Showing papers by "Vrije Universiteit Brussel published in 2000"

Sources of toxoplasma infection in pregnant women: European multicentre case-control study

Abstract: OBJECTIVE: To determine the odds ratio and population attributable fraction associated with food and environmental risk factors for acute toxoplasmosis in pregnancy. DESIGN: Case-control study. SETTING: Six large European cities. PARTICIPANTS: Pregnant women with acute infection (cases) detected by seroconversion or positive for anti-Toxoplasma gondii IgM were compared with pregnant women seronegative for toxoplasma (controls). MAIN OUTCOME MEASURES: Odds ratios for acute infection adjusted for confounding variables; the population attributable fraction for risk factors. RESULTS: Risk factors most strongly predictive of acute infection in pregnant women were eating undercooked lamb, beef, or game, contact with soil, and travel outside Europe and the United States and Canada. Contact with cats was not a risk factor. Between 30% and 63% of infections in different centres were attributed to consumption of undercooked or cured meat products and 6% to 17% to soil contact. CONCLUSIONS: Inadequately cooked or cured meat is the main risk factor for infection with toxoplasma in all centres. Preventive strategies should aim to reduce prevalence of infection in meat, improve labelling of meat according to farming and processing methods, and improve the quality and consistency of health information given to pregnant women.

Multiple gestation pregnancy

Abstract: The ESHRE Capri Workshop Group* rates in most circumstances. Embryo reduction involves extremely difficult decisions for infertile couples and should Correspondence should be addressed to Professor P.G. Crosignani, be used only as a last resort. Assisted reproductive treatClinica Ostetrica e Ginecologica I, Facolta de Medicina e Chirurgia, Universita Degli Studi di Milano, Via Commenda, ment centres and registries should express cycle results as 12-20122 Milano, Italy. E-mail: piergiorgio.crosignani@unimi.it the proportion of singleton live births; twin and triplet rates should be reported separately as complications of the Multiple gestation pregnancy rates are high in assisted procedures. Reducing the multiple gestation pregnancy reproductive treatment cycles because of the perceived need rate should be a high priority for assisted reproductive to stimulate excess follicles and transfer excess embryos in treatment programmes, despite the pressure from some order to achieve reasonable pregnancy rates. Perinatal patients to transfer more embryos in order to improve mortality rates are, however, 4-fold higher for twins and success. If nothing is done, public concern may lead 6-fold higher for triplets than for singletons. Since the goal to legislation in many countries, a step that would be of infertility therapy is a healthy child, and multiple unnecessary if assisted reproductive treatment programmes gestation puts that goal at risk, multiple pregnancy must be and registries took suitable steps to reduce multiple pregregarded as a serious complication of assisted reproductive nancy rates. treatment cycles. The 1999 ESHRE Capri Workshop

Cardiac Troponins I and T Are Biological Markers of Left Ventricular Dysfunction in Septic Shock

Abstract: Background: Cardiac depression in severe sepsis and septic shock is characterized by left ventricular (LV) failure. To date, it is unclear whether clinically unrecognized myocardial cell injury accompanies, causes, or results from this decreased cardiac performance. We therefore studied the relationship between cardiac troponin I (cTnI) and T (cTnT) and LV dysfunction in early septic shock. Methods: Forty-six patients were consecutively enrolled, fluid-resuscitated, and treated with catecholamines. Cardiac markers were measured at study entry and after 24 and 48 h. LV function was assessed by two-dimensional transesophageal echocardiography. Results: Increased plasma concentrations of cTnI (≥0.4 μg/L) and cTnT (≥0.1 μg/L) were found in 50% and 36%, respectively, of the patients at one or more time points. cTnI and cTnT were significantly correlated ( r = 0.847; P <0.0001). Compared with cTnI-negative patients, cTnI-positive subjects were older, presented higher Acute Physiology and Chronic Health Evaluation II scores at diagnosis, and tended to have a worse survival rate and a more frequent history of arterial hypertension or previous myocardial infarction. In contrast, the two groups did not differ in type of infection or pathogen, or in dose and type of catecholamine administered. Continuous electrocardiographic monitoring in all patients and autopsy in 12 nonsurvivors did not disclose the occurrence of acute ischemia during the first 48 h of observation. LV dysfunction was strongly associated with cTnI positivity (78% vs 9% in cTnI-negative patients; P <0.001). In multiple regression analysis, both cTnI and cTnT were exclusively associated with LV dysfunction ( P <0.0001). Conclusions: These findings suggest that in septic shock, clinically unrecognized myocardial cell injury is a marker of LV dysfunction. The latter condition tends to occur more often in severely ill older patients with underlying cardiovascular disease. Further studies are needed to determine the extent to which myocardial damage is a cause or a consequence of LV dysfunction.

