Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model

BACKGROUND: Many inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation. However, the endogenous modulators for mast cell activation and the underlying mechanism have yet to be elucidated. Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N-arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation. OBJECTIVE: In order to investigate the effect of cannabinoid receptor-1 (CB1R) agonists on mast cell activation, AEA-derived compounds were newly synthesized and evaluated for their effect on mast cell activation. METHODS: The effects of selected compounds on FcepsilonRI-induced histamine and beta-hexosaminidase release were evaluated in a rat basophilic leukemia cell line (RBL-2H3). To further investigate the inhibitory effects of CB1R agonist in vivo, an oxazolone-induced atopic dermatitis mouse model was exploited. RESULTS: We found that CB1R inhibited the release of inflammatory mediators without causing cytotoxicity in RBL-2H3 cells and that CB1R agonists markedly and dose-dependently suppressed mast cell proliferation indicating that CB1R plays an important role in modulating antigen-dependent immunoglobulin E (IgE)-mediated mast cell activation. We also found that topical application of CB1R agonists suppressed the recruitment of mast cells into the skin and reduced the level of blood histamine. CONCLUSION: Our results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis.

Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain

O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2±2 vs 7.9±1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4±2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3±2 vs 7.5±2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1±2 vs 7.4±2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca2+/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction.

The anti-inflammatory effect of Cheongseoikki-tang ethanol extract on allergic reactions mediated by bone marrow-derived mast cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>Cheongseoikki-tang (CIT, Korean), also called Qingshu Yiqi decoction () and Seisho-ekki-to (Japanese), is well known as an effective traditional combination of herbs for treating cardiovascular diseases. This study was to research its effects on bone marrow-derived mast cell (BMMC)-mediated allergy and inflammation mechanisms.</p><p><b>METHODS</b>In this study, the biological effect of Cheongseoikki-tang ethanol extract (CITE) was evaluated, focusing on its effects on the production of allergic mediators by phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 (A23187)-stimulated BMMCs. These allergic mediators included interleukin-6 (IL-6), prostaglandin D2 (PGD2), leukotriene C4 (LTC4), and β-hexosaminidase (β-hex).</p><p><b>RESULTS</b>Our data revealed that CITE inhibited the production of IL-6, PGD2, LTC4, and β-hex induced by PMA plus A23187 (P<0.05).</p><p><b>CONCLUSION</b>These findings indicate that CITE has the potential for use in the treatment of allergy.</p>

Suppressive effects of Schizandra chinensis Baillon water extract on allergy-related cytokine generation and degranulation in IgE-antigen complex-stimulated RBL-2H3 cells

Schizandra chinensis Baillon is a traditional folk medicine plant that is used to treat and prevent several inflammatory diseases and cancer in Korea, but the underlying mechanisms involved in its anti-allergic activity are not fully understood. This study was designed to investigate mechanisms of anti-allergic activity of a Schizandra chinensis Baillon water extract (SCWE) in immunoglobulin E (IgE)-antigen complex-stimulated RBL2H3 cells and to assess whether gastric and intestinal digestion affects the anti-allergic properties of SCWE. Oxidative stress is an important consequence of the allergic inflammatory response. The antioxidant activities of SCWE increased in a concentration-dependent manner. RBL-2H3 cells were sensitized with monoclonal anti-dinitrophenol (DNP) specific IgE, treated with SCWE, and challenged with the antigen DNP-human serum albumin. SCWE inhibited beta-hexosaminidase release and expression of interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-alpha) mRNA and protein in IgE-antigen complex-stimulated RBL2H3 cells. We found that digested SCWE fully maintained its antioxidant activity and anti-allergic activity against the IgE-antigen complex-induced activation of RBL-2H3 cells. SCWE may be useful for preventing allergic diseases, such as asthma. Thus, SCWE could be used as a natural functional ingredient for allergic diseases in the food and/or pharmaceutical industries.

