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PubMed2000

The influence of alkali fatty acids on the properties and the stability of parenteral O/W emulsions modified with solutol HS 15.

Arachis oil based parenteral O/W emulsions were prepared using soya bean phosphatidylcholine (SPC) and different combinations of co-emulsifiers containing polyethylene glycol fatty acid esters (Solutol HS 15) and alkali fatty acids (sodium laurate, sodium stearate). The parameters measured were droplet size (both by photon correlation spectroscopy and laser diffractometry), pH and zeta potential. All emulsions were subjected to autoclaving. The addition of polyethylene glycol 12-hydroxy stearate (Solutol HS 15) led to a significant decrease of mean oil droplet size. For long-term stability the amount added turned out to be the most important factor. With increased amounts of Solutol HS 15 the packing density of the emulsifier layer and the zeta potential decreased leading to instability. The optimum load of Solutol HS 15 was found to be 15 micromol/ml. Alkali fatty acids markedly improved the physical stability of the emulsions. Improved stability properties conferred to emulsions by alkali fatty acids could be attributed to the zeta potential increase even in the presence of Solutol HS 15. Consequently a mixed emulsifier film was established in which the ionized fatty acids determined the interface charge. In addition to this a strengthening of the molecular interactions occurring between phospholipid and Solutol HS 15 emulsifier in the presence of ionized fatty acids at the O/W interface can be assumed (L. Rydhag, The importance of the phase behaviour of phospholipids for emulsion stability, Fette Seifen Anstrichm. 81 (1979) 168-173). Different co-emulsifier mixtures were shown to have a pronounced impact on the plasma protein adsorption onto emulsion droplets.

Adsorption↗
PubMed2002

Nucleophilic aliphatic substitution reactions of propachlor, alachlor, and metolachlor with bisulfide (HS-) and polysulfides (Sn2-).

Reactions of bisulfide and polysulfides with alachlor, propachlor, and metolachlor were examined in aqueous solution to investigate the role reduced sulfur species could play in effecting abiotic transformations of chloroacetanilide herbicides. Experiments at 25 degrees C demonstrated that reactions were approximately first-order in HS- concentration and revealed that polysulfides are considerably more reactive than HS-. delta H not equal to values for reactions of the three chloroacetanilides with HS- are statistically indistinguishable at the 95% confidence level, as are delta S not equal to values, despite significant differences in second-order rate constants (kHS-). Transformation products were characterized by GC/MS (in some cases following methylation) and were found to be consistent with substitution of chlorine by the sulfur nucleophile. Products containing multiple sulfur atoms were observed for the reactions of chloroacetanilides with polysulfides, while products resulting from reaction with HS- only possessed a single sulfur atom. When second-order rate constants at 25 degrees C are multiplied by HS- and polysulfide concentrations reported in salt marsh porewaters, predicted half-lives range from minutes to hours. HS- and especially polysulfides could thus exert a substantial influence on the fate of chloroacetanilide herbicides in aquatic environments. Oxidation of the resulting sulfur-substituted products could generate ethane sulfonic acid derivatives, previously reported as prevalent chloroacetanilide degradates.

Acetamides↗
PubMed1999

The Enthalpy of Insertion of Sulfur into the Metal-Hydrogen Bond. Synthetic, Structural, and Calorimetric Study of the Complexes HS-M(CO)(3)C(5)R(5) [M = Cr, Mo, W; R = H, Me].

