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PubMed1994

Protein targeting and secretion in filamentous fungi. A progress report.

Although the application of filamentous fungi, such as Aspergillus niger for the production of extracellular proteins is well established for several decades, hardly any information is available about the molecular mechanisms of the process of protein secretion in these organisms. Two lines of research initiated towards a systematic analysis of the mechanism of protein targeting and secretion are presented in this paper. 1--To study routing and targeting of proteins in filamentous fungi the availability of a versatile reporter/carrier protein will be of considerable importance. Experiments towards the identification of such a protein are presented. 2--In analogy to the situation in Saccharomyces cerevisiae, the availability of defined (conditional) mutations in the secretion pathway will provide very important information about the organisation of the pathway. Therefore, based on results obtained in S. cerevisiae, the cloning of several fungal 'secretion' genes was started. The results of the cloning and characterisation of one of these genes is presented.

Amino Acid Sequence↗
PubMed1989

Trypanosoma cruzi: the effect of variations in experimental conditions on the levels of macrophage infection in vitro.

A comparative and systematic analysis of the different experimental conditions used in Trypanosoma cruzi-macrophage interaction assays is presented. A pH range from 6.2 to 6.9 is favorable for parasite invasion, as is the use of Dulbecco's Modified Eagle Medium (DMEM). The washing procedures used in purification protocols also enhance the parasites' ability to penetrate macrophages. However, the main factor affecting the quantitative parameter of this in vitro infection, regardless of the parasite: cell ratio, is the number of macrophages provided to the parasites. These results, reviewed and compared with the corresponding literature, strongly suggest that macrophage surface areas and/or receptors are the limiting factors for optimal quantitative determination of the interaction of T. cruzi in vitro.

Animals↗
PubMed1978

Effects of concomitant aspirin administration on the pharmacokinetics of indomethacin in man.

Ten healthy volunteers each received single and multiple 50-mg doses of indomethacin orally and a single 25-mg dose of [14C]indomethacin intravenously in the absence of and concomitantly with 1200 mg of aspirin as a single dose and in a chronic t.i.d. regimen. Systematic analysis of the data resulted in the isolation and quantification of aspirin's effects on the absorption, distribution, biotransformation, excretion, enterohepatic circulation, and accumulation of indomethacin. The effects of chronic aspirin were to suppress the renal clearance, to increase the biliary clearance, to decrease the efficiency of gastrointestinal absorption, and to enhance the enterohepatic circulation of indomethacin. On concomitant administration of 1200 mg of aspirin t.i.d., mean plasma levels of indomethacin were depressed by 20% after a single oral dose, by a smaller margin after multiple oral doses, and not at all after a single intravenous dose of indomethacin. The mean plasma concentration of orally administered indomethacin was decreased by 8% when given concurrently with a single 1200 mg dose of aspirin. Concomitant chronic therapeutic dosages of indomethacin had no effect on salicylate accumulation from repetitive doses of aspirin.

Adult↗
PubMed1991

An algorithm for converting a virtual-bond chain into a complete polypeptide backbone chain.

A systematic analysis is presented of the algorithm for converting a virtual-bond chain, defined by the coordinates of the alpha-carbons of a given protein, into a complete polypeptide backbone. An alternative algorithm, based upon the same set of geometric parameters used in the Purisima-Scheraga algorithm but with a different "linkage map" of the algorithmic procedures, is proposed. The global virtual-bond chain geometric constraints are more easily separable from the loal peptide geometric and energetic constraints derived from, for example, the Ramachandran criterion, within the framework of this approach.

Algorithms↗
PubMed1983

Sex and the media: three decades of best-selling books and major motion pictures.

The expression of sexuality in best-selling novels and major motion pictures was examined. There are two reasons that such stimuli merit systematic analysis. First and foremost is the finding that best-selling novels and major motion pictures exist as a primary source of sexual information. Of equal importance, however, is the need to examine such stimuli for myths and fallacies. The novels and films analyzed in the present study were selected from the last years of three consecutive decades: 1959, 1969, and 1979. Inclusion in this study was based on ranking in either a best-seller list (i.e., books) or a rental-receipts list (i.e., movies). The use of such criteria serves the dual purpose of allowing for the examination of stimuli that are accessible to large masses of people and at the same time allowing for the examination of sexually relevant stimuli. The results are discussed in terms of historical changes (over the three decades) and manifest themes (i.e., general characteristics or consistent themes). An additional section was included to address the broader implications of the present findings and to suggest alternatives.

