The interrelationship between attentional and executive deficits in major depressive disorder.

OBJECTIVE: Cognitive dysfunction is an established feature of major depressive disorder (MDD). However, it remains unclear whether deficits in different cognitive domains are relatively independent or originate from a circumscribed 'primary deficit'. This study tested the hypothesis that a deficit in attention represents a primary deficit in depression. METHOD: Neuropsychological function was assessed in 30 depressed patients with MDD and 34 control participants. Cognitive composites were derived from a minimum of three tests and included attention, executive function, visuospatial memory and verbal memory. A multivariate analysis of variance was used to assess group differences in overall cognitive performance, and multiple regression models were used to evaluate the role of attention in deficits in other domains. RESULTS: The cognitive deficit in the depressed sample was found to be characterized by poorer performance in attention and executive function. When evaluating the interrelationship between the two deficits, the attentional deficit was found to persist when variability in executive function was statistically accounted for, whilst the executive deficit was eliminated when attention was accounted for. CONCLUSION: The results demonstrated that the attentional deficit could not be explained by deficits in executive function, which provides support for a primary attention deficit in depression.

Influence of growth conditions and developmental stage on N-glycan heterogeneity of transgenic immunoglobulin G and endogenous proteins in tobacco leaves.

Plants are regarded as a promising system for the production of heterologous proteins. However, little is known about the influence of plant development and growth conditions on N-linked glycosylation. To investigate this, transgenic tobacco (Nicotiana tabacum cv Samsun NN) plants expressing a mouse immunoglobulin G antibody (MGR48) were grown in climate rooms under four different climate conditions, i.e. at 15 degrees C and 25 degrees C and at either low or high light conditions. N-glycans on plantibodies and soluble endogenous proteins were analyzed with matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). Antibodies isolated from young leaves have a relatively high amount of high- mannose glycans compared with antibodies from older leaves, which contain more terminal N-acetylglucosamine. Senescence was shown to affect the glycosylation profile of endogenous proteins. The relative amount of N-glycans without terminal N-acetylglucosamine increased with leaf age. Major differences were observed between glycan structures on endogenous proteins versus those on antibodies, probably to be attributed to their subcellular localization. The relatively high percentage of antibody N-glycan lacking both xylose and fucose is interesting.

Galactose-extended glycans of antibodies produced by transgenic plants.

Plant-specific N-glycosylation can represent an important limitation for the use of recombinant glycoproteins of mammalian origin produced by transgenic plants. Comparison of plant and mammalian N-glycan biosynthesis indicates that beta1,4-galactosyltransferase is the most important enzyme that is missing for conversion of typical plant N-glycans into mammalian-like N-glycans. Here, the stable expression of human beta1,4-galactosyltransferase in tobacco plants is described. Proteins isolated from transgenic tobacco plants expressing the mammalian enzyme bear N-glycans, of which about 15% exhibit terminal beta1,4-galactose residues in addition to the specific plant N-glycan epitopes. The results indicate that the human enzyme is fully functional and localizes correctly in the Golgi apparatus. Despite the fact that through the modified glycosylation machinery numerous proteins have acquired unusual N-glycans with terminal beta1,4-galactose residues, no obvious changes in the physiology of the transgenic plants are observed, and the feature is inheritable. The crossing of a tobacco plant expressing human beta1,4-galactosyltransferase with a plant expressing the heavy and light chains of a mouse antibody results in the expression of a plantibody that exhibits partially galactosylated N-glycans (30%), which is approximately as abundant as when the same antibody is produced by hybridoma cells. These results are a major step in the in planta engineering of the N-glycosylation of recombinant antibodies.

Effect of climate conditions and plant developmental stage on the stability of antibodies expressed in transgenic tobacco.

