Molecular follow-up of disease progression and interferon therapy in chronic myelocytic leukemia

We previously reported that the abl promoter (Pa) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia (CML). The clinical implications of this finding are the subject of the present study in which samples of CML patients, including a group treated with interferon alpha (IFNalpha) were surveyed. The methylation status of the abl promoter was monitored by polymerase chain reaction (PCR) amplification of the Pa region after digestion with several site-methylation sensitive restriction enzymes. Some 74% of the DNA samples from blood and marrow drawn in the chronic phase were nonmethylated, similar to control samples from non-CML patients. The remaining 26% were partially methylated in the abl Pa region. The latter samples were derived from patients who were indistinguishable from the others on the basis of clinical presentation. Methylated samples were mostly derived from patients known to have a disease of longer duration (26 months v 7.5 months, P = .01). Samples of 30 IFNalpha-treated patients were sequentially analyzed in the course of treatment. Fifteen patients with no evidence of Pa methylation before treatment remained methylation-free. The remainder, who displayed Pa methylation before treatment, reverted to the methylation-free status. The outcome is attributed to IFNalpha therapy, as the Pa methylation status was not reversed in any of the patients treated with hydroxyurea. Methylation of the abl promoter indicates a disease of long-standing, most likely associated with a higher probability of imminent blastic transformation. It appears to predict the outcome of IFNalpha therapy far better than the cytogenetic response.     

Phototherapy and lithium prophylaxis

A random sample of patients (n = 43) had been investigated to detect any difference in response of bright light therapy in lithium-treated inpatients (n = 18) suffering from depression. Only 27% of the lithium-based inpatients respond to bright light therapy, but 73% of patients respond who were not treated with lithium. We conclude that lithium therapy reduces the chance of achieving t remission of depression by bright light therapy.     

The arterioportal fistula syndrome: clinicopathologic features, diagnosis, and therapy

BACKGROUND & AIMS: Arterioportal fistulas (APFs) are rare vascular disorders of the mesenteric circulation. The aim of this study was to determine the etiology, anatomical location, and main symptom at presentation of APFs, and analyze the various modes of treatment. METHODS: The etiology, clinical presentation, radiographs, and treatment of 12 patients with APFs are reported in detail, and another 76 cases published since 1980 are reviewed. RESULTS: APFs result from trauma (n = 25, 28%), iatrogenic procedures (n = 14, 16%), congenital vascular malformations (n = 13, 15%), tumor (n = 13, 15%), aneurysm (n = 12, 14%), and other causes (n = 11, 12%). The origin of APFs is the hepatic artery in the majority of patients (n = 56, 65%). The main symptoms at presentation are lower or upper gastrointestinal bleeding (n = 29, 33%), ascites (n = 23, 26%), heart failure (n = 4.5%), or diarrhea (n = 4.5%). Radiological intervention provides definitive treatment in 42% (n = 33) of patients, whereas the remainder are treated by surgery alone (n = 27, 31%) or a combination of radiological intervention and surgery (n = 8, 9%). CONCLUSIONS: APFs result in a protean syndrome variously combining portal hypertension and other hemodynamic imbalances (heart failure, intestinal ischemia). Single or multiple interventional radiological procedures using arterial and/or venous approaches allow definitive treatment of most APFs. With increasing technological advances, it is anticipated that surgery will only be indicated in rare instances after failure of radiological intervention(s).     

HoxA is a transcriptional regulator for expression of the hup structural genes in free-living Bradyrhizobium japonicum

A chromosomally integrated Bradyrhizobium japonicum hoxA mutant is unable to oxidize hydrogen in free-living conditions. Derepressing conditions that induce hydrogenase activity in free-living, wild-type B. japonicum cells cannot induce expression of the hydrogenase structural genes in the hoxA mutant. The DNA-binding capacity of HoxA at the hup promoter region was studied by means of gel retardation. Both heterotrophically growing cells and cells induced to express hydrogenase activity contain a protein that specifically binds to the hup promoter region. Crude protein extracts isolated from a B. japonicum hoxA mutant do not contain this binding compound. The HoxA protein was overexpressed in E. coli and isolated in the form of a maltose-binding protein (MBP)-HoxA fusion. The MBP-HoxA hybrid protein specifically bound to a 50 bp region of the hupSL promoter known to be important for regulation of hupSL expression.     

Potency comparison of peptidomimetic inhibitors against HIV-1 and HIV-2 proteinases: design of equipotent lead compounds

The results of investigation of haptoglobin (Hp) types in 596 donor blood samples in some towns of Ukraine (Dnepropetrovsk, Kharkov, Odessa, Kiev, Uzhgorod, Zhitomir) are presented. Three normal Hp types (Hp1-1, Hp2-1 and Hp2-2) have been found. The reliable interpopulation differences in the Hp types frequency were not found. On the whole the Hp types frequency in the type Hp1-1 comprised 12.7%. In the type Hp2-1-48.1% and in the type Hp2-2-36.5%. The frequency of the gene Hp1 is 0.38. The frequency of the Hp types and of the gene Hpl in Ukraine is similar to that in population of Eastern Europe and European Part of Russia.     

