Effects of interleukin-11 on the proliferation and cell cycle status of myeloid leukemic cells

Interleukin-11 (IL-11) is a pleiotropic cytokine with effects on many different targets. Within the hematopoietic system, the effects of IL- 11 are largely manifest only through combination with other cytokines, including IL-3 and Steel factor (SF). In the present study, we addressed the question of IL-11 responsiveness within the different types of human leukemic cells, as well as the mechanism of action of IL- 11 at the cellular level. Analysis of a panel of samples from different patients with acute myeloblastic leukemia (AML) and myeloid leukemic cell lines indicated that IL-11 alone was ineffective in supporting myeloid leukemic cell growth but frequently enhanced growth supported by IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), or SF. In contrast, three acute pre-B lymphocytic leukemia (pre-B-ALL) and two acute T lymphocytic leukemia (T-ALL) lines failed to respond to IL- 11 alone or when combined with other cytokines. The growth enhancement of IL-11 among the AML patient samples was dose dependent and remarkably constant with half-efficient concentrations in the range of 0.3 to 0.4 ng/mL. The thymidine suicide studies with the patient samples revealed that 40% to 50% of the blast cells were in S-phase when exposed for 16 hours to IL-3 and this level was increased to 70% to 90% in response to either IL-11 or IL-6. Our data suggest that the latter two interleukins act synergistically with the direct mitogenic factor, IL-3, in triggering AML blast-cell proliferation. Detailed analysis with several patient samples further revealed that SF and IL- 11 both enhance IL-3-supported clonogenic growth of AML blasts and the combination of all three growth factors yields optimal growth. In contrast, IL-6 does not further enhance the effect of IL-11. These results indicate that SF and IL-11 enhance IL-3-dependent clonogenic growth through two distinct pathways, whereas IL-6 and IL-11 may trigger the same pathway.     

New experimental melting properties as access for predicting amino-acid solubility

The properties of melting are required for the prediction of solubility of solid compounds. Unfortunately, direct determination of the enthalpy of fusion and melting temperature by using conventional DSC or adiabatic calorimetry is often not possible for biological compounds due to decomposition during the measurement. To overcome this, fast scanning calorimetry (FSC) with scanning rates up to 2 × 10⁴ K s⁻¹ was used in this work to measure the melting parameters for l-alanine and glycine. The enthalpy of fusion and melting temperature (extrapolated to zero heating rate) were Δ_fusH = (22 ± 5) kJ mol⁻¹ and T_fus = (608 ± 9) K for l-alanine, and Δ_fusH = (21 ± 4) kJ mol⁻¹ and T_fus = (569 ± 7) K for glycine. These melting properties were used in the modeling framework PC-SAFT to predict amino-acid solubility in water. The pure-component PC-SAFT parameters and one binary parameter were taken from literature, in which these parameters were fitted to solubility-independent thermodynamic properties such as osmotic coefficients or mixture densities. It was shown that this allowed accurately predicting amino-acid solubility in water over a broad temperature range. The combined methodology of PC-SAFT and FSC proposed in this work opens the door for predicting solubility of molecules that decompose before melting.

New experimental melting properties combined with PC-SAFT allow quantitative solubility predictions of amino acids in water.     

Characterization of SCCA-IgM as a biomarker of liver disease in an Asian cohort of patients

Viral hepatitis infection is a major global issue and a leading cause of liver disease and associated deaths. Over time, patients infected with hepatitis B (HBV) or C virus (HCV) develop cirrhosis and, eventually, hepatocellular carcinoma (HCC). For this reason, they need to be constantly monitored. Current Asian guidelines recommend the determination of serum alpha-fetoprotein (AFP) together with liver ultrasounds every six months to detect HCC nodules. However, both methods have several limitations, and other biomarkers have been studied for monitoring cirrhosis, including SCCA-IgM, an immune-complex formed by Squamous Cell Carcinoma Antigen and IgM. To date, SCCA-IgM has been validated as a novel biomarker for liver diseases only in European populations. The aim of our study was to analyze SCCA-IgM as a biomarker to monitor cirrhosis evolution in an Asian cohort of patients and to compare its performance to that of AFP. We analyzed the concentration of AFP and SCCA-IgM in serum samples obtained from a group of Asian adult patients with cirrhosis or HCC and a control group of patients admitted for gastrointestinal disorders. In untreated patients and similarly to AFP, SCCA-IgM levels were significantly higher in patients with cirrhosis compared to those with HCC. In addition, SCCA-IgM, but not AFP serological levels, were significantly lower in HCC patients who were treated with surgical resection compared to those who received a different therapy.     

Sampling Males Who Inject Drugs in Haiphong,Vietnam: Comparison of Time-Location and Respondent-Driven Sampling Methods

Accurate measurements of HIV prevalence and associated risk factors among hidden and high-risk groups are vital for program planning and implementation. However, only two sampling methods are purported to provide representative estimates for populations without sampling frames: time-location sampling (TLS) and respondent-driven sampling (RDS). Each method is subject to potential biases and questionable reliability. In this paper, we evaluate surveys designed to estimate HIV prevalence and associated risk factors among people who inject drugs (PWID) sampled through TLS versus RDS. In 2012, males aged ≥16 years who reported injecting drugs in the previous month and living in Haiphong, Vietnam, were sampled using TLS or RDS. Data from each survey were analyzed to compare HIV prevalence, related risk factors, socio-demographic characteristics, refusal estimates, and time and expenditures for field implementation. TLS (n = 432) and RDS (n = 415) produced similarly high estimates for HIV prevalence. Significantly lower proportions of PWID sampled through RDS received methadone treatment or met an outreach worker. Refusal estimates were lower for TLS than for RDS. Total expenditures per sample collected and number of person-days of staff effort were higher for TLS than for RDS. Both survey methods were successful in recruiting a diverse sample of PWID in Haiphong. In Vietnam, surveys of PWID are conducted throughout the country; although the refusal estimate was calculated to be much higher for RDS than TLS, RDS in Haiphong appeared to sample PWID with less exposure to services and required fewer financial and staff resources compared with TLS.