Synthetic and calorimetric studies of the sulfhydryl complexes HS-M(CO)(3)C(5)R(5) (M = Cr, R = Me; M = Mo, W, R = H, Me) are reported. The Mo and W complexes can be obtained in high yield by reaction of the hydrido complexes H-M(CO)(3)C(5)R(5) with Ph(3)Sb=S, which readily undergoes single S atom transfer to the metal-hydrogen bond yielding the metal-sulfhydryl complex. Direct reaction between the metal hydrides and a limited amount of sulfur also yields the sulfhydryl complexes as the dominant organometallic product. At sulfur atom/metal hydride ratios higher than 1/1, additional products formulated as HS(n)()-M(CO)(3)C(5)R(5) are detected. The enthalpies of insertion of sulfur from Ph(3)Sb=S and S(8) into the metal-hydrogen bond have been determined by solution calorimetry. The HS-M(CO)(3)C(5)R(5) complexes (M = Mo, W) are readily desulfurized by PCy(3) for R = H, but not for R = Me. The M-SH bond strength estimates for the complexes HS-M(CO)(3)C(5)Me(5) increases in the order Cr (46) < Mo (55) < W (63) (kcal/mol). The HS-Mo(CO)(3)C(5)Me(5) group has a pK(a) value at least 4 pK(a) units less acidic than that of H-Mo(CO)(3)C(5)Me(5). The crystal structure of HS-W(CO)(3)C(5)Me(5) is reported.

Journal Article↗
PubMed2000

Non-erythroid genes inserted on either side of human HS-40 impair the activation of its natural alpha -globin gene targets without being themselves preferentially activated.

The human alpha-globin gene complex includes three functional globin genes (5'-zeta2-alpha2-alpha1-3') regulated by a common positive regulatory element named HS-40 displaying strong erythroid-specific enhancer activity. How this enhancer activity can be shared between different promoters present at different positions in the same complex is poorly understood. To address this question, we used homologous recombination to target the insertion of marker genes driven by cytomegalovirus or long terminal repeat promoters in both possible orientations either upstream or downstream from the HS-40 region into the single human alpha-globin gene locus present in hybrid mouse erythroleukemia cells. We also used CRE recombinase-mediated cassette exchange to target the insertion of a tagged alpha-globin gene at the same position downstream from HS-40. All these insertions led to a similar decrease in the HS-40-dependent transcription of downstream human alpha-globin genes in differentiated cells. Interestingly, this decrease is associated with the strong activation of the proximal newly inserted alpha-globin gene, whereas in marked contrast, the transcription of the non-erythroid marker genes remains insensitive to HS-40. Taken together, these results indicate that the enhancer activity of HS-40 can be trapped by non-erythroid promoters in both upstream and downstream directions without necessarily leading to their own activation.

Animals↗
PubMedDate not supplied

Mechanistic study of solubility enhancement of nifedipine using vitamin E TPGS or solutol HS-15.

The objective of our study was to find mechanisms responsible for solubility enhancement of nifedipine in solid dispersions of vitamin E TPGS and/or solutol HS-15. Solid dispersions of nifedipine with selected polymers such as vitamin E TPGS, solutol HS-15, PEG(1,000), and lipocol C-10 of varying drug/polymer ratios were prepared by a fusion method. The solubility enhancement was found to be in the order of vitamin E TPGS > solutol HS-15 > lipocol C-10 > PEG(1,000). Lipocol C-10, with a similar hydrophilic-lipophilic value as vitamin E TPGS, showed a comparable retained solubility enhancement during saturation solubility studies but had lower dissolution profile. Overall, vitamin E TPGS showed the best solubility and dissolution performance, while solutol HS-15 and lipocol C-10 demonstrated moderate solubility enhancements. Solid dispersions of vitamin E TPGS as prepared by microfluidization technique initially showed slightly higher solubility compared with samples prepared by fusion method, but eventually it became the same as the study progressed. However, solid dispersion of solutol HS-15 as prepared by microfluidization demonstrated a significant, sustained increased in solubility over its sample when prepared by fusion method. Based on these results, we concluded that enhanced solubility using vitamin E TPGS and solutol HS-15 resulted from a partial conversion of crystalline drug to the amorphous form, increase in wettability of the drug by water soluble polymers, better separation of drug particles, micellar solubilization of drug by high concentrations of surfactant polymers, and interaction between polymer and drug at the molecular level.

Calcium Channel Blockers↗
PubMed2003

Synthetic chenodeoxycholic acid derivative HS-1200-induced apoptosis of p815 mastocytoma cells is augmented by co-treatment with lactacystin.

