Showing papers by "University of Lausanne published in 1999"
TL;DR: This work has shown that direct expression of PPAR mRNAs in the absence of a specific carrier gene results in down-regulation in the activity of other PPARs, and these properties are consistent with those of a “spatially aggregating substance”.
Abstract: I. Introduction II. Molecular Aspects A. PPAR isotypes: identity, genomic organization and chromosomal localization B. DNA binding properties C. PPAR ligand-binding properties D. Alternative pathways for PPAR activation E. PPAR-mediated transactivation properties III. Physiological Aspects A. Differential expression of PPAR mRNAs B. PPAR target genes and functions in fatty acid metabolism C. PPARs and control of inflammatory responses D. PPARs and atherosclerosis E. PPARs and the development of the fetal epidermal permeability barrier F. PPARs, carcinogenesis, and control of the cell cycle IV. Conclusions
3,028 citations
TL;DR: Results add further support to previous studies for the clinical utility of the Los Angeles system for endoscopic grading of oesophagitis and to the risk for symptom relapse off therapy over six months.
Abstract: Background—Endoscopic oesophageal changes are diagnostically helpful and identify patients exposed to the risk of dis- ease chronicity. However, there is a seri- ous lack of agreement about how to describe and classify the appearance of reflux oesophagitis Aims—To examine the reliability of crite- ria that describe the circumferential ex- tent of mucosal breaks and to evaluate the functional and clinical correlates of pa- tients with reflux disease whose oesoph- agitis was graded according to the Los Angeles system. Methods—Forty six endoscopists from diVerent countries used a detailed work- sheet to evaluate endoscopic video record- ings from 22 patients with the full range of severity of reflux oesophagitis. In separate studies, Los Angeles system gradings were correlated with 24 hour oesophageal pH monitoring (178 patients), and with clini- cal trials of omeprazole treatment (277 patients). Results—Evaluation of circumferential extent of oesophagitis by the criterion of whether mucosal breaks extended be- tween the tops of mucosal folds, gave acceptable agreement (mean Œ value 0.4) among observers. This approach is used in the Los Angeles system. An alternative approach of grouping the circumferential extent of mucosal breaks as occupying 0-25%, 26-50%, 51-75%, 76-99%, or 100% of the oesophageal circumference, gave unacceptably high interobserver variation (mean Œ values 0-0.15) for all but the low- est category of extent (mean Œ value 0.4). Severity of oesophageal acid exposure was significantly (p<0.001) related to the se- verity grade of oesophagitis. Preteatment oesophagitis grades A-C were related to heartburn severity (p<0.01), outcomes of omeprazole (10 mg daily) treatment (p<0.01),and the risk for symptom relapse oV therapy over six months (p<0.05). Conclusions—Results add further support to previous studies for the clinical utility of the Los Angeles system for endoscopic grading of oesophagitis. (Gut 1999;45:172-180)
1,994 citations
TL;DR: Atomic force microscopy (AFM) force-distance curves have become a fundamental tool in several fields of research, such as surface science, materials engineering, biochemistry and biology.
1,559 citations
TL;DR: It is shown that to accommodate the increased requirement for hepatic fatty acid oxidation, PPAR α mRNA is induced during fasting in wildtype mice, indicating that PPARα plays a pivotal role in the management of energy stores during fasting.
Abstract: Prolonged deprivation of food induces dramatic changes in mammalian metabolism, including the release of large amounts of fatty acids from the adipose tissue, followed by their oxidation in the liver. The nuclear receptor known as peroxisome proliferator-activated receptor alpha (PPARalpha) was found to play a role in regulating mitochondrial and peroxisomal fatty acid oxidation, suggesting that PPARalpha may be involved in the transcriptional response to fasting. To investigate this possibility, PPARalpha-null mice were subjected to a high fat diet or to fasting, and their responses were compared with those of wild-type mice. PPARalpha-null mice chronically fed a high fat diet showed a massive accumulation of lipid in their livers. A similar phenotype was noted in PPARalpha-null mice fasted for 24 hours, who also displayed severe hypoglycemia, hypoketonemia, hypothermia, and elevated plasma free fatty acid levels, indicating a dramatic inhibition of fatty acid uptake and oxidation. It is shown that to accommodate the increased requirement for hepatic fatty acid oxidation, PPARalpha mRNA is induced during fasting in wild-type mice. The data indicate that PPARalpha plays a pivotal role in the management of energy stores during fasting. By modulating gene expression, PPARalpha stimulates hepatic fatty acid oxidation to supply substrates that can be metabolized by other tissues.
