The Changing American Hospital in the Twenty-first Century 14th Annual Herbert Lourie Memorial Lecture on Health Policy

One is always hesitant to speak about the future. A famous philosopher from New York, Yogi Berra, said "Making predictions is difficult, especially about the future," and I have some trepidation about doing so now. There is also the difficulty of understanding what really has happened in the past. I recall the Bolshevik general in 1917 who said "The future is clear, but the past is very murky." We anticipate the future with more clarity than is justified, even as we disagree on what is happening right now or what happened before. In that vein, I will describe the role of the American hospital in our health care system, and the challenges it must meet, reviewing first the murky past by summarizing trends that have made hospitals what they are today.

The Changing American Hospital in the Twenty-first Century

One is always hesitant to speak about the future. A famous philosopher from New York, Yogi Berra, said Making predictions is difficult, especially about the future, and I have some trepidation about doing so now. There is also the difficulty of understanding what really has happened in the past. I recall the Bolshevik general in 1917 who said The future is clear, but the past is very murky. We anticipate the future with more clarity than is justified, even as we disagree on what is happening right now or what happened before. In that vein, I will describe the role of the American hospital in our health care system, and the challenges it must meet, reviewing first the murky past by summarizing trends that have made hospitals what they are today

The membrane proteins of the vacuolar system II. bidirectional flow between secondary lysosomes and plasma membrane

Lactoperoxidase covalently coupled to latex spheres (LPO-latex) has been used to selectively iodinate the phagolysosome (PL) membrane within living macrophages, as discussed in the accompanying article. This procedure labeled ~24 polypeptides in the PL membrane; these were similar to those iodinatable on the external surface of the plasma membrane (PM). We now report on the translocation and fate of these proteins when the cells are returned to culture. TCA-precipitable radioactivity was lost from cells with biphasic kinetics. 20-50% of the cell-associated radiolabel was rapidly digested (t1/2 ≅ 1 h) and recovered in the culture medium as monoiodotyrosine. 50-80% of the label was lost slowly from cells (t1/2 ≅ 24-30 h). Quantitative analysis of gel autoradiograms showed that all radiolabeled proteins were lost at the same rate in both the rapid and slow phases of digestion. Within 15-30 min after labeling of the PL membrane, EM autoradiography revealed that the majority of the cell-associated grains, which at time 0 were associated with PL, were now randomly dispersed over the plasmalemma. At this time, analysis of PM captured by a second phagocytic load revealed the presence of all labeled species originally present in the PL membrane. This demonstrated the rapid, synchronous centrifugal flow of PL polypeptides to the cell surface. Evidence was also obtained for the continuous influx of representative samples of the PM into the PL compartment by way of pinocytic vesicles. This was based on the constant flow of fluid phase markers into latex-containing PL and on the internalization of all iodinatable PM polypeptides into this locus. These observations provide evidence for the continuous, bidirectional flow of membrane polypeptides between the PM and the secondary lysosome and represent an example of a membrane flow and recycling mechanism

The membrane proteins of the vacuolar system I. analysis by a novel method of intralysosomal lodination

A method has been developed to deliver an iodinating system into the confines of the phagolysosome, allowing us to study the nature of the phagolysosomal membrane. Lactoperoxidase (LPO) is covalently coupled to carboxylated latex spheres (LPO-latex) in a stable, enzymatically active form. The addition of LPO-latex to cultured macrophages leads to their rapid attachment, ingestion, and enclosure in a plasma membrane-derived phagocytic vacuole. These organelles rapidly fuse with preexisting lysosomes and are converted to phagolysosomes (PL) that demonstrate both acid phosphatase and lactoperoxidase activities. The exposure of LPO-latex containing cells to 125l- and an extracellular peroxide-generating system, glucose oxidase-glucose, at 4°C leads to incorporation of label into TCA-precipitable material. The incorporated cell-associated label was present as monoiodotyrosine, and negligible amounts were found in lipids. Cell viability remained \u3e99%. Autoradiography at both the light and EM level revealed that \u3e97% of the cells were labeled, and quantitative analysis demonstrated the localization of grains to LPO-latex containing PL. PL were separated on sucrose gradients, and their radiolabel was confined almost exclusively to the membrane rather than soluble contents. SDS-polyacrylamide gel electrophoretic analysis of the peptides iodinated from within PL demonstrated at least 24 species with molecular weights ranging from 12,000 to 250,000. A very similar group of proteins was identified on the plasma membrane (PM) after surface iodination, and on latex phagosomes derived from iodinated PM. No novel proteins were detected in PL, either immediately after phagosome-lysosome fusion or after 1 h of intracytoplasmic residence. We conclude that the membrane proteins accessible to LPO-catalyzed iodination on the luminal surface of the PL and on the external face of the PM are similar, if not identical

Automated Hovering in Health Care — Watching Over the 5000 Hours

The dominant form of health care financing in the United States supports a reactive, visit-based model in which patients are seen when they become ill, typically during hospitalizations and at outpatient visits. That care model falls short not just because it is expensive and often fails to proactively improve health, but also because so much of health is explained by individual behaviors,1 most of which occur outside health care encounters. Indeed, even patients with chronic illness might spend only a few hours a year with a doctor or nurse, but they spend 5000 waking hours each year engaged in everything else — including deciding whether to take prescribed medications or follow other medical advice, deciding what to eat and drink and whether to smoke, and making other choices about activities that can profoundly affect their health

Endocytosis and the recycling of plasma membrane

[No abstract available