Camel heavy‐chain antibodies: diverse germline VHH and specific mechanisms enlarge the antigen‐binding repertoire

Abstract: The antigen‐binding site of the camel heavy‐chain antibodies devoid of light chain consists of a single variable domain (V H H) that obviously lacks the V H –V L combinatorial diversity. To evaluate the extent of the V H H antigen‐binding repertoire, a germline database was constructed from PCR‐amplified V H H/V H segments of a single specimen of Camelus dromedarius . A total of 33 V H H and 39 VH unique sequences were identified, encoded by 42 and 50 different genes, respectively. Sequence comparison indicates that the V H H s evolved within the V H subgroup III. Nevertheless, the V H H germline segments are highly diverse, leading to a broad structural repertoire of the antigen‐binding loops. Seven V H H subfamilies were recognized, of which five were confirmed to be expressed in vivo . Comparison of germline and cDNA sequences demonstrates that the rearranged V H H s are extensively diversified by somatic mutation processes, leading to an additional hypervariable region and a high incidence of nucleotide insertions or deletions. These diversification processes are driven by hypermutation and recombination hotspots embedded in the V H H germline genes at the regions affecting the structure of the antigen‐binding loops.

Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-antagonist cetrorelix and the LHRH-agonist buserelin

Abstract: In this prospective and randomized study, 188 patients received the luteinizing hormone-releasing hormone (LHRH) antagonist cetrorelix, and 85 patients the LHRH agonist buserelin to prevent endogenous luteinizing hormone (LH) surges during ovarian stimulation in in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Ultimately, 181 patients (96.3%) in the cetrorelix group, and 77 (90.6%) in the buserelin group, reached the day of the human chorionic gonadotrophin (HCG) injection. The mean number of human menopausal gonadotrophin (HMG) ampoules administered and the mean number of stimulation days with HMG were significantly less in the cetrorelix group than in the buserelin group (P < 0.01). A rise in LH and progesterone concentrations was observed in three of the 188 patients (1.6%) who received cetrorelix. On the day of the HCG administration, more follicles of a small diameter (11-14 mm) were observed in the buserelin group than in the cetrorelix group (P = 0. 02) and the mean serum oestradiol concentration was significantly higher in patients who received buserelin than in those who received cetrorelix (P < 0.01). Similar results were observed in fertilization, cleavage and pregnancy rates in the two groups. In conclusion, the use of the LHRH antagonists might be considered more advantageous because of the short-term application needed to inhibit gonadotrophin secretion, so allowing a reduction in the treatment time in a clinically significant manner.

B Lymphocytes Regulate Dendritic Cell (Dc) Function in Vivo: Increased Interleukin 12 Production by DCs from B Cell–Deficient Mice Results in T Helper Cell Type 1 Deviation

Abstract: Increasing evidence indicates that dendritic cells (DCs) are the antigen-presenting cells of the primary immune response. However, several reports suggest that B lymphocytes could be required for optimal T cell sensitization. We compared the immune responses of wild-type and B cell-deficient (muMT) mice, induced by antigen emulsified in adjuvant or pulsed on splenic dendritic cells. Our data show that lymph node cells from both control and muMT animals were primed, but each released distinct cytokine profiles. Lymph node T cells from control animals secreted interferon (IFN)-gamma, interleukin (IL)-2, and IL-4, whereas those from muMT mice produced IFN-gamma and IL-2 but no IL-4. To test whether B cells may influence the T helper cell type 1 (Th1)/Th2 balance by affecting the function of DCs, we immunized mice by transferring antigen-pulsed DCs from wild-type or mutant mice. Injection of control DCs induced the secretion of IL-4, IFN-gamma, and IL-2, whereas administration of DCs from muMT animals failed to sensitize cells to produce IL-4. Analysis of IL-12 production revealed that DCs from muMT mice produce higher levels of IL-12p70 than do DCs from wild-type animals. These data suggest that B lymphocytes regulate the capacity of DCs to promote IL-4 secretion, possibly by downregulating their secretion of IL-12, thereby favoring the induction of a nonpolarized immune response.