Plants are regarded as a promising system for the production of heterologous proteins. However, little is known about the influence of plant physiology and plant development on the yield and quality of the heterologous proteins produced in plants. To investigate this, tobacco (Nicotiana tabacum cv Samsun NN) was transformed with a single construct that contained behind constitutive promotors the light- and heavy-chain genes of a mouse antibody. The in planta stability of the antibody was analyzed in transgenic plants that were grown under high and low irradiation at 15 degrees C and 25 degrees C. High-light conditions favored the production of biomass, of total soluble protein, and of antibody. The plants grown at 25 degrees C developed faster and contained less antibody per amount of leaf tissue than the plants grown at 15 degrees C. Both endogenous protein and antibody content showed a strong decline during leaf development. The heavy chains of the antibody underwent in planta degradation via relatively stable fragments. In vitro incubations of purified plantibody with leaf extracts of wild-type tobacco indicated the involvement of acidic proteases. It is interesting that the same antibody produced by mouse hybridoma cells exhibited higher stability in this in vitro assay. This may be explained by the assumption that the plant type of N-glycosylation contributes less to the stability of the antibody than the mouse-type of N-glycosylation. The results of this study indicate that proteolytic degradation during plant development can be an important factor affecting yield and homogeneity of heterologous protein produced by transgenic plants.

New techniques for liver transplantation: reduced-size, split-liver, living-related and auxiliary liver transplantation.

Mortality among patients on a waiting list for orthotopic liver transplantation continues to be 10-15%; this is of particular concern in the pediatric population and may become more problematic in adult patients as longer waiting lists for cadaveric transplantation accrue. The longer cold ischemia times afforded by use of University of Wisconsin (UW) solution and improved hepatic surgery techniques have allowed the development of reduced-size liver transplantation (RSLT), split-liver transplantation (SLT), and living-related liver transplantation (LRLT). These new surgical techniques have been predominantly employed in children, up to 40% of whom may be candidates for one of these modified procedures. With the exception of SLT, these approaches have been associated with comparable rates of biliary tract and vascular complications, rejection episodes and graft and patient survival when compared to whole organ transplantation. Right hepatic lobe graft recipients have approximately 15% decreased graft survival rates, limiting the acceptance of SLT as a standard approach to decrease waiting list times. Application of LRLT to the adult population, where 5-10% of recipients are potential candidates, is expected to increase. Over 100 LRLTs have been performed worldwide and while recipient survival with LRLT is excellent, concerns about donor morbidity and mortality, psychosocial factors and reimbursement issues remain obstacles. Living-unrelated liver transplantation and auxiliary orthotopic partial liver transplantation are developing approaches to be considered only in highly selected cases.

Nasointestinal tube for decompression or enteroclysis: experience with 150 patients.

The initial clinical experience with the use of a triple lumen long tube designed for gastrointestinal decompression and enteroclysis is reported in 150 patients. Based on clinical observations, this tube is effective in suctioning retained gastric and intestinal fluid but requires frequent irrigation of the sump port for effective decompression of distended small bowel. In all patients with a preexisting nasogastric tube, the replacement by the decompression/enteroclysis tube was considered more comfortable by the patients. Successful placement of the tube in the jejunum was achieved in 147 of 150 consecutive patients on the initial attempt. The use of this tube obviates dual intubations for decompression and enteroclysis, the attendant discomfort on the patient, and it expedites subsequent performance of enteroclysis if needed. The complications reported with other long intestinal tubes were not observed with this device.

Subcellular localization of tryptophan decarboxylase, strictosidine synthase and strictosidine glucosidase in suspension cultured cells of Catharanthus roseus and Tabernaemontana divaricata.

The subcellular localization of tryptophan decarboxylase, strictosidine synthase and strictosidine glucosidase in suspension cultured cells of Catharanthus roseus (L.) G. Don and Tabernaemontana divaricata (L.) R. Br. ex Roem. et Schult, was investigated. It was found that tryptophan decarboxylase is an extra-vacuolar enzyme, whereas strictosidine synthase is active inside the vacuole. Strong indications were obtained for the localization of strictosidine glucosidase on the outside of the tonoplast. The results suggest that tryptamine is transported into the vacuole where it is condensed with secologanin to form strictosidine, and that strictosidine passes the tonoplast and is subsequently hydrolysed outside the vacuole.

Dual-purpose tube for enteroclysis and nasogastric-nasoenteric decompression.

A catheter designed for the dual purpose of nasogastric-nasoenteric decompression and enteroclysis is described. The catheter facilitates direct decompression of the obstructed small bowel and, if necessary, subsequent performance of enteroclysis. The use of this tube obviates dual intubation and its accompanying discomfort.

Hepatic artery thrombosis in infants. A comparison of whole livers, reduced-size grafts, and grafts from living-related donors.

