Lobectomy combined with volume reduction for patients with lung cancer and advanced emphysema

Methanol-induced conformational transitions of hen egg white lysozyme were investigated with a combined use of far- and near-UV CD and NMR spectroscopies, ANS binding and small-angle X-ray scattering. Addition of methanol induced no global change in the native conformation itself, but induced a transition from the native state to the denatured state which was highly cooperative, as shown by the coincidence of transition curves monitored by the far- and near-UV CD spectroscopy, by isodichroic points in the far- and near-UV CD spectra and by the concomitant disappearance of individual 1H NMR signals of the native state. The ANS binding experiments could detect no intermediate conformer similar to the molten globule state in the process of the methanol denaturation. However, at high concentration of methanol, e.g., 60% (v/v) methanol/water, a highly helical state (H) was realized. The H state had a helical content much higher than the native state, monitored by far-UV CD spectroscopy, and had no specific tertiary structure, monitored both by near-UV CD and NMR spectroscopy. The radius of gyration in the H state, 24.9 angstroms, was significantly larger than that in the native state (15.7 angstroms). The Kratky plot for the H state did not show a clear peak and was quite similar to that for the urea-denatured state, indicating a complete lack of globularity. Thus we conclude that the H state has a considerably expanded, flexible broken rod-like conformation which is clearly distinguishable from the "molten globule" state. The stability of both N and H states depends on pH and methanol concentration. Thus a phase diagram involving N and H was constructed.     

Combined hyperlipidemia in transgenic mice overexpressing human apolipoprotein Cl

We have generated transgenic mice over-expressing human apolipoprotein CI (apo CI) using the native gene joined to the downstream 154-bp liver-specific enhancer that we defined for apo E. Human apo CI (HuCI)-transgenic mice showed elevation of plasma triglycerides (mg/dl) compared to controls in both the fasted (211 +/- 81 vs 123 +/- 52, P = 0.0001) and fed (265 +/- 105 vs 146 +/- 68, P < 0.0001) states. Unlike the human apo CII (HuCII)- and apo CIII (HuCIII)-transgenic mouse models of hypertriglyceridemia, plasma cholesterol was disproportionately elevated (95 +/- 23 vs 73 +/- 23, P = 0.002, fasted and 90 +/- 24 vs 61 +/- 14, P < 0.0001, fed). Lipoprotein fractionation showed increased VLDL and IDL + LDL with an increased cholesterol/triglyceride ratio (0.114 vs 0.065, P = 0.02, in VLDL). The VLDL apo E/apo B ratio was decreased 3.4-fold (P = 0.05) and apo CII and apo CIII decreased in proportion to apo E. Triglyceride and apo B production rates were normal, but clearance rates of VLDL triglycerides and postlipolysis lipoprotein "remnants" were significantly slowed. Plasma apo B was significantly elevated. Unlike HuCII- and HuCIII-transgenic mice, VLDL from HuCI transgenic mice bound heparin-Sepharose, a model for cell-surface glycosaminoglycans, normally. In summary, apo CI overexpression is associated with decreased particulate uptake of apo B-containing lipoproteins, leading to increased levels of several potentially atherogenic species, including cholesterol-enriched VLDL, IDL, and LDL.     

Imported measles. A potential control problem

From Dec 23, 1978, through Jan 31, 1979, an outbreak of five laboratory-confirmed cases and four clinical cases of measles occurred in a Vietnamese refugee population living in a single housing complex in Albuquerque, NM. The index cases were in two refugee siblings in whom measles was incubating on arrival in the United States. Despite spread through three subsequent generations of disease transmission within the Vietnamese population, there was no additional spread into the general Albuquerque population. Responsible factors included the age distribution of susceptible persons, the social isolation of the refugee population, and the physical structure of the housing complex. There is a need to identify the problem of imported measles in "ethnic islands" in need of vaccination.     