1,535 citations
TL;DR: Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti–DNA autoantibodies, and immunoglobulin deposition in the kidneys.
Abstract: The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti–DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.
1,524 citations
TL;DR: A novel member of the T NF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells is described, suggesting that BAFF plays an important role as costimulator of B cell proliferation and function.
Abstract: Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M-stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center-like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.
1,399 citations
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TL;DR: The Perspective of Magistretti et al. deduce some of the cellular and molecular events that accompany neuronal activity in the working brain, ultimately laying the groundwork for determining the biochemistry that underlies human cognition.
Abstract: New imaging techniques can see into the functioning brain, revealing the regions that are active during certain tasks and sensations. Magistretti
et al., in their Perspective, take this notion one step further and, by careful analysis of the biochemistry that gives rise to imaging signals, they deduce some of the cellular and molecular events that accompany neuronal activity in the working brain, ultimately laying the groundwork for determining the biochemistry that underlies human cognition.
1,123 citations
TL;DR: The rate of virological failure of HAART was high among patients with a history of antiretroviral treatment, but the probability of clinical progression was low even in patients with viral rebound.
963 citations
TL;DR: Administration of PIs to HIV-infected individuals is associated with a marked, compound-specific dyslipidemia, and the risk of pancreatitis and premature atherosclerosis due to PI-associated dys Lipoprotein remains to be established.
Abstract: Background—Administration of protease inhibitors (PIs) to HIV-infected individuals has been associated with hyperlipidemia In this study, we characterized the lipoprotein profile in subjects recei
611 citations
TL;DR: It is reported here that CD3-induced proliferation and interleukin 2 production by human T cells are blocked by inhibitors of caspase activity, extending the role of death receptors to the promotion of T cell growth in a casp enzyme-dependent manner.
Abstract: Triggering of Fas (CD95) by its ligand (FasL) rapidly induces cell death via recruitment of the adaptor protein Fas-associated death domain (FADD), resulting in activation of a caspase cascade It was thus surprising that T lymphocytes deficient in FADD were reported recently to be not only resistant to FasL-mediated apoptosis, but also defective in their proliferative capacity This finding suggested potentially dual roles of cell growth and death for Fas and possibly other death receptors We report here that CD3-induced proliferation and interleukin 2 production by human T cells are blocked by inhibitors of caspase activity This is paralleled by rapid cleavage of caspase-8 after CD3 stimulation, but no detectable processing of caspase-3 during the same interval The caspase contribution to T cell activation may occur via TCR-mediated upregulation of FasL, as Fas-Fc blocked T cell proliferation, whereas soluble FasL augmented CD3-induced proliferation These findings extend the role of death receptors to the promotion of T cell growth in a caspase-dependent manner
483 citations
TL;DR: In this paper, the authors investigated the catalytic reaction that is the oxidation of CO on platinum and observed a distinct atom by atom size dependency for monodispersed platinum clusters on thin MgO(100) films.
Abstract: Nanoclusters open fascinating opportunities for quantum engineering because quantum-size effects become dominant in determining catalytic,1-3 optical,4 electronic,5 and magnetic6 properties. We succeeded in the controlled production of low-energy and high-flux monodispersed cluster beams, which allow for a systematic study of their reactivity after deposition onto a chemically inert substrate. We investigated the catalytic reaction that is the oxidation of CO on platinum and observed a distinct atom by atom size dependency for monodispersed platinum clusters on thin MgO(100) films. These results clearly show that the efficiency of a heterogeneous catalytic reaction can be tuned by the judicious choice of particle size.
TL;DR: In this article, the authors demonstrate the complementary of experimental studies and computer simulations or quantum chemical calculations performed on the water exchange reaction between coordination shells around metal ions in aqueous solution.