Utilization of mangrove wood products around Mida Creek (Kenya) amongst subsistence and commercial users

Abstract: Mida Creek (Kenya) comprises mangrove forests and other marine resources that are of economic, ecological, and environmental importance to the local village communities. In total 116 households (100 of which could be used for numerical analysis), which are estimated to correspond to a coverage of ca. 30% of the total Mida Creek population, were interviewed to assess the human reliance on mangrove resources in Mida Creek. The survey indicates that mangroves are a major resource of wood for house construction, fuel wood, charcoal, and boat building. Minor uses of mangrove products include pharmaceutical and medicinal applications, tanning material, and furniture making. Rhizophora mucronata, Ceriops tagal, and Bruguiera gymnorrhiza are the major resources for house construction and fuel wood, while Sonneratia alba and Xylocarpus granatum were reported to be useful for boat building and medicinal uses respectively. The survey further describes harvesting activities and house construction, and reveals species preferences within this one particular use. As a result of depletion of the supply and the banning of mangrove harvesting, the local people are turning to other wood materials and to poaching. In our view, local utilization patterns rather than global usefulness data are required to establish a conservation policy of both mangroves and users’ subsistence requirements.

Mutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease.

Abstract: Camurati-Engelmann disease (CED; MIM 131300), or progressive diaphyseal dysplasia, is a rare, sclerosing bone dysplasia inherited in an autosomal dominant manner. Recently, the gene causing CED has been assigned to the chromosomal region 19q13 (refs 1-3). Because this region contains the gene encoding transforming growth factor-beta 1 (TGFB1), an important mediator of bone remodelling, we evaluated TGFB1 as a candidate gene for causing CED.

An Empirical Process Approach to the Uniform Consistency of Kernel-Type Function Estimators

Abstract: We use general empirical process methods to determine under mild regularity conditions exact rates of uniform strong consistency of kernel-type function estimators. In the process a useful new bound on the expectation of the supremum of the empirical process is obtained

Technology Aspects Related to the Application of Functional Starter Cultures

Abstract: Summary The market of pro- and prebiotics as applied in fermented milk drinks is expanding worldwide. More consumers become interested in the potential, health-promoting properties of functional foods. However, the industrial processors need to adapt their production processes and technologies, if they wish to use probiotics in a variety of food products. Indeed, the food matrix composition, the interaction(s) and stability of the culture, the inoculum level, the technological process conditions, etc. influence the viability of the probiotic bacteria considerably. In this paper some problems are discussed related to the application of probiotics in the dairy sector. In the food sectort there is a fast increasing request for 100 % natural products, not only from the point of view of the consumer but also from that of the authorities. Two examples are given in this paper: the use of natural food preservatives (antimicrobial proteins or bacteriocins) and the application of natural texturisers (microbial exopolysaccharides), both through the application of functional lactic acid bacterium starter cultures. Also, one has to take into account the influence of several factors of the food matrix and the applied process technology on the functionality of the strains used.

Glucagon receptors on human islet cells contribute to glucose competence of insulin release.