Communication↗
PubMed1990

The reproducibility of cytomorphometrical grading of bladder tumours.

The reproducibility of cytomorphometrical nuclear area measurements on transitional cell carcinoma is studied. The inter-individual consistency is low (r = 0.55, P = 0.0005) when nuclei for measurement are chosen at random. When we use a systematic analysis based on cell situation and cytological features of malignancy to select the 50 nuclei for measurement per slide, the consistency between two technicians appears to be significantly higher (r = 0.90, P = 0.015). Not only interindividual consistency increases using the selection, but the correlation with histological tumour grade also improves significantly for both technicians. The results show that cytomorphometry is a method of grading bladder carcinoma when an accurate selection of nuclei to measure is used. Cytomorphometrical studies should contain a clear description of the way the nuclei for measurement are chosen.

Humans↗
PubMed1995

Penetrating gunshots to the head and lack of immediate incapacitation. II. Review of case reports.

Because of the enhanced intracranial tissue disruption (see companion paper) and the functional significance of the central nervous system, penetrating gunshot wounds of the head commonly result in immediate incapacitation. However, in the last century numerous publications reported sustained capability to act following penetrating gunshot wounds of the head. These are reviewed. A large number of case reports had to be excluded from re-examination because of doubtful capability to act or lack of morphological documentation. There remained 53 case reports from 42 sources for systematic analysis. Favourable conditions for sustained capability to act are present in cases where the additional wounding resulting from the special wound ballistic qualities of the head (see companion paper) are minimized. Thus, more than 70% of the guns used fired slow and lightweight bullets: 6.35 mm Browning, .22 rimfire or extremely ineffective projectiles (ancient, inappropriate or selfmade). A centre-fire rifle or a shotgun from close range were never employed in cases involving intracerebral tracts. A coincidence of several lucky circumstances made sustained capability to act possible in two cases of military centrefire rifle bullets passing longitudinally between the frontal lobes without direct contact with brain tissue. Only two large handguns resulting in intracerebral wounding were used: one firing a .38 special bullet, which solely wounded the base of the right temporal lobe and one firing a .45 lead bullet, which seriously injured the left frontal lobe but whose trajectory was limited to the anterior fossa of the skull. Of the trajectories, 28% were outside the neurocranium. At least 70% of the craniocerebral tracts passed above the anterior fossa of the skull, wounding the frontal parts of the brain. Apart from a neurophysiological approach, this preference can be explained by the fact that the base of the anterior cranial fossa and the sella turcica area serve as a bony barrier protecting the parts of the brain located in its "shadow"' relative to the trajectory against cavitational tissue displacement and associated overpressures. This is particularly true of the brain stem. Intracerebral trajectories not located above the anterior fossa were caused by slow and lightweight bullets preferring one temporal lobe. Additionally, one parietal and one occipital lobe were each injured once by a very ineffective projectile and by a 7.65-mm bullet reduced in velocity. Not a single case of injury to the brain stem, the diencephalon, the cerebellum or major paths of motor conduction and only one grazing shot of the anterior parts of the nucleus caudatus (basal ganglia) were described. Morphological signs of high intracranial pressure peaks (cortical contusion zones, indirect skull fractures, perivascular haemorrhages) and secondary missiles were poorly documented. It is suggested that these findings are at least very rare and not obvious in cases of sustained capability to act.

Brain Injuries↗
PubMed1996

Dose-time-dependent histological changes following irradiation of the small intestine of rats.

The distal ileum of 48 male Sprague-Dawley rats was exteriorized and irradiated either with low dosis (9-12 Gy, N = 18 rats), moderate dosis (15-18 Gy, N = 18 rats) or high dosis (21-24 Gy, N = 12 rats). A shielded segment of the ileum in the same animals as well as the sham-irradiated exteriorized ileum of 10 rats served as controls. The animals were allowed to survive for 3, 10, or 30 days. A total of 16 histologic parameters were found to be relevant for this study. Cell necrosis, loss of goblet cells, crypt abscesses, structural changes of the crypts, loss of Paneth cells, decreased number of mitoses, appearance of clear basal cells, loss of margination of lymphocytes, increased colagen in the submucosa, muscularis propria and subserosa, ectopic mucosal glands, as well as mucosal ulcerations, were found to be dose-time-dependent irradiation changes. Racket-shaped superficial epithelial cells, capillary congestion, and an increased number of round cells in the lamina propria mucosa were found to be time-dependent histological parameters. Preparations from the shielded ileum or from the sham-irradiated control animals showed normal histology. This study appears to be the first in which the systematic analysis of several postirradiation histologic changes have been found to be dose- and/or time-dependent. The knowledge that some radiation changes are dose-time-depeendent, whereas others are exclusively time-dependent, may open new vistas on the study of postradiation enteritis in the rat.

