Increased risk of end-stage renal disease in patients with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organs, including the kidneys. There is a lack of long-term renal prognosis studies on patients with SSc. The aim of this study was to assess the risk of end-stage renal disease (ESRD) in patients with SSc. METHOD: We designed a prospective cohort study based on the National Health Insurance Research Database of Taiwan. Patients with SSc and a non-SSc control group were selected from 1 January 2000 to 31 December 2013. The SSc cohort and control group were matched on the propensity score in a 1:2 ratio. The primary outcome was development of ESRD. Cox proportional hazard regression was performed to assess the effects of SSc on ESRD. RESULTS: After propensity score matching, we enrolled 2012 patients in the SSc group and 4024 patients in the control group. During a mean follow-up of 6.5 years, 86 individuals [SSc group, n = 41 (2.04%); control group, n = 45 (1.12%)] had developed ESRD. The risk of ESRD in the SSc group was approximately two times higher than that in the control group [hazard ratio (HR) = 2.12, 95% confidence interval (CI) 1.39-3.24]. Subgroup analysis revealed that the higher risk of ESRD was predominantly in males (HR = 4.14, 95% CI 1.97-8.71) and the younger population (HR = 7.09, 95% CI 2.31-21.80). CONCLUSION: There was a significantly higher risk of ESRD among SSc patients than among the general population, with males and younger generations being the most vulnerable groups.

Immunohistochemistry of lymphocytes in benign lymphoadenosis of oral mucosa.

Benign lymphoadenosis of oral mucosa (BLOM) is a common oral mucosa disease and may be regarded as a precancerous lesion. However, the association between its biological behavior and lymphocyte distribution remains unclear. Therefore, to investigate the characteristics of BLOM, we studied the infiltration of lymphocytes associated with it. The expression levels of CD74, CD20, CD3, and CD45RO were evaluated by immunohistochemical staining in 14 sam-ples from BLOM, 9 samples from BLOM with atypia hyperplasia, 11 samples from BLOM with canceration, and 10 samples from normal oral mucosa tissues. The results were analyzed by two-sample t-test using SPSS 10.0 for Windows, and P < 0.05 was considered to be sig-nificant. In normal oral mucosa, positive expression levels of CD3 and CD45RO were presented in the extra-lymphoid follicle, and the expres-sion levels of CD74 and CD20 were negative. In all BLOM groups, the expression level of CD20 was positive except for one case of BLOM with canceration; the expression levels of CD74 were all positive. Posi-tive expression levels of CD3 and CD45RO could be found not only in extra-lymphoid follicles but also in inner-lymphoid follicles in the BLOM groups. The expression levels of CD74 and CD20 in extra-lym-phoid follicles, and CD3 and CD45RO in inner-lymphoid follicles in BLOM were significantly higher than in BLOM with canceration. The infiltrated lymphocytes in BLOM comprise T- and B-cells. This indi-cates that the lymphoid tissue in BLOM is mucosa-associated lymphoid tissue and BLOM is a proliferative lesion.

Increased IL-21 expression in chronic rhinosinusitis with nasalpolyps.

BACKGROUND: IL-21 is a key cytokine for regulating B cell immunity, which is involved in several inflammatory conditions. This study sought to define a role for IL-21 in activated B lymphocytes and enhanced tissue eosinophilia in NP tissues during the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: NP and uncinate process tissues were collected from 64 CRSwNP patients, 25 CRSsNP patients, and 29 control subjects. IL-21 expression was examined using IHC staining, qRT-PCR, flow cytometry, and ELISA, and its clinical implication was evaluated. Moreover, the effects of IL-21 on B cell differentiation and Ig production in cultured NP cells were examined in vitro. RESULTS: The mRNA and protein levels of IL-21 were significantly increased in polyp tissues compared with control tissues (P < 0.05). Polyp IL-21 level was significantly associated with polyp size, tissue eosinophilia and asthma comorbidity, and recurrence after surgery (P < 0.05). Both Th1 and Th17 cells were the main cellular sources of IL-21 in polyp tissues. The percentage of IL-21(+) CD4(+) cells was significantly higher in polyp tissues compared with control tissues and matched PBMCs (P < 0.01). Accordingly, the percentage of CD19(+) CD20(+/-) CD38(high) cells was significantly higher in polyp tissues compared with control tissues (P < 0.01). Moreover, recombinant IL-21 significantly increased the percentage of CD19(+) CD20(+/-) CD38(high) cells (plasmablasts) and IgG and IgA production in cultured NP cells in vitro (P < 0.05). CONCLUSION AND CLINICAL RELEVANCE: Increased IL-21 level in polyp tissues was associated with disease severity, local B cell activation, and immunoglobulin production, suggesting that IL-21 might play an important role in promoting persistent mucosal inflammation in CRSwNP patients.

