Synthesis in vitro of intrinsic membrane proteins by free, membrane-bound, and Golgi apparatus-associated polyribosomes from rat liver

A fraction of intrinsic membrane proteins was prepared from the major membranous cell components of rat liver by extraction of the membranes with KCl and deoxycholate. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the compositions of the intrinsic protein fractions from rough and endoplasmic reticulum, smooth endoplasmic reticulum. Golgi apparatus, plasma membrane, and nuclear envelope were similar to each other but distinct from that of mitochondria. Among endomembranes, differences were in the ratios of protein constituents plus a few protein bands of Golgi apparatus and plasma membranes not found in endoplasmic reticulum or nuclear envelope. The abilities of total rough endoplasmic reticulum, polysomes released from rough endoplasmic reticulum, and free polysomes to incorporate amino acids into the intrinsic protein fraction were tested in vitro. Polysomes bound to endoplasmic reticulum has the greatest capacity to synthesize proteins of this fraction as shown by co-purification of radioactive products and by immunoprecipitation. Although the majority of the radioactive products synthesized by bound polysomes were distinct from those synthesized by free polysomes, certain radioactive products synthesized by free polysomes also co-purified with intrinsic membrane proteins. The results show no absolute segregation between free and bound polysomes in the synthesis of intrinsic membrane proteins. However, the majority of these proteins appear to be synthesized by polysomes bound to the endoplasmic reticulum. Several intrinsic proteins found in plasma membranes do not appear in rough endoplasmic reticulum. To determine where these proteins were synthesized, the ability of other endomembrane components to support in vitro incorporation of [14C]leucine into protein was examined. In contrast to plasma membranes, isolated Golgi apparatus fractions did incorporate [14C]leucine to an extent greater than could be explained by contamination with rough endoplasmic reticulum. Golgi apparatus in situ and isolated from rat liver have polyribosomes associated with a zone of cytoplasm at the Golgi apparatus periphery occupied by tubules and vesicles. The polysomes are not directly attached to membranes as with rough endoplasmic reticulum and may represent a special class of "Golgi apparatus-associated" polysomes. The polysomes, when associated with Golgi apparatus membranes, incorporated amino acids in vitro. The products synthesized in vitro were analyzed by treatment with KCl and deoxycholate and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Certain proteins synthesized by the Golgi apparatus-associated polysomes remained insoluble after the treatment with KCl and deoxycholate. The proteins synthesized by the Golgi apparatus fraction had mobilities similar to proteins in plasma membranes which were absent from endoplasmic reticulum, and which were relatively minor components of Golgi apparatus...     

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.     

The prevalence of hepatitis B surface antigen in commercially prepared plasma products

Commercially available lots of plasma derivatives prepared between 1957 and 1975 were tested for hepatitis B surface antigen (HBsAg) by radioimmunoassay. In all, 69 per cent of lots of plasma protein fraction, 40 per cent of factor IX concentrate, 20 per cent of normal serum albumin, 13 per cent of antihemophilic factor, 3 per cent of fibrinogen, and 0.7 per cent of immune serum globulin lots tested were HBsAg-positive. There was great variation in the prevalence of HBsAg-positive lots of each product among the different manufacturers, reflecting not only differences in methods of processing plasma, but also differences in donor populations. Those manufacturers relying upon volunteer donor plasma or placental source material demonstrated lower rates of HBsAg-positive lots of final products than those relying upon commercial donor plasma. There was a marked decrease in the prevalence of positive lots during the period 1971 to 1973, coincident with the onset of routine plasma donor screening for HBsAg. However, current requirements for plasma screening have not resulted in totally HBsAg-free plasma products. Use of more sensitive and more reliable tests for HBsAg will probably reduce contamination of plasma pools with HBsAg to undetectable levels. Despite HBsAg-status, however, the "high-risk" plasma products (fibrinogen, antihemophilic factor, factor IX concentrate) must still be considered capable of transmitting hepatitis and used only with the strictest indications.     

Outpatient chemotherapy of advanced breast cancer in a community setting: a five-drug regimen

Forty-two (37 evaluable) unselected women with advanced breast carcinoma were treated with a modified "Cooper regimen" in a community setting. After 12 weeks of induction therapy, the patients were evaluated for response and toxicity. The 74% overall response rate (78% in the evaluable group) compares favorably with that of other series. The median duration of remission was 13.7 months. The median survival was 17 months for the evaluable patients and 14 months for the entire group. Twenty-two percent of the patients required hospitalization during the induction phase, and 35% were treated exclusively as outpatients during all phases of therapy. There was only one drug-related death. It is concluded that a complex chemotherapeutic regimen can be managed adequately by physicians experienced in chemotherapy in a community setting with results comparable to those from cancer centers.     

A continuous-wave hybrid AlGaInAs-silicon evanescent laser

We report a novel laser architecture, the hybrid silicon evanescent laser (SEL), that utilizes offset AlGaInAs quantum wells (QWs) bonded to a silicon waveguide. The silicon waveguide is fabricated on a silicon-on-insulator wafer using a complimentary metal-oxide-semiconductor-compatible process, and is subsequently bonded with the AlGaInAs QW structure using low temperature O/sub 2/ plasma-assisted wafer bonding. The optical mode in the SEL is predominantly confined in the passive silicon waveguide and evanescently couples into the III-V active region providing optical gain. The SEL lases continuous wave (CW) at 1568 nm with a threshold of 23 mW. The maximum temperature for CW operation is 60/spl deg/C. The maximum single-sided fiber-coupled CW output power at room temperature is 4.5 mW.     

Background Checks: Series introduction

Networks dominate today's computing landscape and commercial technical protection is lagging behind attack technology. As a result, protection programme success depends more on prudent management decisions than on the selection of technical safeguards. Managing Network Security takes a management view of protection and seeks to reconcile the need for security with the limitations of technology.     

Psychological Research Online: Report of Board of Scientific Affairs' Advisory Group on the Conduct of Research on the Internet.

As the Internet has changed communication, commerce, and the distribution of information, so too it is changing psychological research. Psychologists can observe new or rare phenomena online and can do research on traditional psychological topics more efficiently, enabling them to expand the scale and scope of their research. Yet these opportunities entail risk both to research quality and to human subjects. Internet research is inherently no more risky than traditional observational, survey, or experimental methods. Yet the risks and safeguards against them will differ from those characterizing traditional research and will themselves change over time. This article describes some benefits and challenges of conducting psychological research via the Internet and offers recommendations to both researchers and institutional review boards for dealing with them. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Venom Peptide Toxins Targeting the Outer Pore Region of Transient Receptor Potential Vanilloid 1 in Pain: Implications for Analgesic Drug Development

The transient receptor potential vanilloid 1 (TRPV1) ion channel plays an important role in the peripheral nociceptive pathway. TRPV1 is a polymodal receptor that can be activated by multiple types of ligands and painful stimuli, such as noxious heat and protons, and contributes to various acute and chronic pain conditions. Therefore, TRPV1 is emerging as a novel therapeutic target for the treatment of various pain conditions. Notably, various peptides isolated from venomous animals potently and selectively control the activation and inhibition of TRPV1 by binding to its outer pore region. This review will focus on the mechanisms by which venom-derived peptides interact with this portion of TRPV1 to control receptor functions and how these mechanisms can drive the development of new types of analgesics.     

Constance Kamii's research and recent math reforms

Constance Kamii. (1990). Multiplication of two‐digit numbers: Two teachers using Piaget's theory. [Videotape.] New York: Teachers College Press. ISBN 0–8077–3086–6, Cdn $86.