An analog of myristic acid with selective toxicity for African trypanosomes.

Trypanosoma brucei, the protozoan parasite responsible for African sleeping sickness, evades the host immune response through the process of antigenic variation. The variant antigen, known as the variant surface glycoprotein (VSG), is anchored to the cell surface by a glycosyl phosphatidylinositol (GPI) structure that contains myristate (n-tetradecanoate) as its only fatty acid component. The utilization of heteroatom-containing analogs of myristate was studied both in a cell-free system and in vivo. Results indicated that the specificity of fatty acid incorporation depends on chain length rather than on hydrophobicity. One analog, 10-(propoxy)decanoic acid, was highly toxic to trypanosomes in culture although it is nontoxic to mammalian cells.

How does Cryptococcus get its coat?

During the past few decades, increasing attention has focused on pathogenic fungi both as fascinating research subjects and as the agents of serious illness in diverse patient populations. In particular, opportunistic fungi such as Cryptococcus neoformans command notice as the ranks of their immunocompromised victims grow. C. neoformans is unique among fungal pathogens for its major virulence factor, a complex polysaccharide capsule. In this article, our current understanding of the structure and biosynthesis of the capsule is reviewed, as are the many questions that remain to be answered about how Cryptococcus gets its coat.

Normal ultrastructure, but altered stratum corneum lipid and protein composition in a mouse model for epidermolytic hyperkeratosis.

Recently, we established keratin 10-deficient mice, serving as a model for the hyperkeratotic skin disorder epidermolytic hyperkeratosis. The considerable ichthyosis in these mice suggested alterations in terminal differentiation and in the formation of a functional epidermal barrier. Here, we report on the ultrastructural organization and composition of the stratum corneum lipids and on the expression of two major cornified envelope proteins. Electron microscopy of ruthenium tetroxide postfixed skin samples demonstrated a normal extrusion and morphology of lamellar bodies as well as the formation of bona fide lamellar layers in neonatal keratin 10-deficient mice. When we studied the composition of the major stratum corneum lipids, however, we found significant changes. Most importantly, the analysis of ceramide subpopulations revealed that the total amount of ceramide 2 was elevated in keratin 10-deficient mice, whereas ceramides 1, 3, 4, and 5 were decreased among total stratum corneum lipids. The amount of the ceramide precursors sphingomyelin and glucosylceramide was reduced in the stratum corneum without accompanying changes in the mRNA coding for acid sphingomyelinase. Notably, we found an increased mRNA and protein content for involucrin in neonatal keratin 10-deficient mice, whereas the expression of loricrin was not changed. Our data demonstrate that, although the formation of lipid layers in the stratum corneum appeared to be normal, its lipid composition is significantly altered in keratin 10-deficient mice.

Accumulation of protein-bound epidermal glucosylceramides in beta-glucocerebrosidase deficient type 2 Gaucher mice.

The epidermal permeability barrier for water is essentially maintained by extracellular lipid membranes within the interstices of the stratum corneum. Ceramides, the main components of these membranes, derive in large part from hydrolysis of glucosylceramides mediated by the lysosomal enzyme beta-glucocerebrosidase. As analyzed in this work, the beta-glucocerebrosidase deficiency in type 2 Gaucher mice (RecNci I) resulted in an accumulation of all epidermal glucosylceramide species accompanied with a decrease of the related ceramides. However, the levels of one ceramide subtype, which possesses an alpha-hydroxypalmitic acid, was not altered in RecNci I mice suggesting that the beta-glucocerebrosidase pathway is not required for targeting of this lipid to interstices of the stratum corneum. Most importantly, omega-hydroxylated glucosylceramides which are protein-bound to the epidermal cornified cell envelope of the transgenic mice accumulated up to 35-fold whereas levels of related protein-bound ceramides and fatty acids were decreased to 10% of normal control. These data support the hypothesis that in wild-type epidermis omega-hydroxylated glucosylceramides are first transferred enzymatically from their linoleic esters to proteins of the epidermal cornified cell envelope and then catabolized to protein-bound ceramides and fatty acids, thus contributing at least in part to the formation of the lipid-bound envelope.

A glycolipid from Trypanosoma brucei related to the variant surface glycoprotein membrane anchor.

