Cell Lp Research Articles

Digital pathology in pediatric nodular lymphocyte-predominant Hodgkin lymphoma: correlation with treatment response

Early-stage pediatric nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) can be treated effectively with low-intensity chemotherapy, most frequently cyclophosphamide in combination with vinblastine and prednisone (CVP). Descriptive histological risk factors based on the disease-defining lymphocyte predominant cells (LP cells) as used within the Fan classification, are less predictive in early-stage patients. We used deep learning-based cell detection and spatial analysis on digitized biopsy slides from 53 early-stage pediatric NLPHL patients to quantitatively assess LP cell histomorphometry. We found that poor responding patients had significantly fewer LP cells per cluster and lower LP cell density than good responding patients. In our exploratory analysis, we found no correlation between Fan classes or B cell pattern variables and therapy response. We hypothesize that the relationship between poor treatment response and decreased LP cell density may be explained by differences in LP cell proliferation.

Comparison of the Anticancer Effects of Arvanil and Olvanil When Combined with Cisplatin and Mitoxantrone in Various Melanoma Cell Lines-An Isobolographic Analysis.

Due to the unique structures of arvanil and olvanil, the drugs combine certain properties of both cannabinoids and vanilloids, which makes them able to stimulate both TPRV1 and CB1 receptors and causes them to be interesting agents in the setting of carcinoma treatment. The aim of this study was to investigate the cytotoxic and anti-proliferative effects of arvanil and olvanil when administered alone and in combination with cisplatin (CDDP) and mitoxantrone (MTX), using various primary (A375, FM55P) and metastatic (SK-MEL 28, FM55M2) human malignant melanoma cell lines. The results indicate that both arvanil and olvanil inhibited (dose-dependently) the viability and proliferation of various malignant melanoma cells, as demonstrated by MTT and BrdU assays. The safety profile of both arvanil and olvanil tested in human keratinocytes (HaCaT) and normal human melanocytes (HEMa-LP) revealed that neither arvanil nor olvanil caused significant cytotoxicity in HaCaT and HEMa-LP cell lines in LDH and MTT assays. Isobolographically, it was found that both arvanil and olvanil exerted additive interactions with MTX and antagonistic interactions with CDDP in the studied malignant melanoma cell lines. In conclusion, the combinations of arvanil or olvanil with MTX may be considered as a part of melanoma multi-drug therapy; however, the combination of these compounds with CDDP should be carefully considered due to the antagonistic interactions observed in the studied malignant melanoma cell lines.

Nodular Lymphocyte Predominant Hodgkin Lymphoma: A Rare Subtype with Distinct Clinicopathological Features

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL) characterized by a distinct morphology, an older median age at onset, less incidence of mediastinal involvement, more frequent relapse and better prognosis as compared to Classical-HL (CHL). In contrast to CHL, the tumor cell (LP cell) of NLPHL almost always retains its B cell phenotype and is a CD30 non-expresser. Due to its rarity, only a handful of studies on this entity are available in the lit

Characterization of Binary Biofilms of Listeria monocytogenes and Lactobacillus and Their Response to Chlorine Treatment.

In nature, Listeria may interact competitively and cooperatively with other organisms, resulting in unique spatial organization and functions for cells within the community. This study was undertaken to characterize the biofilm architecture of binary biofilms of Listeria monocytogenes and Lactobacillus species and to assess their effect on the survival of Listeria during exposure to hypochlorite. Three L. monocytogenes strains, ATCC 19115 (Lm5), ATCC 19117 (Lm7), and Coleslaw (LmC), were selected and combined individually with three Lactobacillus strains: L. fermentum (Lf), L. bavaricus (Lb), and L. plantarum (Lp). In binary Lm-Lp biofilms, the Lm cell counts were similar to single-species biofilms (8.5 log CFU/well), and the Lp cell numbers declined by 1.0 log CFU/well. In the presence of Lb, the Lm cell counts were reduced by 1.5 log CFU/well (p < 0.05), whereas the Lf cell counts increased at least by 3.5 log CFU/well. Confocal laser scanning microscopy (CLSM) determined that interspecies interactions significantly affected the spatial organization of three binary biofilms. Biofilm surface-to-volume ratio increased from 0.8 μm2/μm3 for Lm5 in the monoculture to 2.1 μm2/μm3 for Lm5-Lp in the dual-species model (p < 0.05), and was characterized by a thicker structure with a largely increased surface area. Biofilm roughness increased from 0.2 for Lm7 to 1.0 for Lm7-Lb biofilms (p < 0.05), which appeared as interspecific segregation. Biofilm thickness increased from 34.2 μm for LmC to 46.3 μm for LmC–Lf (p < 0.05), which produced flat and compact structures that covered the entire surface available. The biomass of the extracellular matrix was higher in the case of some binary biofilms (p < 0.05); however, this effect was dependent upon the species pair. When treated with hypochlorite, Lm5 in binary biofilms had an approximately 1.5 log CFU/well greater survival than individually. The unique spatial organization and greater protein production may explain the protective effect of Lp after hypochlorite exposure.

