Effects of recombinant tumour necrosis factor on antibody-dependent eosinophil-mediated damage to Schistosoma japonicum larvae

Human recombinant tumour necrosis factor (rTNF) enhanced monoclonal IgE-dependent eosinophil-mediated cytotoxicity to schistosomula of Schistosoma japonicum in a dose-dependent manner. The enhancing effect of rTNF was also observed for the antibody-dependent cytotoxicity of a human eosinophilic leukemia cell line, EoL-3, but not of another cell line, EoL-1. Observation by a slow-motion movie camera demonstrated that activated EoL-3 cells adhered to the surface of schistosomula by 6 h after incubation, which triggered intracellular movement of eosinophil granules. The granules were concentrated toward the surface of the larvae and then degranulation started. The cell membrane was left as a balloon-like remnant. Cell sorting analysis by FACStar indicated that the expression of receptors for C3bi (CR3) and low affinity FcR for IgE (Fc epsilon RII) increased on the surface of EoL-3 cells after stimulation with rTNF, while this was not observed for EoL-1 cells.     

Long-term administration of natural interferon-α in patients with chronic hepatitis C: Relationship to serum RNA concentration, HCV-RNA genotypes, histological changes and hepatitis C virus

To virologically assess the efficacy of interferon therapy in chronic hepatitis C, either 5 or 10 MU/day natural interferon-α (IFNα) was administered to 57 patients with chronic hepatitis C for 38 weeks. A complete and sustained response (CR-SR), as evidenced by the absence of serum hepatitis C virus (HCV)-RNA during the administration period and at 6 months after the final administration of IFNα and a normal GPT level at 6 months after final administration, occurred in 42.6% (23/54) of subjects. Liver tissue was histologically evaluated using the histological activity index (HAI) score before and after the administration period. In CR-SR cases, significant improvements (P <0.01) occurred in periportal necrosis, intralobular necrosis, portal inflammation and total score. A comparison, by HCV genotypes, revealed that CR-SR occurred in 60% (9/15) of subjects with type 2a and 30.3% (10/33) of subjects with type Ib. A comparison by virus concentration revealed that CR-SR occurred in 71.4% (15/21) of those subjects having a virus concentration of < 10⁵ copies/mL, but in only 24.2% (8/33) of those having a virus concentration of > 10⁵ copies/mL. Analysis by a multiple logistic model revealed a strong correlation between the therapeutic effect of interferon therapy and the pre-administration virus concentration (P=0.0061) and genotype (P=0.0015). These results suggest that the preadministration virus concentration and genotype are both key factors affecting the therapeutic effect of interferon therapy in chronic hepatitis C and that the therapeutic effect of interferon is satisfactorily high, irrespective of virus concentration, in subjects with type 2a HCV, but varies depending on virus concentration in subjects with type 1b.     

Acquired pure red cell aplasia in a hemodialyzed patient

A 68-year-old male had end-stage renal disease secondary to hypertension. He was placed on chronic dialytic therapy and was given recombinant human erythropoietin (epoetin) for renal anemia. One month later, rapidly progressing anemia was noted. The anemia was unresponsive to maximal doses of epoetin and the patient soon became transfusion-dependent. Erythroid hypoplasia was demonstrated by bone marrow biopsy. A detailed search for the cause of the erythroblastopenia revealed nothing. A diagnosis of acquired pure red cell aplasia was made. The use of immunosuppressive agents improved the patient's symptoms and laboratory data. Antibodies for erythropoietin (EPO) were negative after the treatment. It is suggested that patients with EPO-resistant anemia with no obvious etiology should be examined for underlying hematologic disorders.     