The variant surface glycoprotein (VSG) of Trypanosoma brucei is covalently linked to a phosphatidylinositol-containing glycolipid which serves as a membrane anchor. We previously identified a molecule, glycolipid A, which appears to be a biosynthetic precursor to the anchor [9]. In this paper we describe a related molecule, glycolipid C, which is similar to glycolipid A but which is more hydrophobic. Chromatographic analyses indicate that the polar head groups in glycolipids A and C are similar or identical. Both glycolipids contain phosphatidylinositol, but the inositol in glycolipid C is modified by a hydrophobic moiety. Since treatment of glycolipid C with mild alkali results in partial conversion to a molecule chromatographically identical to glycolipid A, it is likely that glycolipid C has an alkali-sensitive hydrophobic group, such as a fatty acid, linked to its inositol moiety.

[Movement and its significance: natural healing physiotherapy and modern pharmacological therapy of osteoporosis in the semantic differential. A quantitative study of a self-help group and two comparison groups]. / Bewegung und Bedeutung: Naturheilkundliche Physiotherapie und moderne Pharmakotherapie der Osteoporose im semantischen Differential. Quantitative Untersuchung einer Selbsthilfegruppe und zweier Vergleichsgruppen.

BACKGROUND: Physiotherapy is a frequently applied concomitant therapy for patients with osteoporosis. Compared to modern pharmacological therapy physiotherapy appears to receive sustained high regard, which should be further examined in view of the attribution pattern of the patients. OBJECTIVE: Elements of physiotherapy and Kneipp therapy were quantitatively examined in terms of their semantic content in a three-dimensional space of meaning. This was done in comparison with elements of modern pharmacological therapy. The questions regarding possible patterns of the attributions and a possible hierarchy of the therapy forms were analyzed by a survey of a self-help group for osteoporosis patients and two control groups. MATERIAL AND METHODS: According to the methods of semantic differentials, a self-help group for osteoporosis patients and two control groups (high-school female pupils, breast carcinoma patients) were queried about the individual elements of physiotherapy and modern pharmacological therapy in a polar profile of a questionnaire. The results were arranged onto a numerical matrix and by means of factor analysis, a location in a three-dimensional space of meaning was calculated for each element questioned. For purpose of illustration, the results were transferred to a succession of diagrams so that the assessments for the three axes of meaning became more distinct. The results are discussed on the background of a current neurolinguistic theory of meaning: Sensomotoric experience generates meaning in form of 'primary metaphors'; if reactivated e.g. by physiotherapy, these metaphors can give fundaments for an emergent and salutogenic system of meaning, which helps to reconstruct the patient's 'subjective anatomy' and helps to create new values of living one's life. HYPOTHESES: If sensomotoric experience has a central function in generating meaning, the axis of 'motion' and therapies stressing on sensomotoric experience (e.g. exercise group) will show a corresponding profile of evaluation throughout the three groups. RESULTS: For the axis 'motion' the interventions examined in all three groups show a harmonious profile. The most stable position for all three axes is reflected by 'exercise group', followed by 'whole-body pack'. This stability concerning the axis 'motion' as well as 'exercise group' is discussed in terms of a neurolinguistic theory of meaning, giving sensomotoric experiences the central function for generating meaning. CONCLUSIONS: The results allow conclusions concerning the concrete 'meaning-oriented' combination of physiotherapy with modern pharmacotherapy. Moreover, sensomotoric experiences in physiotherapy are possible reasons for an emergent system of meaning reconstructing the patient's 'subjective anatomy' from basic 'primary metaphors' of bodily experiences up to a whole salutogenetic system of meaning.

[Metaphorical aspects of mistletoe therapy in patients' experiences--a qualitative study]. / Metaphorische Aspekte der Misteltherapie im Patientenerleben--eine qualitative Studie.

OBJECTIVE: Mistletoe therapy is an item of research because of its immunological features. Nevertheless, mistletoe should be also an item of research because of its semiotics. Long before R. Steiner proposed mistletoe as an anticancer drug, this plant seemed to have its meaning not by pharmacodynamics but by pharmacosemiotics and magic. Thus, metaphorical aspects of mistletoe therapy should be described by processing the transcript and paintings from a therapeutic group session of cancer patients. Especially the relation between individually and historically coded metaphors should be looked at. MATERIAL AND METHODS: Sample of this qualitative study is the transcript of a therapeutic session of 12 female malignoma patients getting mistletoe infusions (Isorel(r)) since 1.5 years in a general practitioners' practice. Sequential coding of the transcript, inventory of themes, and structural hypothesis are the first steps. The structural hypothesis is triangulated by a textual corpus containing anthroposophic and ethnographic material; then a grounded theory is made. RESULTS: The material is divided. On the one hand, there is a huge amount of historically coded, stereotypic metaphors (sun, cancer, ritual). On the other hand, 'ritual' seems not only a stereotypic metaphor but also a container of individually coded metaphors concerning body experiences (proprioceptive etc.). Metaphors from anthroposophy are rare - the metaphors seem to stem from a deeper level of ethnographic sources. The whole session has a polyphone narrative structure. Categories of semiotics such as icon, index and symbol are only by the context of interaction a suitable description for mistletoe's metaphoric function. CONCLUSIONS: Problems of bias (denominator problem, valid but not reliable) are discussed, and a proposal is made for further forms of generalization of the results (semantic differentials). Moreover, it has to be asked if different preparations of mistletoe (e.g. lectine standard, draft from planta tota) make different halos of metaphors.