Animals↗
PubMed1995

On chronic illness and quality of life: a conceptual framework.

In this paper I focus on the topic of chronic illness in the context of quality of life. I offer a conceptual explanation of these notions and then try to systematise the various species of suffering connected with chronic illness. Suffering in illness rarely attracts systematic analysis. Part of the reason for this is that the topic is in a way an aspect of common sense. It has an air of self-evidence and seems not to require analysis. However, it is my contention that the nature of human suffering is not at all self-evident. In many ways we know very little about the content and extent of suffering. And, although it may not be sensible to borrow traditional scientific techniques for the study of suffering, we need as much intellectual penetration and rigorous analysis in order to clarify the nature of suffering as for any other scientific investigation. Moreover, there are good reasons for saying that we ought to direct much more of our attention to this humanistic aspect of medicine. We ought to remember that the existence of suffering is one of the main motives, if indeed not the most important motive, for undertaking the medical enterprise.

Attitude to Health↗
PubMedDate not supplied

Serum IL-8 as a possible marker for determining the status of Helicobacter pylori infection in patients with untreated and treated peptic ulcer.

Failure to eradicate Helicobacter pylori can lead to peptic ulcer recurrence and gastric malignancy. Therefore, the objective of this study was to develop a noninvasive method for determining whether H. pylori infection was eradicated with antibiotic-based triple therapy. A total of 17 patients with duodenal ulcer (DU) and 17 with gastric ulcer (GU) were evaluated both before and after treatment. Outcomes included serum levels of interleukin-8 (IL-8), pepsinogen I, and gastrin, and the Wilcoxon signed rank test was used to test significance. Changes in these parameters were also correlated with disease status. In those patients where both GU and DU healing occurred as a result of treatment, most showed an increase in serum IL-8 and a decrease in serum pepsinogen. Serum gastrin levels were not significantly changed in either group. Posttreatment increases in serum IL-8 were seen in 15 of 17 (88%) recovered DU patients and 14 of 17 (82%) recovered GU patients (P<.05 for each). Posttreatment decreases in pepsinogen I were found in 15 of 17 DU and 15 of 17 GU patients (P<.05 for each). These preliminary findings suggest that an increase in serum IL-8 and possibly a decrease in pepsinogen I may be useful in identifying the successful eradication of H. pylori infection in patients with peptic ulcer treated with antibiotics. A more systematic analysis of these putative diagnostic markers is now warranted.

Adolescent↗
PubMed2004

Hydrocarbon charging histories of the Ordovician reservoir in the Tahe oil field, Tarim Basin, China.

The Ordovician reservoir of the Tahe oil field went through many tectonic reconstructions, and was characterized by multiple hydrocarbon chargings. The aim of this study was to unravel the complex charging histories. Systematic analysis of fluid inclusions was employed to complete the investigation. Fluorescence observation of oil inclusions under UV light, and microthermometry of both oil and aqueous inclusions in 105 core samples taken from the Ordovician reservoir indicated that the Ordovician reservoir underwent four oil chargings and a gas charging. The hydrocarbon chargings occurred at the late Hercynian, the Indo-Sinian and Yanshan, the early Himalaya, the middle Himalaya, and the late Himalaya, respectively. The critical hydrocarbon charging time was at the late Hercynian.

China↗
PubMed2002

Phytoremediation of polyaromatic hydrocarbons, anilines and phenols.

