Increased expression of laminin-5 and its prognostic significance in lung adenocarcinomas of small size. An immunohistochemical analysis of 102 cases

BACKGROUND: Laminin-5 plays an important role in cell migration during tissue remodeling and tumor invasion. METHODS: The authors studied the expression of laminin-5 immunohistochemically in 102 cases of small-sized lung adenocarcinoma (maximum dimension < or = 2 cm) using a monoclonal antibody against the laminin gamma2 chain, and they also investigated the associations of laminin-5 with clinicopathologic characteristics. Prognostic significance of increased laminin-5 expression was evaluated using the Kaplan-Meier method and the Cox proportional hazard model. RESULTS: Overall, laminin-5 expression was observed in 82 cases (80.4%): 7 of 18 (38.9%) bronchioloalveolar carcinomas and 75 of 84 (89.3%) invasive adenocarcinomas. Laminin-5 was preferentially localized in the cytoplasm of tumor cells at the tumor-stromal interface, where budding or dissociation of cancer cells was frequently observed. Overexpression of laminin-5 (24 cases, 23.5%) was associated with vascular invasion (P = 0.021) and stromal fibroblastic reaction (P = 0.005) but not with nodal involvement, lymphatic invasion, or pleural invasion. Survival analysis revealed that overexpression of laminin-5 was associated with shorter patient survival (P = 0.0027 by log rank test). On multivariate analysis, overexpression of laminin-5 was an independent prognostic factor (P = 0.030), as were nodal involvement (P < 0.0001), vascular invasion (P = 0.047), and lymphatic invasion (P = 0.0047) in a whole cohort of patients. Moreover, when patients with Stage I (International Union Against Cancer [UICC] staging system) disease were considered in multivariate analysis, overexpression of laminin-5 was the only significant prognostic factor (P = 0.022), whereas vascular invasion had a marginally significant impact (P = 0.07) on patient survival. CONCLUSIONS: The authors' results showed that laminin-5 is frequently expressed by cancer cells at the invasive front of lung adenocarcinoma. The study concluded that overexpression of laminin-5 may be a useful prognostic factor in patients with small-sized lung adenocarcinoma, especially in Stage I cases.     

Bidirectional migration of SeqA-bound hemimethylated DNA clusters and pairing of oriC copies in Escherichia coli

BACKGROUND: We previously found that SeqA protein, which binds preferentially to newly replicated hemimethylated DNA, is localized as discrete fluorescent foci in Escherichia coli cells. A single SeqA focus, localized at midcell, separates into two foci and these foci migrate abruptly in opposite directions. RESULTS: The present study shows that (i) appearance of SeqA foci depends on continuous DNA replication, suggesting that the SeqA foci represent clusters consisting of SeqA and newly replicated hemimethylated DNA, (ii) in a synchronous round of replication, a single SeqA focus at midcell separates into two foci and these foci abruptly migrate in opposite directions midway through replication from oriC to the terminus, and (iii) oriC is replicated at midcell but replicated oriC copies remain linked with each other at midcell for 40 min after replication at 30 degrees C. Subsequently, the linked oriC copies separate and migrate gradually towards both borders of the nucleoid before cell division. CONCLUSIONS: A single cluster of SeqA-bound hemimethylated DNA segment separates into two clusters and these clusters migrate abruptly in a bipolar fashion during progress of replication and prior to separation of linked sister oriC copies.     

The 7.5-kb common plasmid is unrelated to the drug susceptibility of Chlamydia trachomatis

Using a new plaque cloning technique, we obtained unique Chlamydia trachomatis strains, which were confirmed to be free of the 7.5-kb common plasmid and glycogen in inclusions. The inclusions in plasmid-free and glycogen-negative strains were characterized by a target-like bull's eye morphology that appeared with the formation of a central translucent area that began to be seen clearly at 30 h postinoculation. The clear zone was composed of gel materials originating from reticulate bodies (RBs) that were abnormally large in size and irregular in shape, although one could not differentiate the aberrant RBs from normal RBs at early stages of development. The in-vitro susceptibility of these strains to various chemotherapeutic antibiotics was tested by comparison with their parent strains possessing the common plasmid. No difference was detected for any of the antibiotics tested, indicating that the 7.5-kb common plasmid is unrelated to the drug susceptibility of C. trachomatis. Received: August 7, 2000 / Accepted: December 11, 2000     

Peer-Led Seeking Safety: Results of a Pilot Outcome Study with Relevance to Public Health

There is a rich history of peer-led recovery efforts related to substance use disorder (SUD). Yet we know of no peer-led approaches for co-occurring SUD and trauma-related problems. This combination is widespread, has impact on multiple life domains, and presents major recovery challenges. In this pilot, we evaluated peer-led Seeking Safety (SS). SS is the most evidence-based and widely implemented therapy for SUD with co-occurring PTSD or other trauma-related problems. Eighteen women in residential substance-abuse treatment participated. All met SUD criteria (primarily opiate and cocaine dependence); most had a comorbid mental health disorder; and they had elevated trauma-related symptoms. The 25 SS topics were conducted twice-weekly. Participants were assessed at baseline and end-of-treatment, with some measures also collected monthly. Results showed significant positive outcomes in trauma-related problems (the Trauma Symptom Checklist-40); psychopathology (the Brief Symptom Inventory); functioning (the BASIS-32, including impulsive-addictive behavior); self-compassion (the Self-Compassion Scale); and SS coping skills. Effect sizes were consistently large. SS satisfaction and fidelity ratings were high. Substance use levels could not be assessed due to the residential setting. Qualitative data indicated enthusiasm for peer-SS by both peers and staff. Study limitations, future research, and public health relevance are discussed.     

