Detailed characterization of Act d 12 and Act d 13 from kiwi seeds: implication in IgE cross-reactivity with peanut and tree nuts.

BACKGROUND: Act d 12 (11S globulin) and Act d 13 (2S albumin) are two novel relevant allergens from kiwi seeds that might be useful to improve the diagnostic sensitivity and the management of kiwifruit-allergic patients. OBJECTIVE: To perform a comprehensive structural and immunological characterization of purified Act d 12 and Act d 13 from kiwi seeds. METHODS: Sera from 55 well-defined kiwifruit-allergic patients were used. Act d 12 and Act d 13 were purified by chromatographic procedures. Circular dichroism, mass spectrometry, concanavalin A detection, immunoblotting, enzyme-linked immunosorbent assays, basophil activation tests, and IgE-inhibition experiments were used. RESULTS: Act d 12 and Act d 13 were purified from kiwi seeds to homogeneity by combining size-exclusion, ion-exchange, and RP-HPLC chromatographies. Both purified allergens preserve the structural integrity and display typical features of their homologous counterparts from the 11S globulin and 2S albumin protein families, respectively. These allergens are released from kiwi seeds after oral and gastric digestion of whole kiwifruit, demonstrating their bioavailability after ingestion. The allergens retain the capacity to bind serum IgE from kiwifruit-allergic patients, induce IgE cross-linking in effector-circulating basophils, and display in vitro IgE cross-reactivity with homologous counterparts from peanut and tree nuts. CONCLUSION: Purified Act d 12 and Act d 13 from kiwi seeds are well-defined molecules involved in in vitro IgE cross-reactivity with peanut and tree nuts. Their inclusion in component-resolved diagnosis of kiwifruit allergy might well contribute to improve the diagnostic sensitivity and the management of kiwifruit-allergic patients.

Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome.

During a study of the familial aggregation of Down syndrome (DS) and Alzheimer disease (AD), we observed an increase in mosaicism for disomy 21 in older individuals with DS. In a total of 213 DS subjects who were studied cytogenetically, only 1 of 121 (0.8%) under age 45 exhibited mosaicism, while 14 of 92 (15.2%) who were age 45 or older had mosaicism. Mosaicism in this report connotes "low-level" mosaicism, where all 15 individuals exhibited a modal chromosome number of 47 (i.e., trisomy 21), and at least two cells lacked one of the three chromosomes 21. The occurrence of aneuploidy for chromosomes 15, 17, and X increased with age, and an inverse correlation between chromosome loss and size was also observed. Because older individuals had not been karyotyped at birth, it was not possible to determine whether our observations were due to either increased survival of mosaic individuals or accumulation of disomy 21 cells via increased chromosome loss with aging of the trisomy 21 individual. Using a modeling approach involving life table methods, we obtained results that suggested acquired mosaicism as the predominant mechanism to explain our findings. These results support the hypothesis that as individuals with DS age, there is an increased loss of chromosome 21.

Onset of dementia is associated with apolipoprotein E epsilon4 in Down's syndrome.

We examined the influence of apolipoprotein E (apoE) genotype on risk of dementia in 82 adults with Down's syndrome (DS). Compared with those with an apoE 3/3 genotype, the group of adults with DS with apoE 2/4, 3/4, and 4/4 genotypes were 5 times more likely to become demented (RR = 4.7; 95% CI = 1.2, 17.9). We hypothesize that the increased risk of dementia may be mediated by exacerbation of beta-amyloid deposition.

Presence of serotonin1A (5-HT1A) receptor mRNA without binding of [3H]-8-OH-DPAT in peripheral blood mononuclear cells.

The authors investigated the presence of serotonin receptor type 1A (5-HT1A) as labeled by the specific ligand 3H-8 hydroxy-2-(di-N-propylamino)tetralin (3H-8-OH-DPAT) in saturation experiments, and the expression of the mRNA encoding them, in human peripheral blood mononuclear cells (PBMC). In situ hybridization experiments were performed as well. The results, showing that the binding of [3H]-8-OH-DPAT to lymphocyte membranes increased linearly up to 100 nM without reaching saturation, may indicate that the 3H-8-OH-DPAT was not specifically labeling the 5-HT1A receptor. By contrast, the expression studies revealed 5-HT1A mRNA in PBMC. These findings suggest that, despite the presence of mRNA, 5-HT1A receptors are not expressed in PBMC, at least in healthy controls.

L-carnitine and some of its analogs delay the onset of apoptotic cell death initiated in murine C2.8 hepatocytic cells after hepatocyte growth factor deprivation.

Addition of L-carnitine and some of its analogs to low-serum incubation medium of murine hepatocytic C2.8 cells prolonged maintenance of life and enhanced cell growth, as compared to controls. The drug acted synergistically with hepatocyte growth factor (HGF). Addition of L-carnitine to cells that had grown confluently in medium supplemented with HGF, significantly delayed the onset of cell death (apoptosis) initiated after HGF deprivation. Protection by L-carnitine was dose-dependent and stereospecific. Similar findings were obtained with three analogs of L-carnitine (i.e. isovaleryl-L-carnitine-HCl, isovaleryl-L-carnitine acid fumarate and butyryl L-carnitine taurine amide). In contrast, four different analogs (i.e. isovaleryl-L-carnitine-eptyl-ester-HCl, isovaleryl-L-carnitine-idroxy-butyric-HCl, L-threonyl-L-carnitine-HCl and L-paramethyl-cinnamoil-carnitine-HCl) were inactive. Although the mechanism of cytoprotection stimulated by L-carnitine remains unresolved, the data suggest that this compound serves as a co-factor that influences C2.8 cells to become less susceptible to damaging actions of noxious agents or conditions initiated after HGF withdrawal.

Apoptosis of serum-free C2.8 mouse embryo hepatocytic cells caused by hepatocyte growth factor deprivation.

C2.8 mouse embryo hepatocytic cells, acutely required exogenous hepatocyte growth factor (HGF) to survive and proliferate in serum-free Dulbecco's modified Eagle's medium supplemented with insulin, transferrin and Na-selenite. Greater than 90% of cultured C2.8 cells died within 48 hours from plating in the absence of HGF. Conversely, HGF prolonged maintenance of life and stimulated cell proliferation. Removal of HGF from the medium of cultures that had grown to confluency, also resulted in a rapid decreased cell survival. In the last circumstance, light microscopic observations revealed, with high frequency, morphological features characteristic of apoptosis. DNA within the affected cells underwent rapid fragmentation, revealed as a ladder of DNA fragments in multiples of about 200 base pairs. HGF prevented loss of cell viability, morphological damages and retarded DNA fragmentation in confluent C2.8 cells. Cycloheximide delayed cell death caused by HGF deprivation.

Glomerulonefritis crescentica aguda con insuficiencia renal rapidamente progresiva. Empleo de metilprednisolona a dosis alta con recuperacion de la funcion renal. Comunicacion de un caso. / Acute crescentic glomerulonephritis with progressive renal faillure. Use of high doses of methylprednisolone with renal function recovery. Communication of a case

Se estudia un paciente con la llamada glomerulonefritis crescentica aguda acompanada de insuficiencia renal progresiva y la cual fue tratada con metilprednisolona con respuesta satisfactoria, comentandose sobre la enfermedad y sus caracteristicas