Hepatic artery thrombosis (HAT) is a major cause of patient morbidity and graft loss in pediatric liver transplantation (OLT). Although some grafts may be salvaged by arterial thrombectomy and reconstruction, many patients require retransplantation. Patient survival is reduced by HAT. It has been suggested that the incidence of HAT may be altered by the use of reduced-size grafts (RSG). We analyzed our series of infants receiving OLT to determine the frequency of HAT in full-size OLT, cadaveric RSG, and living-related RSG. The role of arterial anastomotic technique in the development of HAT was also examined. Between 10/1/84 and 12/7/90 433 liver transplants were performed. During this period 100 patients between 3 months and 2 years of age (mean 13 months) received 134 liver grafts. The mean weight at the time of transplant was 7.9 kg. (range: 1.9-15 kg). Of the 134 grafts, 60 were whole livers, 61 were cadaveric RSGs, and 13 were living-related RSGs. The cadaveric RSGs were 9 right lobe grafts, 21 left lobe grafts, and 31 left lateral segment grafts. Twenty-seven of the cadaveric RSGs were from split livers, while the other 34 were simple reductions. All 13 living-related RSGs were left lateral segments. HAT occurred in 15 of 60 (25%) whole livers, 9 of 61 (15%) cadaveric RSGs, and 3 of 13 (23%) of the living-related-donor RSGs (P = NS). Subdividing the cadaveric RSGs revealed that HAT occurred in 3 of 9 (33%) right lobe grafts, 3 of 21 (14%) left lobe grafts, and 3 of 31 (10%) left lateral segment grafts (P = NS). The site of the arterial anastomosis in the recipient correlated with the incidence of HAT (hepatic artery 21/86 [24%], celiac axis 1/9 [11%], aorta 2/32 [6%], P = 0.06). In conclusion, it appears that use of a cadaveric left lobe or left lateral segment graft and an aortic arterial anastomosis reduces the risk of hepatic artery thrombosis in liver transplant recipients less than 2 years of age.

Death occurring within one week of cardiac transplantation: findings in eight patients.

Between October 1982 and July 1988, 85 patients underwent orthotopic heart transplantation at Methodist Hospital of Indiana. Excluding perioperative deaths, survival rates at six months, one year, two years and three years were 94%, 80%, 74% and 61%, respectively. However, eight patients (9.4%) died within one week of the transplantation. Causes of death included acute failure of the right side of the heart in four patients; compression of the proximal portions of the coronary arteries in one patient; hyperacute rejection in one patient; acute pneumonia and the adult respiratory distress syndrome in one patient; and sudden death of unknown etiology in one patient. The varied causes of death in this group of patients made it inaccurate to assume a particular cause of death for an individual patient, based on the length of the postoperative period alone. We reviewed these eight deaths in detail to better understand and, therefore, reduce the risk of early postoperative death in future patients.

The use of reduced-size liver transplants in children, including split livers and living related liver transplants.

One of the key problems facing children awaiting liver transplantation is the shortage of donor organs. Surgical procedures that address this problem include: reduced-size liver transplantation (RLT), split liver transplantation (SLT), and living related liver transplantation (LRLT). RLT makes more of the current donor pool accessible to the pediatric recipient. SLT furnishes 2 liver grafts from 1 cadaveric donor, and LRLT provides an innovative supply of donor organs. This report compares the results achieved with RLT, SLT, and LRLT to those seen with full-size orthotopic liver transplantation (OLT). Between November 1984 and February 1991, 457 liver transplants were performed at the University of Chicago. Two hundred fourteen of these transplants were placed into recipients less than 13 years of age. Of these 214 pediatric orthotopic liver transplants (OLT), 103 were full-size livers and 111 were some type of reduced graft (RLT, SLT, or LRLT). There were 57 RLT, 34 SLT, and 20 LRLT. The recipients of the reduced grafts (RLT, SLT, or LRLT) averaged 1.9 +/- 1.8 years of age and 9.6 +/- 6.4 kg compared to the recipients of the full-size livers who averaged 3.5 +/- 3.4 years of age and 14.1 +/- 8.8 kg (p = 0.0001). The most common indication for transplantation was biliary atresia (105 patients). Overall patient survival after primary full-size OLT was 71.8%. Reduced-size OLT (RLT, SLT, and LRLT) resulted in an overall patient survival of 72.6% after primary transplantation. Patient survivals for primary transplants with specific types of reduced-size grafts were: RLT 76.5% (after RLT was used routinely), SLT 66.7%, and LRLT 89.5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Assay of strictosidine synthase from plant cell cultures by high-performance liquid chromatography.

