Immunoregulatory effects of phospholipase A2 (PLA2) on the proliferation of human lymphocytes

Extracellular phospholipase A2 (PLA2) is a proinflammatory enzyme found especially in the inflammatory exudate to modulate blood flow to areas of antigen stimulation. In this study we found that PLA2 exerted a biphasic effect on the proliferation of phytohemagglutinin (PHA)-stimulated human mononuclear cells (PHA MNC). At low concentrations range from 0.001 to 1 U/ml, PLA2 enhanced the proliferation of PHA MNC (maximal increase was 37.0 +/- 5.67%). Conversely, at concentrations over 10 U/ml, PLA2 markedly suppressed the PHA-induced MNC proliferation (maximal decrease was 88.86 +/- 2.89%). PLA2 was non-toxic to lymphocytes after three days culture, unless the concentration was higher than 100 U/ml. The membrane polarization of PHA-stimulated lymphocytes was also increased by PLA2 at a low concentration. In addition, PLA2 displayed a similar effect on the proliferation of streptokinase-streptodornase (SK/SD) or allogeneic cell stimulated lymphocytes. The change of lymphocyte proliferation by PLA2, was parallel to the change of percentage of helper T cells. Furthermore--a CD4-rich population was proved more susceptible to PLA2 effect than a CD8-rich population. Para-bromophenacyl bromide (pBPB), an irreversible inhibitor of PLA2, abrogated the biphasic effect of PLA2 on PHA MNC proliferation. These results suggest that PLA2 plays a regulatory role on immune reactions by modulating the percentage of helper T cells.     

Effect of a low-protein diet on doxorubicin pharmacokinetics in the rabbit

Summary Malnutrition involving protein deficiency, which commonly occurs in cancer patients receiving anthracycline treatment, is considered to be a risk factor for the development of cardiotoxicity. Protein deficiency has been shown to impair the metabolism of drugs such as theophylline and acetaminophen. If protein deficiency also impairs anthracycline metabolism, it could explain at least in part the enchanced anthracycline toxicity associated with malnutrition. We tested this idea by determining the effect of a low- protein, isocaloric diet on doxorubicin pharmacokinetics in rabbits. The animals were randomized into two groups for 8–12 weeks. Rabbits in group 1 received a low-protein (5%), isocaloric diet, whereas those in group 2 received a normal-protein (15%) diet. Both groups (group 1,n=15; group 2,n=14) were given 5 mg/kg doxorubicin by i.v. bolus. After doxorubicin injection, blood samples were obtained over the next 52 h for the measurement of doxorubicin and doxorubicinol plasma concentrations by high-performance liquid chromatography (HPLC) with fluorometric detection. The low-protein diet significantly decreased doxorubicin clearance (48±3 vs 59±4 ml min^–1 kg^–1;P<0.05), prolonged the terminal climination half-life (28±2 vs 22±2 h;P<0.05), and increased the area under the plasma concentration/time curve extrapolated to infinity (1722±122 vs 1405±71 ng h ml^–1;P<0.05) as compared with the values determined for rabbits fed the standard rabbit chow (15% protein). The volume of distribution for doxorubicin was not altered by the low-protein diet. In addition, in rabbits fed the the low-portein diet, the terminal elimination half-life of the alcohol metabolite, doxorubicinol was prolonged (52±5 vs 40±2 h;P<0.05). Thus, a low-protein diet causes a reduction in the ability of rabbits to eliminate doxorubicin and possibly its alcohol metabolite doxorubicinol. If a similar alteration in anthracycline pharmacokinetics occurs in malnourished cancer patients, this phenomenon may contribute to their increased risk of developing cardiotoxicity associated with anthracycline therapy.Supported by the Department of Veterans Affairs and the American Heart Foundation     

In Vivo Proton Spectroscopy of Intracranial Infections and Neoplasms

The chemical characteristics of 10 neoplastic and 11 infectious brain masses were studied by in vivo ¹H magnetic resonance spectroscopy. In tumors, peak height ratios of n-acetyl-L-aspartate to choline were decreased compared to those in normal brain tissue and infectious masses (p < 0.02), but the ratios in normal brains and those with infections did not differ. N-acetyl-L-aspartate—to-creatine/phosphocreatine ratios were significantly lower in infectious masses and tumors compared to normal brain tissue (p = 0.003). However, in progressive multifocal leukoencephalopathy, N-acetyl-L-aspartate appeared relatively unchanged. Lactate was greater than choline in 9 of 11 brains with infection, 0 of 14 control brains, and 1 of 10 tumors. Lactate-to-choline ratios were significantly elevated in infectious masses compared with tumors (p < 0.01). ¹H magnetic resonance spectroscopy is promising for the noninvasive diagnosis of focal brain masses.     

