Plasminogen Activator in Differentiating Mouse Keratinocytes

The activity of the serine protease plasminogen activator (PA) was measured in cell lysates from primary mouse keratinocyte cultures as well as from a number of established mouse keratinocyte lines. Enzyme activity was generally higher in the transformed lines than in the primary cultures; however, among the lines tested, those that expressed the highest degree of morphologic differentiation had the highest levels of cell-associated PA. In both the normal (primary) and transformed (established) keratinocyte cultures, PA activity increased when cultures reached confluence and morphologic evidence of differentiation was noted. The highest specific activity of the enzyme was found in cells shed from differentiating cultures, which consisted predominantly of detergent-resistant cornified envelopes. As the cultures differentiated and these cells were shed from the culture surface, the total cell-associated PA activity of the culture decreased accordingly. In both the normal and transformed keratinocyte cultures, peak PA activity occurred at a time when DNA synthesis was declining. These findings indicate that as keratinocytes differentiate, their intracellular levels of PA increase. The modulation of this endogenous keratinocyte enzyme may play an important, although as yet undefined, role in the normal maturation and terminal differentiation of these cells

Nutrition policy critical to optimize response to climate, public health crises

The effects of unanticipated crises on health care and first-responder systems are reflected in climate-fueled environmental emergencies, to which human resilience is diminished by our chronic disease epidemic. For example, people who depend on specialized medications, like refrigerated insulin for diabetes, will likely face additional challenges in receiving treatment and care during extreme heat, floods, disasters, and other adverse events. These circumstances may be compounded by staff and equipment shortages, lack of access to fresh food, and inadequate healthcare infrastructure in the wake of a disaster. Simply put, our health care and first-response systems struggle to meet the demands of chronic disease without such crises and may be fundamentally unable to adequately function with such crises present. However, nutrition’s primacy in preventing and controlling chronic disease directly enhances individual and public resilience in the face of existential threats. Highlighting the shared diet-related etiology clearly demonstrates the need for a national policy response to reduce the disease burden and potentiate mitigation of the sequelae of climate risks and capacity limits in our food and health care systems. Accordingly, this article proposes four criteria for nutrition policy in the Anthropocene: objective government nutrition recommendations, healthy dietary patterns, adequate nutrition security, and effective nutrition education. Application of such criteria shows strong potential to improve our resiliency despite the climate and public health crises

AN ENZYMATIC FUNCTION ASSOCIATED WITH TRANSFORMATION OF FIBROBLASTS BY ONCOGENIC VIRUSES : I. CHICK EMBRYO FIBROBLAST CULTURES TRANSFORMED BY AVIAN RNA TUMOR VIRUSES

Chick embryo fibroblast cultures develop fibrinolytic activity after transformation by Rous sarcoma virus (RSV). This fibrinolytic activity is not present in normal cultures, and it does not appear after infection with either nontransforming strains of avian leukosis viruses or cytocidal RNA and DNA viruses. In cultures infected with a temperature sensitive mutant of RSV the onset of fibrinolysis appears after exposure to permissive temperatures and precedes by a short interval the appearance of morphological evidence of transformation. See PDF for Structure The rate of fibrinolysis in transformed cultures depends on the nature of the serum that is present in the growth medium: some sera (e.g., monkey or chicken serum) promote high enzymatic activity, while others (calf, fetal bovine) do not. Some sera contain inhibitors of the fibrinolysin. Based on the effect of a small number of known inhibitors, at least one step of the fibrinolytic process shows specificity resembling that of trypsin. The sera of sarcoma-bearing chickens contain an inhibitor of the fibrinolysin, whereas normal chicken sera do not. For general discussion, conclusions, and summary see the accompanying paper, part II, (J. Exp. Med. 137:112)

Low-frequency characterization of quantum tunneling in flux qubits

We propose to investigate flux qubits by the impedance measurement technique (IMT), currently used to determine the current--phase relation in Josephson junctions. We analyze in detail the case of a high-quality tank circuit coupled to a persistent-current qubit, to which IMT was successfully applied in the classical regime. It is shown that low-frequency IMT can give considerable information about the level anticrossing, in particular the value of the tunneling amplitude. An interesting difference exists between applying the ac bias directly to the tank and indirectly via the qubit. In the latter case, a convenient way to find the degeneracy point in situ is described. Our design only involves existing technology, and its noise tolerance is quantitatively estimated to be realistic.Comment: 6 pages, 11 figures, to appear in Phys.Rev.

