Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia.

WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated ß-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in ∼40% of the patients. When ß-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL.

FT-IR, FT-Raman spectra, density functional computations of the vibrational spectra and molecular conformational analysis of 2,5-di-tert-butyl-hydroquinone.

The purpose of finding conformer among six different possible conformers of 2,5-di-tert-butyl-hydroquinone (DTBHQ), its equilibrium geometry and harmonic wavenumbers were calculated by the B3LYP/6-31G(d,p) method. The infrared and Raman spectra of DTBHQ were recorded in the region 400-4000 cm(-1) and 50-3500 cm(-1), respectively. In addition, the IR spectra in CCl(4) at various concentrations of DTBHQ are also recorded. The computed vibrational wavenumbers were compared with the IR and Raman experimental data. Computational calculations at B3LYP level with two different basis sets 6-31G(d,p) and 6-311++G(d,p) are also employed in the study of the possible conformer of DTBHQ. The complete assignments were performed on the basis of the potential energy distribution (PED) of the vibrational modes, calculated using VEDA 4 program. The general agreement between the observed and calculated frequencies was established.

FT-IR, FT-Raman spectra, density functional computations of the vibrational spectra and molecular geometry of butylated hydroxy toluene.

The FT-IR spectrum of 2,6-di-tert-butyl-4-methylphenol [butylated hydroxy toluene] was recorded in the region 4000-400 cm(-1). The FT-Raman spectrum of butylated hydroxy toluene was also recorded in the region 3500-50 cm(-1). The molecular structure and vibrational frequencies of butylated hydroxy toluene (BHT) have been investigated with combined experimental and theoretical study. Two stable conformers of the title compound were obtained from the result of geometry optimizations of these possible conformers. The conformer 1 is (approximately 2.6 kcal/mol) more stable than conformer 2. Geometry optimizations and vibrational frequency calculations were performed by BLYP and B3LYP methods using 6-31G(d), 6-31G(d,p) and 6-31+G(d,p) as basis sets. The scaled frequencies were compared with experimental spectrum and on the basis of this comparison; assignments of fundamental vibrational modes were examined. Comparison of the experimental spectra with harmonic vibrational wavenumbers indicates that B3LYP/6-31G(d) results are more accurate. Predicted electronic absorption spectra of BHT from TD-DFT calculation have been analyzed and compared with the experimental UV-vis spectrum. The calculated HOMO and LUMO energies show that the charge transfer occurs within the molecule.

The effects of iron deficiency on neutrophil/monocyte apoptosis in children.

OBJECTIVES: Iron is essential for DNA synthesis; its deficiency may lead to impaired DNA synthesis and subsequent alterations in levels of apoptosis. Here, we have aimed to investigate effects of iron deficiency anaemia (IDA) on apoptotic response of phagocytic cells and to understand whether the effect is reversible after iron supplementation. MATERIALS AND METHODS: Forty-nine IDA patients and 26 healthy controls, aged between 6 months and 12 years with similar demographic status, were considered. Neutrophil- and monocyte-apoptotic responses of IDA patients and the control group were compared by flow cytometry. Then, IDA patients were provided with oral iron supplementation. On day 15 of iron therapy, neutrophil- and monocyte-apoptotic responses of IDA patients were rechecked and were compared to those of control group. RESULTS: Neutrophil- and monocyte-apoptotic responses in terms of early and late percentages of apoptosis, and percentages of necrotic cells, were significantly less in IDA patients compared to the control group. The significantly low apoptotic responses of IDA patients rose to levels of the control group by day 15 of iron therapy. Besides, the effect of IDA on apoptotic responses was found to be more enhanced in severe IDA patients that those of mild IDA patients. CONCLUSION: Correction of differences after iron supplementation therapy implies that IDA might be a cause for changes in neutophil- and monocyte-apoptotic responses. The impact of this diminution of apoptotic cellular function in IDA should be further investigated, with longitudinal studies, in order to document the impact of any severe and/or long-lasting IDA on autoimmunity and malignancy.

Partial intestinal obstruction due to childhood refractory hon-Hodgkin's lymphoma, successfully treated with taxol.

In this report, we present a six-year-old male patient with partial intestinal obstruction due to refractory Non-Hodgkin's lymphoma (NHL) whose partial obstruction was successfully treated with Taxol(R) without any surgical intervention. Following an unsuccessful treatment attempt to treat his high-grade (stage 3) B-cell lymphoma with standard and second-line chemotherapy regimens he was started on radiotherapy and third line chemotherapy during which he was admitted with partial obstructive ileus as a result of tumor progression. Treatment was continued with Taxol(R) and resulted in total cure of the ileus with reduction of palpable tumor mass over 24 h without necessitating any surgery. Taxol(R) (200 mg/m (2)/week) was administered without any major side effects/toxicities for six courses. A control CT of the abdomen revealed a significant reduction in tumor size. After the next course, the patient developed severe thrombocytopenia that unfortunately did not resolve before the patient died as a result of further tumor growth and dissemination. Although there are studies that report response to Taxol(R) treatment in adult patients with refractory NHL, our review of the literature failed to demonstrate any report about the effectiveness of Taxol(R) in childhood NHL. In conclusion, our case may indicate that Taxol(R) can be effective and be administered safely in an outpatient setting in children with refractory NHL with the aim of prolonging the survival without sacrificing good quality of life. Studies on larger number of patients are needed to make a definitive conclusion about the value of Taxol(R) in refractory childhood NHL.

[Economic evaluation of the mother-child health/family planning project in Yozgat (author's transl)]. / Yozgat ana-cocuk sagligi/aile planlamasi projesi ekonomik degerlendirmesi.

PIP: In this paper, the alternatives are discussed for the health expenditure in Turkey. These are: 1) to abolish the socialization of health services; 2) to continue to implement the existing socialization program; 3) to implement an ideal socialization program for health services; and 4) to increase the efficiency of the existing socialization program by providing a new model. Alternatives 2 and 4 are discussed here. Data from the Yozgat province indicate that the existing socialization program is less efficient than reputed. In this program, the benefits obtained for every Turkish lira spent is as little as 6 kurus (1 Turkish lira=100 kurus). On the other hand, if an additional project is applied to the existing system of socialization as in the case of the Yozgat MCH/FP, the economic efficiency rises considerably. Hence, the benefit obtained for every Turkish lira spent, even at the lowest estimates, is over 100 kurus. Thus, the example of Yozgat shows that the socialization of health services plus MCH/FP is an alternative choice to implementing an ideal socialization program. A comparison has not been made between alternatives 3 and 4 because the economic evaluation of an ideal socialization program is not yet concluded. Only the feasibility of the Yozgat example can be demonstrated. (author's modified)^ieng