Immunomodulators from Paris formosana Hayata.

Eight glycosides PF-1 to PF-8 were isolated from the leaves and stems of Paris formosana Hayata (Liliaceae), of which PF-3 (III) was the main compound. It was found that PF-1 to PF-3 (I-III) caused proliferative responses of mouse lymphocytes to concanavalin A and augmentation of mouse granulocyte/macrophage colony forming cells in mouse fibroblast cell L929 conditioned medium. PF-4(IV) and PF-8 showed significant immunomodulatory effects with very low toxicity: they not only caused the same immune responses as PF-1, 2 & 3 but also enhanced the proliferative response of human peripheral whole blood to phytohemagglutinin. PF-5 (V) also increased 3H-thymidine incorporation in ConA-stimulated lymphocytes and in PHA-stimulated human peripheral whole blood, and enhanced the proliferative response of granulocyte/macrophage colony stimulating activity. PF-6(VI) and PF-7(VII) augmented 3H-thymidine incorporation in granulocyte/macrophage colony-forming cells and mitogenic response of PHA-stimulated human peripheral whole blood cells from healthy adults. However, PF-1, 2 and 3 showed hemolytic action, while PF-4 to PF-8 had no hemolytic action at all. On the other hand, the hemolytic action of PF-3 derivatives was reduced as compared with PF-3 but their immune responses did not equal those of PF-3, only showing granulocyte/macrophage colony stimulating activity.     

Odontoma: a clinicopathologic study of 81 cases.

BACKGROUND AND PURPOSE: Odontoma is the most common odontogenic tumor. It includes 2 types, the compound and complex odontomas. There has not been a series study of the clinical and histologic features of odontomas from Taiwan. This study evaluated the clinicopathologic features of odontoma in Taiwanese. METHODS: Cases of odontoma treated from 1998 to 2002 identified from medical records were included. The microscopic features, radiographic features, and clinical history of the patients were reviewed and analyzed. RESULTS: A total of 81 odontomas in 81 patients (36 males and 45 females) were included. There were 62 compound and 19 complex odontomas. The mean age of the patients was 18 years with the majority of odontomas occurring in the first (32%) and second decade (38%) of life. Odontomas had a marked predilection for the maxilla (70%) and for the anterior region of the jaw (83%), particularly for the anterior maxilla (62%). Sixty four (79%) of the 81 odontomas were associated with 80 impacted teeth, including 71 permanent teeth, 2 deciduous teeth, and 7 supernumerary teeth. Of the 71 impacted permanent teeth, the maxillary central incisor (27%) was most commonly affected, followed by the maxillary canine (26%) and mandibular canine (24%). Histologic examination revealed enamel matrix in 90%, dentin in 100%, cementum in 88%, pulp tissue in 96%, fibrous capsule in 93%, ghost cells in 83%, reduced enamel epithelium in 86%, and nests of odontogenic epithelium in 58% of odontomas. Dentigerous cyst was associated with 9% of odontomas. CONCLUSIONS: In this series, odontomas occurred most often in the first and second decade of life. Although complex odontomas are usually found in the posterior jaw, in this Taiwanese series they were most commonly found in the anterior maxilla. Odontoma is frequently associated with an impacted tooth and occasionally with a dentigerous cyst. No recurrence of odontomas was found after surgical excision with follow-up of 1 to 15 years.     

Inhibitory effects of physalin B and physalin F on various human leukemia cells in vitro.