The antitumor activity of a synthetic chenodeoxycholic acid derivative, HS-1200, on the p815 mastocytoma cell line was investigated. We present several lines of evidence indicating that HS-1200 at 35 microM induced apoptosis of p815 cells. Reduction of mitochondrial membrane potential, the release of cytochrome to cytosol, activation of caspase-3, nuclear condensation, production of poly(ADP-ribose) polymerase cleavage, generation of DNA fragmentation and nuclear condensation were demonstrated. Importantly, HS-1200 inhibited proteasome activity. Next, the combination treatment of HS-1200 or a proteasome inhibitor lactacystin was undertaken. Although the single treatment of 20 microM HS-1200 or 1 microM lactacystin induced apoptosis slightly, the combination treatment of them augmented prominently the extent of apoptosis. The combination therapy of HS-1200 and lactacystin could be potentially a therapeutic strategy reducing the extent and severity of treatment-related toxicity.

Acetylcysteine↗
PubMed1995

Neural computation of motion in the fly visual system: quadratic nonlinearity of responses induced by picrotoxin in the HS and CH cells.

1. A computational model accounting for motion detection in the fly was examined by comparing responses in motion-sensitive horizontal system (HS) and centrifugal horizontal (CH) cells in the fly's lobula plate with a computer simulation implemented on a motion detector of the correlation type, the Reichardt detector. First-order (linear) and second-order (quadratic nonlinear) Wiener kernels from intracellularly recorded responses to moving patterns were computed by cross correlating with the time-dependent position of the stimulus, and were used to characterize response to motion in those cells. 2. When the fly was stimulated with moving vertical stripes with a spatial wavelength of 5-40 degrees, the HS and CH cells showed basically a biphasic first-order kernel, having an initial depolarization that was followed by hyperpolarization. The linear model matched well with the actual response, with a mean square error of 27% at best, indicating that the linear component comprises a major part of responses in these cells. The second-order nonlinearity was insignificant. When stimulated at a spatial wavelength of 2.5 degrees, the first-order kernel showed a significant decrease in amplitude, and was initially hyperpolarized; the second-order kernel was, on the other hand, well defined, having two hyperpolarizing valleys on the diagonal with two off-diagonal peaks. 3. The blockage of inhibitory interactions in the visual system by application of 10-4 M picrotoxin, however, evoked a nonlinear response that could be decomposed into the sum of the first-order (linear) and second-order (quadratic nonlinear) terms with a mean square error of 30-50%. The first-order term, comprising 10-20% of the picrotoxin-evoked response, is characterized by a differentiating first-order kernel. It thus codes the velocity of motion. The second-order term, comprising 30-40% of the response, is defined by a second-order kernel with two depolarizing peaks on the diagonal and two off-diagonal hyperpolarizing valleys, suggesting that the nonlinear component represents the power of motion. 4. Responses in the Reichardt detector, consisting of two mirror-image subunits with spatiotemporal low-pass filters followed by a multiplication stage, were computer simulated and then analyzed by the Wiener kernel method. The simulated responses were linearly related to the pattern velocity (with a mean square error of 13% for the linear model) and matched well with the observed responses in the HS and CH cells. After the multiplication stage, the linear component comprised 15-25% and the quadratic nonlinear component comprised 60-70% of the simulated response, which was similar to the picrotoxin-induced response in the HS cells. The quadratic nonlinear components were balanced between the right and left sides, and could be eliminated completely by their contralateral counterpart via a subtraction process. On the other hand, the linear component on one side was the mirror image of that on the other side, as expected from the kernel configurations. 5. These results suggest that responses to motion in the HS and CH cells depend on the multiplication process in which both the velocity and power components of motion are computed, and that a putative subtraction process selectively eliminates the nonlinear components but amplifies the linear component. The nonlinear component is directionally insensitive because of its quadratic non-linearity. Therefore the subtraction process allows the subsequent cells integrating motion (such as the HS cells) to tune the direction of motion more sharply.

Animals↗
PubMed2004

Deletion of the major GATA1 enhancer HS 1 does not affect eosinophil GATA1 expression and eosinophil differentiation.