TL;DR: An involvement of CD95 ligand and TRAIL in the pathophysiology of postischemic neurodegeneration is suggested and alternative strategies for the treatment of cardiovascular brain disease are offered.
Abstract: Programmed cell death plays an important role in the neuronal degeneration after cerebral ischemia, but the underlying mechanisms are not fully understood. Here we examined, in vivo and in vitro, whether ischemia-induced neuronal death involves death-inducing ligand/receptor systems such as CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). After reversible middle cerebral artery occlusion in adult rats, both CD95 ligand and TRAIL were expressed in the apoptotic areas of the postischemic brain. Further recombinant CD95 ligand and TRAIL proteins induced apoptosis in primary neurons and neuron-like cells in vitro. The immunosuppressant FK506, which most effectively protects against ischemic neurodegeneration, prevented postischemic expression of these death-inducing ligands both in vivo and in vitro. FK506 also abolished phosphorylation, but not expression, of the c-Jun transcription factor involved in the transcriptional control of CD95 ligand. Most importantly, in lpr mice expressing dysfunctional CD95, reversible middle cerebral artery occlusion resulted in infarct volumes significantly smaller than those found in wild-type animals. These results suggest an involvement of CD95 ligand and TRAIL in the pathophysiology of postischemic neurodegeneration and offer alternative strategies for the treatment of cardiovascular brain disease.
TL;DR: Patients with NTG have a thinner CCT than do patients with POAG or controls, while overestimation of the IOP in normal subjects who have thick corneas may lead to a misdiagnosis of OHT.
Abstract: Objectives To determine the effect of central corneal thickness (CCT) on the measurement of intraocular pressure (IOP) and on the resultant reclassification of patients as having primary open-angle glaucoma (POAG), normal tension glaucoma (NTG), or ocular hypertension (OHT). Methods Intraocular pressure (Goldmann applanation tonomety) and CCT (ultrasound pachymetry) were measured in 22 patients with NTG, 49 with POAG, 44 with OHT and in 18 control subjects. The CCT was used to obtain a corrected value for the IOP and to reclassify the type of glaucoma. Results There was no significant difference in CCT between controls (552±35 µm) and patients with POAG (543±35 µm), but the CCT in the group with NTG (521±31 µm) was significantly lower than that in the control group or the group with POAG ( P P Conclusions Patients with NTG have a thinner CCT than do patients with POAG or controls. Underestimation of the IOP in patients with POAG who have thin corneas may lead to a misdiagnosis of NTG, while overestimation of the IOP in normal subjects who have thick corneas may lead to a misdiagnosis of OHT.
TL;DR: Present evidences suggest that genetic and environmental factors influence eating behavior of people prone to obesity and that diets that are high in fat or energy dense undermine body weight regulation by promoting an overconsumption of energy relative to need.
Abstract: The mechanisms involved in body weight regulation in humans include genetic, physiological, and behavioral factors. Stability of body weight and body composition requires that energy intake matches...
TL;DR: Two-dimensional supramolecular clusters and chains are observed upon submonolayer deposition of 1-nitronaphthalene (NN) onto reconstructed Au(111) as discussed by the authors.
Abstract: Two-dimensional supramolecular clusters and chains are observed upon submonolayer deposition of 1-nitronaphthalene (NN) onto reconstructed Au(111) The molecules become pseudochiral upon adsorption Their handedness is determined from high-resolution scanning tunneling microscope images and local-density calculations Modeling shows that hydrogen bonds cause the observed self-assembly Clusters and chains mutually interact via electrostatic repulsion
TL;DR: The Balanced Scorecard has emerged in recent years as what can perhaps best be described as a strategic control tool as mentioned in this paper, which is a tool which adds value by providing both relevant and balanced information in a concise way for managers, creating an environment which is conducive to learning organisations and eliminating the need for managers to ''choose'' which type of control system to use at any given time.
TL;DR: It is demonstrated that Nedd4 is a negative regulator of ENaC and suggested that the loss of Nedd 4 binding sites in EN aC observed in Liddle's syndrome may explain the increase in channel number at the cell surface, increased Na+ reabsorption by the distal nephron, and hence the hypertension.
