Ultrastructural myeloperoxidase activity and expression of myeloid-associated antigens in acute lymphoblastic leukemia

Ultrastructural myeloperoxidase (MPO) activity and myeloid-associated antigen (MyAg) expression were investigated in 12 adult patients with acute lymphoblastic leukemia (ALL). Ultrastructural MPO was detected by 3 different methods. Immunophenotyping was performed by flow cytometry, using a series of monoclonal antibodies. Ultrastructural MPO-positive blast cells were detected in 6 patients (50%). In 5 of these 6 patients, the methods detecting both MPO and platelet peroxidase (PPO) activities found MPO-positive blast cells more frequently than those detecting MPO activity alone. In 2 patients (17%), at least one kind of MyAg was positive. Ultrastructural MPO activity was detected more frequently than MyAg expression in ALL patients. This method of detecting PPO and MPO is recommended for detection of ultrastructural MPO-positive ALL.     

Sulfidopeptide-leukotriene peptidases in pulmonary edema fluid from patients with the adult respiratory distress syndrome

The human pulmonary edema fluid concentrations of LTC₄ and of LTD₄ and LTE₄, derived peptidolytically from LTC₄, were assessed by radioimmunoassays of the mediators resolved by reverse-phase high-performance liquid chromatography. The mean pulmonary edema fluid concentration (± SD) of LTD₄ of 19.2±25.6 nM for 12 patients with the adult respiratory distress syndrome and of LTE₄ of 192±309 nM for 10 of the patients were significantly higher (P<0.005 andP<0.05) than those of 2.2±2.4 and 11.0±18.2 nM, respectively, for 10 patients with cardiogenic pulmonary edema, whereas the lower mean concentrations of LTC₄ were not significantly different for the two groups. Pulmonary edema fluid from five patients with adult respiratory distress syndrome, one with cardiogenic pulmonary edema, and one with an indeterminate syndrome contained similar concentrations of peptidoleukotriene peptidases. The LTC₄ and LTD₄ peptidolytic activities in ARDS fluids were 81 and 142 kD, respectively, by gel filtration. The extents of peptidolysis of [³]LTC₄ and [³]LTD₄ by 100 µl of pulmonary edema fluid attained respective mean maximum levels of 74.5±2.9% (N=5) and 37.7±10.2% (N=4) after 30 min at 37°C and were inhibited by serine-borate and by cysteine, respectively. The predominance of LTD₄ and LTE₄ over LTC₄ in states of altered pulmonary vascular pressure and permeability thus is attributable to two distinct peptidases.     

Effects of ageing on the alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells in monkey lungs

The effects of ageing on the numbers of alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells were studied in monkey lungs by scanning and transmission electron microscopy. Lung tissue from 26 female and three male pigtail macaques whose ages ranged from 1 month to 31 years (life span is 35 years) was analysed. From the age of 1 month to 10 years there was a significant increase in the number of alveolar pores (r = 0.85, p less than 0. 001); however, between the ages of 14 years to 31 years there was no significant change. In seven animals ranging in age from 1 month to 4 years (mean 2.4 years) the number of pores was 5.8 +/- 3.9 (mean +/- S.D.), whereas in 10 animals aged 16 to 31 years (mean 20.3 years) the number of pores was 32.7 +/- 17.5 (mean +/- S.D.) per alveolar profile, a significant difference (p less than 0.002). In older animals (15-20 years) there was a significant decrease, both in the number of lamellar bodies per alveolar type II cell (p less than 0.01) and in the volume density of lamellar bodies to cytoplasmic volume (p less than 0.05) compared with young animals (1 month to 4.8 years). In older animals, there was also a significant increase in the volume density of a vacuole-like dilatation of the endoplasmic reticulum in alveolar type II cells (p less than 0.05) compared with young animals. These findings suggest impaired pulmonary surfactant production with aging. Both the increased number of alveolar pores and the postulated decrease of surfactant production could play a role in the pathogenesis of pulmonary emphysema.     

Defective Treg response in acute kidney injury was caused by a reduction in TIM-3+ Treg cells

Background: Despite years of research, the treatment of acute kidney injury (AKI) remains a significant challenge. Animal studies presented causal links between elevated regulatory T cell (Treg) response and better prognosis in AKI. Previous studies in mice and humans showed that TIM-3+ Treg cells were more potent than TIM-3- Treg cells. In this study, we investigated the role of TIM-3 in Treg in AKI patients.

Methods: Peripheral blood from AKI patients and healthy controls were gathered, and TIM-3+ Treg subset was examined.

Results: Compared to healthy controls, the AKI patients presented a significant upregulation in the frequency of circulating CD4+CD25+ T cells; however, the majority of this increase was from the CD4+CD25+TIM-3- subset, and the frequency of CD4+CD25+TIM-3+ T cells was downregulated in AKI patients. In both healthy controls and AKI patients, the CD4+CD25+TIM-3+ T cells expressed higher levels of Foxp3, and were more potent at expressing LFA-1, LAG-3, CTLA-4, IL-10 and TGF-β. In addition, the CD4+CD25+TIM-3+ T cells from both healthy controls and AKI patients presented higher capacity to suppress CD4+CD25- T cell proliferation than the CD4+CD25+TIM-3- T cells. Interestingly, the total CD4+CD25+ T cells from AKI patients presented significantly lower inhibitory capacity than those from healthy controls, indicating that the low frequency of CD4+CD25+TIM-3+ T cells was restricting the efficacy of the Treg responses in AKI patients.