Wernicke's encephalopathy and dialysis: report of two cases

Wernicke encephalopathy is considered a complication of dialytic therapy, but there are few reports of this complication. We report a 57 years old man and a 45 years old woman, with grade IV renal failure, who after acute peritoneodialysis and chronic hemodialysis respectively, had a confusional syndrome that responded to the administration of thiamine. CT scans in both patients discarded abnormal blood collections or new cerebrovascular episodes. The man bad two previous cerebrovascular episodes, a severe anemia that was corrected, angina and an episode of arrhythmia during the dialytic procedure previous to the confusional episode. The woman had an acute uremic syndrome and a concomitant urinary tract infection during the confusional episode. Wernicke encephalopathy must be suspected in patients in dialysis with confusional episodes.     

AsK-edge EXAFS study of the ternary system Sb2S3–As2S3–Tl2S

The local environment of arsenic atoms in vitreous samples of the system Sb₂S₃–As₂S₃–Tl₂S has been studied by EXAFS at the AsK-edge. The crystalline compound Tl_5.6As₁₅S_25.3 situated within the zone of glass formation of the Sb₂S₃–As₂S_3–Tl₂S phase diagram was used as reference compound in order to derive appropriate phase and amplitude functions. The structure parameters determined were the number of first neighbours N _As–S, the arsenic-sulphur distance, R _As–S, and the Debye-Waller factor, σ_As–S. The influence of the glass-forming antimony sulphide Sb₂S₃ and the glass-modifying thallium sulphide Tl₂S on the As₂S₃ host matrix has been shown. This revised version was published online in November 2006 with corrections to the Cover Date.     

Multicenter study on the clinical value of fetal pulse oximetry. I. Methodologic evaluation. The French Study Group on Fetal Pulse Oximetry

OBJECTIVE: Our purpose was to evaluate the feasibility of intrapartum fetal pulse oximetry, the distribution of fetal oxygen saturation values, and the relationship with the neonatal outcome in a population with an abnormal fetal heart rate. STUDY DESIGN: A prospective multicenter observational study was performed from June 1994 to November 1995. Fetal oxygen saturation was continuously recorded with use of a Nellcor N-400 fetal pulse oximeter in case of an abnormal fetal heart rate during labor. Simultaneous readings of fetal oxygen saturation and fetal blood analysis were obtained at inclusion and before birth. Feasibility, adverse effects, distribution of fetal oxygen saturation values, and relationship with neonatal outcome were assessed. RESULTS: One hundred seventy-four patients were included. From 172 attempted sensor placements, the procedure was impossible in three cases and fetal oxygen saturation values were obtained in 164 cases (95.3%). Physicians considered sensor placement an easier task than an attempt at fetal blood analysis (easy in 87.5% vs 78.9% for fetal blood analysis, p = 0.03). The mean reliable signal time (+/- SD) was 64.7% +/- 32% during the first stage. There were no serious adverse effects in the study population. The mean fetal oxygen saturation during the first stage of labor was 42.2% +/- 8.0% (10th to 90th percentile range 30% to 53%). Fetal oxygen saturation was significantly correlated with scalp pH (r = 0.29, p = 0.01) but not with neonatal umbilical artery pH or gas values. There was a significant association between low fetal oxygen saturation (< 30%) and poor neonatal condition. CONCLUSION: The feasibility of fetal pulse oximetry is satisfactory in clinical practice. It is easy to use and provides a fair rate of recorded values, even in a population with suspicion of fetal distress. A low fetal oxygen saturation is significantly associated with an abnormal neonatal outcome.     

Na+ channel modulation and force-frequency relationship in human myocardium

Insect cell lines in culture are used for a variety of studies. In this laboratory imaginal disc cell lines have been established from primary cultures from third instar larvae, and used for a number of experiments. The effect of ageing on the morphology and physiology of Drosophila cell lines has received very little attention, although problems of genotypic or phenotypic changes in cell lines with age are recognized in other areas of animal cell culture. We tested our cell line Cl8+ for any difference in growth, morphology and response to 20-hydroxyecdysone (20HE) at different ages (passage numbers). The cells were found to multiply faster, adhere less firmly to the substrate and to lose the tendency to aggregate at higher passages. The response to 20HE in terms of cell numbers and induction of beta-galactosidase was similar at all passage numbers but morphological changes in hormone-treated cells were less obvious in the higher passages. Cell lines are likely to vary in the extent of ageing effects but workers are advised to be aware of the possibilities. We suggest the effects of age on cell lines should be established, and passage numbers noted in experimental reports.