Recombinant interleukin 3 induces interleukin 2 receptor expression on early myeloid cells in normal human bone marrow.

Human interleukin 3 (IL-3) is a multipotential cytokine that supports the growth of early hematopoietic progenitors and promotes their response to other, later-acting cytokines. We found that IL-3 was able to induce the expression of interleukin 2 (IL-2) receptor (IL-2R) (CD25) on a subset of early myeloid cells in normal human bone marrow that had been first depleted of mature hematopoietic cells and E-rosette-positive T cells by treatment with soybean lectin and sheep erythrocytes (SBA-E-BM). Immunofluorescence analysis revealed that the CD25+ cells were contained almost entirely within the lymphoblastoid gate of the IL-3-cultured marrow. CD25 was undetectable on freshly isolated marrow and less than 10% CD25+ cells could be detected following liquid culture at 37 degrees C in the presence of 10% human serum, 10% fetal calf serum, or under serum-free conditions. Addition of IL-3 (100 U/ml) significantly increased the expression of CD25 to 37%, 31%, and 24%, respectively. CD25 could also be induced by granulocyte-macrophage colony-stimulating factor (GM-CSF), but no IL-2R was detectable following exposure to granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), interleukin 1 (IL-1), interleukin 4 (IL-4), or IL-2. Expression of CD25 was dependent on the dose of IL-3 or GM-CSF added and was maximal within 24 h of exposure. Two-color immunofluorescence analysis demonstrated that CD25 was not expressed by cells of lymphoid lineage or by mature monocytes, but rather was present on cells that coexpressed CD13, CD33, CD34, MY8, and HLA-DR, and that lacked CD14 or CD11b, thus placing the CD25+ cells at or near the myeloblast stage of differentiation. An identical phenotype was found for CD25+ cells induced by GM-CSF. Cycloheximide completely inhibited the IL-3-induced expression of CD25, indicating the necessity for protein synthesis, and although most of the CD25+ cells were in G0/G1 phase, 25% of the cells were in S or G2M phase, indicating that receptor expression was not cell-cycle dependent. The p75 chain of IL-2R was not detected on the CD25+ cells. IL-3 was also found to directly induce CD25 in greater than 46% of SBA-E-BM enriched for CD34+ cells by panning. Consistent with the expression of only p55 IL-2R, the functional activity of IL-2 on enriched CD34+ cells exposed to IL-3 could not be demonstrated in either granulocyte-macrophage colony-forming unit (CFU-GM) assays or proliferation assays.(ABSTRACT TRUNCATED AT 400 WORDS)     

Contact dermatitis in patients with leg ulcers

100 patients with leg ulcers were patch tested against a standard battery of allergens. The readings were carried out daily from the 2nd to the 7th days. 55 patients showed positive reactions to one or more allergens. 32% of positive reactions developed for the first time after 48 h and 11% after 72 h. No single day or combination of two days gave 100% positive results. A single reading on the 4th day gave the highest number of positive reactions at 92%. The prevalence of positive patch tests was significantly higher in patients with surrounding eczema, and in patients with positive patch tests the ulcer duration was significantly longer than in those with negative patch tests. The total number of positive results in individuals increased linearly with the duration of the ulcer. Of allergens to which the ulcer was exposed, the occurrence of multiple sensitivity was significantly greater than predicted from the prevalence of individual sensitivities. However, there was no association between medicaments and metal sensitivity. This, together with the absence of an exponential rise in the number of allergens with the duration of ulcer, does not support the theory of systemic ampliative allergy.     

A corneal model for slit-scanning elevation topography

Computerised videokeratography is increasing in sophistication and accuracy. The Orbscan II Videokeratographer combines the advantages of Placido derived and slit-scanning derived topography, to acquire shape information on the posterior surface of the cornea. The purpose of this paper is to construct a model of slit-scanning elevation topography and highlight potential sources of variation in this methodology. Ray tracing calculations were performed on a defined, theoretical, spherical model to obtain a pachymetric measurement. These calculations were tested by comparing the pachymetry measurement derived from the model, over a refractive index shift from 1.376 to 1.400 with the pachymetry measurement obtained by Orbscan II, of a human eye, with an identical alteration in refractive index. The two methods of measurement differed by only 0.157 microm, suggesting that the model is a good representation of slit-scanning elevation topography, and that refractive index variations have only a minimal effect on Orbscan II pachymetry measurement.     

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147- 325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61- 140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64- 206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.     

Mortality on dialysis--on the influence of early start, patient characteristics, and transplantation and acceptance rates

We compared changes from 1965 to 1987 in patients accepted to chronic dialysis, in a Swedish and a US dialysis center, by medical and clinical parameters at the start of dialysis and by duration of the dialysis. We also studied cause of death, outcome, and cumulative survival and tried to relate them to changes in patients and procedures. Finally, we studied how cumulative survival of dialysis patients was dependent on acceptance rates and transplant rates in five European regions and the United States. At both centers, the number of patients accepted grew, but since 1980, the only patient group that has increased has been older patients with many other diseases; these comorbid conditions have increased from approximately 1.2 to 1.4. In both centers, the number of patients with systemic disease, diabetes, and nephrosclerosis doubled. Cause of death showed a decrease in cardiovascular deaths and an increase in deaths due to stopping dialysis. The hemoglobin level increased from 70 to 90 g/L (7.0 to 9.0 g/dL) and the diastolic blood pressure decreased from 100 to 90 mmHg. The creatinine level decreased 30%, with an unchanged urea. Cumulative 3-year survival for patients without complications increased from 60% to approximately 90% and in patients with complications, it improved from 20% to 60% in Sweden and remained at approximately 60% in the US center. In the United States, many more patients were accepted to dialysis and the transplant rate was high. Cumulative survival on dialysis was inversely correlated both to the acceptance rates to dialysis and to the percent of patients transplanted. These factors explained over 90% of the differences in dialysis survival.     

Favorable results of coronary artery bypass grafting in patients older than 75 years

There is controversy whether the short-term and long-term results of coronary artery bypass grafting in elderly patients justify performing the procedure. Between January 1977 and December 1986, 4580 patients underwent coronary artery bypass grafting, of whom 222 (4.9%) were 75 years old or older (mean 77 years). There were 143 men and 79 women and 139 (63%) were in New York Heart Association class IV. One hundred forty-six patients (66%) had had at least one preoperative myocardial infarction. Myocardial revascularization was performed under emergency conditions in 17 patients (18%). The mammary artery was used in 43%, 96% of the patients received two or more grafts. The mean number of bypass grafts was 3.1 per patient. The overall hospital mortality rate was 10.8% (24/222), 3.6% for elective procedures, 14.9% in urgent cases, and 35% in emergencies. In contrast, the overall early mortality rate was 3.1% in 4358 patients less than 75 years old. Complications occurred in 83 patients (37%). Of the patients discharged from the hospital, 198 were followed up for a mean of 48 months (1 to 130). Actuarial probability of survival was 75% at 48 months. Postoperatively 70% were in New York Heart Association class I or II and only 21% were rehospitalized for cardiac problems. During the follow-up period 77% of the patients were free from angina, and of those experiencing angina the mean time from operation to the first episode was 75 months. Although elderly patients have a somewhat increased operative mortality rate, particularly if operated on urgently or emergently, long-term survival and freedom from angina are excellent and justify continued performance of coronary bypass grafting in selected patients over 75 years of age.