Cytogenetic molecular delineation of a terminal 18q deletion suggesting neo-telomere formation

Deletion of the long arm of chromosome 18 is one of the most common segmental aneusomies compatible with life and usually involves a deletion of the terminal chromosomal region. However, the mechanisms implicated in the stabilization of terminal deletions are not well understood. In this study, we analyzed a girl with moderate mental retardation who had a cytogenetically visible terminal 18q deletion. In order to characterize the breakpoint in the terminal 18q region, we used fluorescence In situ hybridization (FISH) with bacterial artificial chromosomes (BACs) and pan-telomeric probes and also the array technique based on comparative genomic hybridization (array-CGH). FISH with pan-telomeric probes revealed no signal in the terminal region of the deleted chromosome, indicating the absence of normal telomere repeat (TTAGGG)n sequences in 18q. We suggest that neo-telomere formation by chromosome healing was involved in the repair and stabilization of this terminal deletion.     

Dental and skeletal maturation as simultaneous and separate predictors of chronological age in post-pubertal individuals: a preliminary study in assessing the probability of having attained 16 years of age in the living

The goal of this paper is to explore whether combining dental and skeletal maturation data increases the reliability of determining whether an individual is 16 years old or older. This is tentatively done by building probabilistic models for age estimation based on dental and skeletal maturation using a longitudinal sample of eight males, with annual assessments between the ages of 13 and 19, totalling 56 observations. Skeletal maturity was assessed for the radius and ulna using the TW2 method, and dental maturity was assessed for the second and third molars using Demirjian’s scheme. Logistic regression was selected to determine the probability of an individual being 16 years of age and older, by combining dental and skeletal maturity scores and using them separately. The age estimation models combining dental and skeletal maturity scores seem to perform better than either dental or skeletal maturity in isolation. In addition, when in isolation or combination, models based on skeletal maturity scores seem to outperform models based on dental maturity scores. The findings seem to support the notion that dental development is less reliable than skeletal maturity for age estimation in adolescents, but these results have to be confirmed by further studies.     

Niacin inhibits carrageenan-induced neutrophil migration in mice

Several emerging lines of evidence support an anti-inflammatory role for nicotinic acid (niacin); however, its role in the regulation of leukocyte migration in response to inflammatory stimuli has not been elucidated until now. Herein, we have examined the effect of nicotinic acid on neutrophil recruitment in experimentally induced inflammation. We demonstrated that nicotinic acid treatment inhibited interleukin (IL)-8-induced, leukotriene (LT)B₄-induced, and carrageenan-induced neutrophil migration into the pleural cavity of BALB/c mice and reduced neutrophil rolling and adherence in a mouse cremaster muscle preparation. Surprisingly, nicotinic acid treatment increased the level of the neutrophil chemoattractant KC in response to carrageenan. These results suggest that nicotinic acid plays an important role in the regulation of inflammation due to its ability to inhibit the actions of the neutrophil chemoattractants IL-8 and LTB₄. Further inhibition of chemoattractants leads to impairment of leukocyte rolling and adherence to the vascular endothelium in the microcirculation of inflamed tissues.     

The Role of L‐Arginine and Inducible Nitric Oxide Synthase in Intestinal Permeability and Bacterial Translocation

Background: Arginine has been shown to have several immunological and trophic properties in stressful diseases. Its metabolites, nitric oxide (NO) and polyamines, are related to arginine's effects. Thus, the aim of this study was to determine the effects of the NO donor L‐arginine and the role of inducible NO synthase (iNOS) on intestinal permeability and bacterial translocation in a model of intestinal obstruction (IO) induced by a simple knot in the terminal ileum. Material and Methods: Male C57BL6/J wild‐type (WT) and iNOS knockout (iNOS–/–) mice were randomized into 6 groups: Sham and Sham–/– (standard chow), IO and IO–/– (standard chow +IO), and Arg and Arg–/– (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chows, IO was induced and intestinal permeability and bacterial translocation were evaluated. The small intestine and its contents were harvested for histopathological and morphometric analysis and the determination of polyamine concentration. Results: Pretreatment with arginine maintained intestinal permeability (P > .05; Arg and Arg–/– groups vs Sham and Sham–/– groups), increased polyamine concentration in intestinal content (P < .05; Arg vs IO group), and decreased bacterial translocation in WT animals (Arg group vs IO and IO–/– groups). Absence of iNOS also presented a protective effect on permeability but not on bacterial translocation. Conclusion: Arginine supplementation and synthesis of NO by iNOS are important factors in decreasing bacterial translocation. However, when intestinal permeability was considered, NO had a detrimental role.     

Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: preclinical studies.

We have previously shown that leukemia-specific cytotoxic T cells (CTL) can be generated from the bone marrow of most patients with B-cell precursor acute leukemias. If these antileukemia CTL are to be used for adoptive immunotherapy, they must have the capability to circulate, migrate through endothelium, home to the bone marrow, and, most importantly, lyse the leukemic cells in a leukemia-permissive bone marrow microenvironment. We demonstrate here that such antileukemia T-cell lines are overwhelmingly CD8(+) and exhibit an activated phenotype. Using a transendothelial chemotaxis assay with human endothelial cells, we observed that these T cells can be recruited and transmigrate through vascular and bone marrow endothelium and that these transmigrated cells preserve their capacity to lyse leukemic cells. Additionally, these antileukemia T-cell lines are capable of adhering to autologous stromal cell layers. Finally, autologous antileukemia CTL specifically lyse leukemic cells even in the presence of autologous marrow stroma. Importantly, these antileukemia T-cell lines do not lyse autologous stromal cells. Thus, the capacity to generate anti-leukemia-specific T-cell lines coupled with the present findings that such cells can migrate, adhere, and function in the presence of the marrow microenvironment enable the development of clinical studies of adoptive transfer of antileukemia CTL for the treatment of ALL.     

Changes in symptoms, lipid and hormone levels after the administration of a cream with phytoestrogens in the Climacteric--preliminary report.

OBJECTIVE: To establish the changes in lipid and hormone levels, as well as in symptoms, after topical application of a cream with phytoestrogens in postmenopausal women. METHODS: 30 postmenopausal women were studied. At baseline and 1 month after the beginning of treatment, levels of FSH, estradiol, estrone, testosterone, androstenedione, dehydroepiandrosterone, total cholesterol, HDL-C, LDL-C, and triglycerides were measured. Climacteric symptoms were evaluated with a modified Kupperman's index (KI). The subjects received a cream with phytoestrogens (n = 15) or placebo (cold cream) (n = 15) in a randomized, double-blind manner. Statistically significant differences were determined by Student's t test. RESULTS: No differences were found in hormones, lipids, or in KI between the groups. When comparing each group separately, only a significant decrease in KI was found, in both groups, at the end of the treatment. CONCLUSIONS: This cream with phytoestrogens had an effect only in climacteric symptoms, but similar to the placebo. The lack of effect in the other variables was probably due to the administration route, or to a lack of effect of this product.     

Leukocyte-technetium-99m uptake in Crohn’s disease: Does it show subclinical disease?

AIM: To evaluate inflammatory activity in patients with Crohn’s disease (CD) using technetium-99m-hexamethylpropyleneamine oxime (99mTc-HMPAO) granulocyte scintigraphy.METHODS: Twenty patients (7 male and 13 female) with CD and five healthy volunteers were selected for 99mTc-HMPAO granulocyte scintigraphy. The Crohn’s Disease Activity Index (CDAI), blood tests and C-reactive protein (CRP) of each patient were performed 7 d before the scintigraphic images. The leukocytes were labeled according to the International Society of Radiolabeled Blood Elements (ISORBE) consensus protocol and the scintigraphic images, including single photon emission computed tomography, were obtained 30 min and 2 h after injection of the radiolabeled leukocytes.RESULTS: The labeling yield of the leukocytes with the lipophilic complex 99mTc-HMPAO was 55.0% ± 10%. Six of the 20 patients (30%) presented congruent results for the three parameters investigated (CDAI, Scintigraphic Index and CRP). On the other hand, 14 patients (70%) did not show congruent results. There was no significant correlation between the indices analyzed according to the Spearman test (P > 0.05, n = 20).CONCLUSION: The results suggest that 99mTc-HMPAO-labeled leukocyte scintigraphy could be important for determining inflammatory activity in CD even in the absence of clinical symptoms.