Nonneoplastic Chronic Diseases Research Articles

Single Cell Biology: Exploring Somatic Cell Behaviors, Competition and Selection in Chronic Disease.

The full range of cell functions is under-determined in most human diseases. The evidence that somatic cell competition and clonal imbalance play a role in non-neoplastic chronic disease reveal a need for a dedicated effort to explore single cell function if we are to understand the mechanisms by which cell population behaviors influence disease. It will be vital to document not only the prevalent pathologic behaviors but also those beneficial functions eliminated or suppressed by competition. An improved mechanistic understanding of the role of somatic cell biology will help to stratify chronic disease, define more precisely at an individual level the role of environmental factors and establish principles for prevention and potential intervention throughout the life course and across the trajectory from wellness to disease.

Vitamin D and Myofibroblasts in Fibrosis and Cancer: At Cross-purposes with TGF-β/SMAD Signaling.

The multifaceted involvement of the active vitamin D metabolite 1,25-dihydroxyvitamin D3 (henceforth referred to by the synonyms 1,25(OH)2D3, calcitriol or vitamin D) in blunting the growth of cancer cells is amply recognized. In this review we focused our attention on the cross-talk between 1,25 (OH)2D3 and the tumor microenvironment (TME), signaling out stromal cancer-associated fibroblasts (CAFs), the most abundant TME population, as a target for calcitriol anticancer action. In view of the commonality of the phenotypic signature in myofibroblasts, resident in the cancer stroma and in non-neoplastic fibrotic loci, we examined modes of action of vitamin D in non-neoplastic chronic diseases and in cancer to assess mechanistic similarities and divergences. A constant observation was that 1,25(OH)2D3 or synthetic ligands via the active vitamin D receptor (VDR) impede transforming growth factor (TGF)-β/mothers against decapentaplegic homologs (SMADs) signaling in myofibroblasts regardless of the initiating insult. The translational impact of 1,25(OH)2D3 in targetting stromal CAFs is discussed.

Health status in older hospitalized patients with cancer or non-neoplastic chronic diseases

BackgroundWhether cancer is more disabling than other highly prevalent chronic diseases in the elderly is not well understood, and represents the objective of the present study.MethodsWe used data from the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study, a large collaborative observational study based in community and university hospitals located throughout Italy. Our series consisted of three groups of patients with non-neoplastic chronic disease (congestive heart failure, CHF, N = 832; diabetes mellitus, N = 939; chronic obstructive pulmonary disease, COPD, N = 399), and three groups of patients with cancer (solid tumors without metastasis, N = 813; solid tumors with metastasis, N = 259; leukemia/lymphoma, N = 326). Functional capabilities were ascertained using the activities of daily living (ADL) scale, and categorical variables for dependency in at least 1 ADL or dependency in 3 or more ADLs were considered in the analysis. Cognitive status was evaluated by the 10-items Hodgkinson Abbreviated Mental Test (AMT).ResultsCognitive impairment was more prevalent in patients with CHF (28.0%) or COPD (25.8%) than in those with cancer (solid tumors = 22.9%; leukemia/lymphoma = 19.6%; metastatic cancer = 22.8%). Dependency in at least 1 ADL was highly prevalent in patients with metastatic cancer (31.3% vs. 24% for patients with CHF and 22.4% for those with non-metastatic solid tumors, p < 0.001). In people aged 80 years or more, metastatic cancer was not associated with increased prevalence of physical disability. In multivariable analysis, metastatic cancer was associated with a greater prevalence of physical (OR 2.09, 95%CI 1.51–2.90) but not cognitive impairment (OR 1.34, 95%CI 0.94–1.91) with respect to CHF patients. Finally, diabetes was significantly associated with cognitive impairment (OR 1.40, 95%CI 1.11–1.78).ConclusionCancer should not be considered as an ineluctable cause of severe cognitive and physical impairment, at least not more than other chronic conditions highly prevalent in older people, such as CHF and diabetes mellitus.

Herpetic tracheobronchitis detected at bronchoscopy: cytologic diagnosis by the immunoperoxidase method.

Herpes simplex virus (HSV) infection of the respiratory tract requires rapid specific diagnosis to avoid late complications and maximize the efficacy of available drug therapy. We report a method of accomplishing this that was tested in 33 cytologic specimens derived from sputum, washings, or brushings from 25 debilitated elderly males suffering from a variety of underlying neoplastic and nonneoplastic chronic diseases. All specimens had shown either single cells (54%), multinucleated groups (8%), or both (38%); they displayed the ground-glass appearance (86%), discrete nuclear inclusions (4%), or both (10%), as appreciated by the Papanicolaou stain. The specimens were processed by the peroxidase-antiperoxidase technique utilizing anti-HSV-1 antibody and 3,3'-diaminobenzidine (DAB) as the chromogen. In six cases, aminoethylcarbazol (AEC) was used for comparison. Twenty-nine of the 33 specimens (88%) stained positively for HSV-1 as did control sections of herpetic encephalitis and esophagitis; there were no false positives with appropriate negative controls. All 12 bronchoscopic specimens revealed virocytes with HSV immunopositivity; in contrast, 17 of 21 (80%) sputum specimens were positive for HSV. The strongest positivity was noted in bronchial brushings and washings whereas the only four negative smears were from sputum specimens. The DAB immunostain was coarser and stronger at the periphery of the cytoplasm, and the hematoxylin counterstain permitted a clear identification of nuclear viral changes. With AEC, the immunostain was more vivid and evenly distributed, but counterstaining was impaired due to the greater solubility of the chromogen. The technique is sensitive, reproducible, and less expensive and time-consuming than electron microscopy (EM) or viral cultures.