Conclusions: We demonstrated that TIM-3 downregulation impaired the function of Treg cells in AKI. The therapeutic potential of CD4+CD25+TIM-3+ T cells in AKI should be investigated in future studies.     

Patient-ventilator interaction: A general model for nonpassive mechanical ventilation

A general mathematical model for the dynamic behaviour of asingle-compartment respiratory system in response to an arbitraryapplied inspiratory airway pressure and arbitrary respiratorymuscle activity is investigated. The model is used to computeexplicit expressions for ventilation and pressure variablesof clinical interest for clinician-selected and impedance-determinedinputs. The outcome variables include tidal volume, end-expiratorypressure, minute ventilation, mean alveolar pressure, averagepleural pressure, as well as the work performed by the ventilatorand the respiratory muscles. It is also demonstrated that undersuitable conditions, there is a flow reversal that can occurduring inspiration.     

Pneumonien bei akuten Leukämien

Summary Acute leukaemia was complicated by pneumonia in 38 (34.8%) of 109 patients treated between 1979 and 1983; in 39.5% of the patients pneumonia occurred more than once. In 23 patients (60.5%) pneumonia occurred during cytostatic therapy, and 25 patients (65.8%) had less than 1000 mm² granulocytes. Antibiotic therapy had no or only little effect in 70%. A total of 21 patients (55.3%) died of pneumonia. In 15 patients a direct relationship could be seen between pneumonia and the bacterial spectrum in the sputum. A prevalence of gram-negative bacteria was found (24 of 40 bacteria isolated, especially Enterobacteriaceae (19). Fungi were cultivated in 10 cases. Each of the typical pneumonia bacteria was only seen once respectively. It is most important that therapy begin immediately, even before the bacteria have been identified. Only then is there hope that the survival time of patients with acute leukaemia can be influenced.

     

Determinants of pulmonary blood volume. Effects of acute changes in pulmonary vascular pressures and flow

To examine the effects of pulmonary vascular pressures and flow on pulmonary blood volume (PBV), experiments were performed at constant heart rate and zone 3 conditions (mean left atrial pressure (LAP) above airway pressure) in six anesthetized, open-chest dogs. PBV was calculated as the product of electromagnetic aortic flow and pulmonary mean transit time for ascorbate, obtained without blood withdrawal by polarographic recording of aortic ascorbate changes. In three series of experiments LAP was raised similarly in three steps, from 4.5 to 14.8 mmHg: by mitral constriction which reduced pulmonary blood flow, by blood volume expansion which more than doubled pulmonary blood flow, or by a combination of the two procedures which kept pulmonary blood flow constant. In all three series, LAP and mean pulmonary arterial pressure (PAP) rose in proportion, but PBV was better correlated to PAP (r=0.87±0.02) than to LAP (r=0.66±0.09). These experiments suggest that PAP is the most important factor in determining PBV under zone 3 conditions, whether PAP is raised by increasing pulmonary blood flow or by mitral constriction.     

Reproducibility of the parameters of the on-transient cardiopulmonary responses during moderate exercise in patients with chronic obstructive pulmonary disease

To be clinically useful as indices reflective of altered physiological function consequent to interventions in patients with chronic obstructive pulmonary disease (COPD), the time constant (τ) and steady-state amplitude of the kinetic responses for oxygen uptake ( ) carbon dioxide output ( ) ventilation ( ) and heart rate (HR) have to be appropriately differentiable and reproducible. We therefore assessed the reproducibility of τ and steady state amplitude values in 41 patients with severe COPD [mean (SD)] [forced expiratory volume in 1 s=41 (7)% predicted], aged 64 (5) years. Of the total, 6 of the patients (15%) did not produce breath-by-breath data of sufficient quality to warrant kinetic analysis. The remaining 35 patients completed two moderate-intensity 10 min square-wave exercise tests separated by 2 h, both before and after an endurance training programme. Tests were conducted on an electromagnetically-braked cycle ergometer at an exercise intensity corresponding to 80% of the estimated lactate threshold (θ_La) or 50% of peak oxygen uptake if θ_La was insufficiently differentiable. Breath-by-breath measurements of , , and HR were averaged into 10 s bins and the on-transient response kinetics were estimated using a mono-exponential model. Analysing the pre-training and the post-training test 1 and test 2 comparisons together, the test 1 –test 2 differences were not significantly different from 0 for either τ or A. The standard deviation of the test 1 –test 2 differences allowed us to define the magnitude of change that would reach statistical significance. For τ, this averaged some 8, 10, 11 and 8 s, for , , and HR, respectively, for a one-tailed paired-comparisons test (i.e. appropriate for assessing hypothesised improvements resulting from an intervention); for a two-tailed comparison, the differences were approximately 2 s greater. The corresponding one-tailed values for A were 100 ml·min^–1, 95 ml·min^–1, 2.5 1·min^–1 and 4 beats·min^–1, respectively; the two-tailed values were 10%–15% greater. We therefore conclude that both τ and A for moderate-intensity exercise can be reproducibly estimated in patients with COPD when the data set provides a sufficiently large amplitude of response and sufficiently low sample variability to allow appropriate parameter estimation. Electronic Publication     

Isolations of Corynebacterium kroppenstedtii from a breast abscess

The recently described species Corynebacterium kroppenstedtii was isolated from a breast abscess in a 38-year-old woman on two occasions. We discuss the pathogenic role of this bacteria and the methods used for its isolation.