Expression of the myeloid transcription factor GATA1 is required for early stages of eosinophil differentiation. Defining mechanisms regulating eosinophil GATA1 expression will be important to understand development of this lineage. However, the cis-elements required for eosinophil GATA1 expression are not fully characterized. Previous work identified HS 1 as a major GATA1 enhancer, but its role in eosinophil GATA1 expression is unclear. Here, we show that mouse HS 1 deletion leaves eosinophil GATA1 mRNA expression and eosinophil differentiation unaffected. Chromatin isolated from eosinophils and encompassing HS 1 is weakly enriched for acetylated histones H3/H4. HS 1 deletion does not alter eosinophil GATA1 locus histone acetylation. In eosinophils, GATA1 and CCAAT/enhancer binding protein epsilon (C/EBP epsilon) do not bind HS 1 but bind selectively a cis-element in the first GATA1 intron. Thus, HS 1 is not required for eosinophil GATA1 expression. Instead, this study suggests a previously unsuspected role for the GATA1 intron element for this function.

Acetylation↗
PubMed1994

Anti-human sperm monoclonal antibody HS-11: a potential marker to detect bovine sperm capacitation and acrosome reaction in vitro.

The crossreactivity between bull spermatozoa and monoclonal antibodies initially raised against mouse spermatozoa and human spermatozoa was tested by indirect immunofluorescent assay. The three anti-human spermatozoa monoclonal antibodies examined (HSK-9, HS-11, HS-63) crossreacted with methanol-fixed bull spermatozoa, whereas the anti-mouse spermatozoa monoclonal antibodies (MS-4 and MS-7) did not. A separate experiment was conducted to determine the binding ability of HSK-9, HS-11 and HS-63 with live (fresh) bull spermatozoa incubated (39 degrees C in CO2 incubator) in a capacitation medium (modified Tyrode's supplemented with 10 micrograms heparin ml-1). The binding of the monoclonal antibodies to the intra-acrosomal antigens of live bull spermatozoa was determined at 0, 2, 4, 6 and 8 h of incubation. At the beginning of incubation, binding was minimal (3.2 +/- 1.7%), but a much higher percentage of spermatozoa exhibited fluorescent staining after 2 h. The maximal binding was observed after incubation for 8 h (72.0 +/- 8.2%). The third experiment was performed to determine binding of HS-11 to frozen-thawed spermatozoa and to test whether there was any variation among bulls in HS-11 binding to spermatozoa, and to assess whether such binding is an indication of sperm capacitation. Frozen-thawed semen samples from five bulls were assessed for antibody binding after 0, 2, 4 and 6 h of incubation. Maximal binding was observed at 4 h. Lysophosphatidylcholine (100 micrograms ml-1) induced acrosome reaction assay was performed to assess sperm capacitation at various intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrosome↗
PubMed2006

Relationship between adhesion molecules with hs-CRP and changes therein after ARB (Valsartan) administration in patients with obstructive sleep apnea syndrome.

It has been reported that a relationship exists between obstructive sleep apnea syndrome (OSAS) and cardiovascular and cerebrovascular diseases. To address this issue, we evaluated whether OSAS is associated with adhesion molecules and inflammatory signs, important indicators of atherosclerosis. Levels of high-sensitivity CRP (hs-CRP) and intercellular adhesion molecule-1 (ICAM-1) were measured in 30 patients with ischemic heart disease, confirmed by coronary arteriography (IHD group). Twenty healthy volunteers without sleep apnea were used as controls (Group N). Sleeping respiratory information was collected using a portable sleep polygraph, together on information about oronasal flow, tracheal sound, chest respiration, and percutaneous oxygen saturation (SpO2) to obtain the apnea-hypopnea index (AHI). In the IHD group, 9 (30%) of the 30 patients showed evidence of OSAS [IHD(AHI> or = 40) group] and 21 did not [IHD(AHI<40) group]. The levels of hs-CRP and ICAM-1 were significantly higher in the IHD group than in the N group (p<0.01). Moreover, the levels of hs-CRP and ICAM-1 were significantly higher in the IHD(AHI > or = 40) group than in the IHD(AHI<40) group (p<0.01). However, after the administration of valsartan, angiotensin II receptor antagonists (ARB) to both IHD groups, the levels of hs-CRP and ICAM-1 decreased significantly in both groups. Moreover, a multivariate analysis revealed that the levels of hs-CRP and ICAM-1 were associated with the severity of sleep apnea. These findings suggest that, in OSAS the levels of hs-CRP and ICAM-1 are decreased and that the administration of ARB decreases the risk of atherosclerosis.

