Code of Ethics

Principles of Ethical Behaviour for all physicians, including those who may not be engaged directly in clinical practice. [List: see text]     

Promoting prevention in primary care: controlled trial of low technology,low cost approach.

A study is described in which three general practices were provided with low cost, low technology support from a "facilitator" and were compared with control practices in the ascertainment of major risk factors for cardiovascular disease in middle aged patients. Patients who were attending for a consultation with their general practitioners were recruited to make an appointment with a practice nurse for a health check, and this was compared with ordinary consultations in the control practices. Practices were helped by the facilitator to develop the nurse''s role. During the study the increase between intervention and control practices in blood pressure recording was doubled and in the recording of smoking habit it was quadrupled, and there was a fivefold increase in the recording of weight. This model can be applied to other aspects of prevention and general practice care.     

The valyl-tRNA synthetase from Bacillus stearothermophilus has considerable sequence homology with the isoleucyl-tRNA synthetase from Escherichia coli

We report the DNA sequence of the valS gene from Bacillus stearothermophilus and the predicted amino acid sequence of the valyl-tRNA synthetase encoded by the gene. The predicted primary structure is for a protein of 880 amino acids with a molecular mass of 102,036. The molecular mass and amino acid composition of the expressed enzyme are in close agreement with those values deduced from the DNA sequence. Comparison of the predicted protein sequence with known protein sequences revealed a considerable homology with the isoleucyl-tRNA synthetase of Escherichia coli. The two enzymes are identical in some 20-25% of their amino acid residues, and the homology is distributed approximately evenly from N-terminus to C-terminus. There are several regions which are highly conservative between the valyl- and isoleucyl-tRNA synthetases. In one of these regions, 15 of 20 amino acids are identical, and in another, 10 of 14 are identical. The valyl-tRNA synthetase also contains a region HLGH (His-Leu-Gly-His) near its N-terminus equivalent to the consensus HIGH (His-Ile-Gly-His) sequence known to participate in the binding of ATP in the tyrosyl-tRNA synthetase. This is the first example of extensive homology found between two different aminoacyl-tRNA synthetases.     

Neuronal calcium channel antagonists. Discrimination between calcium channel subtypes using omega-conotoxin from Conus magus venom

The omega-conotoxins from the venom of fish-hunting cone snails are probably the most useful of presently available ligands for neuronal Ca channels from vertebrates. Two of these peptide toxins, omega-conotoxins MVIIA and MVIIB from the venom of Conus magus, were purified. The amino acid sequences show significant differences from omega-conotoxins from Conus geographus. Total synthesis of omega-conotoxin MVIIA was achieved, and biologically active radiolabeled toxin was produced by iodination. Although omega-conotoxins from C. geographus (GVIA) and C. magus (MVIIA) appear to compete for the same sites in mammalian brain, in amphibian brain the high-affinity binding of omega-conotoxin MVIIA has narrower specificity. In this system, it is demonstrated that a combination of two omega-conotoxins can be used for biochemically defining receptor subtypes and suggested that these correspond to subtypes of neuronal Ca2+ channels.     

Purification and partial characterization of a corticosteroid-binding globulin from hamster serum

Our objective was to characterize and purify the corticosteroid-binding proteins in hamster pregnancy serum. When [3H]cortisol-labeled pregnancy and proestrous serum were subjected to native polyacrylamide gel electrophoresis, a single peak of specific steroid-binding activity was detected in each, with identical electrophoretic mobility. The steroid-binding affinity (Ka = 1.07.10(8) M-1 for cortisol) is typical of corticosteroid-binding globulin from other species, but the steroid-binding specificity (cortisol greater than testosterone greater than progesterone) is not. An ultraviolet photoaffinity-labeling protocol was developed using 17 beta-hydroxy-4,6-[1,2-3H]androstadiene-3-one ([3H]androstadienolone), permitting analysis of ultraviolet photoaffinity-labeled proestrous and pregnancy serum by two-dimensional polyacrylamide gel electrophoresis and fluorography. Both sera contained the same labeled protein species. Corticosteroid-binding globulin was purified from pregnancy serum by DEAE-cellulose chromatography followed by steroid affinity chromatography on androstadienolone-17 beta-hemisuccinate-ethylenediamine-AffiGel 10. The purified protein (Mr = 62,250; pI = 3.95; n = 1; Stokes radius = 3.5; S = 4-5) was determined to be a glycoprotein. When analyzed by gel filtration and two-dimensional polyacrylamide gel electrophoresis, purified corticosteroid-binding globulin behaved the same as in unfractionated serum, and when ultraviolet photoaffinity-labeled with [3H]androstadienolone, purified corticosteroid-binding globulin produced the same fluorogram spot pattern seen in unfractionated serum. A specific corticosteroid-binding globulin antiserum was raised in rabbits, and this antiserum reacted with a single spot in Western blots of unfractionated serum. Thus, hamster pregnancy serum was determined to have one corticosteroid-binding protein. This protein is identical to the corticosteroid-binding globulin found in proestrous serum, with a higher titer in pregnancy serum. No other steroid-binding component is observed in hamster serum.     