Cortex cell hydraulic conductivity, endodermal apoplastic barriers and root hydraulics change in barley (Hordeum vulgare L.) in response to a low supply of N and P.

Mineral nutrient limitation affects the water flow through plants. We wanted to test on barley whether any change in root-to-shoot ratio in response to low supply of nitrogen and phosphate is accompanied by changes in root and cell hydraulic properties and involves changes in aquaporin (AQP) gene expression and root apoplastic barriers (suberin lamellae, Casparian bands). Plants were grown hydroponically on complete nutrient solution or on solution containing only 3.3 % or 2.5 % of the control level of nutrient. Plants were analysed when they were 14-18 d old. Nutrient-limited plants adjusted water flow to an increased root-to-shoot surface area ratio through a reduction in root hydraulic conductivity (Lp) as determined through exudation analyses. Cortex cell Lp (cell pressure probe analyses) decreased in the immature but not the mature region of the main axis of seminal roots and in primary lateral roots. The aquaporin inhibitor HgCl2 reduced root Lp most in nutrient-sufficient control plants. Exchange of low-nutrient for control media caused a rapid (20-80 min) and partial recovery in Lp, though cortex cell Lp did not increase in any of the root regions analysed. The gene expression level (qPCR analyses) of five plasma membrane-localized AQP isoforms did not change in bulk root extracts, while the formation of apoplastic barriers increased considerably along the main axis of root and lateral roots in low-nutrient treatments. Decrease in root and cortex cell Lp enables the adjustment of root water uptake to increased root-to-shoot area ratio in nutrient-limited plants. Aquaporins are the prime candidate to play a key role in this response. Modelling of water flow suggests that some of the reduction in root Lp is due to increased formation of apoplastic barriers.

Root and cell hydraulic conductivity, apoplastic barriers and aquaporin gene expression in barley (Hordeum vulgare L.) grown with low supply of potassium.

Limited supply of mineral nutrients often reduces plant growth and transpirational water flow while increasing the ratio of water-absorbing root to water-losing shoot surface. This could potentially lead to an imbalance between water uptake (too much) and water loss (too little). The aim of the present study was to test whether, as a countermeasure, the hydraulic properties (hydraulic conductivity, Lp) of roots decrease at organ and cell level and whether any decreases in Lp are accompanied by decreases in the gene expression level of aquaporins (AQPs) or increases in apoplastic barriers to radial water movement. Barley plants were grown hydroponically on complete nutrient solution, containing 2 mm K+ (100 %), or on low-K solution (0.05 mm K+; 2.5 %), and analysed when they were 15-18 d old. Transpiration, fresh weight, surface area, shoot water potential (ψ), K and Ca concentrations, root (exudation) and cortex cell Lp (cell pressure probe), root anatomy (cross-sections) and AQP gene expression (qPCR) were analysed. The surface area ratio of root to shoot increased significantly in response to low K. This was accompanied by a small decrease in the rate of water loss per unit shoot surface area, but a large (~50 %) and significant decrease in Lp at root and cortex cell levels. Aquaporin gene expression in roots did not change significantly, due to some considerable batch-to-batch variation in expression response, though HvPIP2;5 expression decreased on average by almost 50 %. Apoplastic barriers in the endodermis did not increase in response to low K. Barley plants that are exposed to low K adjust to an increased ratio of root (water uptake) to shoot (water loss) surface primarily through a decrease in root and cell Lp. Reduced gene expression of HvPIP2;5 may contribute to the decrease in Lp.