An HPLC assay is described for the enzyme strictosidine synthase in which the formation of strictosidine and the decrease of tryptamine can be followed at the same time. In cell cultures of Catharanthus roseus significant amounts of strictosidine glucosidase activity were detected. In crude preparations, the strictosidine synthase reaction is therefore best measured by the secologanin-dependent decrease of tryptamine. In this way, the specific synthase activity in a cell free extract was found to be 56 pkat/mg of protein. Inclusion of 100 mM D(+)-gluconic acid-delta-lactone in the incubation mixture inhibited 75% of the glucosidase activity, without inhibiting the synthase activity. The synthase activity was readily separated from the glucosidase activity by gel filtration on Sephadex G-75 or Ultrogel AcA-44. Cell cultures of Tabernaemontana orientalis did not contain measurable amounts of strictosidine glucosidine activity. The specific strictosidine synthase activity was 130-200 pkat/mg of protein during the growth of this cell culture. Strictosidine synthase is stable at -20 degrees C for at least 2 months.

Methyl linoleate ozonide as a substrate for rat glutathione S-transferases: reaction pathway and isoenzyme selectivity.

The 9,10-mono-ozonide of methyl linoleate was shown to be a substrate for rat hepatic cytosolic, rat lung cytosolic and rat hepatic microsomal glutathione S-transferases (GST). The activities of lung cytosol and liver microsomes with methyl linoleate ozonide (MLO) were found to be high relative to the activity demonstrated by liver cytosol, as compared with their respective activities towards 1-chloro-2,4-dinitrobenzene (CDNB). Only a slight catalytic activity towards the ozonide was noticed for rat lung microsomes. Isoenzyme 2-2 exhibited the highest specific activity (208 nmol/min/mg) when isoenzymes 1-1, 1-2, 2-2, 3-3, 3-4, 4-4 and 7-7 were compared. This isoenzyme accounts for approx. 25% of cytosolic GST protein in rat lung, while in rat liver it represents approx. 9%. This may partly explain the high activity towards the ozonide noticed for rat lung cytosol. No stable conjugates were formed as products of the reaction of MLO with glutathione; although two glutathione-conjugates were noticed on TLC, they were only formed as intermediate compounds. Coupling of an aldehyde dehydrogenase assay or a glutathione reductase assay to the GST-catalyzed conjugation, demonstrated that oxidized glutathione and aldehydes are formed as the major products in the reaction. To further confirm the formation of aldehydes, the products of the GST-catalyzed reaction were incubated with 2,4-dinitrophenylhydrazine, which resulted in hydrazone formation. In conclusion, the activity of the GST towards the ozonide of methyl linoleate is similar to their peroxidase activity with lipid hydroperoxides as substrates.

Left atrial myxoma: pulmonary infarction caused by pulmonary venous occlusion.

Atrial myxomas are the most common primary cardiac tumors. Typical complications include congestive heart failure, systemic emboli, or vasculitic type syndromes. Presented is a case of postpartum congestive heart failure in a 17-year-old girl. Echocardiography revealed a left atrial mass. Intraoperatively this mass was found to be extending into and occluding the left pulmonary veins. Left pulmonary infarction had occurred, and left pneumonectomy was required to completely remove the lesion. This case thus represents an unusual complication of left atrial myxoma.

Continuous nasogastric phosphorus infusion in hypophosphatemic rickets of prematurity.

Radiologic and biochemical abnormalities associated with nutritional hypophosphatemic rickets were discovered in a 945-g preterm infant despite daily supplementation with 800 to 1,600 IU of ergocalciferol (vitamin D2) and an elevated serum 25-hydroxyvitamin D concentration. Vitamin D supplementation was stopped, and the rickets was corrected by phosphorus supplement alone with the use of a unique technique of long-term, continuous nasogastric phosphorus infusion. Normophosphatemia was rapidly achieved and effectively maintained. Hypocalcemia did not occur at rates of infusion of 100 mg of elemental phosphorus per day. The data are consistent with specific phosphorus deficiency as the cause of rickets in this infant, rather than insufficient vitamin D intake or disturbed vitamin D metabolism. We speculated that continuous phosphorus infusion prevents the intermittent hyperphosphatemia of bolus phosphorus supplement and that continuous phosphorus infusion may be useful in the treatment of other hypophosphatemic states of infancy.