Aged↗
PubMed2006

Serum hs-CRP as a useful marker for predicting the efficacy of lumbar epidural steroid injections on pain relief in patients with lumbar disc herniations.

INTRODUCTION: We examined systemic inflammatory serum markers and pain responses to image-guided lumbar epidural steroid injections (LESI) both before and after LESI in patients with lumbar disc herniations with various pathological intervertebral disc changes. METHODS: Sixty male patients were scheduled for LESI every two weeks for three injections. Prior to injection therapy the following laboratory tests were performed: a complete blood count (CBC), high-sensitivity C-reactive protein (hs-CRP), and an erythrocyte sedimentation rate (ESR). Five groups of fifteen patients each were classified according to MRI observation: I) control group, II) disc protrusion, III) disc prolapse, IV) disc extrusion, and V) sequestered disc herniation. LESI were scheduled two weeks apart and were done with fluoroscopy using 40 mg of triamcinolone with 5 ml of preservative-free lidocaine. All patients returned 6 weeks following their initial injection and repeat hs-CRP assays were obtained. RESULTS: No patient in this study had an abnormal CBC or ESR. No patient in the control group had an elevated hs-CRP. The percentage and number of patients in each experimental group with elevated hs-CRP levels were: II) 0% (0/15), III) 20% (3/15), IV) 80% (12/15), and V) 73% (11/15). LESI was more efficacious in the two contained disc herniation groups (II and III). It was found that the higher the hs-CRP levels prior to LESI therapy, the less improvement in pain scores following LESI. DISCUSSION: The results of this study suggest that elevated hs-CRP levels may be useful for objectively evaluating and predicting responses to LESI in those patients with lumbar disc pathology with lower extremity radiculitis.

Adult↗
PubMed1993

Human fetuin/alpha 2 HS glycoprotein in colloid and parenchymal cells in human fetal pituitary gland.

An immunohistochemical study was undertaken, in an attempt to identify the acidic glycoprotein(s) present in colloid and in parenchymal cells in human fetal pituitary gland. As the colloid has been proposed to represent disintegrating cells, a series of antibodies against plasma glycoproteins and plasma proteins was applied; their presence intracellularly would generally be an indicator of plasma membrane leakage in dying parenchymal cells. In tissue sections from 9- to 20-week-old fetuses, the colloid showed prominent staining with an antibody to human fetuin/alpha 2 HS glycoprotein. Anti-alpha 2-HS glycoprotein labelled parenchymal cells in pars anterior and intermedia. Apart from a minor immunoreactivity for alpha 1 beta glycoprotein, no other plasma glycoprotein was seen in colloid or parenchymal cells. An antibody against bovine fetuin showed staining of the colloid and of some parenchymal cells in pars distalis and intermedia; the plasma and stroma of the pituitary gland were unstained. In contrast, the anti-human plasma protein antibodies all stained the stroma. The presence of alpha 2 HS glycoprotein in parenchymal cells and absence of other plasma glycoproteins imply integrity of the parenchymal cell plasma membrane. Thus, alpha 2 HS glycoprotein is either synthesized locally or taken up specifically in the parenchymal cells, which are proposed to participate in the formation of colloid. It is suggested that alpha 2 HS glycoprotein is part of a homeostatic system, which controls remodelling and physiological cell death during development.

Animals↗
PubMed1991

Serum alpha 2-HS glycoprotein concentration in patients with hematological malignancies. A follow-up study.

