6q deletions define distinct clinico-pathologic subsets of non- Hodgkin's lymphoma

Commonly observed in lymphoid neoplasms, deletions of 6q have been correlated with histologic and clinical subsets of non-Hodgkin's lymphoma (NHL). Our recent analysis of loss of heterozygosity of 6q loci in NHL showed two regions of minimal molecular deletion (RMD), an RMD1 at 6q25-27 and an RMD2 at 6q21-23. To establish correlations between these RMDs and regions of minimal cytogenetic deletions (RCDs) on 6q, and to define associations between RCDs and clinico-pathologic features, we have analyzed chromosome 6 abnormalities in 459 consecutively ascertained, karyotypically abnormal cases of NHL. Among these, 126 (27.5%) cases had structural abnormalities of chromosome 6, of which 94 were deletions. Analysis of these deletions identified three RCDs. An RCD1 encompassing 6q25-27 was seen in 45 intermediate- grade NHL. An RCD2 at 6q21 was observed in 11 high-grade NHL, 9 of which were of the immunoblastic subtype. An RCD3 at 6q23 was noted in 18 low-grade NHL lacking a t(14;18) translocation. Of these 18 cases, 12 were small lymphocytic NHL and, in 2 of these, del(6q) was the sole karyotypic abnormality. In 20 cases of low-grade NHL with t(14;18), the deletions spanned both RCD1 and RCD3. These data suggested the presence of at least 3 tumor suppressor genes on 6q within RCD1, RCD2, and RCD3; they also showed associations between RCDs in 6q and subsets of NHL, including a specific association between a group of well-differentiated lymphoid neoplasms and RCD3. The apparent heterogeneity of breakpoints when all NHLs are considered together explains the inability of previous studies to reliably establish correlations between recurring 6q deletions and histologic and clinical features of NHL.     

Regenerative Cell and Tissue-based Therapies for Pulmonary Arterial Hypertension

Within the span of 2 decades, cell-based regenerative therapies for pulmonary arterial hypertension have progressed from bench-side hypotheses to clinical realities. Promising preclinical investigations that examined the therapeutic potential of endothelial progenitor cell and mesenchymal stem cell populations have demonstrated the safety and efficacy of these cell types and provided the foundation for first-in-man clinical trials. Moreover, these studies have improved our understanding of the therapeutic mechanisms by which stem/progenitor cells exert their regenerative functions. Ultimately, these discoveries have led to new applications for stem and progenitor cells including the autologous cell reseeding of decellularized or synthetic lung scaffolds. In this review, an overview of established and emerging cell and tissue regenerative therapies for pulmonary lung diseases are presented, along with discussion of recent advancements in the emerging field of repopulating decellularized or bioengineered lung scaffolds with stem/progenitor cells for allogeneic transplant.     

Immune cell infiltration in malignant middle cerebral artery infarction: comparison with transient cerebral ischemia

We tested whether significant leukocyte infiltration occurs in a mouse model of permanent cerebral ischemia. C57BL6/J male mice underwent either permanent (3 or 24 hours) or transient (1 or 2 hours+22- to 23-hour reperfusion) middle cerebral artery occlusion (MCAO). Using flow cytometry, we observed ∼15,000 leukocytes (CD45^+high cells) in the ischemic hemisphere as early as 3 hours after permanent MCAO (pMCAO), comprising ∼40% lymphoid cells and ∼60% myeloid cells. Neutrophils were the predominant cell type entering the brain, and were increased to ∼5,000 as early as 3 hours after pMCAO. Several cell types (monocytes, macrophages, B lymphocytes, CD8⁺ T lymphocytes, and natural killer cells) were also increased at 3 hours to levels sustained for 24 hours, whereas others (CD4⁺ T cells, natural killer T cells, and dendritic cells) were unchanged at 3 hours, but were increased by 24 hours after pMCAO. Immunohistochemical analysis revealed that leukocytes typically had entered and widely dispersed throughout the parenchyma of the infarct within 3 hours. Moreover, compared with pMCAO, there were ∼50% fewer infiltrating leukocytes at 24 hours after transient MCAO (tMCAO), independent of infarct size. Microglial cell numbers were bilaterally increased in both models. These findings indicate that a profound infiltration of inflammatory cells occurs in the brain early after focal ischemia, especially without reperfusion.     

Prevalence of Candida spp., xerostomia,and hyposalivation in oral lichen planus – A controlled study

Objective

To determine the frequency of Candida spp., xerostomia, and salivary flow rate (SFR) in three different groups: patients with OLP (OLP group), patients with oral mucosal lesions other than OLP (non‐OLP group), and subjects without oral mucosal lesions (control group).

Material and methods

Xerostomia as well as SFR was investigated in the three groups. Samples for isolation of Candida spp. were collected from OLP lesions (38 patients), non‐OLP lesions (28 patients), and healthy subjects (32 subjects).

Results

There was no statistically significant difference regarding the frequency of xerostomia and hyposalivation among the three groups (P > 0.05). A higher prevalence for colonization by Candida spp. was found in the healthy subject as compared to that of patients with OLP (P = 0.03) and non‐OLP (P = 0.02) groups. Low SFR was not a factor for colonization by Candida spp.

Conclusions

Xerostomia and hyposalivation occur with similar frequency in subjects with and without oral lesions; also, the presence of oral lesions does not increase the susceptibility to colonization by Candida spp. It seems that any study implicating Candida spp. in the malignant transformation of oral lesions should be carried out mostly on a biochemical basis, that is, by testing the capability of Candida spp. to produce carcinogenic enzyme.     

Identification of Candida species in the clinical laboratory: a review of conventional,commercial, and molecular techniques

In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so‐called non‐albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time‐consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species.     

Chronic hepatitis B virus infection and rubella susceptibility in pregnant women

Summary. Increased rubella susceptibility has been shown in subjects from the Asian‐Pacific region where chronic hepatitis B virus (HBV) infection is endemic. This study was performed to explore the relationship between chronic HBV infection and rubella susceptibility in the obstetric population. We conducted a retrospective cohort study on 50556 pregnant women delivered in a university obstetric unit from January 1998 to June 2008. The incidence of rubella susceptibility according to maternal HBV carrier status was examined. HBV infection and rubella susceptibility were found in 5105 (10.1%) and 6102 (12.1%) women, respectively. Rubella susceptibility was more common in women with HBV (13.1%vs 12.0%, P = 0.017), even after adjusting for other confounding factors (odds ratio 1.11, 95% confidence interval 1.01–1.21). Advancing age was associated with progressively decreasing odds of rubella susceptibility, from 0.48 at age 20–24 years to 0.34 at age ≥40 years in women without HBV infection, but had no effect in women with hepatitis B. In conclusion, our study is the first to demonstrate an association between chronic HBV infection with rubella susceptibility. Further studies are warranted to confirm whether chronic HBV infection, especially that acquired by vertical transmission, may impair the immune response to rubella vaccine or natural infection throughout the reproductive age.