Ontogeny of hematopoietic stem cell development: reciprocal expression of CD33 and a novel molecule by maturing myeloid and erythroid progenitors

We have identified a molecule expressed by human marrow granulocyte/monocyte colony-forming cells (CFU-GM), erythroid colony- forming cells (CFU-E), and erythroid burst-forming units (BFU-E), but not their precursors detectable in long-term bone marrow culture. This antigen, detected by flow microfluorimetry using monoclonal antibody 7B9, is coexpressed with CD33 on many CD34+ CFCs, although only the 7B9 antigen was detected on a portion of BFU-E and CFU-E, whereas only CD33 was found on a portion of CFU-GM. Antibody 7B9 appears to be useful for isolating subsets of progenitors based on their common or selective expression of 7B9 antigen and CD33.     

Associations of Urinary Caffeine and Caffeine Metabolites With Arterial Stiffness in a Large Population-Based Study

Objective

To assess the influence of caffeine on arterial stiffness by exploring the association of urinary excretion of caffeine and its related metabolites with pulse pressure (PP) and pulse wave velocity (PWV).

Activation of muscarinic receptors elicits inotropic responses in ventricular muscle from rats with heart failure through myosin light chain phosphorylation

Background and purpose:

Muscarinic stimulation increases myofilament Ca²⁺ sensitivity with no apparent inotropic response in normal rat myocardium. Increased myofilament Ca²⁺ sensitivity is a molecular mechanism promoting increased contractility in failing cardiac tissue. Thus, muscarinic receptor activation could elicit inotropic responses in ventricular myocardium from rats with heart failure, through increasing phosphorylation of myosin light chain (MLC).

Experimental approach:

Contractile force was measured in left ventricular papillary muscles from male Wistar rats, 6 weeks after left coronary artery ligation or sham surgery. Muscles were also frozen, and MLC-2 phosphorylation level was quantified.

Key results:

Carbachol (10 µmol·L⁻¹) evoked a positive inotropic response only in muscles from rats with heart failure approximating 36% of that elicited by 1 µmol·L⁻¹ isoproterenol (20 ± 1.5% and 56 ± 6.1% above basal respectively). Carbachol-evoked inotropic responses did not correlate with infarction size but did correlate with increased left ventricular end diastolic pressure, heart weight/body weight ratio and lung weight, primary indicators of the severity of heart failure. Only muscarinic receptor antagonists selective for M₂ receptors antagonized carbachol-mediated inotropic effects with the expected potency. Carbachol-evoked inotropic responses and increase in phosphorylated MLC-2 were attenuated by MLC kinase (ML-9) and Rho-kinase inhibition (Y-27632), and inotropic responses were abolished by Pertussis toxin pretreatment.

Conclusion and implications:

In failing ventricular muscle, muscarinic receptor activation, most likely via M₂ receptors, provides inotropic support by increasing MLC phosphorylation and consequently, myofilament Ca²⁺ sensitivity. Enhancement of myofilament Ca²⁺ sensitivity, representing a less energy-demanding mechanism of inotropic support may be particularly advantageous in failing hearts.     

Purification and activity standardisation of a Ho solution

As part of a project to use the long-lived (T_1/2=1200a) ^166mHo as reference source in its reference ionisation chamber, IRA standardised a commercially acquired solution of this nuclide using the 4πβ–γ coincidence and 4πγ (NaI) methods. The ^166mHo solution supplied by Isotope Product Laboratories was measured to have about 5% Europium impurities (3% ¹⁵⁴Eu, 0.94% ¹⁵²Eu and 0.9% ¹⁵⁵Eu). Holmium had therefore to be separated from europium, and this was carried out by means of ion-exchange chromatography. The holmium fractions were collected without europium contamination: 162 h long HPGe gamma measurements indicated no europium impurity (detection limits of 0.01% for ¹⁵²Eu and ¹⁵⁴Eu, and 0.03% for ¹⁵⁵Eu). The primary measurement of the purified ^166mHo solution with the 4π (PC) β–γ coincidence technique was carried out at three gamma energy settings: a window around the 184.4 keV peak and gamma thresholds at 121.8 and 637.3 keV. The results show very good self-consistency, and the activity concentration of the solution was evaluated to be 45.640±0.098 kBq/g (0.21% with k=1). The activity concentration of this solution was also measured by integral counting with a well-type 5″×5″ NaI(Tl) detector and efficiencies computed by Monte Carlo simulations using the GEANT code. These measurements were mutually consistent, while the resulting weighted average of the 4π NaI(Tl) method was found to agree within 0.15% with the result of the 4πβ–γ coincidence technique. An ampoule of this solution and the measured value of the concentration were submitted to the BIPM as a contribution to the Système International de Référence.     

Ultra-rapid opiate detoxification using deep sedation and prior oral buprenorphine preparation: long-term results

BACKGROUND: New methods of ultra-rapid opiate detoxification (URD) under intravenous sedation have been criticized because of limited data on safety and long-term follow-up. Premedication with buprenorphine has been advocated to improve safety by decreasing vomiting. Prior research has not explored URD in socially impaired patients. METHOD: Sixteen patients were detoxified with URD and prospectively evaluated over at least 30 months. Data of this procedure were compared with those of our previous study without buprenorphine preparation (Drug Alcohol Depend. 52(3) (1998) 243). The 16 patients were followed up by a general practitioner (GP) before and after URD. The GPs also supervised the 7-day course of buprenorphine treatment prescribed for the 16 patients prior to URD. RESULTS: During the procedure, only one episode of vomiting occurred instead of 13 out of 20 in our previous study. Post-procedure, only two patients experienced moderate withdrawal symptoms, such as persistent nausea, abdominal cramps and vomiting lasting from 24 to 48 h, in comparison with most patients in the previous study without buprenorphine. After a period of at least 30 months (36.0+/-6.38), the 16 patients were still alive and were regularly monitored by their GP. Only two of the 16 never relapsed after URD and reported total opiate abstinence. Fourteen patients relapsed; 12 of these were prescribed a licensed methadone substitution program and two were still using heroin. CONCLUSION: In this small sample, the data indicated that URD with buprenorphine preparation was safe and that it markedly decreased post-procedure morbidity. No patient died over a minimum 30-month follow-up period. Furthermore, the procedure was employed with socially impaired patients. In the long term, a few patients were still free of opiates, while the majority opted for a methadone maintenance program, showing that URD can serve as one possible step in a long-term treatment program.     

Search for lesions in mammograms: statistical characterization of observer responses

We investigate human performance for visually detecting simulated microcalcifications and tumors embedded in x-ray mammograms as a function of signal contrast and the number of possible signal locations. Our results show that performance degradation with an increasing number of locations is well approximated by signal detection theory (SDT) with the usual Gaussian assumption. However, more stringent statistical analysis finds a departure from Gaussian assumptions for the detection of microcalcifications. We investigated whether these departures from the SDT Gaussian model could be accounted for by an increase in human internal response correlations arising from the image-pixel correlations present in 1/f spectrum backgrounds and/or observer internal response distributions that departed from the Gaussian assumption. Results were consistent with a departure from the Gaussian response distributions and suggested that the human observer internal responses were more compact than the Gaussian distribution. Finally, we conducted a free search experiment where the signal could appear anywhere within the image. Results show that human performance in a multiple-alternative forced-choice experiment can be used to predict performance in the clinically realistic free search experiment when the investigator takes into account the search area and the observers' inherent spatial imprecision to localize the targets.