Basic fibroblast growth factor-stimulated endothelial cell movement is mediated by a pertussis toxin-sensitive pathway regulating phospholipase A2 activity

Basic fibroblast growth factor (bFGF) stimulates migration and proliferation of vascular endothelial cells (EC). Fibroblast growth factor (FGF) receptors have an intrinsic tyrosine kinase activity involved in FGF-mediated proliferation, but the signal transduction pathway(s) responsible for movement is not known. We compared the role of signal-transducing G-proteins in migratory and proliferative responses of bovine aortic EC in vitro. Pertussis toxin, which ADP-ribosylates susceptible G-proteins, reduced bFGF-stimulated EC migration by 80%. The toxin did not block serum-stimulated movement, indicating that structural components required for motility were not impaired. The toxin did not inhibit bFGF-stimulated EC proliferation, showing that distinct intracellular signaling mechanisms are involved in the migratory and proliferative responses to bFGF. Three experimental approaches indicated that promigratory responses were due to release of arachidonic acid: (i) of the second messengers induced by G-protein-coupled effectors, only arachidonic acid over-came the pertussis toxin block, (ii) bFGF stimulated arachidonic acid release from EC in a pertussis toxin-sensitive manner, and (iii) phospholipase A2 inhibitors blocked the EC migration in response to bFGF. These data provide evidence that the migratory response of vascular EC to bFGF may be mediated by a G-protein-coupled phospholipase A2 activity.     

Clinical evaluation of a renal mass diagnostic expert system

In this paper, we describe our clinical evaluation of the diagnostic accuracy of the renal mass diagnostic system (RMDS) and of seven physicians. To investigate the value of intravenous urography (IVU) and/or retrograde urography (RU) in diagnosing renal parenchymal tumors and tumors of the renal pelvis, RMDS and the seven physicians were tested with and without the information regarding IVU/RU at two different times. From this study we believe that RMDS can help residents in making more accurate presurgical renal mass diagnosis, and may eliminate the need for IVU/RU in the diagnosing process for a specific group of patients.     

Metabolism of benz[a]anthracene by human liver microsomes

The metabolism of benz[a]anthracene (BA) by human hepatic microsomes was investigated. Only dihydrodiols were observed when BA was the substrate. No tetrahydrotetrols were detected, indicating lack of diol epoxide formation. The BA-dihydrodiols identified by GCMS analysis and comparison to authentic standards were BA-8,9-dihydrodiol (42.4% of total metabolites), BA-5,6-dihydrodiol (25%), BA-10,11-dihydrodiol (24.8%), BA-3,4-dihydrodiol (5.3%), and BA-1,2-dihydrodiol (< 1.5%). BA-dihydrodiols were also used individually as substrates. Only BA-1,2-dihydrodiol, the least abundant isomer produced from BA, was converted efficiently to a tetrahydrotetrol (> 72% conversion). BA-10,11-dihydrodiol was converted to BA-8,9,10,11-tetrahydrotetrols in < 12% yield. BA-10,11- and BA-3,4-dihydrodiols were not converted to tetrahydrotetrols.     

Predictors of burden among lower socioeconomic status caregivers of persons with chronic mental illness

This study uses a stress-coping-support framework to examine the predictors of caregiver burden with a sample of 103 lower social class family caregivers of persons with chronic mental illness. Results of multiple regression analyses show that the greater the frequency of client behavioral symptoms and the lower the amount of perceived support from family members, the higher the level of overall caregiver burden. Examination of the predictors of specific types of burden-family disruption, stigma, strain, and dependency-reveal that different constellations of variables predict different types of burden. The need for mental health agencies to address caregiver and client concerns is addressed. Implications are presented for practice and future research.     

Makaluvic acids A and B: novel alkaloids from the marine sponge Zyzzya fuliginosus

Two new substituted pyrrolecarboxylic acids, makaluvic acids A (5) and B (6), were isolated from the sponge Zyzzya fuliginosus, which was collected in Chuuk Atoll, Federated States of Micronesia. The known alkaloids 3,7-dimethylisoguanine (1) and makaluvamines A (2), E (3), and K (4) were also isolated.     

Electrical stimulation of the lingual musculature in obstructive sleep apnea

The influence of lingual muscle activity on airflow dynamics in the upper airway was examined in nine patients with obstructive sleep apnea. Muscles that retract the tongue (hyoglossus and styloglossus) and protrude the tongue (genioglossus) were selectively stimulated electrically during sleep with fine wire electrodes placed intramuscularly transorally. We confirmed that stimulation with 50 Hz and 40-microseconds pulse duration did not elicit changes in electroencephalographic patterns or heart rate or alter airflow after the stimulation burst had ceased. The highest stimulus intensity that did not arouse patients from sleep was then utilized to examine the effect of lingual muscle recruitment on airflow dynamics during steady-state periods of inspiratory airflow limitation. When applying a stimulus burst during single inspirations, maximal inspiratory airflow decreased by 239 +/- 177 ml/s (P < 0.05) during retractor stimulation, whereas maximal inspiratory airflow increased by 217 +/- 93 ml/s during protrusor stimulation (P < 0.001) compared with breaths immediately before and after the stimulated breath. When consecutive inspirations were stimulated repeatedly, protrusor stimulation decreased the frequency of obstructive breathing episodes in four patients breathing at 3.9 +/- 3.4 (SD) cmH2O nasal pressure. The findings suggest that stimulation of the lingual muscles can increase or decrease airflow depending on the specific muscles stimulated without arousing patients from sleep.     