Abstract: Liddle's syndrome is an inherited form of hypertension linked to mutations in the epithelial Na+ channel (ENaC). ENaC is composed of three subunits (α, β, γ), each containing a COOH-terminal PY motif (xPPxY). Mutations causing Liddle's syndrome alter or delete the PY motifs of β- or γ-ENaC. We recently demonstrated that the ubiquitin–protein ligase Nedd4 binds these PY motifs and that ENaC is regulated by ubiquitination. Here, we investigate, using the Xenopus oocyte system, whether Nedd4 affects ENaC function. Overexpression of wild-type Nedd4, together with ENaC, inhibited channel activity, whereas a catalytically inactive Nedd4 stimulated it, likely by acting as a competitive antagonist to endogenous Nedd4. These effects were dependant on the PY motifs, because no Nedd4-mediated changes in channel activity were observed in ENaC lacking them. The effect of Nedd4 on ENaC missing only one PY motif (of β-ENaC), as originally described in patients with Liddle's syndrome, was intermediate. Changes were due entirely to alterations in ENaC numbers at the plasma membrane, as determined by surface binding and immunofluorescence. Our results demonstrate that Nedd4 is a negative regulator of ENaC and suggest that the loss of Nedd4 binding sites in ENaC observed in Liddle's syndrome may explain the increase in channel number at the cell surface, increased Na+ reabsorption by the distal nephron, and hence the hypertension.
J. Clin. Invest. 103:667–673 (1999)
TL;DR: In low-risk patients with cancer who have fever and granulocytopenia, oral therapy with ciprofloxacin plus amoxicillin-clavulanate is as effective as intravenous therapy.
Abstract: Background Intravenously administered antimicrobial agents have been the standard choice for the empirical management of fever in patients with cancer and granulocytopenia. If orally administered empirical therapy is as effective as intravenous therapy, it would offer advantages such as improved quality of life and lower cost. Methods In a prospective, open-label, multicenter trial, we randomly assigned febrile patients with cancer who had granulocytopenia that was expected to resolve within 10 days to receive empirical therapy with either oral ciprofloxacin (750 mg twice daily) plus amoxicillin–clavulanate (625 mg three times daily) or standard daily doses of intravenous ceftriaxone plus amikacin. All patients were hospitalized until their fever resolved. The primary objective of the study was to determine whether there was equivalence between the regimens, defined as an absolute difference in the rates of success of 10 percent or less. Results Equivalence was demonstrated at the second interim analysis,...
TL;DR: The Eastern Ghats belt is a large high-grade terrane exposed along the east coast of India as mentioned in this paper, which represents an important part of the reconstructed global Southwest-United States-East-Antarctica (SWEAT) orogen.
TL;DR: The mucoadhesive polysaccharide chitosan was evaluated as a potential component in ophthalmic gels for enabling increased precorneal drug residence times and showed excellent tolerance after topical administration onto the corneal surface.
TL;DR: La1 culture supernatant shown to be effective in vitro has a partial, acid-independent long-term suppressive effect on H. pylori in humans.
Abstract: Background: Specific strains of Lactobacillus acidophilus are known to inhibit intestinal cell adhesion and invasion by enterovirulent bacteria. As L. ac
TL;DR: TNF–related apoptosis–inducing ligand has selective antitumor activity in mice without causing toxic side effects and may have potential as a cancer therapeutic (157–163).
Abstract: TNF–related apoptosis–inducing ligand has selective antitumor activity in mice without causing toxic side effects and may have potential as a cancer therapeutic (
157–163
).
TL;DR: In this study, antibody single-chain Fv fragments were labeled to high specific activities (90 mCi/mg), and the label was very stable to serum and all other challenges tested, and thus scFV fragments labeled by the new method will be suitable for biodistribution studies.
Abstract: Stable one-step technetium-99m labeling of His-tagged recombinant proteins
with a novel Tc(I)–carbonyl complex
TL;DR: In this paper, the authors measured the efficiency of international airlines using stochastic frontier production functions adjusted to account for environmental influences such as network conditions, geographical factors, etc., and found that Asian/Oceanic airlines are more efficient than European and North American airlines.