We observed significantly reduced serum alpha 2-HS glycoprotein concentrations in patients with acute lymphocytic, acute nonlymphocytic, chronic granulocytic and chronic myelomonocytic leukemias, Hodgkin's and non-Hodgkin's lymphomas, myelofibrosis, and multiple myeloma, but not in patients with chronic lymphocytic leukemia and polycythemia vera, as compared with healthy controls. We followed the serum level of the protein for 18 months. Patients with infectious complications, those receiving cytostatic treatment, and those in the preterminal period had further reduced serum alpha 2-HS glycoprotein levels. The reduction of serum alpha 2-HS glycoprotein concentration was primarily due to decreased production caused by infiltration of the liver, a hepatotoxic effect of cytostatic treatment, and, to a lesser degree, to increased consumption. We found statistically significant negative correlations between serum alpha 2-HS glycoprotein concentration and erythrocyte sedimentation rate, serum aspartate aminotransferase and alkaline phosphatase activities, and IgG and IgM concentrations. The determination of the alpha 2-HS glycoprotein concentration is useful for the assessment and follow-up of the clinical status and therapy of patients with hematological malignancies and also has prognostic significance.

Adolescent↗
PubMed1988

Cystatin domains in alpha-2-HS-glycoprotein and fetuin.

We have found that chain A of alpha-2-HS-glycoprotein contains two cystatin domains that show closest similarity to those of kininogen. Most likely, the two proteins diverged after the primary duplication of a single cystatin domain as the two cystatin domains of alpha-2-HS-glycoprotein are more similar, especially in disulfide bonding, to the corresponding domains of kininogen than to each other. We also propose that the carboxyl-terminal (non-cystatin) parts of kininogen and alpha-2-HS-glycoprotein contain homologous segments. We suggest that alpha-2-HS-glycoprotein may act as an inhibitor of the cysteine proteinases responsible for bone resorption. We have also found that fetuin is closely related to alpha-2-HS-glycoprotein.

Amino Acid Sequence↗
PubMed1998

Effects of antibodies to transferrin and alpha 2-HS glycoprotein on in vitro sperm motion: implications in infertility associated with endometriosis.

PROBLEM: Women with endometriosis have antibodies to endometrial transferrin and alpha 2-HS glycoprotein in their serum and peritoneal fluid. The objective of this study was to determine whether antibodies to transferrin and alpha 2-HS glycoprotein adversely affect sperm motility and survival. METHOD OF STUDY: Spermatozoa obtained from normal fertile donors and washed free of seminal plasma were incubated with the medium (control), 1:2 and 1:100 dilutions of antitransferrin, 1:4, 1:8 and 1:100 dilutions of anti-alpha 2-HS glycoprotein, and a 1:2 dilution of antialbumin antiserum (negative control). Sperm motion characteristics in 10 microliters aliquots were evaluated at 30 min, 1 hr, 2 hr, 4 hr, and 24 hr using computerized sperm motion analysis. A paired t-test was done to analyze the effects of the various antibodies on sperm motion characteristics. RESULTS: Antibodies to albumin failed to adversely affect sperm motility in general or the several sperm motion characteristics in particular. In contrast, antibodies to transferrin at the dilution of 1:2 adversely affected the percentage of motile and rapid spermatozoa, progressive and path velocities, straightness, linearity, track speed, and anterior-lateral head displacement (P < 0.001) at all the time intervals, whereas a 1:100 dilution of this antiserum adversely affected these parameters only at 24 hr. Elongation and beat cross-frequency were significantly affected at 4 and 24 hr by a 1:2 dilution of antitransferrin antiserum. The effects of anti-alpha 2-HS glycoprotein were more pronounced than those of antitransferrin, but they were similar. Dilutions of 1:4 and 1:8 were effective at all time intervals, whereas a 1:100 dilution was effective in reducing the track speed and the percentage of rapid cells at 24 hr (P < 0.001). CONCLUSION: Antibodies to endometrial transferrin and alpha 2-HS glycoprotein present in the peritoneal fluid, and possibly in the oviductal fluid, of patients with endometriosis may adversely affect postcoital sperm motility and sperm survival.