Effects of antiandrogen-estrogen treatment on sexual and endocrine parameters in hirsute women

Sexual activity was evaluated in 51 women with hirsutism associated with increased levels of circulating androgens before and while on combined treatment with the antiandrogen cyproterone acetate (CA) and ethinyl estradiol (EE₂) and compared to a reference group of 52 subjects. The percentage of unbound testosterone (T) was higher (p < 0.001), the coital frequency lower (p < 0.05), and the masturbation frequency higher (p< 0.04) in hirsute women. Mean frequency of total activity (coitus plus masturbation) was similar in the two groups. Treatment with combination of CA and EE₂ resulted in a decline of unbound T (p< 0.001). There was no change of total sexual activity, but coital frequency increased (p < 0.05) and masturbation frequency declined (p < 0.04). It is concluded that raised levels of circulating androgens, as judged by free T concentration, are not of crucial importance in the expression of sexual behavior in hirsute women.     

Immunohistochemical HLA-DR antigen expression with lymphocyte subsets and proliferative activity in pterygium

The immunohistochemical expression of HLA-DR antigen, CD8, CD4, CD68, S1OO, PCNA and Ki-67 was performed in order to investigate the role of immune mechanisms in pterygium, in correlation with proliferative activity. A series of 98 surgically-excised pterygia, 18 pingueculae and 20 normal conjunctivae, was studied by the avidin-biotin method, on formalin-fixed, paraffin-embedded tissue. HLA-DR antigen was abundantly expressed in pterygium epithelial cells, whereas almost no expression was found in pinguecula and normal conjunctiva. A high value of Ki-67 and PCNA expression coexisted in the same areas with HLA-DR antigen expression in pterygium and a statistically significant positive correlation resulted between them (p = 0.002). Aberrant infiltration of inflammatory cells (CD4, CD8, CD68, S100) was detected in pterygium, while lower densities were found in pinguecula and conjunctiva. The data suggest that immunopathological mechanisms may contribute in the pathogenesis of pterygium. In addition, the aberrant HLA-DR antigen expression seems to be correlated with the growth fraction of the lesion.     

Two Cases of Focal Choroidal Excavation Detected by Spectral-Domain Optical Coherence Tomography

Purpose

To report the clinical findings of 2 patients with focal choroidal excavation in the macula detected by spectral-domain optical coherence tomography (SD-OCT).

Methods

Three eyes of 2 patients with a focal macular choroidal excavation detected by SD-OCT were studied. The eyes were examined by fundus autofluorescence (FAF), fluorescein angiography, fundus-related microperimetry, and multifocal electroretinography (mfERG).

Results

In spite of a complaint of metamorphopsia, the visual acuity was normal in 2 eyes. SD-OCT demonstrated a choroidal excavation in the macula but the foveal contour was normal in 3 eyes. The excavation involved the outer retinal layers up to the external limiting membrane in all eyes, and a type 2 secondary choroidal neovascularization (CNV) developed in 1 of the 3 eyes. There were areas of hypoautofluorescence in the FAF images, and areas of decreased retinal sensitivity determined by microperimetry. These areas corresponded to the choroidal excavation in all eyes. The P1 amplitudes of the mfERGs were decreased in the fovea of 1 eye without a CNV.

Conclusions

The choroidal excavation remained stable for 3 years in 2 eyes, a secondary CNV developed in 1 eye during the course of the disease. More cases and longer follow-up periods will be necessary to determine the etiology, clinical course, and visual prognosis of eyes with a choroidal excavation.Key Words: Choroidal excavation, Choroidal neovascularization, Optical coherence tomography     

Whole Grain Consumption and Breast Cancer: A Case-Control Study in Women

Objective: Whole grain consumption has long been associated with human health. However, its relationship with breast cancer remains not well understood and appreciated. The aim of this work was to evaluate the association between whole grain consumption and breast cancer in women. Methods: A case-control study was designed. Two hundred and fifty consecutive, newly diagnosed breast cancer female patients (56 ± 12 years) and 250 one-to-one age-matched controls were enrolled. A standardized, validated questionnaire assessing various sociodemographic, clinical, lifestyle, and dietary characteristics was applied through face-to-face interviews. Moreover, data on regular consumption of whole grains (i.e., never/rarely, 1–6 times/week, >7 times/week) were recorded. Overall dietary habits were assessed through the level of adherence to the Mediterranean diet using the MedDietScore (theoretical range 0–55). Results: Whole grain consumption of more than 7 times/week was associated with a 0.49-fold (odds ratio = 0.49; 95% confidence interval, 0.29, 0.82) lower likelihood of having breast cancer, after adjustments were made. Conclusions: This study suggested that whole grain consumption more than 7 times/week was consistently associated with reduced risk of breast cancer.     

A multivariate method for meta‐analysis and comparison of diagnostic tests

We present here an extension of the classic bivariate random effects meta‐analysis for the log‐transformed sensitivity and specificity that can be applied for two or more diagnostic tests. The advantage of this method is that a closed‐form expression is derived for the calculation of the within‐studies covariances. The method allows the direct calculation of sensitivity and specificity, as well as, the diagnostic odds ratio, the area under curve and the parameters of the summary receiver operator's characteristic curve, along with the means for a formal comparison of these quantities for different tests. There is no need for individual patient data or the simultaneous evaluation of both diagnostic tests in all studies. The method is simple and fast; it can be extended for several diagnostic tests and can be fitted in nearly all statistical packages. The method was evaluated in simulations and applied in a meta‐analysis for the comparison of anti‐cyclic citrullinated peptide antibody and rheumatoid factor for discriminating patients with rheumatoid arthritis, with encouraging results. Simulations suggest that the method is robust and more powerful compared with the standard bivariate approach that ignores the correlation between tests. Copyright © 2016 John Wiley & Sons, Ltd.