BCG Treatment of Crohn''s Disease

Among 53 patients with documented Crohn's disease, 30% manifested a defect in delayed hypersensitivity demonstrated by negative DNCB skin tests and significant (p less than 0.01) T-lymphocyte hyporeactivity. A double-blind controlled trial was conducted to evaluate oral Bacillus Calmette-Guerin (BCG) therapy in nine of these patients with Crohn's disease and deficient cellular immunity. All patients had a Crohn's Disease Activity Index (CDAI) greater than 150 (at least moderate activity) upon randomization to BCG (five patients) or placebo (four patients) treatment for six to 12 months. No significicant differences between BCG and placebo treatment were found in the CDAI, laboratory tests and gastrointestinal roentgenograms. We conclude that the disturbance in cell-mediated immunity in patients with Crohn's disease probably is a manifestation of the disease rather than an etiological factor and that immunostimulation with oral BCG is not effective therapy.     

Relation Between HLA-DW and the B-Lymphocyte Specificities

Homozygous DW typing cells were tested for six B-lymphocyte specificities. All four of the second locus specificities of B lymphocytes were strongly associated with the DW specificities. DW1 typing cells were B group 6, DW2 were B4, DW3 were B5, and LD107 were B3. The first B-cell locus antigens 1 and 2 tended to be uniform within the DW groups. From an analysis of the typing responses of a panel of cells to the homozygous typing cells, it has become apparent that the first B-locus specificity present on the homozygous typing cells also plays a role in determining whether a typing response is obtained or not. Thus, the DW3 typing cells were themselves B2 and B5, and cells having B2-B5 were most frequently nonreactive to DW3 in mixed lymphocyte culture. Homozygous typing cells therefore mainly detect the second B-cell locus antigens and, to a lesser degree, the first locus specificities. Stated another way, homozygous typing cells do not define a single specificity, but rather the presence of two B-lymphocyte specificities, even though their responses often reflect matching of only the second B-locus specificity.     

Analysis of HL-A Incompatibility in Human Renal Transplants

The matching criteria of counting the number of HL-A incompatibilities, the number of compatible antigens, and of ratios (net histocompatibility ratio) were evaluated. In order to avoid bias, the data were analyzed with the aid of computers, taking many different cutoff points. The probability value of statistical significance can be shown to vary considerably depending on the time selected for evaluating the clinical ranks and the clinical ranks which are considered to be "successful" or "failure." Overall, the data indicate that because of the large number of patients who do well in spite of incompatibility, a more suitable means by which successful transplants can be predicted will be required. Since HL-A antigens are still the primary transplantation antigens (as shown by the successful HL-A-identical sibling transplants), empiric knowledge on the types of incompatibilities which can result in good graft survival must be developed.     

Determination of the relative probability for prostate cancer to avoid unnecessary biopsy

BACKGROUND: To investigate whether using a new concept of relative probability for prostate cancer (RPpca) can increase sensitivity and specificity in detecting prostate cancer. METHODS: For 217 patients with total prostate-specific antigen (PSA) level of 4-20 ng/mL, prostate volume and free to total PSA (F/T) ratio were measured. From the fitted curves between positive predictive values for prostate cancer and age, prostate volume, total PSA or the F/T ratio, each function predicting prostate cancer was determined. RPpca defined by the combined functions of age, prostate volume, total PSA and F/T ratio was calculated for each individual patient. The probability of prostate cancer was also calculated, using logistic regression analysis (LRPpca). Receiver-operating characteristic analysis was performed to elucidate the areas under the curve (AUC), sensitivities and specificities and cutoff values of the conventional and new parameters. Finally, we investigated the applicability of the above parameters in the other patient group using a different PSA assay kit (AxSYM). RESULTS: Although RPpca had the largest AUC in the total PSA range of 4-20 ng/mL, it did not reach statistical significance between RPpca and F/T ratio or LRPpca. The cutoff values of F/T ratio, LRPpca and RPpca were determined as 0.15, 0.12 and 0.20, respectively. Using these cutoff values in AxSYM data, RPpca had the highest sensitivity (91%) and specificity (57%). CONCLUSIONS: RPpca can provide more precise information to avoid unnecessary biopsy than LRPpca or F/T ratio. RPpca could be valuable to decide whether to perform prostate biopsy when using various PSA kits.