Abstract: Aims/hypothesis. Synergism between glucose and cAMP in the stimulation of insulin secretion has been suggested to regulate beta cells. This study assessed the importance of an interaction between glucose and cAMP in the stimulation of insulin secretion from human islet cells by investigating expression and functional activity of receptors recognising glucagon, glucagon-like peptide-1 (7–36)amide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Methods. Expression of the glucagon, GLP-1 and GIP receptors in human islets was investigated by northern blots and reverse transcription-polymerase chain reaction analysis. Functional activity of these receptors was assessed by the effects of peptides (agonists and antagonists) on glucose-induced insulin release. Results. Human islet cells express transcripts encoding glucagon, GLP-1 and GIP receptors. Glucose (10 mmol/l) stimulated insulin release 4.5 ± 0.6-fold over basal (2.5 mmol/l). This glucose effect was amplified by 10 nmol/l GLP-1, GIP or glucagon. It was reduced by 51 ± 6 % in the presence of 1 μmol/l of the glucagon-receptor antagonist des-His1-[Glu9]-glucagon-amide (n = 8; p < 0.05), indicating participation of endogenously released glucagon in the process of glucose-induced insulin release. The glucagon-receptor antagonist also suppressed the potentiation of glucose-induced insulin release by addition of 10 nmol/l glucagon. Conclusion/interpretation. These data suggest that human beta cells express functional glucagon receptors which can, similar to incretin hormone receptors, generate synergistic signals for glucose-induced insulin secretion. [Diabetologia (2000) 43: 1012–1019]

Results from the EISMINT model intercomparison : the effects of thermomechanical coupling

Abstract: This paper discusses results from the second phase of the European Ice sheet Modelling Initiative (EISMINT). It reports the intercompartison of ten operational ice-sheet models and uses a series of experiments to examine the implications of thermomechanical coupling for model behaviour. A schematic, circular ice sheet is used in the work which investigates both steady states and the response to stepped changes in climate. The major finding is that radial symmetry implied in the experimental design can, under certain circumstances, break down with the formation of distinct, regularly spaced spokes of cold ice which extended from the interior of the ice sheet outward to the surrounding zone of basal melt. These features also manifest themselves in the thickness and velocity distributions predicted by the models. They appear to be a common feature to all of the models which took part in the intercomparison, and may stem from interactions between ice temperature, flow and surface form. The exact nature of these features varies between models, and their existence appears to be controlled by the overall thermal regimne of the ice sheet. A second result is that there is considerable agreement between the models in their predictions of global-scale response to imposed climate change.

The treatment of meltwater retention in mass-balance parameterisations of the Greenland ice sheet

Abstract: Retention of melt-water runoff by percolation and/ or refreezing in the snowpack cannot be neglected when studying the surface mass balance of the Greenlandice sheet. In this paper, we make a detailed comparison of several treatments proposed in the literature to account for this process in large-scale mass-balanceparameterizations. The melt on the Greenland ice sheet is calculated with a revised degree-day model using updated datasets of surface elevation and precipitationrate on a 5 km grid. Crucial model parameters are recalibrated by comparing mass-balance characteristics with available observations on a regional basis. Wediscuss the role of meltwater retention in the light of the overall mass-balance of the Greenland ice sheet and its sensitivity to climatic change, and displaypatterns of effective retention fractions for the various methods. As a main conclusion, it appears that overall results are quite similar for the various models, butthat meltwater retention has a large spatial variation not described by the simple treatments. Using the most comprehensive retention model, the sensitivity of therunoff is found to be +0.35 mm/ deg C of sea-level change per year. We also present a new map of the different zones (facies) that characterize the accumulationarea of the Greenland ice sheet, that is useful for interpreting field data and calibrating satellite observations.

Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency.

Abstract: Defects in the pyruvate dehydrogenase (PDH) complex are an important cause of primary lactic acidosis, a frequent manifestation of metabolic disease in children. Clinical symptoms can vary considerably in patients with PDH complex deficiencies, and almost equal numbers of affected males and females have been identified, suggesting an autosomal recessive mode of inheritance of the disease. However, the great majority of PDH complex deficiencies result from mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1). The major factors that contribute to the clinical variation in E1alpha deficiency and its resemblance to a recessive disease are developmental lethality in some males with severe mutations and the pattern of X-inactivation in females. To date, 37 different missense/nonsense and 39 different insertion/deletion mutations have been identified in the E1alpha subunit gene of 130 patients (61 females and 69 males) from 123 unrelated families. Insertion/deletion mutations occur preferentially in exons 10 and 11, while missense/nonsense mutations are found in all exons. In males, the majority of missense/nonsense mutations are found in exons 3, 7, 8 and 11, and three recurrent mutations at codons R72, R263 and R378 account for half of these patients with missense/nonsense mutations (25 of 50). A significantly lower number of females is found with missense/nonsense mutations (25). However, 36 females out of 55 affected patients have insertion/deletion mutations. The total number of female and male patients is thus almost the same, although a difference in the distribution of the type of mutations is evident between both sexes. In many families, the parents of the affected patients were studied for the presence of the PDHA1 mutation. The mutation was never present in the somatic cells of the father; in 63 mothers studied, 16 were carriers (25%). In four families, the origin of the new mutation was determined to be twice paternal and twice maternal.

