Bond strength,compositional, and structural properties of hydroxyapatite coating on Ti,ZrO2-coated Ti,and TPS-coated Ti substrate

The effect of titanium plasma-sprayed (TPS) and zirconia (ZrO(2))-coated titanium (Ti) substrates on the adhesive, compositional, and structural properties of plasma-sprayed hydroxyapatite (HA) coatings were evaluated. X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, surface roughness, and adhesive strength were used to characterize the coatings. Apatite-type and alpha-tricalcium phosphate phases were observed for all HA coatings. A structural change due to the absence of a 960 cm(-1) peak during FTIR analysis was observed for all HA coatings. The coating surfaces appeared rough and melted, with surface roughness correlating to the size of the starting powder. No significant difference in the Ca/P ratio of HA on Ti and TPS-coated Ti substrates was observed. However, the Ca/P ratio of HA on ZrO(2)-coated Ti substrate was significantly increased. Interfaces between all coatings and substrates were observed to be dense and tightly bound, except for HA coatings on TPS-coated Ti substrate interface. However, an intermediate TPS or ZrO(2) layer between the HA and Ti substrate resulted in a lower adhesive strength as compared to HA on Ti substrate.     

Group IIA secretory phospholipase A2 stimulates exocytosis and neurotransmitter release in pheochromocytoma-12 cells and cultured rat hippocampal neurons

Recent evidence shows that secretory phospholipase A2 (sPLA2) may play a role in membrane fusion and fission, and may thus affect neurotransmission. The present study therefore aimed to elucidate the effects of sPLA2 on vesicle exocytosis. External application of group IIA sPLA2 (purified crotoxin subunit B or purified human synovial sPLA2) caused an immediate increase in exocytosis and neurotransmitter release in pheochromocytoma-12 (PC12) cells, detected by carbon fiber electrodes placed near the cells, or by changes in membrane capacitance of the cells. EGTA and a specific inhibitor of sPLA2 activity, 12-epi-scalaradial, abolished the increase in neurotransmitter release, indicating that the effect of sPLA2 was dependent on calcium and sPLA2 enzymatic activity. A similar increase in neurotransmitter release was also observed in hippocampal neurons after external application of sPLA2, as detected by changes in membrane capacitance of the neurons. In contrast to external application, internal application of sPLA2 to PC12 cells and neurons produced blockade of neurotransmitter release. Our recent studies showed high levels of sPLA2 activity in the normal rat hippocampus, medulla oblongata and cerebral neocortex. The sPLA2 activity in the hippocampus was significantly increased, after kainate-induced neuronal injury. The observed effects of sPLA2 on neurotransmitter release in this study may therefore have a physiological, as well as a pathological role.     

Lupus-like autoimmune disease induced by interferon therapy for myeloproliferative disorders.

Symptoms of autoimmune disease were evaluated in 125 patients with chronic myelogenous leukemia (CML) and in 12 patients with essential thrombocythemia undergoing treatment with recombinant interferon (IFN)-alpha-2b plus/minus low-dose recombinant IFN-gamma. Twenty-seven of 137 patients (20%) developed rheumatoid symptoms. Furthermore, the incidence of antinuclear antibody (ANA) formation was studied. Elevated ANA titers were found in 5/19 (26%) of CML patients at the time of diagnosis and in 3/18 (17%) of patients treated with hydroxyurea or busulfan. During IFN treatment, 18 of 25 tested patients (72%) had elevated ANA titers. In 15 of these ANA-positive patients, clinical signs of autoimmune disease appeared. All these patients were under long-term IFN treatment and were in remission of disease. In three patients criteria for systemic lupus erythematosus were fulfilled. Severity of side effects had led to the discontinuation of IFN treatment in these patients. The data indicate that IFN-alpha and IFN-gamma can induce ANA associated with autoimmune disease in patients with myeloproliferative disorders.     

Characterization of SV40 enhancer motifs involved in positive and negative regulation of the constitutive late promoter activity; effect of T-antigen.

By analyzing the late promoter activity of a series of nonreplicative recombinants mutated within the different enhancer motifs of SV40 we identified both positive and negative regulatory elements. In the absence of T-antigen, the motifs Sph and/or octamer, and to a lesser extent the motifs GTI and P, account for the constitutive expression of the late promoter. The motif GTII overlaps elements that negatively regulate the expression of the late promoter. These results indicate that the late promoter is down-regulated not only at the level of the GC motifs but also at the enhancer level. Moreover, we showed that T-antigen interacts with both positive and negative regulatory elements.     

The polymorphism of HLA-DR3 in South African populations

The polymorphism of HLA-DR3 was investigated in families and unrelated individuals of three population groups: South African (SA) Negroes, Cape Coloureds and SA Caucasoids. Serological and restriction fragment length polymorphism (RFLP) analysis indicated that DR3 could be subdivided into DRw17 (previously DR3.1) and DRw18 (previously DR3.2). In contrast, the two-dimensional (2-D) gel electrophoresis patterns could not distinguish between the DRB1 gene products of the HLA-DRw17 and DRw18 cells. Two DRB3 variants, correlating with the T-cell defined specificities Dw24 and Dw25 were identified at the genomic and product level. Of ten haplotypes studied with the newly defined HLA-DRw18 specificity, all had the DRB3 RFLP pattern associated with Dw24. HLA-DRw17 was found in all three population groups tested, although in the SA Negroes HLA-DRw18 was the prevalent DR3 subgroup. This subgroup was also present in the Cape Coloureds but was absent in the SA Caucasoid tested. HLA-DRw18 forms part of the most characteristic SA Negro haplotype, Bw42, DQw4, Dw“RSH,” while HLA-DRw17 is part of the classic Caucasoid haplotype, B8, DQw2, Dw3.     

