Ornithine decarboxylase transformation of NIH/3T3 cells is mediated by altered epidermal growth factor receptor activity

Ornithine decarboxylase (ODC) has been shown to be oncogenic in transfected NIH/3T3 cells overexpressing the enzyme from a heterologous promoter. These cells, designated as NODC-2 cells, acquire proliferative properties associated with tumorigenic transformation such as loss of contact inhibition, decreased population doubling time, anchorage-independent growth, and tumor production in nude mice. At least one of these parameters, loss of contact inhibition, remains dependent on elevated ODC levels. We have used these cells to investigate the molecular mechanisms by which ODC overexpression drives cell transformation and to examine the involvement of other proto-oncogene products in this process. An interaction between ODC overexpression and the epidermal growth factor receptor (EGF-R) was suggested initially by the elevation of both basal (300%) and ligand-induced (457%) EGF-R tyrosine kinase activities in NODC-2 cells compared to similarly treated control NLK cells. Disruption of EGF-R mediated signal transduction in NODC-2 cells both by treatment with tyrphostin-25 or by transfection with a vector expressing a dominant negative EGF-R mutant resulted in reacquisition of contact-inhibited growth and suppression of anchorage-independent, clonogenic growth in soft agar. We conclude that ODC-induced transformation of NIH/3T3 cells is mediated, at least partly, by alterations in EGF-R signal transduction activity.     

Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy

Based on successful results in animal models, it has been proposed that high-dose myeloablative therapy followed by autologous bone marrow or stem cell transplantation (ABMT/ASCT) may cure autoimmune disease. The coexistence of autoimmune disease and hematologic malignancy provides an opportunity to examine the response of autoimmune disease to ABMT or ASCT. We describe 4 patients with autoimmune disease (3 with psoriasis and 1 with rheumatoid arthritis) and hematologic malignancy. In each patient, the autoimmune disease remitted posttransplantation, but, in 4 patients with long-term followup, it recurred at 8-24 months. The earliest relapse occurred in a patient treated with interferon-alpha. Our experience suggests that a single autograft with unpurged stem cells is unlikely to cure autoimmune disease, but that other strategies building on this approach are worthy of investigation.     

Investigation of perceived environment, perceived outcome, and person variables in relationship to voluntary development activity by employees.

Examined perceived environment, perceived incentive and outcome, and person constructs for relationships with interest and participation in voluntary learning and development activity by nonmanagement employees. All 3 groups of constructs were related to development activity. In relationships with development activity, perceived outcome and environment variables interacted with workers' personal values relevant to aspects of a development setting, illustrating the potentially important role that differences in values may play in a development context. Additionally, small relationships were observed between several demographic variables and values within a development setting. Results provide implications for the design and implementation of successful development programs and highlight the need to carefully consider individual differences in this context when targeting many different types of employees for participation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The case of Gary: In search of post-hoc quixotic flexibility.

Responds to M. F. Hoyt's (see record 1995-22250-001) commentary on T. F. Van Denburg and E. J. Van Denburg's (see record 1994-18427-001) response to Hoyt's (see record 1994-18395-001) commentary on Van Denburg and Van Denburg's (see record 1993-06526-001) article about a case of premature therapy termination. Issues related to limits and flexibility in treatment are addressed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

HIV, health care workers and patients: how to ensure safety in the dental office

What can be done to preserve the high standards of patient care, give reasonable assurances to patients and acknowledge the rights of health care workers? Conscientious adherence to infection control is the most responsible option available.     

Testing an implantable intraspinal drug delivery device in the ewe

OBJECTIVE: The authors report the use of multiple implanted intraspinal port and catheter systems per test animal to study the in vivo functional characteristics and reliability of a new implantable spinal drug delivery port system. METHODS: Four ewes were each implanted with two epidural and one subarachnoid silicone elastomer catheters at the lumbar level. Each catheter was connected in series to one of three Therex filtered spinal delivery ports implanted subcutaneously in a similar grid pattern in each ewe to facilitate percutaneous identification. Saline (2 ml) was injected 3 times weekly in each port. The ease of injection and behavioral responses were recorded for 207-213 days of implantation until sacrifice/necropsy. RESULTS: All ports functioned reliably during the study. However, injection through two of the four subarachnoid catheters resulted in behavioral withdrawal responses intermittently. This behavioral pattern was much less common after epidural port injections. All four subarachnoid and four of eight epidural port and catheter systems were tested with local anesthetic just before sacrifice. Motor block was observed in three of four subarachnoid and three of four epidural port and catheter systems tested. Integrity of the other four epidural ports was tested by injection of methylene blue at sacrifice. This dye did not distribute in the epidural space in one of the latter four epidural ports (not local anesthetic tested) because of a concentric fibrotic reaction about the catheter. Similar fibrotic reactions surrounded the catheters that failed a functional test with local anesthetic. CONCLUSIONS: The implantable intraspinal port system tested functions reliably under repetitive percutaneous access. However, filtering such ports, though desirable to prevent entry of debris into the spinal canal, did not eliminate pericatheter chronic subarachnoid and epidural reaction. The number of test animals required to test 12 ports chronically was reduced by two-thirds without undue trauma to the individual test subject. Chronic percutaneous injection of an implanted subarachnoid system is feasible but may be associated with behavioral effects similar to that seen with chronic epidural systems. Fibrosis around chronic silicone catheters limited functional utility in one-fourth of the implanted test systems. Further study of the potential reactivity of chronic epidural and subarachnoid catheters is indicated.     

The mouse embryo culture system: improving the sensitivity for use as a quality control assay for human in vitro fertilization

Endurance training leads to an increase in the content of individual mitochondrial hemeproteins in skeletal muscle. To deduce the control mechanisms involved, cytochrome oxidase (COX) activity was compared with 1) the content of COX subunits III and IV and 2) 5-aminolevulinate synthase (ALAS) activity and mRNA content. In the plantaris muscle of female rats run daily for up to 28 days, ALAS activity was elevated 100% (P < 0.01) after 3 days and remained 150 and 125% higher (P < 0.001) after 7 and 28 days of running, respectively, than control. COX activity was also increased, but not until day 7 (40%; P < 0.05), and reached a maximal value 80% higher than control (P < 0.001) in the 28-day group. Compared with control, the content of COX subunit III and IV and ALAS mRNAs was not significantly changed by the training. The increased activities of COX and ALAS appear to be regulated by translational or posttranslational steps in the protein expression pathway. The induction of ALAS before COX suggests that the increased activity of COX may require increased synthesis of heme.     

Invasive angiology in acute arterial pathology in a critically ill newborn infant

Four patients who complained of symptoms and signs compatible with biliary tract disease and in whom the diagnosis of gallbladder (three cases) and common bile duct ascariasis (one case) was made sonographically are reported. In two patients with gallbladder ascariasis, cholecystectomy corroborated the presence of the round-worms, and was curative. The third patient was a pregnant woman (32nd gestational week) who took piperazine citrate, and a second sonogram performed 29 days later was completely normal. The fourth patient with common bile duct ascariasis underwent choledochotomy with extraction of one ascaris lumbricoides from the common duct, and a T tube was left in place for 15 days. All patients received antiparasitics and had a favorable outcome. Ultrasonography is an important noninvasive diagnostic procedure in the work-up of these patients, who usually describe a clinical picture suggesting gallstone disease: this is especially true in the presence of pregnancy.