Distinct gene expression profiles in subsets of chronic lymphocytic leukemia expressing stereotyped IGHV4-34 B-cell receptors

Background

Numerous subsets of patients with chronic lymphocytic leukemia display similar immunoglobulin gene usage with almost identical complementarity determining region 3 sequences. Among IGHV4-34 cases, two such subsets with “stereotyped” B-cell receptors were recently identified, i.e. subset #4 (IGHV4-34/IGKV2-30) and subset #16 (IGHV4-34/IGKV3-20). Subset #4 patients appear to share biological and clinical features, e.g. young age at diagnosis and indolent disease, whereas little is known about subset #16 at a clinical level.

Design and Methods

We investigated the global gene expression pattern in sorted chronic lymphocytic leukemia cells from 25 subset/non-subset IGHV4-34 patients using Affymetrix gene expression arrays.

Results

Although generally few differences were found when comparing subset to non-subset 4/16 IGHV4-34 cases, distinct gene expression profiles were revealed for subset #4 versus subset #16. The differentially expressed genes, predominantly with lower expression in subset #4 patients, are involved in important cell regulatory pathways including cell-cycle control, proliferation and immune response, which may partly explain the low-proliferative disease observed in subset #4 patients.

Conclusions

Our novel data demonstrate distinct gene expression profiles among patients with stereotyped IGHV4-34 B-cell receptors, providing further evidence for biological differences in the pathogenesis of these subsets and underscoring the functional relevance of subset assignment based on B-cell receptor sequence features.     

Effects of prolonged warm and cold ischemia in a solitary kidney animal model after partial nephrectomy: an ultrastructural investigation

Ischemia-reperfusion injury can be detrimental to the solitary kidney, especially when it is accompanied by ablation. To the authors' knowledge, the effects of partial nephrectomy with prolonged application of ischemia have never been described at the ultrastructural level. Therefore, the authors used an animal model and focused on putative structural effects in the glomerular basement membrane and the podocytes. They demonstrate the advantageous role of cold ischemia, even in up to 120 min. In contrast, more than 60 min of warm ischemia leads to catastrophic lesions in all the cellular structures, as is reflected by mortality due to acute renal failure.     

Serum anti-Saccharomyces cerevisiae antibodies in Greek patients with Behcet's disease

We tested 59 Greek patients with Behcet's Disease (BD) for serum anti-Saccharomyces cerevisiae antibodies. No increase of these antibodies was detected in the cases compared to 55 healthy unrelated blood donors from the same population. This finding is in contrast with the correlation between Saccharomyces cerevisiae antibodies and BD as reported in other populations. It seems that environmental factors may contribute to disease expression in different populations, producing different effects according to the individual's genetic predisposition. Saccharomyces cerevisiae antibodies do not seem to be of any significance in the Greek population.     

Role of age on the outcome of liver surgery. A single institution experience

Objective: The aim of the present study was to evaluate the role of age on different types of liver surgery. Methodology: Between 2002 and 2007, 50 patients underwent a variety of liver surgical procedures due to primary or metastatic tumours. Of these, 24 were 70 years old or older, and 26 patients were younger than 70 years old at the time of the operation. Results: Among the patients included in the study, 22 underwent radiofrequency ablation. Another 11 underwent non‐anatomical liver resection. The remaining 17 patients underwent liver resection, with more than three segments resected. The type of procedure, duration of operation, estimated blood loss, and postoperative death and morbidity rates were not significantly different between the two groups. The mean survival of patients that underwent radiofrequency ablation or non‐anatomical resection was not significantly different between the two groups. However, in the patients in which liver resection was performed, mean survival was significantly greater in the younger group. Conclusions: These results indicate that hepatic resection is a safe and feasible procedure in elderly patients. The postoperative outcome in this age group is comparable of that of younger patients.     

Prevalence and axial length of hiatus hernia in patients, with nonerosive reflux disease: a prospective study

BACKGROUND AND AIMS: The relationship between hiatus hernia and reflux esophagitis is well established. However, there are conflicting reports regarding its effect on the development of nonerosive reflux disease (NERD). Our aim was to investigate the prevalence and axial length of hiatus hernia in patients with NERD, compared with patients with reflux esophagitis, Barrett esophagus, and controls. METHODS: Axial hernia length of the diaphragmatic hiatus was measured prospectively at endoscopy in controls and patients with typical reflux symptoms occurring at least weekly during the last month relieved by antacids. RESULTS: A final diagnosis of hiatus hernia was established in 21.2% of 249 controls, 60.4% of 346 patients with NERD, 78.1% of 251 patients with reflux esophagitis, and 88.2% of 17 patients with Barrett esophagus. Patients aged >59 years were most likely to have a hiatus hernia. There was an increased prevalence in patients with NERD as compared with controls (P<0.0001), and decreased prevalence as compared with those with reflux esophagitis and Barrett esophagus (P<0.0001 and 0.02, respectively). Axial length of hiatus hernia >3 cm was found more frequently in patients with reflux esophagitis and Barrett esophagus as compared with patients with NERD (P<0.0001 and 0.0052, respectively). There was no statistical significant difference between controls and patients with NERD regarding the prevalence of hiatus hernia >3 cm (P=0.0904). CONCLUSIONS: A small (<3 cm) hiatus hernia may contribute to the development of NERD, whereas an axial length >3 cm is associated with a more severe disease.     

