The human CD40 gene lies within chromosome 20q deletions associated with myeloid malignancies

Deletions of chromosome 20q are associated with myeloid malignancies and have been previously shown to arise in a multipotent progenitor of both myeloid and B cells. However, B-cell differentiation from the abnormal progenitor was impaired. The CD40 antigen is a surface glycoprotein which is expressed in B cells and haemopoietic stem cells and is important for B-cell growth and development. Following the recent mapping of CD40 to chromosome 20q we sought to determine its position relative to 20q deletions. Analysis of lymphoblastoid cell lines carrying 20q deletions placed CD40 within a 19–21 cM interval which is almost coincidental with the common deleted region defined by previous analysis of patient samples. Our results raise the possibility that genetic alteration of this locus may contribute to the pathogenesis of myeloid disorders associated with 20q deletions.     

HHV-6 DNA throughout the tissues of two stem cell transplant patients with chromosomally integrated HHV-6 and fatal CMV pneumonitis

Two patients with the characteristic high human herpesvirus 6 (HHV-6) DNA loads in peripheral blood caused by chromosomally integrated (CI) virus received a haematopoietic stem cell transplant (HSCT) from a donor without CI HHV-6. Both patients died in consequence of cytomegalovirus (CMV) pneumonitis. At autopsy, high amounts of CMV DNA were detected in lungs but at much lower levels in other organs. In contrast HHV-6 DNA was detected at high levels throughout the organs with the exception of donor-derived haematopoietic tissue. In individuals with chromosomal integration, HHV-6 DNA is found in every tissue of recipient origin indicating inheritance through the germ line.     

Nutrition, nutritional behavior, and obesity

THE PURPOSE: Of this investigation is to explore the effect of several alimentary factors--such as diet, nutritional habits, and personal preferences--upon the occurrence of obesity. SUBJECTS: Of the study were 264 workers (203 men and 61 women) from the ammonium production department of a fertilizer plant, divided into two age groups: under 30 years and over 30 years. METHODS: The data are collected by means of a questionnaire about daily nutrition, including the types and average quantity of food (Food Frequency Questionnaires--FFQ). All collected information is analyzed by means of a computer program with a database that includes the chemical structure of food products and takes into account the losses in their nutritional value that occurs in the course of preservation and thermal processing. The nutritional status is assessed on the basis of a Body Mass Index (BMI): group I--normal body mass--BMI 18.5-25 kg/m2; group II--overweight--BMI 25.1-30 kg/m2; group III--obesity--BMI > 30 kg/m2. RESULTS: The assessment of the individual energy intake shows that hyper-energetic nutrition is typical for 67% of the individuals examined. There is no significant age and/or gender difference. This is the result of extra-intake of fat (over 30 E%), which is observed for 87.9% of all workers, and over 40 E% for almost half of the women examined. All age and gender groups display hyper-protein nutrition with pronounced cellulose (fiber) deficit, high daily intake of sodium, and disbalance of mineral salts as well as a relative deficit of vitamin A, B1, and PP. The frequency of overweight individuals is 43.9%, while that of obese individuals is 23.1%. The majority of workers (70.1% of group I, 63.2% of group II, and 79% of group III) have three meals a day. For 43% of group III individuals dinner is the largest meal. A significantly higher percentage of group III individuals (21.3%) think that they overeat. CONCLUSIONS: Hyper-energetic, disbalanced nutrition, and incorrect nutritional-behavioral model are factors that determine the prevalence of overweight and obesity among the workers examined.     

Survival implications of molecular heterogeneity in variant Philadelphia-positive chronic myeloid leukaemia

The BCR-ABL fusion in chronic myeloid leukaemia (CML) is generated by the Philadelphia (Ph) translocation t(9;22) or, in 10% of patients, variants thereof (vPh). Deletion encompassing the reciprocal product (ABL-BCR) from the derivative chromosome 9 [der(9)] occurs in 15% of all patients, but with greater frequency in vPh patients. Reports of physical separation of ABL-BCR in non-deleted patients, as well as evolution from classical to variant Ph, introduce further heterogeneity to the vPh subgroup and raise the possibility that such translocations may herald disease progression. Survival analyses, however, have thus far yielded contradictory results. We assessed the frequency of der(9) deletions, ABL-BCR abrogation, cytogenetic evolution and cryptic rearrangement in a large cohort of 54 patients with vPh CML. Deletions encompassing ABL-BCR were detected in 37% of patients, consistent with a model in which a greater number of chromosome breaks increases the risk of genomic loss. The components of ABL-BCR were physically separated in a further 52% of patients while fused in the remaining 11%. Evolution from classical to vPh was demonstrated in three patients. The difference in survival, as indicated by Kaplan-Meier analysis, was marked between classical and vPh patients (105 vs 60 months respectively; P = 0.0002). Importantly, this difference disappeared when patients with deletions were removed from the analysis. Our study showed that, despite the existence of several levels of genomic heterogeneity in variant Ph-positive CML, der(9) deletion status is the key prognostic factor.     

Opisthorchiasis in the Kemerovo Region

In the Kemerovo Region, the incidence of opisthorchiasis increased among adults and children from 44.0 in 1995 to 78.2 per 100,000. The high risk of Opisthorchis infection in children aged less than 14 years has recently increased from 17.2 to 35.0.     

Chromosome 11q23 translocations in both infant and adult acute leukemias are detected by in situ hybridization with a yeast artificial chromosome.

The yeast artificial chromosome (YAC-13HH4), which spans a 440-kb region of DNA just distal to the CD3 locus on chromosome 11 at band q23, has been used to characterize a range of chromosomal translocations in acute leukemias from both adults and infants. In situ hybridization was performed on metaphase cells from bone marrow of 17 leukemias and two cell lines with a variety of chromosome 11q23 abnormalities. It was established that in infant leukemias the translocations t(11;19), t(4;11), and t(5;11) had occurred in the region defined by YAC 13HH4. Additionally, the translocations t(4;11), t(6;11), t(9;11), t(X;11), and t(10;11) in other leukemias were found to disrupt the same region of chromosome 11q23, although an exception was found in one t(6;11) translocation for which the breakpoint was distal to the YAC. One patient had a t(9;11) translocation in a therapy-related leukemia, suggesting that this class of etoposide-related malignancy has similar breakpoints to those occurring in de novo leukemias. An example of a lymphoma-derived translocation t(4;11) was shown to involve a deletion of the region defined by YAC 13HH4. A leukemia with a deletion on chromosome 11 (q23-q25) was also studied and it was shown that the YAC sequence was unaffected. It was concluded that, with a few exceptions, the translocations at 11q23 in a wide range of acute infant and adult leukemias occur in a common region and may result from a common underlying mechanism.