Copper-dependent reciprocal transcriptional regulation of methane monooxygenase genes in Methylococcus capsulatus and Methylosinus trichosporium

PURPOSE: To better understand the dose and time dependence of radiation therapy (RT)-induced regional lung dysfunction as assessed by changes in regional lung perfusion. METHODS AND MATERIALS: Patients who were to receive RT for tumors in and around the thorax, wherein portions of healthy lung would be incidentally irradiated, were prospectively studied. Regional function was assessed pre- and post-RT with single photon emission computed tomography (SPECT) lung perfusion scans, obtained following the intravenous administration of approximately 4 mCi of technetium-99m macroaggregated albumin. Pre-RT computed tomography (CT) scans were used to calculate the three-dimensional (3D) dose distribution, reflecting tissue density inhomogeneity corrections. Each SPECT scan was correlated with the pre-RT CT scan, and the 3D dose distribution. Changes in regional lung perfusion were correlated with regional RT dose, at various time intervals following radiation. RESULTS: The data from 20 patients (7 breast cancer, 5 lymphoma, 1 esophagus, 1 sarcoma, and 6 lung cancer) have been analyzed. Patients with gross intrathoracic lung cancers causing obstruction of regional pulmonary arteries were not included. For most patients, there is a statistically significant dose-dependent reduction in regional blood flow at all time points following radiation. While a time dependence is suggested in the high dose range, the limited amount of data prevents meaningful statistical evaluation. CONCLUSIONS: Radiation therapy-induced regional lung dysfunction occurs in a dose-dependent manner and develops within 3-6 months following radiation. In contrast to classical "sigmoid" dose-response curves, described mainly for changes following whole lung irradiation, these data suggest a more gradual relationship between regional dysfunction and RT dose. Retraction of irradiated lung with secondary movement of unirradiated lung into the "3D-defined irradiated volume" may have introduced inaccuracies into this analysis. Additional studies are currently underway to assess this possibility and better refine this dose-response curve. Studies are underway to determine if changes in assessments of whole lung function, such as pulmonary function tests, can be predicted by summing the regional changes observed.     

The antioxidant probucol as a regulator of the intensity of free-radical lipid peroxidation processes in the blood of patients with coronary atherosclerosis

Two series of studies were made to assess probucol medicines (lipomal, "Alkaloid"; fenbutol "Akrikhin") effect on clinical symptoms, lipid metabolism, primary and secondary products of lipid peroxidation, activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase) in atherosclerotic patients with hyperlipidemia type IIA and IIB. In both series probucol reduced frequency of anginal attacks, content of total cholesterol and LDL cholesterol. HDL cholesterol remained unchanged or reduced insignificantly. Lipoperoxides and malonic dialdehyde levels in plasma progressively lowered against activation of antioxidant enzymes. These biochemical parameters returned to initial values within 3 months since the drug discontinuation. It is evident that antiatherogenic effect of probucol is due to indirect activation of natural defense systems responsible for enzymic detoxication of active oxygen forms and lipoperoxides rather than to direct interaction of this synthetic antioxidant with lipid radicals.     

Thrombolysis and endovascular stent placement for inferior vena caval thrombosis in a liver transplant recipient

BACKGROUND: Vascular complications remain an important cause of postoperative morbidity in liver transplant patients. Herein, we present an unusual case of nonanastomotic inferior vena cava (IVC) stenosis in a patient with a "piggyback" caval anastomosis. METHODS: A 59-year-old woman underwent liver transplantation using a piggyback IVC anastomosis. Her postoperative course was complicated by IVC thrombosis. Catheter-directed thrombolysis, followed by balloon angioplasty and intravascular stent placement, was used to recanalize the IVC and treat a severe retrohepatic IVC stenosis. RESULTS: After 46 hr of catheter-directed urokinase infusion, there was clot lysis and identification of a severe stenosis in the retrohepatic IVC. The lesion was extremely resistant to balloon dilatation alone and a 22-mm-diameter intravascular stent was placed. Simultaneous dilatation of three high-pressure balloons was necessary for maximal stent expansion. The patient remains asymptomatic with no evidence of IVC compromise through 20 months of follow-up. CONCLUSIONS: IVC stenosis and thrombosis after liver transplantation may be treated favorably in some patients using catheter-directed thrombolytic therapy followed by balloon dilatation and/or stent placement.     