[Literature review of the latest research results concerning the positive effect of exercise therapy in chronic heart insufficiency]. / Literaturübersicht zu aktuellen Forschungsergebnissen zum positiven Effekt von Bewegungstherapie bei chronischer Herzinsuffizienz.

Scientific investigations indicate similarities in the pathophysiology of heart insufficiency and that of physical inactivity: similar changes in peripheral hemodynamics (increased peripheral vascular resistance, worsening of oxygen utilization during exercise), in autonomic control (activation of neurohumoral compensatory mechanisms, e.g. the renin-angiotensin system, overactivation of the sympathicus, reduction of vagal tonus, reduced pressosensitivity), in functional activity (reduced exercise tolerance and reduced maximum oxygen uptake), in skeletal muscle (decrease in mass, changes in structure), and in the psychological state (reduction in activity and feeling of well-being). In several, although small-scale studies it could be shown that patients with advanced left ventricular failure were able to take part in training programs without experiencing any ill effects, and that there was a positive shift in the usual typical effects of physical training, such as increase of heart rate, change in respiratory frequency, and maximum oxygen uptake. It could be shown that exercise therapy can result in a shift in the balance between the sympathetic and the parasympathetic tonus in the low- and high-frequency maxima of the R-R interval variability. The pre-training general predominance of the sympathetic tonus over the vagal tonus was changed dramatically by the training, leading to a predominance of the vagal tonus. Recent controlled studies with a randomized and controlled cross-over design and the application of a training program which was carried out regularly and independently have confirmed the positive effect of aerobic fitness training in cases of heart disease. At the end of the exercise phase, the patients experienced a significant improvement of the symptoms of left ventricular failure and of their capacity for exercise; furthermore, the training altered parts of the neurohumoral activation, which count as the main factors in the progression and death rate of patients with chronic cardiac disease.

[Cerebral hemodynamics in carbon dioxide applications]. / Zerebrale Hämodynamik bei Kohlendioxidapplikationen.

INTRODUCTION: We compare the effect of carbon dioxide (CO(2)) dry and wet applications on cerebral hemodynamics. METHODS: On 22 volunteers measurements were taken during CO(2) application. 10 probands were examined in CO(2) wet application (1,100-1,300 mg/l) and 12 probands in CO(2) dry application (500 g in a 800 l bathtub). The cerebral blood flow velocity (CBFV) in the middle cerebri artery (MCA) was measured as a parameter of cerebral hemodynamics by means of transcranial doppler sonography. Furthermore were recorded CO(2) expiratory concentration (CO(2)et), blood pressure, and sublingual temperature. RESULTS: At CO(2) wet application the CBFV increased during therapy phase by 15% (p = 0.001), parallel to the rise of the CO(2)et by 18% (p = 0.01). During CO(2) dry application CBFV decreased by 11% (p = 0.007), body temperature increased significantly by 0.2 degrees C. CONCLUSION: CO(2) applications have influence on cerebral hemodynamics. Assuming constant diameters of the great brain vessels, CO(2) wet application shows a raising and CO(2) dry application a reducing influence on cerebral blood flow. This influence will attain therapeutic relevance.

[Effects of active and passive movement stimuli on cerebral hemodynamics and the cerebral metabolism]. / Wirkungen kinetischer Stimuli auf die zerebrale Hämodynamik und den zerebralen Stoffwechsel am Beispiel von aktiven und passiv ausgeführten Bewegungen.