Abstract: The principal aim of this paper is to measure the efficiency of international airlines. We obtain measures of technical efficiency from stochastic frontier production functions which have been adjusted to account for environmental influences such as network conditions, geographical factors, etc. We observe that two alternative approaches to this problem have been proposed in the efficiency measurement literature. One assumes that the environmental factors influence the shape of the technology while the other assumes that they directly influence the degree of technical inefficiency. In this paper we compare the results obtained when using these two approaches. The two sets of results provide similar rankings of airlines but suggest differing degrees of technical inefficiency. Both sets of results also suggest that Asian/Oceanic airlines are technically more efficient than European and North American airlines but that the differences are essentially due to more favourable environmental conditions. Nevertheless, it is among Asian companies that the major improvements in managerial efficiency (technical efficiency with environmental factors netted out) took place over the sample period (1977–1990).
TL;DR: H.pylori urease with LT is well tolerated and immunogenic in H. pylori-infected individuals, and an improved vaccine formulation may induce curative immunity.
TL;DR: The success rate of DSCi may be comparable to that of trabeculectomy, with fewer complications, and the number of postoperative complications was significantly lower in the DSCI group than in the trabECUlectomy group.
Abstract: Purpose: To assess the efficacy and postoperative complications of deep sclerectomywith collagen implant (DSCI), a nonpenetrating filtration procedure. Setting: Glaucoma Unit, Department of Ophthalmology, University of Lausanne, Switzerland. Methods: Forty-four eyes of 44 patients with medically uncontrolled open-angle glaucoma had DSCI and a matched control group of 44 patients, trabeculectomy. A superficial scleral flap was raised and a deep sclerectomy performed in the scleral bed. Schlemm's canal was opened, and the cornea was dissected to Descemet's membrane. At that stage, aqueous filtered through the remaining trabeculo-Descemet's membrane. A collagen implant was sutured radially in the scleral bed; the scleral flap and conjunctiva were then closed. Examinations were performed before surgery and postoperatively at 1 and 7 days and 1, 2, 3, 6, 9, 12, 15, 18, and 24 months. Results: The mean follow-up was 14.4 months ± 6.3 (SD) (range 3 to 24 months). The mean preoperative intraoperative pressure (IOP) was 26.7 ± 7.3 mm Hg. The mean postoperative IOP was 6.1 ± 4.5 mm Hg at 1 day and 11.0 ± 4.4 mm Hg at 1 week; it remained stable for the next 24 months. The success rate, defined as an IOP lower than 21.0 mm Hg without medication, was 69% in the DSCI group and 57% in the trabeculectomy group at 24 months postoperatively (P = .047). The number of postoperative complications was significantly lower in the DSCI group than in the trabeculectomy group. Conclusions: The success rate of DSCI may be comparable to that of trabeculectomy, with fewer complications.
TL;DR: Sequence analyses of the plastid genes atp B and rbc L support an expanded order Malvales and propose to merge Sterculiaceae, Tiliaceae and Bombacaceae with Malvaceae and subdivide this enlarged family Malvoideae into nine subfamilies based on molecular, morphological, and biogeographical data.
TL;DR: The riddle of the high Pcr levels in term and particularly in preterm newborns seems to be solved, as the results in the newborn rabbits showed an unexpected underestimation of the Ccr vis-a-vis Cin, which means, as is explained at length in the “Discussion” of this article, that the pre term newborn infant reabsorbs creatinine along the renal tubule.