Wavelets in chemistry.

Abstract: Part headings and chapter headings: Preface. Theory. Finding frequencies in signals the Fourier transform (B. van den Bogaert). When frequencies change in time towards the wavelet transform (B. van den Bogaert). Fundamentals of wavelet transforms (Y. Mallet et al.). The discrete wavelet transform in practice (O. de Vel et al.). Multiscale methods for denoising and compression (M.N. Nounou, B.R. Bakshi). Wavelet packet transforms and best basis algorithms (Y. Mallet et al.). Joint basis and joint best-basis for data sets (B. Walczak, D.L. Massart). The adaptive wavelet algorithm for designing task specific wavelets (Y. Mallet et al.). Applications. Application of wavelet transform in processing chromatographic data (Foo-tim Chau, A. Kai-man Leung). Application of wavelet transform in electrochemical studies (Foo-tim Chau, A. Kai-man Leung). Applications of wavelet transform in spectroscopic studies (Foo-tim Chau, A. Kai-man Leung). Application of wavelet analysis to physical chemistry (H. Teitelbaum). Wavelet bases for IR library compression, searching and reconstruction (B. Walczak, J.P. Radomski). Application of the discrete wavelet transformation for online detection of transitions in time series (M. Marth). Calibration in wavelet domain (B. Walczak, D.L. Massart). Wavelets in parsimonious functional data analysis models (B.K. Alsberg). Multiscale statistical process control and model-based denoising (B.R. Bakshi). Application of adaptive wavelets in classification and regression (Y. Mallet et al.). Wavelet-based image compression (O. de Vel et al.). Wavelet analysis and processing of 2-D and 3-D analytical images (S.G. Nikolov et al.). Index.

Mechanisms of coxsackievirus-induced damage to human pancreatic beta-cells.

Abstract: Enteroviruses may be involved in the pathogenesis of insulin-dependent diabetes mellitus, either through direct β-cell infection or as triggers of autoimmunity. In the present study we investigated the patterns of infection in adult human islet cell preparations (consisting of 56 ± 14% β-cells) by several coxsackieviruses. The cells were infected with prototype strains of coxsackievirus B (CBV) 3, 4, and 5 as well as coxsackievirus A9 (CAV-9). The previously characterized diabetogenic strain of coxsackievirus B4 (CBV-4-E2) was used as a reference. All viruses replicated well in β-cells, but only CBVs caused cell death. One week after infection, the insulin response of the β-cells to glucose or glucose plus theophyline was most severely impaired by CBV-3 and CBV-5 infections. CBV-4 also caused significant functional impairment, whereas CAV-9-infected cells responded like uninfected controls. After 2 days of infection, about 40% of CBV-5-infected cells had undergone morphological changes characteristic of p...

Comparison between different routes of progesterone administration as luteal phase support in infertility treatments

Abstract: Different routes of natural progesterone supplementation have been tried as luteal phase support in infertility treatments. Orally administered progesterone is rapidly metabolized in the gastrointestinal tract and its use has proved to be inferior to i.m. and vaginal routes. Progesterone i.m. achieves serum progesterone values that are within the range of luteal phase and results in sufficient secretory transformation of the endometrium and satisfactory pregnancy rates. The comparison between i.m. and vaginal progesterone has led to controversial results as regards the superiority of one or the other in inducing secretory endometrial transformation. However, there is increasing evidence in the literature to favour the use of vaginal progesterone. Vaginally administered progesterone achieves adequate endometrial secretory transformation but its pharmacokinetic properties are greatly dependent on the formulation used. After vaginal progesterone application, discrepancies have been detected between serum progesterone values and histological endometrial features. Vaginally administered progesterone results in adequate secretory endometrial transformation, despite serum progesterone values lower than those observed after i.m. administration, even if they are lower than those observed during the luteal phase of the natural cycle. This discrepancy is indicative of the first uterine pass effect and therefore of a better bioavailability of progesterone in the uterus, with minimal systematic undesirable effects.