Challenges to physician–patient communication about medication use: a window into the skeptical patient’s world

Patients frequently do not take medicines as prescribed and often do not communicate with their physicians about their medication-taking behavior. The movement for “patient-centered” care has led to relabeling of this problem from “noncompliance” to “nonadherence” and later to a rhetoric of “concordance” and “shared decision making” in which physicians and patients are viewed as partners who ideally come to agreement about appropriate treatment. We conducted a qualitative content analysis of online comments to a New York Times article on low rates of medication adherence. The online discussion provides data about how a highly selected, educated sample of patients thinks about medication use and the doctor–patient relationship. Our analysis revealed patient empowerment and self-reliance, considerable mistrust of medications and medical practice, and frequent noncommunication about medication adherence issues. We discuss how these observations can potentially be understood with reference to Habermas’s theory of communicative action, and conclude that physicians can benefit from better understanding the negative ways in which some patients perceive physicians’ prescribing practices

Femoral Artery Atherosclerosis Is Associated With Physical Function Across the Spectrum of the Ankle-Brachial Index: The San Diego Population Study.

BackgroundThe ankle-brachial index (ABI) is inadequate to detect early-stage atherosclerotic disease, when interventions to prevent functional decline may be the most effective. We determined associations of femoral artery atherosclerosis with physical functioning, across the spectrum of the ABI, and within the normal ABI range.Methods and resultsIn 2007-2011, 1103 multiethnic men and women participated in the San Diego Population Study, and completed all components of the summary performance score. Using Doppler ultrasound, superficial and common femoral intima media thickness and plaques were ascertained. Logistic regression was used to assess associations of femoral atherosclerosis with the summary performance score and its individual components. Models were adjusted for demographics, lifestyle factors, comorbidities, lipids, and kidney function. In adjusted models, among participants with a normal-range ABI (1.00-1.30), the highest tertile of superficial intima media thickness was associated with lower odds of a perfect summary performance score of 12 (odds ratio=0.56 [0.36, 0.87], P=0.009), and lower odds of a 4-m walk score of 4 (0.34 [0.16, 0.73], P=0.006) and chair rise score of 4 (0.56 [0.34, 0.94], P=0.03). Plaque presence (0.53 [0.29, 0.99], P=0.04) and greater total plaque burden (0.61 [0.43, 0.87], P=0.006) were associated with worse 4-m walk performance in the normal-range ABI group. Higher superficial intima media thickness was associated with lower summary performance score in all individuals (P=0.02).ConclusionsFindings suggest that use of femoral artery atherosclerosis measures may be effective in individuals with a normal-range ABI, especially, for example, those with diabetes mellitus or a family history of peripheral artery disease, when detection can lead to earlier intervention to prevent functional declines and improve quality of life

Precursors of Cytochrome Oxidase in Cytochrome-Oxidase-Deficient Cells of Neurospora crassa

Three different cell types of Neurospora crassa deficient in cytochrome oxidase were studied: the nuclear mutant cni-1, the cytoplasmic mutant mi-1 and copper-depleted wild-type cells. * 1. The enzyme-deficient cells have retained a functioning mitochondrial protein synthesis. It accounted for 12–16% of the total protein synthesis of the cell. However, the analysis of mitochondrial translation products by gel electrophoresis revealed that different amounts of individual membrane proteins were synthesized. Especially mutant cni-1 produced large amounts of a small molecular weight translation product, which is barely detectable in wild-type. * 2. Mitochondrial preparations of cytochrome-oxidase-deficient cells were examined for precursors of cytochrome oxidase. The presence of polypeptide components of cytochrome oxidase in the mitochondria was established with specific antibodies. On the other hand, no significant amounts of heme a could be extracted. * 3. Radioactively labelled components of cytochrome oxidase were isolated by immunoprecipitation and analysed by gel electrophoresis. All three cell types contained the enzyme components 4–7, which are translated on cytoplasmic ribosomes. The mitochondrially synthesized components 1–3 were present in mi-1 mutant and in copper-depleted wild-type cells. In contrast, components 2 and 3 were not detectable in the nuclear mutant cni-1. Both relative and absolute amounts of these polypeptides in the enzyme-deficient cells were quite different from those in wild-type cells. * 4. The components of cytochrome oxidase found in the enzyme-deficient cells were tightly associated with the mitochondrial membranes. * 5. Processes, which affect and may control the production of enzyme precursors or their assembly to a functional cytochrome oxidase are discussed