Phytoremediation technologies based on the combined action of plants and the microbial communities that they support within the rhizosphere hold promise in the remediation of land and waterways contaminated with hydrocarbons but they have not yet been adopted in large-scale remediation strategies. In this review plant and microbial degradative capacities, viewed as a continuum, have been dissected in order to identify where bottle-necks and limitations exist. Phenols, anilines and polyaromatic hydrocarbons (PAHs) were selected as the target classes of molecule for consideration, in part because of their common patterns of distribution, but also because of the urgent need to develop techniques to overcome their toxicity to human health. Depending on the chemical and physical properties of the pollutant, the emerging picture suggests that plants will draw pollutants including PAHs into the plant rhizosphere to varying extents via the transpiration stream. Mycorrhizosphere-bacteria and -fungi may play a crucial role in establishing plants in degraded ecosystems. Within the rhizosphere, microbial degradative activities prevail in order to extract energy and carbon skeletons from the pollutants for microbial cell growth. There has been little systematic analysis of the changing dynamics of pollutant degradation within the rhizosphere; however, the importance of plants in supplying oxygen and nutrients to the rhizosphere via fine roots, and of the beneficial effect of microorganisms on plant root growth is stressed. In addition to their role in supporting rhizospheric degradative activities, plants may possess a limited capacity to transport some of the more mobile pollutants into roots and shoots via fine roots. In those situations where uptake does occur (i.e. only limited microbial activity in the rhizosphere) there is good evidence that the pollutant may be metabolised. However, plant uptake is frequently associated with the inhibition of plant growth and an increasing tendency to oxidant stress. Pollutant tolerance seems to correlate with the ability to deposit large quantities of pollutant metabolites in the 'bound' residue fraction of plant cell walls compared to the vacuole. In this regard, particular attention is paid to the activities of peroxidases, laccases, cytochromes P450, glucosyltransferases and ABC transporters. However, despite the seemingly large diversity of these proteins, direct proof of their participation in the metabolism of industrial aromatic pollutants is surprisingly scarce and little is known about their control in the overall metabolic scheme. Little is known about the bioavailability of bound metabolites; however, there may be a need to prevent their movement into wildlife food chains. In this regard, the application to harvested plants of composting techniques based on the degradative capacity of white-rot fungi merits attention.

Aniline Compounds↗
PubMed1991

Distribution of structural and trace elements in human temporal bone.

This study was undertaken to evaluate a systematic analysis of mineral and trace elements of individual functionally determined parts of adult temporal bone. Marked differences were observed in basic structural elements (Ca, P, Mg, and Zn) among different bone regions. The more so, molar Ca/P ratio was significantly different in various regions, being highest in the hammer and vestibular regions. Taxonomic analysis revealed specific differences in the mineral ratio between the two petrous bone regions believed to develop from various embryonal bases. According to results, the observed differences in mineral trace element composition of particular regions of human temporal bone might be explained by their developmental specificities and functional adaptation.

Adult↗
PubMed1998

Reproducibility of irregular radiation fields for malignant lymphoma.

PURPOSE: Radiation treatment for malignant lymphoma requires large field irradiation with irregular blocks according to the individual anatomy and tumor configuration. For determination of safety margins (PTV) we quantitatively analysed the accuracy of field and block placement with regard to different anatomical regions. PATIENTS AND METHODS: Forty patients with malignant lymphoma were irradiated using the classical supra-/infradiaphragmatic field arrangements. Treatment was performed with 10-MeV photons and irregularly shaped, large opposing fields. We evaluated the accuracy of field and block placements during the treatment courses by comparing the regularly performed verification-with the simulation films. Deviations were determined with respect to the field edges and the central axis, along the x- and z-axis. RESULTS: With regard to the field edges, mean deviations of 2.0 mm and 3.4 mm were found along the x- and z-axis. The corresponding standard deviations were 3.4 mm and 5.5 mm, respectively. With regard to the shielding blocks, mean displacement along the x- and z-axis was 2.2 mm and 3.8 mm. In addition, overall standard deviations of 5.7 mm (x-axis) and 7.1 mm (z-axis) were determined. During the course of time an improved accuracy of block placement was notable. CONCLUSION: Systematic analysis of port films gives information for a better defining safety margins in external radiotherapy. Evaluation of verification films on a regular basis improves set-up accuracy by reducing displacements.

Humans↗
PubMed1997

Sperm nuclear basic proteins (SNBPs) of agnathans and chondrichthyans: variability and evolution of sperm proteins in fish.

