M serum concentrations. These results were confirmed by molecular sieve separation of the enriched beta 2M-containing fractions by high-pressure liquid chromatography. We conclude that immunoreactive beta 2M in dialysis patients circulates as an intact monomer without evidence for the formation of aggregates or fragments. The pathogenesis of tissue deposition of this low-molecular-weight protein and its polymerisation to form a specific amyloid remains to be defined.     

Immunological studies in pre-eclamptic toxaemia.

Although five patients with severe pre-eclamptic toxaemia (PET) had increased anticomplementary activity in their serum, there was no evidence of complement activation in the plasma of four of the five patients. These results are not implicated in the pathogenesis of PET. No significant correlation was found between anticomplementary activity and pregnancy-associated alpha2-glycoprotein.     

αm-Crystallin: the native form of the protein?

Evidence is presented that alpha-crystallin isolated at 37 degrees C exists as a species, alpha m, which has a minimum molecular weight of about 320000 and a sedimentation coefficient of about 12 S. The amino acid composition, subunit distribution, near- and far-UV CD spectra and immunochemical properties were identical to those of the previously studied, 19 S protein, alpha c-crystallin (minimum molecular weight, 635000). It was demonstrated that only alpha m-crystallin was present in 37 degrees C lens extracts and that cooling of lenses or extracts resulted in a conversion of alpha m- to alpha c-crystallin. This conversion appears to be a general phenomenon, independent of age or species. It was concluded that alpha c-crystallin is an aggregate, produced by cooling, and that alpha m-crystallin is more likely to represent the in vivo form of the protein.     

Classification of glomerulonephritis.

A classification of glomerulonephritis which is being used as a basis for the New Zealand National Study of Glomerulonephritis is presented, together with comments about the salient pathological features of each type of glomerular disease.