Antigen selection, optimized expression and polyclonal antibody preparation of O-GlcNAcase / 生物工程学报

In order to probe the biological function of O-GlcNAc and the pathogenesis of associated diseases, it is essential to prepare a potent and specific O-GlcNAcase (OGA) antibody. Based on protein sequence analysis, we found N terminal 1-350 amino acids of OGA (sOGA) has high antigenicity and hydrophilicity and then constructed it into plasmid pET28a vector. First, we optimized the expression of sOGA in Escherichia coli BL21(DE3) (0.05 mmol/L IPTG, 10 hours) and purified it with the Ni-NTA affinity chromatography and size exclusion chromatography respectively. SDS-PAGE verified the molecular weight (45 kDa) and the purity (>95%) of sOGA and the purified protein was subjected to immunize New Zealand rabbits. Finally, we obtained OGA polyclonal antibody by affinity purifying the antiserum with CNBr-activated Sepharose 4B beads. Western blotting and ELISA assay showed that this antibody could recognize three OGA isoforms with high specificity and the sensitivity was 0.11 ng/mL (the titer was 1:80 000). These results indicated the prepared polyclonal antibody of OGA can be used for the biological function study of OGA.

Intracellular Ca2+ Mobilization and Beta-hexosaminidase Release Are Not Influenced by 60 Hz-electromagnetic Fields (EMF) in RBL 2H3 Cells

The effects of extremely low frequency electromagnetic fields (EMF) on intracellular Ca2+ mobilization and cellular function in RBL 2H3 cells were investigated. Exposure to EMF (60 Hz, 0.1 or 1 mT) for 4 or 16 h did not produce any cytotoxic effects in RBL 2H3 cells. Melittin, ionomycin and thapsigargin each dose-dependently increased the intracellular Ca2+ concentration. The increase of intracellular Ca2+ induced by these three agents was not affected by exposure to EMF (60 Hz, 1 mT) for 4 or 16 h in RBL 2H3 cells. To investigate the effect of EMF on exocytosis, we measured beta-hexosaminidase release in RBL 2H3 cells. Basal release of beta-hexosaminidase was 12.3+/-2.3% in RBL 2H3 cells. Exposure to EMF (60 Hz, 0.1 or 1 mT) for 4 or 16 h did not affect the basal or 1 microM melittin-induced beta-hexosaminidase release in RBL 2H3 cells. This study suggests that exposure to EMF (60 Hz, 0.1 or 1 mT), which is the limit of occupational exposure, has no influence on intracellular Ca2+ mobilization and cellular function in RBL 2H3 cells.

Effect of chlorogenic acid on degranulation in mast cell RBL-2H3 / 中国中药杂志

<p><b>OBJECTIVE</b>To provide evidences for evaluating the role of chlorogenic acid (CA) on the adverse reaction of traditional Chinese medicine injection and promoting clinical rational usage of CA, the effect of CA and chlorogenic acid-HSA(CA-HSA) on the degranulation in mast cell RBL-2H3 were compared and the allergenic effect and its mechanism were investigated.</p><p><b>METHOD</b>The unsensitized and sensitized RBL-2H3 cells were used. The releasing rate of histamine and beta-hexosaminidase was detected by colormetric assays. The degranulating rate was detected by neutral red staining and Annexin V positive cell rate was detected by flow cytometry.</p><p><b>RESULT</b>CA and CA-HSA could not induce degranulation in unsensitized RBL-2H3 cells. CA and CA-HSA could significantly increase the release of histamine and beta-hexosaminidase, degranulating rate and Annexin V positive cell rate.</p><p><b>CONCLUSION</b>CA has strong allergenicity after combination with serum proteins. As an active ingredient of Shuanghuanglian injection, CA is a kind of possible allergen which caused hypersensitivity reactions induced by Shuanghuanglian injection.</p>

Anti-Oxidative and Anti-Inflammatory Effect of Water Extract from Perillae semen in RBL-2H3 Cells