Antibodies↗
PubMed1995

Comparison of solutol HS 15, Cremophor EL and novel ethoxylated fatty acid surfactants as multidrug resistance modification agents.

Some well-known fatty acid ester surfactants, e.g., Cremophor EL and Solutol HS 15, are modulators of multidrug resistance in vitro and in vivo. Because they are polydisperse, and their active component(s) have not been identified, the therapeutic potential of such surfactants is unclear. To better define the active components of Solutol HS 15 and to make more potent surfactant multidrug resistance modulators, highly purified C-18 fatty acids were esterified with ethylene oxide at 5-200 molar ratios. Unexpectedly, ethylene oxide esters of pure 12-hydroxy stearic acid, the major components of Solutol HS 15, displayed negligible resistance modification activity compared with Solutol HS 15 itself or to stearic and oleic acid esters synthesized under identical conditions. Since oleic acid esters appeared to have good activity, a series of these compounds was prepared to determine the optimal ethylene oxide/fatty acid ratio. The optimal ratio was found to be 20 mole ethylene oxide: I mole fatty acid, with a steep decline in activity for products made with ratios above and below the optimum. The most active oleic acid ester, designated CRL 1337, was 8.4-fold as potent as Solutol HS 15 and over 19-fold as potent as Cremophor EL in promoting rhodamine 123 accumulation in multidrug-resistant KB 8-5-11 cells in vitro. Our results show that the structure of the hydrophobic domain (fatty acid) of surfactants as well as its hydrophile-lipophile balance are critical in determining the potency of surfactants as reversing agents.

Antineoplastic Agents↗
PubMed1995

Autonomous, erythroid-specific DNase I hypersensitive site formed by human beta-globin locus control region (LCR) 5' HS 2 in transgenic mice.

The human beta-globin locus control region (LCR) is composed of four erythroid-specific, DNase I hypersensitive (HS) sites that are located 6 to 18 kb upstream of the epsilon-globin gene. The beta-globin LCR appears to have two major functions. First, the sequences "open" a chromosomal domain that includes the epsilon-, gamma-, and beta-globin genes and, second, the LCR directs high-level, erythroid-specific expression of each globin gene family member. An LCR subfragment containing only 5' HS 2 can confer these properties on a linked beta-globin gene. To determine whether 5' HS 2 can form an erythroid-specific, DNase I hypersensitive site in the absence of a linked globin gene, a 1.9-kb DNA fragment containing this site was injected into fertilized mouse eggs and DNase I hypersensitivity was analyzed in the animals that developed. In 9 of 10 transgenic mouse lines, the human 5' HS 2 fragment formed a DNase I hypersensitive site in fetal liver but not in fetal brain. These results suggest that human 5' HS 2 can function autonomously to organize an open chromatin domain specifically in erythroid cells.

Animals↗
PubMed1991

Morphological characterization of a newly established human osteosarcoma cell line, HS-Os-1, revealing its distinct osteoblastic nature.

A newly established human osteosarcoma cell line, HS-Os-1, from an osteoblastic tumor arising in the left humerus of an 11-year-old girl was morphologically characterized in vitro and in vivo. HS-Os-1 cells in a monolayer have been maintained for more than 2 years since the initial cultivation, and were round or polygonal in shape with marked pleomorphism. Their cytoplasm was strongly positive for specific markers of osteoblasts, such as alkaline phosphatase and osteocalcin. Tumors induced in nude mice by HS-Os-1 cell inoculation at passage 12 or 23 revealed typical histological features of osteoblastic osteosarcoma, similar to those observed in the original tumor, producing prominent osteoid matrix with calcification. Ultrastructurally, HS-Os-1 cells in vitro and tumor cells in vivo showed similar well-developed, markedly dilated rough endoplasmic reticulum, polysomes and microfilaments in their cytoplasm. Additionally, many collagen fibers associated with deposition of electron-dense material were detected in the stroma featuring osteoid matrix. Thus, the HS-Os-1 cell line was shown to exhibit its osteoblastic nature in vitro and in vivo, and therefore might become an extremely useful tool for various pathomorphological investigations on human osteosarcomas.

Animals↗