The donor stage of orthotopic liver transplantation

First clinical experience of the harvesting (donor) stage of orthotopic transplantation of the liver in Russia is represented. During 5-year period in National Research Center of Surgery RAMS 16 orthotopic transplantations of the liver were carried out. Surgical modes of harvesting of the donor liver are detailed ("standard" and "fast"), the regimes and methods of preservation of the liver were determined. The influence of various parameters on function of the graft in postoperative period was established. Adequate selection of donors, correct and proper choice of donor-recipient pair, limited time of preservation allow to decrease the number of graft function failure and to eliminate primarily nonfunctioning grafts.     

Clinical biochemistry, haematology and body weight in piglets

Reference ranges for clinical biochemical parameters commonly investigated in pigs were determined in one- (day 1), 21- and 35-day old piglets. The mean and standard deviation were also estimated for body weight, and haematological and clinical biochemical parameters at these ages. The piglets were divided into 2 investigation groups according to whether they had a haemoglobin concentration < or = 80 g/l ("anaemic group") or > 80 g/l ("normal group") on days 14, 21 and 28. The "anaemic group" was compared to the "normal group" on days 21 and 35. Many of the clinical biochemical parameters varied according to age. Some of the enzymes had high average values and wide reference ranges in piglets, especially on day 1, compared to the reference ranges for sows given in the literature. The reference ranges for some of the metabolic parameters were broader on day 1 than later in the preweaning period. The reference ranges for albumin, total iron-binding capacity and serum iron were, however, lower and more narrow on day 1. On days 21 and 35, relatively high values for phosphorus must be considered "normal" compared to the figures given in the literature for adult pigs. The other minerals seemed to be quite unaffected of age, but some were affected by anaemia. The anaemic piglets had lower average serum iron but higher total iron-binding capacity than the "normal" piglets on days 21 and 35. However, variation between piglets gave wide reference ranges, indicating that these parameters will only have limited usefulness in detecting iron deficiency anaemia in piglets. The electrolytes seemed also to be affected by the existence of anaemia. The body weight and leukocyte counts were significantly lower in the "anaemic group" than the "normal group" on day 35, while the greatest differences in clinical biochemical parameters between the groups were found on day 21, when the piglets in the "anaemic group" were most severely anaemic. Although these piglets suffered from severe iron-deficiency anaemia, only a few clinical biochemical parameters were affected, and the differences between groups were mostly small.     

Contribution of proteasomal beta-subunits to the cleavage of peptide substrates analyzed with yeast mutants

Proteasomes generate peptides that can be presented by major histocompatibility complex (MHC) class I molecules in vertebrate cells. Using yeast 20 S proteasomes carrying different inactivated beta-subunits, we investigated the specificities and contributions of the different beta-subunits to the degradation of polypeptide substrates containing MHC class I ligands and addressed the question of additional proteolytically active sites apart from the active beta-subunits. We found a clear correlation between the contribution of the different subunits to the cleavage of fluorogenic and long peptide substrates, with beta5/Pre2 cleaving after hydrophobic, beta2/Pup1 after basic, and beta1/Pre3 after acidic residues, but with the exception that beta2/Pup1 and beta1/Pre3 can also cleave after some hydrophobic residues. All proteolytic activities including the "branched chain amino acid-preferring" component are associated with beta5/Pre2, beta1/Pre3, or beta2/Pup1, arguing against additional proteolytic sites. Because of the high homology between yeast and mammalian 20 S proteasomes in sequence and subunit topology and the conservation of cleavage specificity between mammalian and yeast proteasomes, our results can be expected to also describe most of the proteolytic activity of mammalian 20 S proteasomes leading to the generation of MHC class I ligands.     

Carisoprodol abuse: a report from India

Carisoprodol, a centrally acting muscle relaxant, has recently been noticed to be abused. A series of 16 cases with carisoprodol abuse or dependence is described. Carisoprodol was started by the majority of patients as a substitute for opiates, although its independent distinct effects, similar to the features of hypomania, were recognized and described by most users. The drug is currently available freely over the counter and is a much cheaper substitute for the legally prohibited "harder" drugs. Unless awareness spreads and cautionary measures are taken, carisoprodol abuse might become a great menace in the near future.