Capillary tone: cyclooxygenase, shear stress, luminal glycocalyx, and hydraulic conductivity (Lp).

Control of capillary hydraulic conductivity (Lp) is the physiological mechanism that underpins systemic hydration. Capillaries form the largest surface of endothelial cells in any species with a cardiovascular system and all capillaries are exposed to the flow-induced force, shear stress (τ). Vasoactive molecules such as prostacyclin (cyclooxygenase product, COX) are released from endothelial cells in response to τ. Little is known about how COX activity impacts capillary Lp. The purpose here was to assess Lp in situ following an acute Δτ stimulus and during COX1/COX2 inhibition. Mesenteric true capillaries (TC) of Rana pipiens (pithed) were cannulated for Lp assessment using the modified Landis technique. Rana were randomized into Control and Test groups. Two capillaries per animal were used (perfusate, 10 mg·mL−1 BSA/frog Ringer's; superfusate, frog Ringer's or indomethacin (10−5 mol·L−1) mixed in frog Ringer's solution). Three distinct responses of Lp to indomethacin (TC2) were demonstrated (TC1 and TC2 medians: Test Subgroup 1, 3.0 vs. 1.8; Test Subgroup 2, 18.2 vs. 2.2; Test Subgroup 3, 4.2 vs. 10.2 × 10−7 cm·sec−1·cm H2O−1). Multiple regression analysis revealed a relationship between capillary Lp and systemic red blood cell concentration or hematocrit, plasma protein concentration, and Δτ (Test Subgroup 1, R2 = 0.59, P < 0.0001; Test Subgroup 2, R2 = 0.96, P = 0.002), but only during COX inhibition. Maintaining red blood cell and plasma protein levels within a normal range may control barrier function in a healthy state. Recovering barrier function may be an unrecognized benefit of transfusions during blood loss or edema formation.

Effects of enzymatically-extracted purple rice bran fiber as a protectant of L. plantarum NRRL B-4496 during freezing, freeze drying, and storage

This study investigated purple rice bran fiber (PRF) as a protectant for Lactobacillus plantarum NRRL B-4496 (LP) during freezing, freeze drying and storage. PRF was enzymatically extracted from purple rice bran. L. plantarum NRRL B-4496 was grown in MRS broth, centrifuged, and immobilized on PRF suspension. LP cells immobilized on PRF (LP-PRF) and free LP cell (control) samples were frozen in either air blast (AF) or cryogenic freezing (CF) before freeze drying. Freeze-dried (FLP) samples were stored either at room temperature or at refrigerated temperature. For either freezing method, PRF protected cells had less than one log reduction of viable cells while the control had reductions greater than six logs after freeze drying. The log reductions of viable LP cells protected with PRF after freeze drying and 12 weeks storage at 4° C for AF and CF treatments were 0.7 and 1.3 log cycle, respectively. The viable LP-PRF cell count for CF was significantly lower than for AF after 12 weeks at room temperature. PRF improved LP survival in both AF and CF samples in bile. This study demonstrated that freezing methods affected LP viability during storage and that PRF could protect at both refrigerated and room temperatures.

Scavenger receptor-BI is a receptor for lipoprotein(a)