The present study was to investigate anti-oxidative and anti-inflammatory activity of Perillae semen in RBL-2H3 basophilic leukemia cells. Inhibitory effect of Perillae semen onto free radical generation was determined by measuring DPPH and hydroxyl radical scavenging activities in vitro. Anti-inflammatory actions of Perillae semen extracts (100, 250, 500 microgram/mL) were assessed by testing their effects on the degranulation of mast cells. For this, beta-hexosaminidase released from RBL-2H3 cells was used and proinflammatory cytokines were measured by an ELISA kit. Our results indicated that Perillae semen water extracts effectively inhibited free radical generation. At the concentration of 500 microgram/mL of water extract, the degranulation of RBL-2H3 cells were inhibited by 42.1%. The IgE-antigen complex increased the accumulation of IL-4 and TNF-alpha secretion in RBL-2H3 cells and treatments with 250 and 500 microgram/mL of Perillae semen extracts suppressed the IgE induced secretion of IL-4 and TNF-alpha protein by 20.5, 26.9% and 14.5, 16.5% respectively. We observed that Perillae semen water extract reduced beta-hexosaminidase, IL-4, and TNF-alpha secretion in RBL-2H3 cells. These results provide that Perillae semen may be beneficial in the treatment of allergic inflammatory disease.

Functions of Siglecs in Allergic Inflammation / 소아알레르기및호흡기학회지

Siglecs are sialic acid binding Ig-like lectins, subset of the immunoglobulin superfamily. They are characterized by a homologous N-terminal V-set Ig-like domain and C2 set Ig-like domains. N-terminal domains have sialic acid binding activity. In humans, 11 Siglecs have been described sialoadhesin(Siglec-1), CD22(Siglec-2), CD33(Siglec-3), MAG(Siglec-4), more recently described CD33-related Siglecs(Siglec 5-11). Siglecs express most signal via immunoreceptor tyrosine-based inhibition motif(ITIM) cytoplasmic domains. The cytoplasmic tails of all Siglecs except sialoadhesin have one or more tyrosine residues within potential signaling motifs. Inhibitory function of other Siglecs such as Siglec-7 or Siglec-9 was shown in RBL-2H3 cells. Co-crosslinking of Siglec-7 or Siglec-9 and Fc epsilon R1 substantially reduced the serotonin release of RBL-7 and RBL-9 cells. Siglec-8 is expressed on human eosinophils, mast cells and basophils. Siglec-8 has two tyrosine motifs, a proximal motif and a distal motif. They have some inhibitory functions in immune system. We have observed that Siglec-8 is able to inhibit the IgE receptor-mediated beta-hexosaminidase release of RBL-2H3 cells following co-crosslinking. Co-crosslinking of Siglec-8 and Fc epsilon R1 reduced the hexosaminidase release of RBL-2H3 cells. These results show that Siglec-8 is as potent as Siglec-7 and Siglec-9 in delivering inhibitory signals to RBL-2H3 cells. Siglec-8 should be a new member of the inhibitory receptor superfamily and the membrane-proximal ITIM is essential for the inhibitory function of Siglec-8 molecules. Although these molecules present specific marker for the allergic cell types, more work is needed to understand the signaling mechanism and the role in various disease processes.

A Case Refort of Sandhoff Disease

Sandhoff disease is a rare autosomal recessive metabolic disease presenting bilateral optic atrophy and a cherry red spot in the macula. This case report presents the characteristics of a patient with Sandhoff disease as assessed by ophthalmic, neuroimaging, and laboratory procedures. Ophthalmologic examination revealed that the patient could not fixate her eyes on objects nor follow moving targets. A pale optic disc and a cherry red spot in the macula were seen in both eyes. Low signal intensity at the thalamus and high signal intensity at the cerebral white matter were noted in a T2-weighted brain MR image. A lysosomal enzyme assay using fibroblasts showed the marked reduction of both total beta-hexosaminidases, A and B. Based on the above clinical manifestations and laboratory findings, we diagnosed the patient as having Sandhoff disease.