Physalins B and F were isolated and characterized from the ethanolic extract of the whole plant of Physalis angulata L. (Solanaceae). Both physalin B and physalin F inhibited the growth of several human leukemia cells: K562 (erythroleukemia), APM1840 (acute T lymphoid leukemia), HL-60 (acute promyelocytic leukemia), KG-1 (acute myeloid leukemia), CTV1 (acute monocytic leukemia) and B cell (acute B lymphoid leukemia). Physalin F showed a stronger activity against these leukemia cells than physalin B, especially against acute myeloid leukemia (KG-1) and acute B lymphoid leukemia (B cell). From the structural features, the active site seems to be the functional epoxy group for physalin F and the double bond for physalin B located at carbon 5 and 6; the former is much more active than the latter as regards anti-leukemic effects.     

The impact of detubularization on ileal reservoirs

For many years, parts of the large or small bowel have been used for bladder augmentation and substitution. Recent controversy over the advantages and disadvantages of continent urinary diversion using detubularized ileum (the Kock pouch) and tubular ileum (the Camey procedure) focussed on how a highly compliant urinary reservoir should be formed. We compared the compliance of isolated intact ileal segments and ileal pouches constructed after transection of the antimesenteric border. Hydrodynamic data was obtained at four different points in time: acute (immediately after pouch construction), and after two, six and twelve weeks. Over the first six weeks the reservoirs were connected to the bladder for drainage. At six weeks, subtotal cystectomy and separate anastomosis of the tubular ileal loop and the detubularized ileal pouch to the trigone was performed to study the influence of cyclic reservoir distention. Statistical analysis of the pressure-volume curves revealed significantly better compliance of the detubularized ileal pouch as compared to the intact ileal segments. The area under the pressure curve values (AUC) were p less than 0.025, p less than 0.02, p less than 0.005 and p less than 0.02 for the acute experiment, after two weeks, after six weeks, and after 12 weeks respectively. Our findings suggest that transection of the circular intestinal wall is an important step in the creation of a good-compliant urinary reservoir.     

Alteration in myelin-associated proteins following spinal cord irradiation in guinea pigs.

The aim of this study was to investigate the pathological and cellular basis for radiation-induced myelopathy in guinea pigs by monitoring biochemical alterations in levels of myelin basic protein and 2',3'-cyclic nucleotide phosphohydrolase. Guinea pigs were irradiated to the lumbar region with various doses of neutrons or cobalt gamma irradiation. The ED50s for paralysis were 17.2 Gy and 67.5 Gy for neutron and cobalt irradiation, respectively, and was histologically associated with demyelination. In spinal cords taken from animals at the onset of paralysis myelin basic protein levels were decreased in direct relationship to the radiation dose. The lowest doses to cause paralysis led to a 25% decrease in MBP levels. In a separate experiment, alterations in MBP were measured in the spinal cords over the time period leading up to paralysis. Surprisingly, decreases in MBP were found immediately after the end of the 4 week irradiation period. These early changes in MBP were not markedly dose dependent and occurred with nonparalyzing doses. Dose-dependent decreases were found only just before the onset of paralysis. CNPase activity measured in the same specimens showed changes that were essentially similar to those for MBP. In the CSF, MBP levels were essentially constant until onset of paralysis. This study showed that demyelination, as assessed by the levels of the myelin-associated proteins MBP and CNPase, can occur soon after spinal cord irradiation but that profound dose-dependent changes are seen only immediately preceding the onset of paralysis. Although increases in MBP in the CSF were associated with the onset of radiation-induced myelopathy, its assay is unlikely to predict this complication of irradiation.     

A framework for evaluating image segmentation algorithms.

The purpose of this paper is to describe a framework for evaluating image segmentation algorithms. Image segmentation consists of object recognition and delineation. For evaluating segmentation methods, three factors-precision (reliability), accuracy (validity), and efficiency (viability)-need to be considered for both recognition and delineation. To assess precision, we need to choose a figure of merit, repeat segmentation considering all sources of variation, and determine variations in figure of merit via statistical analysis. It is impossible usually to establish true segmentation. Hence, to assess accuracy, we need to choose a surrogate of true segmentation and proceed as for precision. In determining accuracy, it may be important to consider different 'landmark' areas of the structure to be segmented depending on the application. To assess efficiency, both the computational and the user time required for algorithm training and for algorithm execution should be measured and analyzed. Precision, accuracy, and efficiency factors have an influence on one another. It is difficult to improve one factor without affecting others. Segmentation methods must be compared based on all three factors, as illustrated in an example wherein two methods are compared in a particular application domain. The weight given to each factor depends on application.