In vitro binding of chloroquine to rat muscle preparations.

Chloroquine (7-chloro-4-[[4-(diethylamino)-1-methylbutyl]amino]quinoline; CQ) accumulates in the insoluble fraction of rat muscle homogenates with an equilibrium distribution ratio of 7.8 L/kg. This is of a similar magnitude to muscle:plasma ratios observed in vivo.

The pH-dependence of chloroquine uptake by phosphatidylcholine vesicles.

The pH-dependence of chloroquine uptake by phosphatidylcholine bilayered vesicles was investigated to examine the relative affinity of ionized and un-ionized chloroquine species to membrane bilayers. The results suggest that the neutral species and monocation are taken up by the bilayers but only the un-ionized species interacts significantly with the hydrocarbon interior.

Determinants for protein translocation across mammalian endoplasmic reticulum. Membrane insertion of truncated and full-length prelysozyme molecules.

The translocation of fragments of prelysozyme lacking varying portions of the COOH terminus of the protein is studied in comparison to full-length prelysozyme using transcription-coupled capping of RNA and subsequent translation in a wheat germ cell-free system. The fragments are generated by restricting cloned lysozyme cDNA at selected sites. We found that fragments of 102 and 74 amino acid residues could still be translocated by mammalian endoplasmic reticulum.

Mutants of the membrane-binding region of Semliki Forest virus E2 protein. II. Topology and membrane binding.

The p62/E2 protein of Semliki Forest virus (SFV) is a typical transmembrane glycoprotein, with an amino-terminal lumenal domain, a transmembrane (hydrophobic) domain, and a carboxy-terminal cytoplasmic domain (or tail). Our hypothesis has been that the membrane-binding polypeptide region (membrane anchor) of this protein consists of both the transmembrane domain and the adjacent positively charged peptide, Arg-Ser-Lys, which is part of the cytoplasmic domain. We have investigated three anchor mutants of the p62 protein with respect to both their disposition and their stability in cell membranes.

Mutants of the membrane-binding region of Semliki Forest virus E2 protein. I. Cell surface transport and fusogenic activity.

Three mutations of the membrane-binding region of the Semliki Forest virus (SFV) p62 polypeptide (the precursor for virion E3 and E2) have been made by oligonucleotide-directed mutagenesis of a cDNA clone encoding the SFV structural proteins. One of the mutations (A2) substitutes a Glu for an Ala in the middle of the hydrophobic stretch which spans the bilayer. A1 and A3 alter the two basic charged amino acids in the cytoplasmic domain next to the hydrophobic region.

Community residential options for the chronically mentally ill.

We have discussed the problems of the new young chronic patients, deinstitutionalized old chronic patients now living in the community, and some of the groups of hard to place patients. We have talked about problems with community barriers, staff training, a spectrum of facilities, and we have looked at what new sorts of facilities may need to be developed. It seems clear that we have not yet developed a spectrum which can deal with all varieties of the chronically mentally ill.

High-performance liquid chromatographic assay for hydroxychloroquine and metabolites in blood and plasma, using a stationary phase of poly(styrene divinylbenzene) and a mobile phase at pH 11, with fluorimetric detection.

A sensitive rapid high-performance liquid chromatographic assay for hydroxychloroquine and three major metabolites, desethylhydroxychloroquine, desethylchloroquine and bisdesethylchloroquine, has been developed. An ion-suppression separation technique is used with a macroporous polymer, poly(styrene divinylbenzene), stationary phase and a mobile phase of methanol--water with triethylamine, pH 11. A single ether extraction from alkalinized plasma or whole blood, with chloroquine added as an internal standard, is used.

Exocytotic pathways exist to both the apical and the basolateral cell surface of the polarized epithelial cell MDCK.

Secretion of a foreign protein--chicken oviduct lysozyme--and of endogenous proteins was studied in the polarized epithelial Madin-Darby Canine Kidney (MDCK) cell line. Cell clones that secrete enzymatically active chicken lysozyme were generated by transforming the cells with lysozyme cDNA inserted in a SV40-pBR322 recombinant vector and a dominant selectable marker gene. The kinetics and polarity of lysozyme secretion from one transformed cell clone were studied using cell monolayers grown on nitrocellulose filters.