Apoptosis: an indicator of radiosensitivity in vitro?

The mechanisms by which ionizing radiation kills cells was a topic of great interest to Dr Alper, and one suspects that she would have delighted in 'clarifying' the role of apoptosis. Indeed, clarification seems necessary in view of the abundance of often conflicting data currently emerging. However, given some simplifying assumptions, important patterns can be discerned. The following comments are thus framed in the context of haematopoietic cell lines, which generally undergo rapid apoptosis (within hours) following irradiation, in contrast to cells of non-haematopoietic origin, which are more likely to be characterized by delayed apoptosis (within days). Tolerance for DNA damage appears to be reduced in cells capable of rapid apoptosis, and those cells are sensitized to ionizing radiation when the apoptotic response mechanisms are fully functional. This rapid apoptotic response shows minor sensitivity to cell cycle position or radiation dose rate. Different considerations apply, however, for the delayed response. Delayed apoptosis appears to be triggered by chromosome damage, and evidence implicating delayed apoptosis as a modifier of cellular radiosensitivity is much less convincing at present.     

Effects of shortening the steeplechase phase (phase B) of a 3-day-event

Thirty-four horses competing in the Endurance Test of a 3-day-event were divided into 3 groups: horses in Group 1 (n = 15) competing in a 3.5 min steeplechase phase; horses in Group 2 (n = 13) in a 3 min steeplechase phase (Phase B) and horses in Group 3 (n = 6) in a 2.5 min steeplechase phase. The shortening of Phase B was associated with a lengthening of Phase C so that the total distance of the event for all horses was 14,940 m. Bodyweight (BW) was measured and total body water (TBW) and water loss estimated. Blood samples were collected from the horses prior to the Endurance Test, at the end of Phase B, the 4 km marker on Phase C (C4K), the end of Phase C, and 20 min after the completion of Phase D for measurement of packed cell volume (PCV), total plasma protein [TPP], lactate, ionised calcium, pH, sodium, potassium, chloride, total calcium and glucose concentrations, and aspartate aminotransferase, creatine kinase and lactate dehydrogenase activities. Mean +/- s.d. ambient environmental temperature during the Endurance Test was 25.3 +/- 1 degrees C (range 20.3 degrees C-29.7 degrees C). Mean relative humidity was 43.8 +/- 2.4% (range 39%-48.6%) and the average 'comfort index' (CI) was 121. There were no significant differences between the groups competing in the Endurance Test, despite the shorter Phase B. However, there were significant decreases in BW, TBW, net exchangeable cations, chloride, ionised calcium, and pH. The sodium and total calcium concentrations remained at near pre-event values. The PCV, TPP, lactate, potassium, glucose, aspartate aminotransferase, and lactate dehydrogenase activity increased during the Endurance Test, when compared to pre-event values. Horses competing in this competition experienced significant fluid and electrolyte losses, reduced glomerular filtration, increased glycogenolysis and had significant leakage of enzymes from working muscles during competition. These changes could not be reduced by shortening Phase B and lengthening Phase C.     

Human anticardiolipin monoclonal autoantibodies cause placental necrosis and fetal loss in BALB/c mice

OBJECTIVE: To analyze the structure, specificity, and in vivo pathogenetic potential of 2 human anticardiolipin (aCL) monoclonal antibodies (MAb). METHODS: Human aCL IgG MAb were generated from hybridized Epstein-Barr virus-induced B cell lines from a healthy subject (MAb 519) and from a patient with primary antiphospholipid syndrome (MAb 516). Studies of antigen-binding specificity and analysis of Ig V-gene mutations were carried out. The MAb were independently injected into mated female BALB/c mice, and their effect on pregnancy outcome was compared with that of MAb 57, a highly mutated and antigen-selected human IgG1lambda rabies virus antibody. RESULTS: Both MAb 519 and MAb 516 utilized minimally mutated V(H)DJ(H) and VkappaJkappa gene segments and bound cardiolipin and other anionic phospholipids in the absence of beta2-glycoprotein I (beta2-GPI). The mice injected with aCL MAb displayed a significantly higher rate of fetal resorption and a significant reduction in fetal and placental weight as compared with those injected with MAb 57. These findings were accompanied by a finding of placental human IgG deposition and necrosis in the aCL MAb-treated animals. CONCLUSION: The results of this study indicate that human aCL IgG that are beta2-GPI independent can induce pathology.