Emergence of NDM-producing non-baumannii Acinetobacter spp. isolated from China.

One hundred and thirty-six bla OXA-51-negative strains were identified from 1,067 Acinetobacter calcoaceticus-A. baumannii complex (ACB complex) isolates, which were collected during October 2010 to March 2013 from 15 general hospitals in 10 cities throughout Zhejiang Province, China. Seven of the 136 bla OXA-51-negative ACB complex isolates were New Delhi metallo-ß-lactamase-1 (NDM-1)-positive, among which three were identified as A. nosocomialis and four were identified as A. pittii strains using 16S-23S rRNA gene intergenic spacer (ITS) sequencing and partial RNA polymerase ß-subunit (rpoB) sequencing. Pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) analysis showed that the seven NDM-positive isolates belonged to three clonal strains with three novel sequence types (STs). Polymerase chain reaction (PCR) assays and DNA sequence analysis of the carbapenemase and other ß-lactamase genes indicated that all the isolates harbored the bla NDM-1 gene, and that only one strain of A. nosocomialis isolates harbored both bla NDM-1 and bla OXA-23. All of them were positive for bla ADC, from which three novel bla ADC genes (designated as bla ADC-69, bla ADC-70, and bla ADC-71) were detected for the first time. The presence of ISAba125 upstream of bla NDM-1 was identified through genetic environment analysis. Carbapenem resistance can be transferred from A. nosocomialis and A. pittii to Escherichia coli EC600 by the conjugation experiment. Plasmid analysis, DNA hybridization, and extraction experiments indicated that bla NDM-1 was located on a plasmid of approximately 50 kb. In conclusion, we characterized the dissemination of NDM-1-positive A. pittii strains in Zhejiang Province, China, and reported the NDM-producing A. nosocomialis for the first time.

Age- and gender-related long-term renal outcome in patients with lupus nephritis.

OBJECTIVE: To investigate age- and gender-related long-term renal outcome in patients with lupus nephritis (LN). METHODS: This is a retrospective, chart review study of patients with LN at Chang Gung Memorial Hospital, Kaohsiung, between January 1986 and June 2004. All had undergone a renal biopsy that showed LN. The end point of outcome was chronic renal insufficiency (CRI), which was defined as 'doubling of baseline serum creatinine lasting for at least 6 months with a value at least 2 mg/dl.' The patients were categorized by age tertiles and gender. A 5-year survival curve was constructed to study the effect of age and gender on the outcome. RESULTS: In total, 121 sets of patient data were evaluated. The study group included 104 women and 17 men. Of the study patients, 26 (21%) developed CRI after 5 years of follow-up. There was no significant difference among age groups in developing CRI (p = 0.23). In terms of gender, men had worse long-term renal outcome (p = 0.004) than women. CONCLUSIONS: The long-term renal outcome of the LN patients did not differ among age groups, but was worse in men.

Random Lasing Action from Randomly Assembled ZnS Nanosheets.

Lasing characteristics of randomly assembled ZnS nanosheets are studied at room temperature. Under 266-nm optical excitation, sharp lasing peaks emitted at around 332 nm with a linewidth less than 0.4 nm are observed in all directions. In addition, the dependence of lasing threshold intensity with the excitation area is shown in good agreement with the random laser theory. Hence, it is verified that the lasing characteristics of randomly assembled ZnS nanosheets are attributed to coherent random lasing action.

Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin's lymphoma.