A novel in vitro transcription-translation system: accurate and efficient synthesis of single proteins from cloned DNA sequences.

A system is described which permits the efficient synthesis of single proteins in vitro. The essential element in this expression system is a strong promoter derived from coliphage T5 which produces, with high efficiency, specific RNAs in capped or uncapped form, depending upon the experimental conditions used. The transcription-coupled capping of RNA allows the direct translation of the RNA in eukaryotic extracts from wheat germ as well as from HeLa cells.

Paediatric admissions to Auckland Hospital for asthma from 1970-1980.

Paediatric admissions to Auckland Hospital were examined for 1970 to 1980. The number of individual patients admitted for asthma each year increased significantly over the study period. The rate was higher in the 0-4 year age group than in the 5-14 year age group and was higher in Maori and Pacific Islander children than in Europeans.

Disseminating the principles of a community support program.

Oregon's Living in the Community (LINC) program for chronic patients succeeds because of effective collaboration between a state hospital and a community treatment and rehabilitation program. The authors trace the development of the LINC program from its beginning in the early 1970s as a progressive retraining project for Eastern Oregon State Hospital's "back ward" patients. They describe principles derived from the original project, such as the provision of training in the patient's natural environment, adoption of these principles into the Oregon community support program, and dissemination of LINC projects to other parts of the state.

Productive activities for the chronic patient.

This paper examines the common characteristics of chronic psychiatric patients and the principles that should guide the development of any program of activities designed to promote their rehabilitation. A range of productive activities in each segment of a support network is described, and an example from Oregon is presented to illustrate how different levels of activities can be used to meet rehabilitation goals.

Essential fatty acids and maladjusted behaviour in children.

It has been suggested that hyperactivity may be produced by a deficiency in essential fatty acids (EFA) leading to a deficit in prostaglandin (PG) formation. The red blood cells EFAs levels were examined in 23 maladjusted children and in 20 normal children. Although no individual EFA showed statistically significant differences between the normal and maladjusted children, multivariate analysis showed that the levels of EFA series 2 PG precursors in maladjusted children were significantly lower than in controls as predicted (P = 0.

The oocyte as a secretory cell.

Xenopus laevis oocytes secrete a large variety of foreign secretory proteins after the microinjection of mRNA or DNA. Two classes of such proteins are discussed in detail. These are the chick oviduct proteins ovalbumin and lysozyme, and the mouse MOPC 21 immunoglobulin.

The CMHC as a setting for residency education.

The authors review four approaches chairmen of departments of psychiatry have used to attempt to ensure quality resident education in CMHCs they do not control. Several examples are presented of administrative problems that may develop in this type of relationship. Based on this material and the author's experience, a four stage administrative process is presented which emphasized clear identification of goals and objectives, negotiation of a relationship that is beneficial to both the development and the CMHC, development of a written contract, and careful monitoring and evaluation of its progress.

Properties of the recirculation model: calculation of the amount of drug in the body from blood concentration data, with application to absorption rate calculations.

Compartment models express the relationship between amounts and concentrations by volumes of distribution, which are fundamental parameters of the models. For a recirculation model, the amount of drug in the body is given by the convolution of the measured blood concentration with a function, termed the retention function, which is a characteristic of the system. The amount of drug in the body can be partitioned into rapidly recirculating and slowly recirculating portions, which are analogous to the amounts of drug in the central and peripheral compartments of a compartment model.

Properties of the recirculation model: matrix description and conditions for a monotonic decreasing single pass response.

The recirculation equation is examined for the case in which the blood concentration is given by a polyexponential expression sigma Ai exp (-ait). A matrix is developed whose eigenvalues are the exponential coefficients of the single pass response. These eigenvalues are real and distinct, and the single pass response is monotonic decreasing, when the Ai are all positive.

Training psychiatrists to work with community support systems for chronically mentally ill persons.

Community support programs are becoming a major priority in community mental health centers throughout the country. The authors present a training design that integrates principles and skills associated with this model into a 4-year residency training program. The aim of such programs is to keep young psychiatrists involved and in the forefront of the newer approaches to the treatment of chronically mentally ill persons.