Production of the macrolide antibiotic tylosin in cyclic fed-batch culture

Tylosin-producing Streptomyces fradiae was cultured on a synthetic medium with a high glutamate-glucose ratio. Tylosin batch fermentations with this medium were characterized by a high initial specific production rate of tylosin (q(tylosin), mg/g h) that decreased as the fermentation progressed. Continuous feeding of glutamate, glucose, and methyloleate at a constant feed rate initiated during the period of high q(tylosin) had been shown to produce some increase in tylosin productivity. By using a cyclic feeding strategy, it was possible to increase tylosin productivity further. Tylosin fed-batch fermentations with glutamate and glucose being fed to the culture in cyclic square-wave profiles with methyloleate in excess showed several-fold increase in final q(tylosin) and tylosin titers. By varying cycle amplitudes and period of the substrates, it was found that maximum tylosin productivity occurred when the glutamate cycle amplitude was 600 mg/L and that of glucose was 42.5 mg/L per cycle period of 24 h. With these cycle amplitudes of glutamate and glucose, the tylosin cyclic fed-batch culture also showed high cellular uptake of methyloleate. Decreasing or increasing glucose cycle amplitude at fixed glutamate amplitude lowered tylosin production, and no further stimulation of tylosin synthesis was observed when alpha-ketoglutarate was supplemented to the cyclic substrate feeds. Under optimum cyclic conditions it was possible to maintain linear tylosin accretion and a constant value of q(tylosin) up to 240 h.     

Behavioral interactions between three birch aphid species and Adalia bipunctata larvae

First and fourth instars of three birch aphid species were exposed to first and fourth instars of Adalia bipunctata (L.), the most common aphid predator on silver birch, Betula pendula Roth, in northern California. Defensive behavior differed by aphid species. Euceraphis betulae (Koch) (Eb), the most successful escapee, was highly mobile and frequently walked away from coccinellid larvae. Betulaphis brevipilosa Börner (Bb), a flat, sessile species, was the least successful aphid at actively escaping from A. bipunctata larvae, but could passively escape detection when coccinellid larvae walked over nymphs and did not perceive them. Active escape behavior was much safer for aphids than passive avoidance of detection. Both instars of Eb and fourth instars of Callipterinella calliptera (Hartig) (Cc) escaped from coccinellid larvae more frequently when approached from the front, apparently using vision for pre-contact detection of A. bipunctata. These aphids avoided physical contact with larger predators more often than with smaller predators. Level of predation by A. bipunctata on these three aphid species is dependent upon types of aphid defense.

