Evolving entities and changing concepts in breast pathology

Among the evolving entities and changing concepts in breast pathology are those relating to columnar cell hyperplasia, pseudoangiomatous stromal hyperplasia, mucocele-like lesions, pleomorphic lobular carcinoma in situ, pseudo-Paget's disease of nipple, microinvasive carcinoma of breast, spindle cell metaplastic carcinoma, and minimal metastatic disease in axillary lymph nodes. Pathologists, as well as physicians involved in the management of breast diseases, need to be aware of these recent developments in breast pathology since the recognition and understanding thereof may have considerable clinical relevance.     

Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is caused by a dominant Th2 immune response to antigens derived from the opportunistic mold Aspergillus, most commonly Aspergillus fumigatus. It occurs in 4%–15% of patients with cystic fibrosis (CF); however, not all patients with CF infected with A. fumigatus develop ABPA. Therefore, we compared cohorts of A. fumigatus–colonized CF patients with and without ABPA to identify factors mediating tolerance versus sensitization. We found that the costimulatory molecule OX40 ligand (OX40L) was critical in driving Th2 responses to A. fumigatus in peripheral CD4⁺ T cells isolated from patients with ABPA. In contrast, CD4⁺ T cells from the non-ABPA cohort did not mount enhanced Th2 responses in vitro and contained a higher frequency of TGF-β–expressing regulatory T cells. Heightened Th2 reactivity in the ABPA cohort correlated with lower mean serum vitamin D levels. Further, in vitro addition of 1,25 OH-vitamin D₃ substantially reduced DC expression of OX40L and increased DC expression of TGF-β. This in vitro treatment also resulted in increased Treg TGF-β expression and reduced Th2 responses by CD4⁺ T cells from patients with ABPA. These data provide rationale for a therapeutic trial of vitamin D to prevent or treat ABPA in patients with CF.     

Controversies in surgical pathology: minimal involvement of sentinel lymph node in breast carcinoma: prevailing concepts and challenging problems

Sentinel lymph node biopsy has attained "standard of care' status in the management of breast carcinoma. However, the pathological interpretation and clinical consequences of "minimally involved' sentinel lymph nodes remain controversial. Herein, we present some of the complex and challenging pathological problems inherent in this evolving setting. Clearly, at least some of our current concepts regarding "minimally involved' sentinel lymph nodes need reappraisal.     

krox-20/egr-2 is up-regulated following non-specific and homophilic adhesion in rat macrophages

Macrophages are known to adhere to a plastic dish via beta2 integrin (CR3) and scavenger receptors. Although their functions such as phagocytosis, endocytosis, and nitric oxide production have been investigated on adherent macrophages in vitro, very little is known about intracellular signals triggered by adhesion to a plastic dish. Recently we reported that the mRNA level of krox-20/egr-2 was significantly increased in rat alveolar macrophages following exposure to fibrous titanium dioxide particles. In the present study we report that up-regulation of krox-20/egr-2 gene expression following adhesion to a plastic dish and homophilic adhesion in rat alveolar macrophages and rat macrophage cell line, NR8383. The mRNA level of krox-20/egr-2 increased with a peak 1 hr after adhesion to a plastic dish in both cell types. Piceatannol inhibited tyrosine-phosphorylation of Syk and decreased both adhesion and krox-20/egr-2 mRNA level. In contrast staurosporine, a serine/threonine kinase inhibitor, increased adherence of macrophages and yet prohibited the adhesion-dependent increase in krox-20/egr-2 gene expression. When NR8383 cells are cultured in suspension, the cells aggregated naturally and produced cell clumps. The mRNA level of krox-20/egr-2 also increased in response to the homophilic intercellular adhesion. The increased mRNA level of krox-20/egr-2 was not caused by inflammatory stimuli, because lipopolysaccharide did not affect the aggregation-dependent up-regulation of krox-20/egr-2 gene. The up-regulation of krox-20/egr-2 gene due to the homophilic cell aggregation was also inhibited either by piceatannol or staurosporine. Those results suggest that krox-20/egr-2 gene expression is triggered by sensing non-specific and homophilic cellular adhesion and the following phosphorylation of signal transducing proteins including Syk and staurosporine-inhibitable kinases.     

Characterization and physical map of choleraphage φ149 DNA

Choleraphage φ149 DNA is a linear double-stranded molecule 69 × 10⁶ Da or 104 kilobase pairs (kbp). From restriction enzyme analysis, it has been concluded that the DNA is circularly permuted. There are at least three S1 nuclease-sensitive sites along the length of the molecule. These sites represent single-strand interruptions repairable by T4 DNA ligase. A physical map of the DNA has been constructed using the restriction endonucleases BamH1 and BglII.     

IMPACT OF AGRO CLIMATIC AND SOCIO-ECONOMIC VARIABILITY ON THE NUTRITIONAL STATUS OF INHABITANTS In THE GARHWAL HIMALAYAS

The Garhwal Himalayas are a part of a unique ecosystem, with sharp agro-climatic variations within a very small geographical area (53,485 km²). The varied agro-climatic situations result in different cropping systems and socio-economic lifestyles that could likely affect the nutritional status of the people living in this region. This article will attempt to explore the impact of these variables (namely, age, family size, education, income, calorie and protein intake, land holding, number of animals, and wheat production) on the body mass index (BMI) of the population residing in the Garhwal Hills. A total of 1,030 subjects were studied from the three agro-climatic zones (406 from the high hills, 292 from the mid hills, and 332 from the low hills). It has been found that the people living in the high hills are the most undernourished, as the lowest percentage of people (52.6 per cent) with an acceptable BMI and the highest percentage of people in the severely malnourished category (11.1 per cent) are found here. People living in urban areas have a better nutritional status. Correlation studies show that the nutritional status of the population improves with age, literacy levels, and small family size. In some cases, calorie and protein intake have a positive impact on the health of the people, whereas size of land holding, number of animals, and income of the family do not have any significant influence on nutritional status.