Immunopathologic studies of rheumatoid arthritis. I. Absence of complement-dependent cytotoxicity of rheumatoid sera for rheumatoid synovial cell cultures.

A sensitive complement-dependent chromium release cytotoxicity assay was used to determine whether sera from rheumatoid arthritis (RA) patients contain antibody specific for an antigen on rheumatoid synovial cell cultures. Two hundred eight RA sera-RA synovial culture combinations were studied employing 21 sera and 16 synovial membranes; control combinations were derived from 5 normal sera and 10 degenerative joint disease synovial membranes. Anticomplementary activity of some rheumatoid sera was overcome using an increased complement concentration. The percent cytotoxicity of RA serum-RA culture combinations, both homologous and autologous, was not significantly greater than that of RA serum-control culture combinations. No correlation between duration of disease or duration of cell culture and percent cytotoxicity was found. Thus a unique antigen on cultured rheumatoid synovial cells was not recognized by rheumatoid serum antibody by use of this cytotoxicity assay.     

Early changes in phosphatidylcholine metabolism in human acute promyelocytic leukemia cells stimulated to differentiate by phorbol ester

The HL-60 leukemia cell line derived from a human acute promyelocytic leukemia is stimulated to differentiate into macrophages within 24-28 hr after exposure to the phorbol ester, 12-O-tetradecanoylphorbol-13- acetate (TPA). We studied early alterations (within 90 min of exposure to TPA) in phosphatidylcholine metabolism in HL-60 cells and found that phosphatidylcholine synthesis by methylation is phosphatidylethanolamine was inhibited in a dose-dependent fashion. In contrast, synthesis of phosphatidylcholine from endogenous choline was enhanced and correlated inversely with the degree of inhibition of the methylation pathway. Phorbol ester congeners of TPA caused similar alterations in phosphatidylcholine metabolism in direct relationship to their capacity to induce differentiation in HL-60 cells. Perturbation of phosphatidylcholine metabolism is an early membrane even in TPA- induced HL-60 cell differentiation.     

Assessment of total anomalous pulmonary venous connection by two-dimensional echocardiography.

Twenty-three patients with total anomalous pulmonary venous connection were studied by two-dimensional echocardiography. In all cases the diagnosis was made before invasive procedures, with surgical or angiocardiographic confirmation. Eleven patients had supracardiac drainage (three to the coronary sinus, two to the right atrium,) and seven had infracardiac drainage. In the majority of cases the precise pattern of drainage could be identified by combining suprasternal, praecordial, and subcostal views. In 12 cases where the suprasternal cut was used a pulmonary venous confluence could be identified, having a cross-like structure in nine, with three others appearing as a dilated channel behind and separate from the left atrium. Thus, two-dimensional echocardiography reliably makes the diagnosis of total anomalous pulmonary venous connection and in the majority the precise pattern of drainage can be determined.     

Autologous bone marrow transplantation for patients with relapsed Hodgkin's disease.

PURPOSE: High-dose therapy and autologous bone marrow transplantation (ABMT) are being increasingly utilized for the management of patients with relapsed Hodgkin's disease. Because patients with relapsed Hodgkin's disease often initially respond to salvage chemotherapy regimens, ABMT is frequently delayed until late in the course of the disease. The optimal timing for ABMT has not been identified. The purpose of this study was to determine the value of ABMT earlier in the course of Hodgkin's disease. PATIENTS AND METHODS: We treated 70 patients between October 1984 and October 1988 with high-dose cyclophosphamide, carmustine, and etoposide, followed by infusion of previously cryopreserved autologous bone marrow, and analyzed the results to determine the impact of timing of ABMT on treatment outcome. One (17 patients), two (24 patients), or three or more (29 patients) chemotherapy regimens had failed in patients before ABMT. RESULTS: The results for all 70 patients included a complete remission rate of 59%, an early death rate of 11%, a 4-year survival of 47%, and 27% of all treated patients alive and in complete remission at 4 years. The median follow-up for patients remaining in complete remission is 56 months (range 26 to 73 months). The frequency of achieving a complete remission was higher in patients in whom fewer regimens had failed before ABMT (i.e., 82% versus 58% versus 45%, p = 0.02), as was the 4-year disease-free survival (i.e., 44% versus 33% versus 21%, p = 0.04). CONCLUSION: ABMT is a more effective therapy when used early for patients with relapsed Hodgkin's disease.     

CD8+ T lymphocytes and progression to AIDS in HIV-infected men: some observations

The relationship between CD8+ lymphocyte counts and progression to AIDS was studied in 340 HIV-1-seropositive men participating in a population-based prospective study. Overall, the relative hazard for developing AIDS during 60 months of observation was slightly elevated (1.08, P = 0.003), indicating an 8% increase in risk of progression for every 100 CD8+ cell count increment. When the data were analyzed in relation to date of diagnosis, the relative hazard was depressed (0.90, P less than 0.001) for the period 6 months prior to diagnosis, but was close to 1.0 for the period 6-36 months prior to diagnosis. These findings suggest a complex relationship between CD8+ cell counts and progression to AIDS, with the possibility that various subsets of the CD8+ compartment play different roles.     

The value of plasmid studies in the epidemiology of infections due to drug-resistant Salmonella wien.

Since 1969 strains of Salmonella wien that are resistant to multiple antibacterial drugs have caused widespread epidemics of enteritis in Europe and North Africa. Of 113 British strains examined between January 1970 and January 1977, 67 were multi-resistant. These strains and 22 strains from six other countries were examined to determine their plasmid content. Two plasmids were found in the vast majority of strains: an FIme factor, conferring resistance to ampicillin, chloramphenicol, kanamycin, streptomycin, spectinomycin, sulfonamides, and tetracyclines (ACKSSpSuT), and a nonautotransferring plasmid of resistance type ASSu. The FIme plasmids have dual incompatibility: they are incompatible with group FI factors and with the MP10 plasmid of Salmonella typhimurium, which belongs to a separate group. Other plasmids found in S. wien included principally a ColIa factor and an autotransferring plasmid that codes for ampicillin resistance and belongs to compatibility group I2. The similarity in plasmid content of strains isolated in widely separated areas suggests that they have a clonal origin.     

A rise in the percentage of large unstained cells in the peripheral blood determined by the Hemalog D90 automated differential counter is a feature of impending myeloid engraftment following bone marrow transplantation

The early phase of bone marrow regeneration has been monitored by automated differential counts on the peripheral blood using a Hemalog D90, following 107 transplant procedures. An elevated percentage of large unstained cells (LUCs) was detected in over 98% of cases and in 72% of cases the rise in percentage LUCs preceded the rise of the total leucocyte count into the detectable range on a Coulter counter (greater than 0.3 X 10(9)/1) by an average of 4 days. These LUCs are shown to be CD8 + T lymphocytes. The ability to detect the earliest signs of regeneration is particularly useful when regeneration is delayed and repeat marrow infusion is considered.