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Résumé Des larves de premier et troisième stades de 3 espèces de pucerons du bouleau: Betulaphis brevipilosa, Callipterinella calliptera et Euceraphis betulae ont été exposées aux attaques des larves du premier et du quatrième stades d'Adalia bipunctata, prédateur le plus fréquent de pucerons sur Betula pendula en Californie du Nord. Le comportement défensif dépend beaucoup de l'espèce de puceron. E. betulae, qui s'échappe avec le plus de succès, est très mobile et s'écarte fréquemment des larves agressives de coccinelles. B. brevipilosa, espèce plate, sessile, a le moins de succès dans la protection active contre les attaques des larves de A. bipunctata, mais elle peut échapper passivement à la détection des larves de coccinelles qui ne peuvent pas les discerner lorsqu'elles circulent parmi les larves de pucerons. E. betulae (aux deux stades) et C. calliptera (au quatrième) échappent le plus aux larves de coccinelles qui attaquent de front, ce qui laisse supposer que la vision permet de détecter A. bipunctata avant le contact. Le succès des larves de coccinelles varie selon les stades du puceron et de la coccinelle. Les possibilités d'obtention de niveaux de prédation élevés de ces 3 pucerons par A. bipunctata dépend du type de protection du puceron.

     

Construction of an Unstable Ring-X Chromosome Bearing the Autosomal Dopa Decarboxylase Gene in Drosophila melanogaster and Analysis of Ddc Mosaics

An unstable Ring-X chromosome, Ddc⁺- Ring-X carrying a cloned Dopa decarboxylase (Ddc) encoding segment was constructed. The construction involved a double recombination event between the unstable Ring-X, R(1)w^vC and a Rod-X chromosome which contained a P-element mediated Ddc ⁺ insert. The resulting Ddc⁺-Ring-X chromosome behaves similarly to the parent chromosome with respect to somatic instability. The Ddc⁺-Ring-X chromosome was used to generate Ddc mosaics. Analyses of Ddc mosaics revealed that while there was no absolute requirement for the Ddc ⁺ expression in either the epidermis or the nervous system, very large mutant clones did affect the viability of the mosaic.     

Diminished steroidogenic response of hamster granulosa cells to estrogen in vitro

Summary We have previously demonstrated that estrogen can exert inhibitory or atretogenic effects on the ovaries of both rats and rhesus monkeys in vivo. This study was designed to test whether the hamster (Mesocricetus auratus) is an appropriate model in which to test the effects of estrogens (diethylstilbestrol and estradiol-17) on steroid accumulation by ovarian granulosa cells in vitro, and whether the effects are similar to those demonstrated for other species in vivo. Immature female hamsters were injected with pregnant mare's serum gonadotropin at 28 to 30 days of age. Animals were sacrificed and follicular contents aspirated three days later. Granulosa cells were either left untreated or treated with diethylstilbestrol or estradiol (1×10^-7 M) in vitro for 72 h in the presence of androstenedione (1×10^-7 M), and in the presence or absence of serum (10%) or human follicle-stimulating hormone (20 ng/ml), and long-term accumulation of estrogen and progesterone was determined. Diethylstilbestrol inhibited accumulation of estrogen regardless of the presence or absence of follicle-stimulating hormone. In contrast, only estradiol plus follicle-stimulating hormone augmented accumulation of progesterone by granulosa cells. These findings that estrogen can be non-stimulatory or inhibitory to function of granulosa cells in vitro parallel those shown in vivo. Our experimental approach may therefore represent an appropriate model for study of the direct effects of estradiol on the function of granulosa cells.     

Glomerular ultrastructure of the trout,Salmo gairdneri: Effects of angiotensin II and adaptation to seawater

Summary The effect of angiotensin infusion on the glomerular ultrastructure of freshwater- and seawater-adapted rainbow trout, Salmo gairdneri, has been examined by scanning and transmission electron microscopy. Adaptation of trout to seawater resulted in epithelial podocyte flattening, primary process broadening and apparent loss of foot processes in almost all glomeruli, features which were uncommon in freshwater-adapted trout. Similar changes were induced by infusion of freshwater-adapted animals with angiotensin, suggesting that the renin-angiotensin system plays a role in the modification of glomerular epithelial ultrastructure. Adaptation of trout to seawater also reduced glomerular diameter, but infusion of freshwater-adapted animals with angiotensin did not mirror this effect. Infusion of angiotensin into seawater-adapted animals increased the overall thickness of glomerular basement membrane by increasing the lamina rara interna and lamina densa. This did not occur when freshwater-adapted fish were either infused with angiotensin or adapted to seawater. These findings suggest that other humoral systems are involved in the control of glomerular diameter and basement membrane thickness as part of an integrated response to increased environmental salinity.