Antibody-drug conjugates (ADCs) are potent cytotoxic drugs linked to antibodies through chemical linkers, and allow specific targeting of drugs to neoplastic cells. The expression of CD22 is limited to B-cells, and we show that CD22 is expressed on the vast majority of non-Hodgkin's lymphomas (NHLs). An ideal target for an ADC for the treatment of NHL would have limited expression outside the B-cell compartment and be highly effective against NHL. We generated an ADC consisting of a humanized anti-CD22 antibody conjugated to the anti-mitotic agent maytansine with a stable linker (anti-CD22-MCC-DM1). Anti-CD22-MCC-DM1 was broadly effective in in vitro killing assays on NHL B-cell lines. We did not find a strong correlation between in vitro potency and CD22 surface expression, internalization of ADC or sensitivity to free drug. We show that anti-CD22-MCC-DM1 was capable of inducing complete tumor regression in NHL xenograft mouse models. Further, anti-CD22-MCC-DM1 was well tolerated in cynomolgus monkeys and substantially decreased circulating B-cells as well as follicle size and germinal center formation in lymphoid organs. These results suggest that anti-CD22-MCC-DM1 has an efficacy, safety and pharmacodynamic profile that support its use as a treatment for NHL.

Ultraviolet Laser Action in Ferromagnetic Zn1-xFexO Nanoneedles.

Fe-doped ZnO nanoneedles (NDs) were fabricated by an Ar+ ion sputtering technique operated at room temperature. The as-grown samples show both ferromagnetic and lasing properties. The saturated magnetization moment was measured from 0.307 to 0.659 emu cm-3 at the field of 10 kOe with various Fe concentrations. Intense ultraviolet random lasing emission was observed from Zn1 - xFexO NDs at room temperature. The X-ray photoelectron spectroscopy result reveals that the doped Fe atoms occupy the Zn sites and lead to a decrease in oxygen deficiency.

Differential expression of apoptosis-related proteins in various cellular components of ameloblastomas.

To evaluate the expression patterns of apoptosis-related proteins, including Fas, Fas-ligand (FasL), caspase-3 and Bcl-2, in various cellular components of ameloblastomas, 39 cases of ameloblastoma were examined using immunohistochemistry. The staining intensity of the antigens in the 4 types of tumour cellular component, peripheral basal cells of tumour nests, central stellate reticulum-like cells, and foci of squamous and granular cells, was scored using a semi-quantitative scale, and comparisons were made by statistical analysis. Expression of Fas, FasL and caspase-3 was detected in the majority of cases, with a similar pattern of strong staining in the foci of squamous metaplasia and granular cells usually situated in the central area of tumour islands. In contrast, expression of Bcl-2 was predominantly seen in the peripheral basal cell layer. There were significant differences in the staining intensity of Fas, caspase-3 and Bcl-2 among the 4 types of tumour cell. The differential expression of apoptosis-related proteins in various cellular components of ameloblastomas, with pro-apoptotic proteins, Fas, FasL and caspase-3 being closely associated with squamous metaplasia and granular transformation of the tumour cells, suggests that Fas/FasL-induced apoptotic cell death may play a role in the disposal of terminally differentiated or degenerative tumour cells in ameloblastomas.

Clinicopathologic study of 24 cases of cherubism.

The authors reviewed 24 cases of familial or nonfamilial cherubism. The age at onset was between 6 and 10 years. It was characterized by bilateral painless swelling of jaws and eyes-to-heaven appearance was visible when the maxillae were affected as well. Radiographs showed well-defined multilocular radiolucencies and with age, thick sclerotic borders were visible. A malocclusive and abnormal dentition, worse in the mandible can be seen. Histopathologically, numerous randomly distributed multinucleated giant cells and vascular spaces within a fibrous connective tissue stroma with or without eosinophilic collagen perivascular cuffing were apparent. Multinucleated giant cells were positive for osteoclastic specific markers, tartrate-resistant acid phosphatase and human alphaV beta3 integrin, 23C6. Results after follow-up were available for 14 cases. Of these, no treatment was carried out in five cases, cherubism resolved (three cases) or grew slowly (two cases); curettage or surgical contouring was performed in seven cases, during the rapid growth of the lesions. This not only gave good immediate results, but also arrested active growth of remnant cherubic lesions and even stimulated bone regeneration. Segmental mandibulectomy followed by reconstruction was performed in two cases with extensive lesion and the risk of pathologic fracture of the mandible, and excellent results were obtained.