Human plasma fibronectin potentiates the mitogenic activity of platelet-derived growth factor and complements its wound healing effects

Integrin-mediated cell adhesion and growth factor stimuli are both required for optimal control of cell proliferation. In the context of skin injury, cell-derived fibronectin and platelet-derived growth factor play important roles in the stimulation of cell proliferation and migration, activities that are crucial to the healing process. To assess the ability of exogenously supplied plasma-derived fibronectin to stimulate wound repair and to study its ability to cooperate with platelet-derived growth factor-BB during healing, we devised a novel topical delivery formulation that allows the controlled release of both molecules to a wound. Using this topical formulation and the rabbit ear model of dermal wound healing, we show that plasma fibronectin is a potent stimulator of the wound healing process. We also show that administration of fibronectin and platelet-derived growth factor-BB in combination has additive wound healing effects. Finally, we report novel findings on the ability of soluble plasma fibronectin to potentiate the mitogenic effects of platelet-derived growth factor-BB in vitro. These findings not only show that optimal concentrations of exogenous fibronectin administered using an effective delivery system stimulate wound healing; they also suggest that PDGF-BB should be administered with fibronectin to achieve optimal therapeutic stimulation of wound healing.     

A Stress‐Busting Program for Family Caregivers

Aging baby boomers, longer life spans, and rising levels of Alzheimer's disease and related dementias (ADRD) will result in a caregiver crisis in the near future. The ways in which caregivers deal with stresses related to caregiving will be critical to both their own well‐being and their ability to care for others. The purpose of this article is to describe the Stress‐Busting Program (SBP) for family caregivers and its effectiveness. The essential components of the SBP are education, stress management, problem solving, and support delivered in a group setting for 9 weeks. Results of the SBP indicate that throughout the program, caregivers experienced significant improvements in general health, vitality, social function, and mental health scores and decreases in anxiety, anger/hostility, depression, perceived stress, and caregiver burden. The SBP is a cost‐effective health‐promotion strategy for caregivers who have substantial ongoing stress.     

Levels of lipoprotein(a) and plasma lipids in Spanish children aged from 4 to 18 years

Increased plasma lipoprotein(a)-Lp(a)-levels are linked to a high risk of cardiovascular disease unrelated to other lipoproteins. It seems that Lp(a) values in childhood remain unaltered up to adulthood. In a randomly chosen population of 1970 children, aged from 4 to 18 years and living in a Spanish community, the following serum parameters were studied: total cholesterol, total triglycerides, Lp(a), high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. Mean Lp(a) serum values were 15.0 ± 14.7mg dl^-1. No differences were seen between either sex in the first years of childhood. Of the studied children, 15.1% presented Lp(a) concentrations above 30 mg dl^-1. A correlation between Lp(a) and total cholesterol concentrations, which disappeared when low-density lipoprotein cholesterol concentrations were corrected according to cholesterol present in Lp(a), was observed.     

Immunological memory induced by genetically transduced tumor cells

Background: Recent studies have demonstrated the usefulness of gene-modified tumor cells for immunotherapy. Using the tumorigenic murine fibrosarcoma, MCA 106, we investigated the effects of localized interferon-γ (IFNg) secretion on tumorigenicity and on long-term memory. Methods: The murine IFNg (MuIFNg) gene was introduced into tumor cells. High and low IFNg-secreting clones were isolated. C57BL/6 mice were injected subcutaneously (s.c.) with either parental (P), high or low IFNg-secreting (H- or L-IFNg) cells, and tumor growth was assessed weekly. Spleens were harvested on different days postinjection (p.i.) to assess in vitro cytolytic activity. In parallel, tissues from injection sites were stained with macrophage-, CD4-, and CD8-detecting antibodies. Mice were injected s.c. with H-IFNg MCA106 tumor. After 150 days the animals were rechallenged s.c. with MCA106P in one leg and with irrelevant syngeneic tumor in the other. Results: Both P- and L-IFNg cells had similar growth, whereas the H-IFNg cells never grew. Only splenocytes from the H-IFNg animals showed in vitro CTL activity persisting until day 30 p.i. Histological data revealed a macrophage and CD4⁺ infiltrate much earlier in the H-IFNg group compared with the P group. Only the irrelevant, syngeneic tumor grew in animals previously injected with H-IFNg cells, whereas both P and irrelevant syngeneic tumors grew in controls. Conclusions: Transduction of MCA106 cells with the MuIFNg gene diminished in vivo tumorigenicity in proportion to the amount of IFNg secreted. Immunization with H-IFNg cells elicited a host response characterized by macrophages and CD4⁺ cells. Long-term tumor-specific memory was seen after immunization with H-IFNg cells.     

Determination of Proliferation Index By MIB-1 Immunostaining in Early Stage Breast Cancer Using Quantitative Image Analysis

Abstract: Several clinicopathologic variables influence prognosis in breast cancer, including stage, histologic grade, nodal status, and tumor size. Multiple studies have shown an independent value of proliferation index as a prognostic variable for the stratification into favorable and unfavorable groups. The monoclonal antibody MIB-1 reacts with the same antigen site, not epitope, as recognized by the Ki-67 antibody. Like Ki-67, MIB-1 reacts with cells in the late G₁, S, M and G₂ phases of the cell cycle, but MIB-1 has the advantage of reacting with formalin-fixed, paraffin-embedded material. The authors investigated the feasibility of using image analysis to quantitate the MIB-1 antibody staining (proliferation index [PI]) and predict survival in a series of 230 patients with stage I and stage II breast cancer. In a univariate Cox regression model, larger values of MIB-1 were related to shorter survival times (p < 0.001). Exploratory statistical procedures were used to categorize the patients into good, intermediate, and poor survival groups using the following proliferation indices as cut-points: <5%, 5–11%, and >11 %, respectively. Higher clinical stage was associated with higher MIB-1 values and shorter survival (p = 0.01, and p = 0.003, respectively). Tumor size (p = 0.02) and nodal status (p = 0.05) were also associated with higher values of MIB-1. After adjusting for age, clinical stage, nodal status, and tumor size in a multivariate analysis, MIB-1 retained its prognostic significance (p < 0.0001) when considered as either a continuous or categorical variable. There were no significant associations between MIB-1 determined proliferation index and age (p = 0.54), histologic grade (p = 0.69), nuclear grade (p = 0.06) or the presence of vascular invasion (p =.66). There is a strong statistical relationship between cell proliferative activity, as determined by MIB-1 expression, and survival in early stage breast cancer.     

Digital subtraction angiography of the thoracic aorta

Forty-three patients with acquired and congenital abnormalities of the thoracic aorta were studied using digital subtraction angiography (DSA) after an intravenous bolus injection of 40 ml of contrast material. Abnormalities studied included coarctation, pseudocoarctation, Marfan syndrome, cervical aorta, double aortic arch, aneurysm, dissection, and tumor. Twenty-four patients also had conventional angiography. DSA was accurate in 95% of cases; in the other 5%, involving patients with acute type I dissection, the coronary arteries could not be seen. The authors concluded that in 92% of their patients, DSA could have replaced the standard aortogram.