Thyroid hormone synthesis and secretion in humans after 80 milligrams of iodine for 15 days and subsequent withdrawal

CONTEXT: In animals, acute iodine administration results in acute intrathyroidal inhibition of iodinations followed by escape of the inhibition if the excessive iodine intake continues. In humans, the intrathyroidal nonhormonal and hormonal iodine concentration after exposure to large doses of iodine for a relatively long period of time is not known. OBJECTIVE: To determine whether, in human thyroid, administration of large doses of iodine for a relatively long time results in alterations of intrathyroidal hormonal (HI) T4 and T3 and total iodine (TI) content, as well as whether changes in serum concentration of thyroid hormones and TSH would occur after iodine administration or discontinuation. DESIGN: In 33 euthyroid patients with single thyroid nodule or hyperparathyroidism, Lugol solution (80 mg iodine) was administered for 15 d before operation. Groups of six to eight patients underwent operation 0, 5, 10, and 15 d after iodine withdrawal. TI, HI in a sample of thyroid tissue, and serum concentration of T4, T3, and TSH were measured. In 21 normal euthyroid subjects who did not undergo operation, a similar protocol was used and serial blood measurements were taken. MAIN OUTCOME MEASURE: Intrathyroidal TI, HI, and serum thyroid hormone and TSH measurements were the main outcome measure. RESULTS: Intrathyroidal HI content and serum T4 and T3 were unchanged during and after iodine discontinuation. TI was increased during iodine administration and returned to control values 5 d after discontinuation of iodine. The ratio of HI/TI was decreased and returned to control values 15 d after the iodine was discontinued. Serum TSH was increased during iodine administration and returned to control values 10 d after iodine withdrawal. CONCLUSIONS: In humans, administration of iodine for a relatively long period of time was accompanied by increased intrathyroidal TI, but no changes in HI or demonstrable increases of serum T4 and T3 were observed. It is hypothesized that the maintenance of normal intrathyroidal HI is the result of the combined inhibitory effect of iodine on thyroid hormone synthesis and on the release of T4 and T3 from the thyroid.     

Hip fracture discrimination by the Achilles Insight QUS imaging device

The importance of osteoporosis as a major health problem is well recognized. Its major clinical manifestation is low energy fractures. Considerable effort has been directed towards search of noninvasive methods for assessing osteoporotic fracture risk. The aim of this study was to evaluate the ability of quantitative ultrasound (QUS) variables measured by a new heel QUS imaging device to discriminate between postmenopausal women with and without hip fracture. The subjects included 30 postmenopausal female patients with hip fracture and 30 age-matched healthy women. Measurements were acquired using the Achilles Insight QUS imaging device. Bone mineral density (BMD) measurements were carried out using the Lunar Prodigy DXA scanner. Achilles Insight provides images of the heel bone and measures broadband ultrasound attenuation (BUA) and speed of sound (SOS) values in a circular region of interest. A third QUS variable, the stiffness index (SI) was also determined. The short-term precision for healthy subjects was 2.05%, 0.17% and 1.91% for BUA, SOS and SI, respectively. Corresponding values for patients with fractures were 1.80%, 0.16% and 2.04%. All QUS variables measured using the Achilles Insight were significant discriminators of hip fractures (area under ROC curve=0.77, 0.74 and 0.77 for BUA, SOS and SI, respectively). BMD measurements of the hip had the greatest discriminatory ability (area under ROC curve=0.88). Statistically significant differences were found between the area under the ROC curve of BMD and the corresponding curves of the QUS variables (P<0.05 for each of the three comparisons). QUS variables measured by Achilles Insight can be expected to be useful as indicators of the risk of hip fracture in postmenopausal women.     