O-GlcNAc modification on IRS-1 and Akt2 by PUGNAc inhibits their phosphorylation and induces insulin resistance in rat primary adipocytes

It has been known that O-linked beta-N-acetylglucosamine (O-GlcNAc) modification of proteins plays an important role in transcription, translation, nuclear transport and signal transduction. The increased flux of glucose through the hexosamine biosynthetic pathway (HBP) and increased O-GlcNAc modification of protein have been suggested as one of the causes in the development of insulin resistance. However, it is not clear at the molecular level, how O-GlcNAc protein modification results in substantial impairment of insulin signaling. To clarify the association of O-GlcNAc protein modification and insulin resistance in rat primary adipocytes, we treated the adipocytes with O-(2-acetamido-2deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), a potent inhibitor of O-GlcNAcase that catalyzes removal of O-GlcNAc from proteins. Prolonged treatment of PUGNAc (100 micrometer for 12 h) increased O-GlcNAc modification on proteins in adipocytes. PUGNAc also drastically decreased insulin-stimulated 2-deoxyglucose (2DG) uptake and GLUT4 translocation in adipocytes, indicating that PUGNAc developed impaired glucose utilization and insulin resistance in adipocytes. Interestingly, the O-GlcNAc modification of IRS-1 and Akt2 was increased by PUGNAc, accompanied by a partial reduction of insulin-stimulated phosphorylations of IRS-1 and Akt2. The PUGNAc treatment has no effect on the expression level of GLUT4, whereas O-GlcNAc modification of GLUT4 was increased. These results suggest that the increase of O-GlcNAc modification on insulin signal pathway intermediates, such as IRS-1 and Akt2, reduces the insulin-stimulated phosphorylation of IRS-1 and Akt2, subsequently leading to insulin resistance in rat primary adipocytes.

Biochemical characterization of the GM2 gangliosidosis B1 variant

The deficiency of the A isoenzyme of á-hexosaminidase (Hex) produced by different mutations of the gene that codes for the alpha subunit (Tay-Sachs disease) has two variants with enzymological differences: the B variant consists of the absence of Hex A isoenzyme and the B1 variant produces an inactive Hex A isoenzyme for the hydrolysis of the GM2 ganglioside and synthetic substrates with negative charge. In contrast to the early childhood form of the B variant, the B1 variant appears at a later clinical stage (3 to 7 years of age) with neurodegenerative symptoms leading to the death of the patient in the second decade of life. The most frequent mutation responsible for the GM2 gangliosidosis B1 variant is R178H, which has a widespread geographic and ethnic distribution. The highest incidence has been described in Portugal, which has been suggested as the point of origin of this mutation. Biochemical characterization of this lysosomal disease is carried out using negatively charged synthetic alpha subunit-specific sulfated substrates, since Hex A isoenzyme heat-inactivation assays are not applicable. However, the determination of the apparent activation energy of Hex using the neutral substrate 3,3'-dichlorophenolsulfonphthaleinyl N-acetyl-á-D-glucosaminide, may offer a valid alternative. The presence of an alpha subunit in the alphaá heterodimer Hex A means that its activation energy (41.8 kJ/mol) is significantly lower than that of the áá homodimer Hex B (75.1 kJ/mol); however, as mutation inactivates the alpha subunit, the Hex A of the B1 variant presents an activation energy that is similar to that of the Hex B isoenzyme.

Lysosomal storage disorders.

This study was conducted to assess the variability of clinical expression of Lysosomal storage disorders (LSDs) and the selection of specific enzyme investigation to reach the differential diagnosis. Initially 150 children in the age range of 15 days to 13 years were screened for common metabolic disorder and based on screening results, clinical signs and symptoms, 30 children(4 mo-12 yr) of these were selected for the leukocyte enzyme study. Of these 21 were confirmed to have LSDs. The most common disorder was GM2-gangliosidosis (47.61%, 10/21) followed by mucopolysaccharidosis (33.33%; 7/21). All showed variable phenotypic expression. Metachromatic leukodystrophy (MLD) was observed in 9.5% (2/21) of children with arylsulphatase A enzyme deficiency, while two children had shown pseudodeficiency of arylsulphatase A. One case each of galactosialidosis and GMI-gangliosidosis were observed. We conclude that children with developmental delay, seizures, dysmorphic features and organomegaly, with or without positive urinary screening for common metabolic disorders, need to be investigated further for LSDs.Variability of clinical expression is commonly observed in LSDs which require further confirmation by specific leukocyte enzyme study.