Sources of suspended organic matter and selective feeding by zooplankton in an estuarine mangrove ecosystem as traced by stable isotopes

Abstract: Between January 1995 and August 1996, suspended matter and zooplankton were sam- pled at different locations in a mangrove ecosystem located in the Gautami Godavari estuary and adjacent Kakinada Bay (Andhra Pradesh, India). Suspended matter was sampled at 13 different sta- tions, and was found to have a highly variable carbon stable isotope composition, with δ 13 C values ranging overall between -30.94 and -19.18 ‰, and a highly variable elemental (C:N) composition. Our data suggest that the phytoplankton component has a seasonally and spatially variable δ 13 C sig- nature, which is surpressed by the terrestrial signal but may at times fall in the same range as the δ 13 C of the allochtonous matter. It is argued that the phytoplankton δ 13 C decreases after the onset of the monsoon rains, most likely due to the 13 C-depletion of the DIC pool caused by the microbial respira- tion of the allochtonous organic matter. At each of the 4 sites selected for concurrent zooplankton sampling, the zooplankton showed a much wider range of δ 13 C than did the suspended matter, with overall δ 13 C values between -30.14 and -16.45‰. In addition, spatial differences in average δ 13 C were much more pronounced for zooplankton than for total suspended matter. These data indicate that zooplankton feed on a component of the suspended matter pool, which has more pronounced seasonal and spatial δ 13 C variations than the total suspended matter. Thus, despite the large amounts of terrestrial and mangrove detritus present in the water column, the locally produced phytoplankton appears to be a more important carbon source for the zooplankton.

40% efficient thin-film surface-textured light-emitting diodes by optimization of natural lithography

Abstract: In conventional light-emitting diodes (LEDs), the external efficiency is limited by total internal reflection at the semiconductor-air interface. The problem can be overcome by the concept of the nonresonant cavity LED, which is an LED with a textured top surface and a rear reflector. The surface is textured using natural lithography. A monolayer of randomly positioned polystyrene spheres acts as a mask for dry etching. We present details about the optimization of the parameters of the texturing process for GaAs/AlGaAs LEDs. The studied parameters are the size of the spheres, the distribution of the spheres on the surface and the etching depth. Using optimized texturing conditions, we have realized un-encapsulated top-emitting oxide-confined GaAs/AlGaAs nonresonant cavity LEDs with an external quantum efficiency of 40%.

exercise capacity in chronic fatigue syndrome

Abstract: Background Patients with chronic fatigue syndrome (CFS) suffer from various symptoms, including debilitating fatigue, muscle pain, and muscle weakness. Patients with CFS can experience marked functional impairment. In this study, we evaluated the exercise capacity in a large cohort of female patients with CFS. Methods Patients with CFS and matched sedentary control subjects performed a maximal test with graded increase on a bicycle ergometer. Gas exchange ratio was continuously measured. In a second stage, we examined only those persons who achieved a maximal effort as defined by 2 end points: a respiratory quotient of at least 1.0 and an age-predicted target heart rate of at least 85%. Data were assessed using univariate and multivariate statistical methods. Results The resting heart rate of the patient group was higher, but the maximal heart rate at exhaustion was lower, relative to the control subjects. The maximal workload and maximal oxygen uptake attained by the patients with CFS were almost half those achieved by the control subjects. Analyzing only those persons who performed a maximal exercise test, similar findings were observed. Conclusions When compared with healthy sedentary women, female patients with CFS show a significantly decreased exercise capacity. This could affect their physical abilities to a moderate or severe extent. Reaching the age-predicted target heart rate seemed to be a limiting factor of the patients with CFS in achieving maximal effort, which could be due to autonomic disturbances.