Death or illness of a family member,violence, interpersonal conflict,and financial difficulties as predictors of sickness absence: longitudinal cohort study on psychological and behavioral links

OBJECTIVE: Although an association between stressful life events and health problems has been demonstrated, the underlying mechanisms have remained unclear. We examined whether psychological problems and health-risk behaviors underpin the health effects of different event categories. METHOD: The initially healthy participants were 2991 (796 men, 2195 women) municipal employees who had taken no sick leave in 1995. In 1997, they completed a questionnaire requesting information on recent life events and psychological and behavioral factors. The outcome was recorded sickness absences in 1998. RESULTS: In men, the death or serious illness of a family member, violence, and financial difficulties increased the risk of later sickness absence. According to structural equation modeling, violence and financial difficulties also induced psychological problems such as anxiety, mental distress, and lowered sense of coherence. Psychological problems were associated with heightened cigarette and alcohol consumption, which in turn increased sickness absence. A corresponding structural model did not fit the data in relation to death or serious illness of a family member. In women, life events were associated with psychological problems and smoking but not sickness absence. CONCLUSIONS: Longitudinal evidence suggests that increased psychological problems and behaviors involving risk to health partially mediate the effect of stressful life events on health, as indicated by sickness absence. This model received support among men and for the event categories of violence and financial difficulties. Women were less affected by stressful life events than men.     

Student's perceptions of a virtual PBL experience.

OBJECTIVE: Our purpose is to present findings regarding student attitudes towards a virtual PBL program used to standardize their pediatric clinical experience. DESCRIPTION: With funding provided by the Fund for the Improvement of Post-Secondary Education, we developed Project LIVE (Learning through Interactive Video Education), a CD-ROM/Web hybrid program that uses digital video cases to conduct "virtual" problem-based learning groups with students doing a clinical rotation in a remote setting. Cases were progressively disclosed by videos of patient/physician encounters on a CD-ROM. Groups of five students and a faculty facilitator collaborated, teaching each other within the discussion section of the program. We conducted a multifaceted evaluation of Project LIVE to study the impact of case modality or distance on student learning and attitudes. We placed students in one of three groups (1) a face-to-face group with a paper case (FFT), (2) a face-to-face group with a video case (FFV), and (3) a virtual group (VG) with the digital video case. We then studied student attitudes about the three teaching formats. Over a six-month period three education specialists, who were not a part of the development team, conducted eight focus groups lasting one hour to assess student attitudes about Project LIVE. No one from the project team was present during these groups, and an independent evaluator analyzed the notes taken by each focus group leader. DISCUSSION: Trends across the groups included the following: (1) Authenticity (video)-Students reported that the authenticity of the case was a critical feature and that, "seeing (videos) made learning more memorable." Virtual and FFV groups reported more confidence in their ability to recognize abnormal findings in their patients. "You can't expect to teach clinical exam skills with a piece of paper." (2) Use of time-Students from all groups believed the cases were a good use of their time and improved their ability to solve clinical problems. They said it gave them an opportunity to "get away from just doing and focus on learning." However, the virtual groups complained of the lack of "a barometer for how much is too much" time. Some students reported spending an average of eight to ten hours per case over the period of a week. (In contrast, face-to-face groups met for three hours.) (3) Modeling clinical reasoning-Students believed the cases were valuable in structuring their knowledge, conceptualizing how to handle difficult situations, distinguishing abnormal from normal physical examination findings, and collaborating with their peers and their mentor to develop critical thinking. "It forced us to be logical" and ". how to think through the process-it mimics the real setting." (4) Technical support-The responsiveness of the Project LIVE staff was essential in assisting students in troubleshooting problems. (5) Distance component-Students preferred to work through the cases in face-to-face groups but agreed that the virtual experience is "good if you are in the middle of nowhere." This program was enjoyed by students and gave us an approach to standardizing experiences across multiple clinical sites.     

Effects of potassium channel blockers on baclofen-induced suppression of paroxysmal discharges in rat neo-cortical slices

Baclofen reduced the frequency and aborted the bursts of spontaneous paroxysmal discharges in rat neocortical slices maintained in magnesium-free medium. This action was prevented by pretreatment with barium or caesium, which each increased the ictaform burst frequency, amplitude and duration. 4-Amino-pyridine also increased the burst frequency but reduced the amplitude and did not completely prevent the action of baclofen. Evidently baclofen suppresses such discharges by opening potassium channels normally involved in limiting the burst activity.     

G protein modulation of voltage-sensitive muscarinic receptor signalling in mouse pancreatic acinar cells

Submaximal stimulation of mouse pancreatic acinar cells by acetylcholine (ACh) generates periodic Ca2+ responses sensitive to the membrane potential. Monitoring the muscarinic Ca2+ responses using patch-clamp whole-cell current recordings, we examined the mechanism of guanine nucleotide-binding protein (G protein)-receptor interaction in terms of the membrane potential. The lowest ACh concentration able to elicit consistent repetitive spikes was 50 nM, in the presence of which hyperpolarization increased and depolarization decreased the spike frequency. The saturating concentration was 10 microM, this induced a sustained response insensitive to voltage. Internal guanosine 5'-tri- and diphosphates (GTP, GDP) depressed and potentiated the voltage sensitivity, respectively, but not for the response to a saturating ACh concentration (10 microM). Internal guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) abolished the voltage sensitivity. The results indicate that the ACh-induced Ca2+ response is sensitive to the membrane potential and that a close linkage exists between voltage sensitivity and the G protein association/dissociation cycle in the muscarinic receptor.