A Case of Tay-Sachs Disease in Korea Diagnosed by Enzyme Assay and DNA Analysis / 소아과

Tay-Sachs disease is an autosomal recessive, neurodegenerative disorder that results from excessive storage of the cell membrane glycolipid, and GM2 ganglioside within the lysosomes of cells. This disease is caused by deficiency of the isoenzyme beta-hexosaminidase A, produced in the endoplasmic reticulum. Patients with Tay-Sachs disease are characterized by normal motor development in the first few months of life, followed by progressive weakness and loss of motor skills beginning around 2 to 6 months of life. Neurodegeneration is relentless, with death occurring by the age of 4 or 5 years. Tay-Sachs disease could be diagnosed by hexosaminidase enzyme assay and DNA analysis of HEXA gene. However, specific treatment has not been developed. We report here on a case of Tay- Sachs disease in 18-month-old male who presented with delayed development and seizure. This patient showed hyperacusis and cherry red spot in macula on examination of the fundus. The hexosaminidase A activity was zero percent in the enzymatic assay and DNA analysis identified a mutation that glutamine is substituted by stop codon at position 390(Q390X). This patient is the first case of Tay-Sachs disease in Korea diagnosed by enzymatic assay and DNA analysis.

Serum hexosaminidase and á-glucuronidase activities in infants: effects of age and sex

We investigated the effect of age and sex on the serum activity of hexosaminidase (HEX) and á-glucuronidase (BGLU) in 275 normal term infants aged 12 h to 12 months. Up to six weeks of life, HEX was significantly higher in boys (P<=0.023). During the age period of 1-26 weeks, BGLU was also higher in boys, but differences were significant only at 2-6 and 7-15 weeks (P<=0.016). The developmental pattern of HEX and BGLU was sex dependent. HEX activity increased in both sexes from 4-7 days of life, reaching a maximum of 1.4-fold the birth value at 2-6 weeks of age in boys (P<0.001) and a maximum of 1.6-fold at 7-15 weeks in girls (P<0.001). HEX activity gradually decreased thereafter, reaching significantly lower levels at 27-53 weeks than during the first three days of life in boys (P = 0.002) and the same level of this age interval in girls. BGLU increased in both sexes from 4-7 days of age, showing a maximum increase at 7-15 weeks (3.3-fold in boys and 2.9-fold in girls, both P<0.001). Then BGLU decreased in boys to a value similar to that observed at 4-7 days of age. In girls, BGLU remained elevated until the end of the first year of life. These results indicate a variation of HEX and BGLU activities during the first year of life and a sex influence on their developmental pattern. This observation should be considered in the diagnosis of GM2 gangliosidosis and mucopolysaccharidosis type VII

Studies on the molecular mechanism of GM(2) gangliosidosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the molecular mechanism of GM(2) gangliosidosis.</p><p><b>METHODS</b>The skin fibroblasts from 4 patients with GM(2) gangliosidosis were subjected to culture. Enzyme activities assay, Western blot and immunocytochemical analysis were performed using the cultured fibroblasts.</p><p><b>RESULTS</b>The hexosaminidase (Hex) activities of 4 patients with GM(2) gangliosidosis were significantly decreased. The activities were 12% 3% 15% and 6% of control values, respectively. Western blot analysis indicated that the amount of Hex mature alpha- and beta- subunits (alpha m, beta m) was decreased in cells from patients 2 and 3, but only decreased alpha m was found in patient 1 and both alpha m and beta m were normal in cells from patient 4. Immunocytochemical analysis revealed the accumulated GM(2) ganglioside in cells from patients 1-4.</p><p><b>CONCLUSION</b>The pathogenesis of GM(2) gangliosidosis was associated with deficiency of Hex alpha m and beta m and GM(2) activator caused by HEXA, HEXB and GM(2)A gene mutations.</p>