INTRODUCTION: In contrast to the well-examined cardiovascular changes during movement stimuli, up to now changes of cerebral hemodynamics and cerebral metabolism have rarely been studied. We investigated the question if active and passive movement stimuli cause changes in the cerebral hemodynamics and the cerebral metabolism. METHOD: Active and passive repetitive movement stimuli on 14 volunteers (8 females, 6 males, age 35 +/- 8 years) were examined. As a parameter of cerebral hemodynamics the mean and the peak blood flow velocity (mCBFV(MCA), pCBFV(MCA)) in the middle cerebral artery (MCA) were recorded by transcranial Doppler sonography. At the same time the noninvasive blood pressure (Penaz method) and the CO(2) expiration concentration were investigated on 8 volunteers of the collective. As cerebral metabolic parameters we examined in 4 volunteers additionally the cerebral respiratory chain enzyme cytochrome aa3 (ccytaa3) and the cerebral oxygen saturation (cHbO(2)) by the transcranial near infrared spectroscopy. With each volunteer 4 measurement series were carried out with a special active and passive exercise program for the right upper as well as the right lower extremity. Each measurement series was formed according to the evoked flow test (R. Aaslid): Exercises were carried out for 20 s, followed by a break of 20 s; this was repeated 10 times for each series. RESULTS: During active exercises of the right lower extremity we found an increase of 13.6% (p < 0.001) of pCBFV(MCA) and an increase of 3.8% (p = 0.003) of mCBFV(MCA). During passive exercises of the lower extremity the increases ran up to 12.3% (p < 0.001) for pCBFV(MCA) and 3.4% (p = 0.004) for mCBFV(MCA). The increases of pCBFV(MCA) came up to 12.5% (p < 0.001) at active exercises of the right upper extremity, those of mCBFV(MCA) to 3.5% (p = 0.15). During passive exercises of the upper extremity the pCBFV(MCA) increased by 12.2% (p < 0.001) and the mCBFV(MCA) by 4.6% (p = 0.007). Significant increases of ccytaa3 were measured during active exercises of the upper extremity (1.6%; p = 0.04) and of the lower extremity (2.7%, p = 0.007). We also found an increase of ccytaa3 during passive exercises of the upper extremity (1.5%, p = 0.04). Significant changes of cHbO(2) were measured with 2.5% (p < 0.05) at active exercises of the lower extremity. CONCLUSION: These studies show that active as well as passive clinical exercises cause an increase of cerebral blood flow velocity. We attribute the increase of cerebral hemodynamics and cerebral metabolism to cerebral activation and autoregulative mechanisms.

[Changes of cognitive brain functions in the elderly by Kneipp therapy]. / Veränderung kognitiver Hirnleistungen im Alter Durch Kneipp-Anwendungen.

INTRODUCTION: Pharmacological and nonpharmacological treatment of brain syndrome is multifarious. Until now, plain external applications of physical stimuli, as used daily in geriatric care, were not explored regarding their influence on cognitive brain function. The aim of this randomized cross-over study was to examine the influence of dermatoreceptive stimuli on cognitive brain function of healty geriatric volunteers. METHODS: 24 healthy volunteers (23 women, 1 man) were randomized into 2 groups (cross-over design). Group A (mean age +/- SD: 68.8 +/- 6.2 years) was treated according to the following regime: at first a 10-12 degrees C cold stimulus for 10 s (a so-called Kneipp face shower) and afterwards a cold wet pack of 10-12 degrees C at the neck for 1 min. Group B (age 69.8 +/- 5.3 years) was subjected to an identical procedure but with warm thermoindifferent temperatures of 34-36 degrees C. After 1 week the two groups were interchanged. The parameters of interest were the critical flicker frequency (CFF) and the latencies of the event-related P300 potentials of the visually evoked potentials (VEP), which can be considered the electroencephalographic substrate of the cognitive functional ability. The CFFs and the P300 latencies and amplitudes were measured directly before and 10 min after the application of the above-mentioned stimuli. Furthermore, the CFFs were recorded a second and third time 30 and 60 min later. RESULTS: Following application of cold-water stimuli, the CFF increased from (mean +/- SE) 32.55 +/- 0.44 s(-1) to 33.06 +/- 0.44 s(-1) (p = 0.003) 10 min after the stimulus. 30 min later the CFF was still elevated at 32.95 +/- 0.47 s(-1) (p = 0.043). The P300 latencies decreased by 4.8% (p < 0.001) after cold-water application from 266.5 +/- 5.28 to 253.7 +/- 4.22 ms. After warm stimuli they increased from 258.69 +/- 3.71 to 266.17 +/- 5.03 ms (p = 0.01). The P300 amplitudes were elevated by 5% only with the cold stimuli (p = 0.004). CONCLUSION: Cold water applied locally to face and neck region is able to provoke significant improvements of cognitive abilities.

