HLA-DRB1*04 subtypes are associated with increased inflammatory activity in early rheumatoid arthritis

The sequence polymorphism of HLA-DRB1 molecules in 84 rheumatoid arthritis (RA) patients with early RA has been analysed to evaluate whether particular HLA-DR alleles influence disease progression in the early stage of the disease. Clinical data were analysed by grouping the patients according to disease-associated haplotype combinations (DRB1*04,04/DRB1*04,01/DRB1*04,X/DRB1*01,X) in comparison to patients who did not carry these haplotypes (DRB1*X,X). Our results indicate that patients with early RA who are homozygous for DRB1*04 exhibit an elevated inflammatory activity and an increase of joint affections. In addition, the amino acid polymorphism (QR/KRAA) at position 70-74 seems to affect the production of rheumatoid factors. These results support the role of HLA-DRB1 alleles in the pathogenesis of RA and indicate that patients with particular HLA-DRB1*04 haplotype combinations may require intensified therapeutic interventions in the early stage of the disease to prevent disease progression.      

Oxygen metabolism of phagocytosing human polymorphonuclear leucocytes in diabetes mellitus

Summary Zymosan stimulated oxygen metabolism was investigated in polymorphonuclear leucocytes (PMN) from 6 diabetic patients. Oxygen uptake and superoxide production were continuously measured in the presence of autologous or control serum and non-opsonized zymosan, or in the absence of serum and preopsonized zymosan. The only significant impairment in the diabetic cells studied was a lower oxygen uptake in the presence of autologous serum. This defect was normalized by addition of control serum or by omitting the serum and stimulating with opsonized zymosan. In the absence of serum, the oxygen consumption was markedly diminished in only one subject, whereas two subjects showed a decrease of superoxide production in the presence of control serum. An inverse correlation between fasting glucose concentration and oxygen uptake could be demonstrated. However, exposure of normal PMN to hyperglycemic glucose concentration in vitro did not significantly alter their oxygen metabolism, suggesting that glucose alone could not be the only factor responsible for the impaired oxygen consumption in diabetic cells.This research was supported by the Fonds National Suisse de la Recherche Scientifique, grant No. 3.271-0.74.     

Elevated nonspecific plasma proteins in allergic patients.

Several allergen-specific plasma proteins, such as IgE and IgG subclasses, are commonly used for the evaluation of grade of allergy. In the present investigation, we compared the concentration of various nonspecific plasma proteins, mostly known as inflammation markers, in an allergic and a healthy population. Plasma from 130 children with single inhalation allergies to grass pollen, birch pollen, or house dust mites as well as from 42 healthy children was obtained during the symptom-free period. Patients showed symptoms including allergic rhinitis, dermatitis, and asthma with one single radioallergosorbent test (RAST) class 3 or higher. Plasma concentrations of soluble intercellular adhesion molecule-1(sICAM-1), soluble interleukin-2 receptor(sIL-2R), sE-selectin, and soluble vascular cell adhesion molecule-1 (1sVCAM-1) were analyzed by enzyme linked immunosorbent assay (ELISA) technique. Concentrations of sICAM-1 and sE-selectin were significantly increased in all patients compared to controls. In the single allergen groups, sICAM-1 elevation was significant in the grass and mite groups, but not in the birch group; while sE-selection increase was significant in the birch and mite groups, but not in the grass group. The elevation of sIL-2R in the allergic patients was obvious in each single allergen group, but not significant. No difference was observed in sVCAM-1 expression. In two groups of patients with mean age of 9.5 years versus 17.5 years, the analyzed parameters were not age dependent. The increased proteins may be useful as additional markers for efficacy and follow-up investigations of allergy therapies.     

Detection of gram-negative bacteraemia in early sepsis by a quantitative chromogenic and kinetic endotoxin assay

A kinetic chromogenic limulus test was carried out in order to investigate the possibility of a sensitive and specific detection of circulating endotoxin during the first 24 h of septic shock or severe sepsis in 76 patients. Two commercial kits, Whittaeker (W) and Chromogenix (C), were used. Blood culture was taken as a reference. At 1 : 10 plasma dilution (a currently used dilution in the end point limulus test) abnormal reaction kinetics were found in 13% and 41% of tests, for C and W respectively ( P  = 0.0008), resulting in unreliable results. Retesting plasma at a greater dilution, until the reaction kinetic was identical to calibration curve control values, gave similar results between the two kits and a better accuracy. Beyond a 0.5 EU mL⁻¹ endotoxin level, the probability of Gram-negative bacteraemia was high (sensitivity = 0.53 and 0.47; specificity = 0.95 and 0.93 for C and W respectively). This kinetic limulus amoebocyte lysate (LAL) test may be useful in therapeutic decisions for treatment of endotoxaemia.     

Outcome of the treatment of invasive non-transitional cell carcinoma

BACKGROUND: We evaluated the treatment outcomes of non-transitional cell carcinoma (non-TCC) cases after radical cystectomy. METHODS: Radical cystectomy was performed in 259 invasive bladder cancer patients in our department and of these, 59 (22.7%) were non-TCC. Primary squamous cell carcinomas (SCC), adenocarcinomas and undifferentiated cancers (UC) were grouped as non-TCC of the bladder. Of the 59 non-TCC; 32 SCC, 20 UC, five adenocarcinoma and two sarcomatoid tumor cases were demonstrated. RESULTS: The 5-year disease-specific survival rate of TCC and non-TCC cases were 48.9 and 28.2%, respectively (P = 0.0016). The 5-year disease-specific survival rates of SCC and UC were 25.1 and 23.4%, respectively. The median survival time of SCC, UC and adenocarcinoma cases were 19, 12 and 6 months, respectively (P = 0.4579). The disease-specific survival rates of TCC and non-TCC cases at stage pT2NoMo were 79.1 and 27.2%, respectively (P = 0.0000). The median survival time of SCC, UC and adenocarcinoma cases were 19, 12 and 13.3 months, respectively, for the same stage. The survival time of TCC, SCC and UC cases at stage pT3NoMo were 23, 26 and 45 months, respectively (P = 0.2307). The median survival time at stages pT2-3N1Mo for the same groups were 18, 16 and 11 months, respectively (P = 0.0939). CONCLUSION: The study presented here demonstrates that both TCC and non-TCC cases have poor survival rates in locally advanced disease and that at the pT2NoMo stage the prognosis of non-TCC cases is poor when compared with TCC cases.     

Phorbol ester induces expression and function of interleukin-2 receptors on a human leukemic cell line with a T-cell precursor phenotype

We show here that a human leukemic cell line, PER-117, bearing the markers of a T-cell precursor phenotype, can be induced to express receptors for interleukin-2 (IL-2). These IL-2 receptors could be demonstrated to mediate a physiologic response to the lymphokine for which the high-affinity form of the IL-2 receptor appears to be essential. The phenotype of PER-117 cells corresponds to the earliest identifiable stage of T-cell differentiation, which is defined by the lack of the T3-T-cell receptor complex and the presence of the 40 Kd protein recognized by monoclonal antibodies of the CD7 group. Further evidence for the clonality and T-cell lineage of this cell line was obtained by analysis of rearrangements of genes for the T-cell receptor (TCR) beta chain and for the immunoglobulin heavy-chain (IgJH) genes. PER-117 cells could be shown to have rearranged TCR beta genes but no rearrangement of the IgJH genes. Cell line PER-117 provides a model to investigate the requirements for induction of IL-2 receptors in a cell expressing the first T-cell-specific marker and may help to elucidate the role of IL-2 during thymic differentiation and in the uncontrolled proliferation of T-cell leukemias.