Biochemical Characteristics of a Korean Patient with Mucolipidosis III (Pseudo-Hurler Polydystrophy)

We performed a biochemical study on the patient with mucolipidosis III (ML-III, pseudo-Hurler polydystrophy) in Korea. Confluent fibroblasts from the patient and from normal controls were cultured for 4, 12, 24, 48, and 72 hr, respectively. Lysosomal enzyme activities in culture media after different incubation times and in plasma, leukocytes, and fibroblasts were determined. Most of the leukocyte lysosomal enzymes were within normal limits or slightly lowered; however, plasma lysosomal enzyme activities such as those of hexosaminidase and arylsulfatase A were markedly increased. Numerous phase-dense inclusions were present in the cytoplasm of cultured fibroblasts. Lysosomal enzyme activities of fibroblasts were markedly decreased except for beta-glucosidase. The rates of increase of the lysosomal enzyme activities with incubation time were greater in the culture medium of the patient than in normal control, whereas no difference in the beta-glucosidase activity of the culture media of the patient and the control was found. This study describes the first case of ML-III in Korea, with its typical biochemical characteristics, i.e., a problem with targeting and transporting of lysosomal enzymes which results in a marked increase in plasma lysosomal enzyme activities and a high ratio of extracellular to intracellular lysosomal enzyme activities in cultured fibroblasts.

Identification of Functionally Different Rat IgE in RBL-2H3 Exocytosis

BACKGROUND: IgE is closely related to the development of allergies. However, the poor relationship between the specific IgE level and the severity of allergic diseases suggests the possibility of functionally different IgE isoforms. With this in mind, rat basophilic leukemia (RBL)-2H3 activation was analyzed with each type of rat IgE for two parameters, exocytosis and IL-4 mRNA production. RBL-2H3 has been well documented in the rat mucosal mast cell line. METHODS: RBL-2H3 cells sensitized with each kind of rat IgE was activated by cross-linking FcRI with B5 (monoclonal anti-rat IgE mouse IgG antibodies). The RBL-2H3 exocytosis was measured by analyzing the beta-hexosaminidase level, and the level of IL-4 mRNA synthesis was analyzed using semi- quantitative RT-PCR. Rat IgE, which was produced by a parasite infection (REP), was prepared using either Paragonimus westermani metacercariae (REP-PW) or Anisakis simplex third stage larvae (REP-AS). A rat IgE prototype of IR162 was prepared by a peritoneal injection of immunocytoma. RESULTS: The level of exocytosis showed a linear relationship with the rat IgE concentration when REP-PW or REP-AS was applied. However, it exhibited a biphasic response with IR162. In addition, the time course of heating at 56oC illustrated the similarity between REP-PW and REP-AS, which differed from that of IR162. In contrast, the level of IL-4 mRNA synthesis in the RBL-2H3 cells with IR162 was comparable to that of either REP-PW or REP-AS. CONCLUSION: These results suggest that functionally different rat IgE isoforms exists in RBL-2H3 exocytosis.

Aspectos genéticos e clínico-terapêuticos da Doença de Tay-Sachs / Genetic and clinical therapeutics aspects of Tay-Sachs disease

A doença de Tay-Sachs apresenta uma freqüência elevada em determinados grupos étnicos, sobretudo nos judeus ashkenazi. É uma desordem neurodegenerativa, presente principalmente em crianças, decorrente de uma atividade deficiente da enzima lisossomal hexosaminidase A, acarretando um acúmulo intracelular de substratos e um progressivo déficit neurológico. O tratamento é discutível, entretanto, resultados promissores têm sido obtidos com a utilização da NB-DNJ e, principalmente, com a terapia genética