Abstract: Background. Plasma creatinine (Pcr) levels at birth are greatly elevated in relation to the size (and the muscle mass) of the newborn infant and remain so for 1 to 2 weeks. Particularly intriguing is the fact that Pcr levels are higher in preterm than in term infants and for a longer postnatal period. The smaller the birth weight, the higher the Pcr. This cannot be explained by maternal transfer of Pcr or by the absolute and relative (to adult body surface area) reduced glomerular filtration rate of the newborn. Perhaps the renal handling of creatinine is involved. Design. In 522 pairs of mothers and fetuses, maternal and fetal Pcr were compared from 16 weeks of gestation until term. Pcr was measured in 66 newborns of various birth weights and followed for 1 month. Creatinine clearance (Ccr) and inulin clearance (Cin) were measured simultaneously in adult ( n = 8) and newborn ( n = 20) New Zealand White rabbits. In the latter, nephrogenesis continues after birth and they are therefore a good animal model for the study of the renal function in premature infants. Patient. A case of a premature male infant is presented (gestation: 29 weeks; birth weight: 1410 g) suspected of having sepsis because of premature rupture of membranes and postpartum maternal fever. This suspicion was not confirmed. Blood chemistry evaluation showed a high Pcr at birth (0.85 mg/dL, 75 μmol/L), even higher than that of the mother (0.77 mg/dL, 68 μmol/L). The Pcr started to decrease after ∼1 week but remained elevated throughout 1 month of follow-up. Results. From the maternal-fetal Pcr measurements it was quite evident that during the second half of gestation the small molecular weight creatinine (113 dalton, 0.3 nm radius) of the mother and fetus equilibrates at all maternal Pcr levels. The newborn Pcr levels were not only high at the time of birth but remained so for more than 3 weeks. It was also shown that the smaller the infant the higher the Pcr levels. The results of the animal experimental data showed that adult rabbits had the normal physiologic pattern in which Ccr overestimates Cin (Ccr/Cin ratio >1.0). In contrast, the results in the newborn rabbits showed an unexpected underestimation of the Ccr vis-a-vis Cin (Ccr/Cin ratio Conclusion. The riddle of the high Pcr levels in term and particularly in preterm newborns seems to be solved. Once the umbilical cord is severed, the perfect intrauterine maternal-fetal biochemical balance is disturbed. Thereafter, the already transferred exogenous, adult-level creatinine will rapidly disappear in the first urine specimens passed by the now autonomous newborn infant. A new steady state is achieved in due time, based on independent neonatal factors. One of these factors is the unusual occurrence of tubular creatinine reabsorption. We hypothesize that this latter temporary phenomenon is attributable to back-flow of creatinine across leaky immature tubular and vascular structures. With time, maturational renal changes will impose a barrier to creatinine. From that point onwards, total body muscle mass, glomerular filtration rate, and tubular secretion will in health determine the Pcr level of the individual. plasma creatinine, tubular handling of creatinine, newborn, premature infants.
TL;DR: In this article, the in situ distribution of heterogeneous nuclear RNA transcription sites after microinjection of 5-bromo-UTP (BrUTP) into the cytoplasm of living cells and subsequent postembedding immunoelectron microscopic visualization after different labeling periods was demonstrated.
Abstract: In this study we demonstrate, at an ultrastructural level, the in situ distribution of heterogeneous nuclear RNA transcription sites after microinjection of 5-bromo-UTP (BrUTP) into the cytoplasm of living cells and subsequent postembedding immunoelectron microscopic visualization after different labeling periods. Moreover, immunocytochemical localization of several pre-mRNA transcription and processing factors has been carried out in the same cells. This high-resolution approach allowed us to reveal perichromatin regions as the most important sites of nucleoplasmic RNA transcription and the perichromatin fibrils (PFs) as in situ forms of nascent transcripts. Furthermore, we show that transcription takes place in a rather diffuse pattern, without notable local accumulation of transcription sites. RNA polymerase II, heterogeneous nuclear ribonucleoprotein (hnRNP) core proteins, general transcription factor TFIIH, poly(A) polymerase, splicing factor SC-35, and Sm complex of small nuclear ribonucleoproteins (snRNPs) are associated with PFs. This strongly supports the idea that PFs are also sites of major pre-mRNA processing events. The absence of nascent transcripts, RNA polymerase II, poly(A) polymerase, and hnRNPs within the clusters of interchromatin granules rules out the possibility that this domain plays a role in pre-mRNA transcription and polyadenylation; however, interchromatin granule-associated zones contain RNA polymerase II, TFIIH, and Sm complex of snRNPs and, after longer periods of BrUTP incubation, also Br-labeled RNA. Their role in nuclear functions still remains enigmatic. In the nucleolus, transcription sites occur in the dense fibrillar component. Our fine structural results show that PFs represent the major nucleoplasmic structural domain involved in active pre-mRNA transcriptional and processing events.