[Guideline development for general medicine: the problem of dichotomized algorithm development]. / Allgemeinmedizinische Leitlinien-Entwicklung: Problematik der dichotomisierenden Algorithmenbildung.

Development of clinical guidelines in Germany is based on two divergent principles. One is the clinical position of individuality and clinical experience. The other is the strong adherence to the principles of evidence-based medicine and the scientific method, as demonstrated by the clear, algorithmic methodology of critical pathway development. We discuss the pros and cons of both concepts and try to find some sort of practical middle ground between the two extremes.

[Diabetes mellitus and physical medicine]. / Diabetes mellitus und Physikalische Medizin.

In the treatment of diabetes, the importance of kinesitherapy increases steadily. In fact, a prospective study (1996) which was done on 897 Finnish middle-aged males over a period of 4 years, showed that the risk of diabetes can be reduced to 50% by moderate physical exercise of 40 minutes per week compared with less active persons of the same age. The amount of kinesitherapeutic measures depends on the physiological resilience of the diabetes patient and on the extent of existing diabetes-induced lesions. An endurance kinesitherapy activates the carbohydrate metabolism and affects the glucosensitive receptors situated in peripheral and central organs. A muscle activity of ten minutes can already multiply by fifteen the increase of glucose absorption from the blood. Another positive result by physical effort is to be seen in the preventine and therapeutic effect of an increased insuline action. The individually adapted kinesitherapeutic endurance stimulation should last from five to ten minutes each day and reach at least 50% of maximum capacity but not more than 70%. This maximum capacity can among other things be gauged from the heart rate as well as from the breathing rate.

[Cerebral hemodynamics during implantation of cardioverter-defibrillator systems]. / Zerebrale Hämodynamik während der Implantation von Kardioverter-Defibrillator-Systemen.

OBJECTIVE: During ICD-implantation it is necessary to prove the function and to determine the optimal threshold by means of induced ventricular fibrillation (VF). Provoked cardiac arrests cause a circulator stop of the cerebral perfusion. Our aim was to examine the changes of cerebral blood flow velocity (CBFV(MCA)) after induced VF depending on the duration of fibrillation and prior values of CBFV(MCA). PATIENTS AND METHODS: Sixty induced episodes of VF in 9 patients (mean age +/- SD 53.5 +/- 8 years) were examined during ICD-implantation. Beside the standardized anaesthesiological monitoring, transcranial Doppler sonography was used to record the cerebral blood flow velocity in the middle cerebri artery CBFV(MCA). The duration of the fibrillation-period and the range and duration of the CBFV increase during the post defibrillation-period were correlated. Additionally, we examined whether systematic differences existed between the episodes of each patient (time-trend) by means of 5 following episodes of a patient. RESULTS: During all episodes of VF and hyperperfusion was present, that means a time interval showing increased values of CBFV(MCA), compared to the values present before VF. The duration of hyperperfusion depended significantly on the fibrillation time (r = 0.57; p < 0.001). The equation of regression is: hyperperfusion time = 11.1 + 1.22 x fibrillation time. The amount of hyperperfusion, that means the maximal CBFV after defibrillation, increase significantly with CBFV(MCA) before VF (correlation = 0.88; p < 0.001). The equations of regression is hyperperfusion height = 6.11 + 1.22 x CBFV(MCA) before VF. The duration of hyperperfusion is not influenced by the maximal CBFV(MCA) after defibrillation (r = 0.08; p = 0.52). In the examined patients no significant differences in the hyperperfusion time maximal CBFV(MCA) after defibrillation between the episodes were found. CONCLUSION: After induced VF you always have to expect a reactive cerebral hyperperfusion. The amount of increase of CBFV after defibrillation depends on the prior values of CBFV before fibrillation and shows a nearly proportional relation to these. The duration of hyperperfusion shows a linear dependency on VF-times. This may show that we had VF-times, in which the cerebral autoregulation and other cerebral physiological reactions compensate the drop of the CBFV(MCA) during VF in the postfibrillation time. In further studies will be examined if there are similar changes in the cerebral metabolism as in CBFV(MCA).

[General medicine malpractice cases]. / Allgemeinmedizinische Behandlungsdefizite.