Regulation of pancreatic PC1 and PC2 associated with increased glucagon-like peptide 1 in diabetic rats

Abstract: The pancreatic processing enzymes, PC1 and PC2, convert proinsulin to insulin and convert proglucagon to glucagon and glucagon-like peptide 1 (GLP-1). We examined the effect of streptozotocin (STZ) treatment on the regulation of these enzymes and the production of insulin, glucagon, and GLP-1 in the rat. Pancreatic PC1 and PC2 mRNA increased >2-fold and >4-fold, respectively, in rats receiving intraperitoneal STZ (50 mg/kg) daily for 5 days. Immunocytochemistry revealed that, although pancreatic islet cells in the STZ-treated rats were sparse and atrophic PC1, PC2, glucagon, and GLP-1 immunoreactivity increased dramatically in the remaining islet cells. Heightened PC1 and PC2 expression was seen in cells expressing glucagon but not in insulin-expressing cells. Furthermore, in STZ-treated rats, bioactive GLP-17–36 amide accumulated in pancreatic extracts and serum 3- and 2.5-fold, respectively, over control animals. This treatment also caused a 2-fold increase in the ratio of amidated forms of GLP-1 immunoreactivity to total glucagon immunoreactivity in the pancreas but did not affect the ratio of proinsulin to insulin. We conclude that hyperglycemic rats have an increased expression of prohormone converting enzymes in islet α cells, leading to an increase in amidated GLP-1, which can then exert an insulinotropic effect on the remaining β cells.

Differential RNA elongation controls the variant surface glycoprotein gene expression sites of Trypanosoma brucei.

Abstract: The protozoan parasite Trypanosoma brucei develops antigenic variation to escape the immune response of its host. To this end, the trypanosome genome contains multiple telomeric expression sites competent for transcription of variant surface glycoprotein genes, but as a rule only a single antigen is expressed at any time. We used reverse transcription-PCR (RT-PCR) to analyse transcription of different segments of the expression sites in different variant clones of two independent strains of T. brucei. The results indicated that RNA polymerase is installed and active at the beginning of many, if not all, expression sites simultaneously, but that a progressive arrest of RNA elongation occurs in all but one site. This defect is linked to inefficient RNA processing and RNA release from the nucleus. Therefore, functional transcription in the active site appears to depend on the selective recruitment of a RNA elongation/processing machinery.

Volume and cellular content of normal pleural fluid in humans examined by pleural lavage.

Abstract: Currently, no reliable data are available on the volume or on the cellular content of pleural fluid in normal humans. In analogy with bronchoalveolar lavage (a technique enabling retrieval of small volumes of epithelial lining fluid from the lung), we developed a pleural lavage (PL) technique consisting of injection and retrieval of 150 ml of saline into the right pleural space, performed during a thoracoscopic sympathicolysis procedure in otherwise healthy subjects suffering from essential hyperhidrosis. With urea used as an endogenous marker of dilution, measured mean right-sided pleural fluid volume was 8.4 +/- 4.3 ml. In a subgroup of subjects, we confirmed that right- and left-sided pleural fluid volumes were similar. Expressed per kilogram of body mass, total pleural fluid volume in normal, nonsmoking humans is 0.26 +/- 0.1 ml/kg. Total cell count in the PL fluid of nonsmoking normal subjects yielded a median of 91 x 10(3) white blood cells (WBC) per milliliter of lavage fluid (interquartile range [IR] = 124 x 10(3) cells/ml). Taking into account a measured dilution factor of 18.86, the total WBC count in the original pleural fluid was 1,716 x 10(3) cells/ml. Differential cell counts yielded a predominance of macrophages (median: 75%; IR: 16%) and lymphocytes (median: 23%; IR: 18%). Mesothelial cells (median: 1%; IR: 2%), neutrophils (median: 0%; IR: 1%), and eosinophils (median: 0%; IR: 0%) were only marginally present. There were no significant differences between males and females or between right- and left-sided pleural fluid in total and differential cell counts. In contrast, in smokers a small but statistically significant increase in pleural fluid neutrophils (median: 1%; IR: 2%; p < 0.015) was observed. In conclusion, PL performed during thoracoscopy for sympathicolysis allowed for the first time determination of the volume and of the total and differential cell contents of the pleural fluid present in normal human pleura.