Temperature-dependent characteristics and single-mode performanceof AlGaInP-based 670-690-nm vertical-cavity surface-emitting lasers

We report on temperature dependent characteristics and single mode performance of one-wave cavity, planar implanted, AlGaInP-based vertical-cavity surface emitting lasers. By optimizing the overlap between the gain peak and the cavity mode of the structure, we demonstrate record device performance, including 8.2 mW maximum output power and 11% power conversion efficiency for multimode operation and 1.9 mW and 9.6% power conversion efficiency for single mode operation at 687 nm. Improved performance at elevated temperatures is also achieved, with 1.5 mW output power demonstrated at 50°C from a 15-μm-diameter device     

Low thermal resistance high-speed top-emitting 980-nm VCSELs

Increasing copper plated heatsink radii from 0 to 4 /spl mu/m greater than the mesa in vertical-cavity surface-emitting lasers (VCSELs) reduced the measured thermal resistance for a range of device sizes to values 50% lower than previously reported over a range of device sizes. For a 9-/spl mu/m diameter oxide aperture, the larger heatsink increases output power and bandwidth by 131% and 40%, respectively. The lasers exhibit a 3-dB modulation frequency bandwidth up to 9.8 GHz at 10.5 kA/cm/sup 2/. The functional dependence of thermal resistance on oxide aperture diameter indicates the importance of lateral heat flow to mesa sidewalls.     

Long‐Term Electrical and Mechanical Function Monitoring of a Human‐on‐a‐Chip System

The goal of human‐on‐a‐chip systems is to capture multiorgan complexity and predict the human response to compounds within physiologically relevant platforms. The generation and characterization of such systems is currently a focal point of research given the long‐standing inadequacies of conventional techniques for predicting human outcome. Functional systems can measure and quantify key cellular mechanisms that correlate with the physiological status of a tissue, and can be used to evaluate therapeutic challenges utilizing many of the same endpoints used in animal experiments or clinical trials. Culturing multiple organ compartments in a platform creates a more physiologic environment (organ–organ communication). Here is reported a human 4‐organ system composed of heart, liver, skeletal muscle, and nervous system modules that maintains cellular viability and function over 28 days in serum‐free conditions using a pumpless system. The integration of noninvasive electrical evaluation of neurons and cardiac cells and mechanical determination of cardiac and skeletal muscle contraction allows the monitoring of cellular function, especially for chronic toxicity studies in vitro. The 28‐day period is the minimum timeframe for animal studies to evaluate repeat dose toxicity. This technology can be a relevant alternative to animal testing by monitoring multiorgan function upon long‐term chemical exposure.     

Sodium nitroprusside: pharmacology, toxicology and therapeutics

Sodium nitroprusside is a potent, effective, and readily reversible direct vasodilating agent. It is broken down by hemoglobin into cyanide, which is in part detoxified by liver and kidney to thiocyanate. Some cyanide, especially in nitroprusside- "resistant" individuals who need large amounts of the drug, appears to remain free to cause cyanide poisoning. Patients requiring inordinate amounts probably should not continue to receive the drug, although maximum dosage limits for long-term therapy are not established. Blood thiocyanate levels do not indicate the extent to which free cyanide is limiting oxygen utilization in essential tissue, nor do blood cyanide levels. Metabolic acidosis, elevated lactate levels, elevated lactate/pyruvate ratios, and elevated mixed venous blood oxygen content are at present the best indications of the presence of cyanide poisoning during nitroprusside administration. Nitroprusside appears useful for induction of hypotension during surgery, and for treatment of hypertensive emergencies from all causes, although continuance for more than a few days is probably unwise. The reductions of cardiac afterload and ventricular filling pressure by nitroprusside appear useful in treatment of severe myocardial failure or infarction, but studies of myocardial cyanide toxicity are needed before complete acceptance of this therapy is warranted. Initial dose rates between 0.5 and 1.5 mug/kg/min are recommended only as starting points for very careful titration. Total projected intra-operative dosage should be calculated as quickly as possible and should not exceed 3-3.5 mg/kg. It is hoped that future studies will reveal the maximum dose of nitroprusside that can safely be metabolized in a 24-hour period, and may indicate that cofactors of rhodanase such as thiosulfate, or cobalamins such as hydroxocobalamin, can be administered with nitroprusside to prevent cyanide poisoning.     

Strain differences among chickens in tonic immobility: evidence for an emotionality component

Substantial strain differences in tonic immobility were found between different breeds of chickens. Crossbreeding between strains showing different immobility durations yielded hybrids that exhibited intermediate reactions. For purpose of relating the strain differences in tonic immobility to more conventional measures of emotionality, data were collected on open-field activity, defecation, and adrenal weight. Overall, the results implicated strain-specific differences in emotionality as being the basis for the observed differences in immobility. Latency to defecate in an open field, however, was highly correlated with latency to ambulate. It was argued that defecation, rather than being an absolute measure of fear or emotionality, may in fact be an intermediate response to gradual fear reduction.