Scavenger receptor class B type I (SR-BI) is a multi-ligand receptor that binds a variety of lipoproteins, including high density lipoprotein (HDL) and low density lipoprotein (LDL), but lipoprotein(a) [Lp(a)] has not been investigated as a possible ligand. Stable cell lines (HEK293 and HeLa) expressing human SR-BI were incubated with protein- or lipid-labeled Lp(a) to investigate SR-BI-dependent Lp(a) cell association. SR-BI expression enhanced the association of both (125)I- and Alexa Fluor-labeled protein from Lp(a). By confocal microscopy, SR-BI was also found to promote the internalization of fluorescent lipids (BODIPY-cholesteryl ester (CE)- and DiI-labeled) from Lp(a), and by immunocytochemistry the cellular internalization of apolipoprotein(a) and apolipoprotein B. When dual-labeled ((3)H-cholesteryl ether,(125)I-protein) Lp(a) was added to cells expressing SR-BI, there was a greater relative increase in lipid uptake over protein, indicating that SR-BI mediates selective lipid uptake from Lp(a). Compared with C57BL/6 control mice, transgenic mice overexpressing human SR-BI in liver were found to have increased plasma clearance of (3)H-CE-Lp(a), whereas mouse scavenger receptor class B type I knockout (Sr-b1-KO) mice had decreased plasma clearance (fractional catabolic rate: 0.63 ± 0.08/day, 1.64 ± 0.62/day, and 4.64 ± 0.40/day for Sr-b1-KO, C57BL/6, and human scavenger receptor class B type I transgenic mice, respectively). We conclude that Lp(a) is a novel ligand for SR-BI and that SR-BI mediates selective uptake of Lp(a)-associated lipids.

Calcium regulates the cell-to-cell water flow pathway in maize roots during variable water conditions

Soil water shortages can decrease root hydraulic conductivity and affect Ca uptake and movement through the plant. In this study, the effects of extra Ca(2+) applied in nutrient solution on the hydraulic properties of the whole roots (Lp(r)) and cortical cells (Lp(cell)) of maize (Zea mays L.) subjected to variable water conditions were investigated. Under well-watered conditions, extra Ca(2+) significantly increased the root Ca content, total root length, and lateral root number; however, it reduced the root cortical cell volume, Lp(r), and Lp(cell). Hg(2+) inhibition experiments suggested that extra Ca(2+) could reduce the contribution of the cell-to-cell water flow pathway. Osmotic stress (10% PEG6000) significantly decreased the cortical cell volume, Lp(r), and Lp(cell) in the control plants, but smaller decreases were observed in the extra Ca(2+) plants. The Hg(2+) treatment reduced the Lp(r) larger in the extra Ca(2+) plants (74.6%) than in the control plants (53.2%), suggesting a higher contribution of the cell-to-cell pathway. The larger Hg(2+) inhibition of the Lp(cell) in the extra Ca(2+) roots (67.2%) when compared to the controls (56.4%) indicated that extra Ca(2+) can mitigate the inhibition of aquaporin expression and/or activity levels via osmotic stress. After 2d of rehydration, the extra Ca(2+) helped the Lp(r) and Lp(cell) to recover almost completely, but these properties only partially recovered in the control plants. In conclusion, extra Ca(2+) may adjust the contribution of cell-to-cell pathway by regulating the expression and/or activity levels of AQPs according to water availability; this regulation may weaken negative effects and optimize water use.

Trefoil factor family-3 is associated with aggressive behavior of colon cancer cells

Trefoil factor family 3 (TFF3) is expressed by intestinal epithelial cells and it mainly functions to protect the mucosa from injury. Expression of TFF3 has been correlated with a poor prognosis in patients with cancer, but little is known about whether TFF3 directly contributes to the malignant behavior of cancer cells. The present study was conducted to determine whether TFF3 expression contributes to the malignant behavior of cancer cells in vitro and in vivo. Two subclones of a metastatic rat colorectal cancer cell line, demonstrated previously to manifest aggressive (LN cells) and non-aggressive (LP cells) growth in vivo, were analyzed for expression of TFF3 and tested in assays of cancer cell migration, invasion, and apoptosis in vitro, and mortality in vivo. The aggressive LN cell line endogenously expressed TFF3 and supported the transcription of a TFF3 promoter-driven reporter construct, whereas the non-aggressive LP cell line did not express TFF3. LN cells demonstrated enhanced migration, invasion, and less apoptosis compared to LP cells. Transfecting TFF3 into LP cells enhanced their ability to migrate, invade, block apoptosis, and behave more aggressively in vivo, thereby resembling the phenotype of LN cells. In rat colon cancer cells, both endogenous and constitutive expression of TFF3 correlates with an aggressive phenotype. These data provide direct evidence that TFF3 contributes to the malignant behavior of cancer cells.

Bifurcation, bursting, and spike frequency adaptation.