Is hybridic positron emission tomography/computerized tomography the only option? The future of nuclear medicine and molecular imaging

As we all know, Nuclear Medicine is the medical science using nuclear radiation for diagnosis, treatment and research. Nuclear Medicine, in contrast to Radiology, makes use of unsealed sources of radiation. Nuclear Medicine a few years ago has partly offered Nuclear Cardiology, the most lucrative of all Nuclear Medicine "children" at that time, to Cardiology. Radiology, has succeeded in being recognized by the European Union Authorities as Clinical Radiology. The word "clinical" offers greater independence to Clinical Radiology and makes it difficult for such a specialty to relinquish any of its equipment i.e. the diagnostic CT scan or the newly developed fast angiography CT, to other specialties. Contrary to Clinical Radiology, Nuclear Medicine being a laboratory specialty in most countries seems to have no right to deny offering, after some period of "proper certified education", its PET camera to Clinical Radiologists. Nuclear Medicine by virtue of its unique diagnostic techniques and treatments, is and should be recognized as a "Clinical Specialty" The interference of other specialties in the fields of Nuclear Medicine is also indicated by the fact that in vitro techniques of Nuclear Medicine are often used by Endocrinologists and Oncologists in their own laboratories. Also in some hospitals the Director of the Radiology Department acts as the Director of Nuclear Medicine Laboratory. Finally at present, Radiologists wish after "proper certified education", to be on equal terms in charge of the new hybridic equipment, the PET/CT scanner. If that is followed to happen, Nuclear Medicine will be in a difficult position losing at least part of PET and consequently should ask for help from its "Overlords and Protectors" i.e. the National and the European Societies of Nuclear Medicine and the Society of Nuclear Medicine of the United States of America. Radiology as a specialty participating om equal terms with the PET camera will then include the study of: a) "open sources of radiation" b) nuclear radiation and c) molecular nuclear medicine. The "European Journal of Nuclear Medicine and Molecular Imaging" shall have to erase the three last words of its title and be renamed. As Professor Abass Alavi et al (2007), have mentioned: "Is PET/CT the only option?" In favor of PET/CT are the following: Attenuation correction (AC) and better anatomical localization of lesions visualized with PET. Also PET/CT can be used as a diagnostic CT scanner (dCT). Against using the PET/CT scanners are the following arguments: a) This equipment is not necessary because we can always ask the Radiologists for a dCT scan. Many patients have already done a dCT scan at the time they are referred for a PET scan to the Nuclear Medicine Department. b) The absolute clinical indications for PET/CT with the use of a contrast agent, are under investigation. c) Although there is at present a list of indications suggested for the PET/CT scanner, there are studies disputing some of these indications, as for example in metastatic colon cancer where a high diagnostic accuracy for PET study alone, has been reported. d) The option of AC performed by the PET/CT scanner has also been questioned. Artifacts may be up to 84%. e) The PET/CT is expensive, time consuming, space occupying, and needs additional medical and technical personnel. f) Not to mention the extra radiation dose to the patients. g) Shall we inform those young medical students who wish to become nuclear medicine physicians, to hold their decision till the content of future Nuclear Medicine is clarified? We may suggest that: Our specialty could be renamed as: "Clinical Nuclear Medicine" and include additional "proper certified education" on the PET/CT equipment. The PET/CT scanner should remain in the Nuclear Medicine Department where Radiologists could act as advisors.     

The use of spray electrocautery to control presacral bleeding: a report of four cases

Bleeding originating from the presacral venous plexus during pelvic operations is difficult to control, constituting a potentially life-threatening complication. Although suture ligatures, packing, and placement of tacks are established hemostatic techniques, they are often proved to be ineffective. We report a simple novel technique using spray diathermy for managing this severe complication. We have applied our method in four patients, two undergoing low anterior resection, and the others undergoing abdominoperineal resection for rectal cancer, that manifested severe presacral bleeding during rectal mobilization. Electrocautery at spray setting was applied slightly above the target bleeders at the presacral fascia, delivering a high-frequency electrical current in combination with drainage suction. In all cases, the method resulted in successful hemostasis. Applying spray electrocautery is a simple and effective method for controlling presacral bleeding. The advantages of using such a method instead of conventional hemostatic techniques include the option of varying the degree of haemostatic effect by altering the frequency and the volume of electric current.     

Chromatin structure and DNA methylation of the <Emphasis Type="Italic">IL-4 gene</Emphasis> in human T<Subscript>H</Subscript>2 cells

Human T_H2 cell differentiation results in the selective demethylation of several specific CpG dinucleotides in the IL-4 and IL-13 genes, which are expressed in activated T_H2, but not T_H1, cells. This demethylation is accompanied by the appearance of six DNase I hypersensitive sites within 1.4 kb at the 5'-end of the IL-4 gene. Micrococcal nuclease (MNase) digestion revealed that in both T_H1 and T_H2 cells nine nucleosomes with a repeat length of 201 bp are identically positioned around the 5'-end of the IL-4 gene. However, only in T_H2 cells are six out of the eight intervening linkers exposed to DNase I. This suggests that a major perturbation of the higher-order chromatin structure occurs above the level of the nucleosome in vivo. It is observed in cells that are poised for expression but which are not actively expressing the gene (i.e. resting T_H2 cells). Notably, all the demethylated CpGs in T_H2 cells are found in DNA that is accessible to DNase I. This may suggest that the opening of the chromatin structure allows binding of specific trans-acting factors that prevent de novo methylation. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Nicole Winkelmann passed away in 2004.