During the last five years legal proceedings about alleged treatment mistakes in Germany more than doubled. Using a standardized questionnaire about legal proceedings in general medicine, involving liability, an anonymous survey with the members of the workgroup law medicine of the Deutsche Anwaltsverein (DAV) was carried out. The questions included among other things the number and reasons of legal proceedings involving liability. Of 322 questioned lawyers who focused on medicine law 122 (38%) answered. 69.9% of the lawyers think poor information is the main reason for legal proceedings involving liability in general medicine. Three disease groups were mentioned more frequently: diseases of the digestive system (22 mentions), diseases of the circulatory system (21) and diseases of the muscles, skeleton and connective tissue (15). 40 mentions of injections as treatment mistakes build the most frequent therapeutic reason for legal proceedings involving liability. Most of the lawyers think that guidelines do not reduce legal proceedings involving liability. The most common reasons for legal proceedings involving liability such as poor information and insufficient medical examination may point out that the budgetary standards for consultation cannot guarantee enough time for firstly giving a sufficient individual information to the patient and secondly for developing a decision satisfactory for both sides.

A unique alpha-1,3 mannosyltransferase of the pathogenic fungus Cryptococcus neoformans.

The major virulence factor of the pathogenic fungus Cryptococcus neoformans is an extensive polysaccharide capsule which surrounds the cell. Almost 90% of the capsule is composed of a partially acetylated linear alpha-1,3-linked mannan substituted with D-xylose and D-glucuronic acid. A novel mannosyltransferase with specificity appropriate for a role in the synthesis of this glucuronoxylomannan is active in cryptococcal membranes. This membrane-associated activity transfers mannose in vitro from GDP-mannose to an alpha-1, 3-dimannoside acceptor, forming a second alpha-1,3 linkage. Product formation by the transferase is dependent on protein, time, temperature, divalent cations, and each substrate. It is not affected by amphomycin or tunicamycin but is inhibited by GDP and mannose-1-phosphate. The described activity is not detectable in the model yeast Saccharomyces cerevisiae, consistent with the absence of a similar polysaccharide structure in that organism. A second mannosyltransferase from C. neoformans membranes adds mannose in alpha-1,2 linkage to the same dimannoside acceptor. The two activities differ in pH optimum and cation preference. While the alpha-1,2 transferase does not have specificity appropriate for a role in glucuronoxylomannan synthesis, it may participate in production of mannoprotein components of the capsule. This study suggests two new targets for antifungal drug discovery.

Spatial and temporal sequence of capsule construction in Cryptococcus neoformans.

The pathogenic yeast Cryptococcus neoformans is distinguished by an extensive polysaccharide capsule, which impedes host defences and is absolutely required for fungal virulence. Despite the biological importance of the capsule, nothing is known about how it is assembled. Substantial capsule growth occurs in two distinct situations relevant to cryptococcal pathogenesis: formation of new buds and induction of capsule on mature cells. We developed pulse-chase protocols to examine these events in a dynamic way using a variety of microscopy techniques. We show that the capsule overlying buds is newly synthesized and differs physically from the corresponding parental material. New capsule formed by mature cells upon induction of synthesis is added at the inner aspect of the existing structure, displacing pre-existing material outwards. Surprisingly, new polysaccharide material is also deposited throughout the capsule, yielding a progressively denser structure. These results yield the first model of capsule synthesis and open new lines of investigation into the underlying mechanisms.

Glycosyl-phosphatidylinositol anchor attachment in a yeast in vitro system.

The yeast mating pheromone precursor prepro-alpha factor was fused to C-terminal signals for glycosyl-phosphatidylinositol (GPI) anchor attachment, based on the sequence of the Saccharomyces cerevisiae protein Gas1p. Maturation of fusion proteins expressed in vivo required the presence of both a functional GPI attachment site and the synthesis of GPI precursors. Constructs were translated in vitro for use in cell-free studies of glycolipid attachment. The radiolabelled polypeptides were post-translationally translocated into yeast microsomes, where at least one third of the molecules received a GPI anchor. This approach offers distinct advantages over anchor attachment reactions that require co-translational translocation of secretory peptide substrates.

Homeopathic remedies as metaphors in family therapy. A narrative-based approach to homeopathy.

OBJECTIVE: To examine a metaphorical, narrative model to explain the outcome of an homeopathic, encounter involving the patient, practitioner and the homeopathic medicine. MATERIAL AND METHODS: The transcript of a videotaped doctor-patient interaction from a European doctor-patient communication study (EUROCOM) was analysed using qualitative methods. RESULTS: Analysis demonstrates a narrative relationship between the protagonists in the therapeutic interaction, with the homeopathic medicine performing a metaphorical role. DISCUSSION: The results justify further investigation of the narrative and metaphorical properties of the therapeutic encounter in homeopathy.