Many neural systems display adaptive properties that occur on time scales that are slower than the time scales associated with repetitive firing of action potentials or bursting oscillations. Spike frequency adaptation is the name given to processes that reduce the frequency of rhythmic tonic firing of action potentials, sometimes leading to the termination of spiking and the cell becoming quiescent. This article examines these processes mathematically, within the context of singularly perturbed dynamical systems. We place emphasis on the lengths of successive interspike intervals during adaptation. Two different bifurcation mechanisms in singularly perturbed systems that correspond to the termination of firing are distinguished by the rate at which interspike intervals slow near the termination of firing. We compare theoretical predictions to measurement of spike frequency adaptation in a model of the LP cell of the lobster stomatogastric ganglion.

Inverse relationships between cell proliferation and basal or androgen-stimulated apolipoprotein D secretion in LNCaP human prostate cancer cells

We have recently demonstrated that the biphasic action of androgens on LNCaP cell proliferation is opposite to their effect on apolipoprotein D (apo-D) secretion, the stimulation of apo-D secretion being associated with a steroid-induced inhibition of cell proliferation. To further characterize the control of apo-D expression in LNCaP cells, we studied basal as well as androgen-induced apo-D secretion in slowly proliferating, low-passage (LP; 20–29th) and rapidly proliferating high-passage (HP; 111–117th) cell cultures. For comparison, the androgen-induced stimulation of prostate specific antigen secretion was also investigated in LP and HP cell cultures. In the absence of androgens, basal cell proliferation of HP cells was significantly higher than that of LP cells, whereas apo-D secretion was higher in LP cells than in HP cells. Furthermore, the biphasic action of dihydrotestosterone and of the synthetic androgenic compound R1881 on apo-D release and cell proliferation was observed in both LP and HP cells. The stimulation of apo-D secretion was inversely related to that of cell proliferation and influenced by cell density. The inhibition of basal and androgen-induced cell proliferation by the calcium channel blocker nifedipine was also associated with an increase in apo-D secretion. The amount of PSA released and the sensitivity of its response to R1881 were increased in LP cells compared with HP cells. The present study thus demonstrates, for the first time, that apo-D secretion is inversely correlated to cell proliferation and cell density in the absence as well as in the presence of androgens in both LP and HP LNCaP human prostate cancer cells. This finding suggests that apo-D expression can be modulated not only by steroid hormones, but also by other factors involved in the control of cell proliferation.

Reduction of a channel-based model for a stomatogastric ganglion LP neuron

Buchholtz et al. constructed a detailed conductance-based model of the LP cell of the stomatogastric ganglion of crustacea based upon the experimental work of Golowasch. Their model incorporated seven ionic currents and had 13 dynamical variables. We have produced a simplification of this model that has a seven-dimensional phase space by using the method of equivalent potentials, suggested by Abbott and Kepler, to combine several dynamical variables with similar time scales. Analysis of the dynamics of the reference and reduced model reveals similar bifurcation diagrams and similar dynamical behavior of the individual ionic currents.

Immunohistochemical analysis of oral lichen-planus-like eruption in graft-versus-host disease after allogeneic bone marrow transplantation.

Immunohistochemical analysis of oral lichen-planus-like eruption (LPLE) in graft-versus-host disease (GVHD) using monoclonal antibodies (MoAbs) was performed on five patients after allogeneic bone marrow transplantation (BMT) for leukemia. In the mucosal lesions of LPLE in GVHD, the major population of infiltrated lymphocytes in the areas of upper lamina propria (Lp), basal cell layer (Bc), and epithelium above the basal cell layer (Ep) were T-cells (Leu-1+, Leu-4+) and expressed the phenotype associated with suppressor/cytotoxic T-cells (Leu-2a+) rather than helper/inducer T-cells (Leu-3a+). Some of the infiltrated lymphocytes in the areas of Lp, Bc, and satellite cell necrosis (SCN) bore interleukin-2 (IL-2) receptor. HLA-DR antigen was expressed on keratinocytes in the LPLE lesions. Immunoelectron micrographs showed various degrees of degeneration of keratinocytes to which Leu-2a+ cells attached, whereas those with accidentally attached Leu-3a+ cells preserved normal structures. These findings suggest that cellular immunity mediated by cytotoxic T-cells may play a major role in the pathogenesis of oral LPLE in GVHD.