We have characterized for the first time SNBPs from the hagfish Eptatratus stouti (Myxini) and the lamprey Lampetra tridentatus (Cephalaspidomorphi) and have found that histones are the major protein components of the sperm of these agnathans. We have also conducted a systematic analysis of SNBPs from different groups of chondrichthyan fishes, including the skate Raja rhina and seven species of sharks. Together with our previous data showing the sporadic nature of SNBP evolution in bony fish (Saperas, N., Ausio, J., Lloris, D. and Chiva, M. [1994] J. Mol. Evol. 39: 282-295), the present study provides a unique insight into the overall evolutionary complexity and variability of the nuclear sperm proteins of fishes. It would appear that despite the discontinuous evolution of these proteins, the macroevolutionary pattern of histone (H type) --> protamine-like (PL type) --> protamine (P type) has been conserved in fish evolution, as it has in the evolution of other Deuterostomes.

Amino Acid Sequence↗
PubMed1999

Amino acid reiterations in yeast are overrepresented in particular classes of proteins and show evidence of a slippage-like mutational process.

Long amino acid repeats are often observed in eukaryotic proteins. In humans, several neurological disorders are caused by proteins containing abnormally long polyglutamines. However, no systematic analysis has attempted to investigate the relationship between reiterations of particular amino acids and protein function, the possible mechanisms involved in the generation of these regions, or the contribution of selection in restricting their genomic distribution, in a large collection of wild-type proteins. We have used baker's yeast open reading frames to study these questions. The most abundant amino acid repeats found in yeast proteins are repeats of glutamine, asparagine, aspartic acid, glutamic acid, and serine. Different amino acid repeats are concentrated in different classes of proteins. Acidic and polar amino acid repeats are significantly associated with transcription factors and protein kinases, while serine repeats are significantly associated with membrane transporter proteins. In most cases the codon structures encoding the repeats at the gene level show a significant bias toward long tracts of one of the possible codons, suggesting that trinucleotide slippage has played an important role in generating these reiterations. However, many, particularly those encoding serine repeats, do not show evidence of slippage. The distributions of codon repeats within proteins and between coding and noncoding regions of the genome, and of amino acids between proteins with different functions, suggest that repeats of these kinds are subject to strong selection.

Base Sequence↗
PubMed2004

[Angiogenesis investigations in tissue engineering. The cylinder model on the chorioallantois membrane].

INTRODUCTION: Tissue engineering (TE) applications include the isolation, culture, and seeding of cells into a suitable matrix or scaffold prior to in vivo transplantation. After transplantation, vascularization of the scaffold is a principal factor limiting cell viability for the first 6-8 days post transplantation. A model has been developed for systematic analysis of this process. METHODS: Fertilized white Leghorn eggs were incubated and opened at day 3 of incubation. Preadipocyte-seeded fibrin constructs were implanted in a specially designed plastic cylinder and placed through the opening onto the surface of the chorioallantoic membrane (CAM) at day 8 of incubation. Vascularization of the constructs by chorioallantoic blood vessels was assessed for up to 8 days post transplantation. RESULTS: The survival rate for embryos receiving constructs was about 90%. Histology confirmed transplant cell viability at day 4 post transplantation, and vascularization of the constructs by avian endothelial cells progressively increased thereafter. CONCLUSION: A new in vivo model to study the effect of angiogenesis in TE constructs including assessments of viability, proliferation, and differentiation of transplanted cells and biomaterial properties is presented. Advantages include easy access to the CAM vascular network, lack of immunocompetence, low cost, and avoidance of animal experiments.

Adipocytes↗
PubMed2006

[Cutaneous lupus erythematosus. Part 1: clinical manifestations and classification].

Cutaneous lupus erythematosus (CLE) is a heterogenous disorder with a wide range of skin manifestations. Therefore, it has been difficult to develop a unifying concept for classifying CLE from the dermatologic perspective in the past. In 2004, the classification system was updated and includes now acute CLE (ACLE), subacute CLE (SCLE), chronic CLE (CCLE), and intermittent CLE (ICLE). Additional rarely described variants are not listed as separate entities but are included in the classical forms. Diagnosis of the different subtypes of CLE is made by considering genetic, clinical, histopathologic, and immunoserologic findings, with a systematic analysis of individual criteria. In the past years, the etiology and pathogenesis of CLE has been subject of intensive research and it has been shown by several groups that exogenous factors, such as ultraviolet light and drugs, can induce CLE. The first part of this review will enable the reader to identify the various clinical manifestations of CLE and to employ characteristic criteria to assess differential diagnostic considerations.

Biopsy↗