Showing papers by "University of Lausanne published in 1992"
TL;DR: Three novel members of the Xenopus nuclear hormone receptor superfamily have been cloned and their multiplicity suggests the existence of hitherto unknown cellular signaling pathways for xenobiotics and putative endogenous ligands.
1,358 citations
TL;DR: The receptor transfected into COS cells binds GLP-1 with high affinity and is coupled to activation of adenylate cyclase, and does not bind peptides of related structure and similar function, such as glucagon, gastric inhibitory peptide, vasoactive intestinal peptides, or secretin.
Abstract: Glucagon-like peptide 1 (GLP-1) is a hormone derived from the preproglucagon molecule and is secreted by intestinal L cells. It is the most potent stimulator of glucose-induced insulin secretion and also suppresses in vivo acid secretion by gastric glands. A cDNA for the GLP-1 receptor was isolated by transient expression of a rat pancreatic islet cDNA library into COS cells; this was followed by binding of radiolabeled GLP-1 and screening by photographic emulsion autoradiography. The receptor transfected into COS cells binds GLP-1 with high affinity and is coupled to activation of adenylate cyclase. The receptor binds specifically GLP-1 and does not bind peptides of related structure and similar function, such as glucagon, gastric inhibitory peptide, vasoactive intestinal peptide, or secretin. The receptor is 463 amino acids long and contains seven transmembrane domains. Sequence homology is found only with the receptors for secretin, calcitonin, and parathyroid hormone, which form a newly characterized family of G-coupled receptors.
964 citations
409 citations
TL;DR: This review article deals with recent developments in molecular and physiological aspects of chitinases from plants, fungi, bacteria, insects and fishes.
Abstract: This review article deals with recent developments in molecular and physiological aspects of chitinases from plants, fungi, bacteria, insects and fishes
343 citations
TL;DR: The role of a family history of selected neoplasms in first‐degree relatives in the risk of gastrointestinal cancers has been investigated, but requires further quantification.
Abstract: Background. The role of a family history of selected neoplasms in first-degree relatives in the risk of gastrointestinal cancers has been investigated, but requires further quantification.
Methods. A case-control study was conducted in northern Italy on 628 histologically confirmed incident cases of stomach cancer, 766 cases of colon cancer, 456 cases of rectal cancer, and 1766 controls admitted to hospital for acute, nonneoplastic, non-digestive tract disorders.
Results. Significant associations were observed between a family history of gastric cancer and stomach cancer risk (relative risk [RR], 2.6), and between a family history of intestinal cancer and colon (RR, 2.4) and rectal cancer (RR, 1.7). There was a tendency for the risks to be above unity for a family history of stomach cancer and for a number of other cancer sites (including esophagus, intestines, liver, pancreas, gallbladder, and lung), and the RR were of borderline statistical significance for cancer of the liver and intestines. The RR for a family history of lung cancer was 1.5 for stomach, 1.2 for colon, and 1.3 for rectal cancer, with none of the estimates being significant. There was no consistent pattern of risk with reference to the type of first-degree relationship; the RR was similar for stomach cancer with reference to parents and siblings, and for colon and rectal cancer, it was only moderately higher with reference to siblings. Significant trends in risk with the number of first-degree relatives were observed for all three cancer sites investigated.
Conclusions. In terms of population attributable risk, approximately 8% of stomach cancers and 3% of colorectal cancers would be related to this familial component.
335 citations
TL;DR: The glycoprotein clusterin has recently entered the scientific arena in diverse guises and may serve important functions in tissue remodelling, immune defense and transport of biologically active peptides.
335 citations
Journal Article•
TL;DR: The striking differences between cytokine profiles as well as the divergent efficacy of anti-TNF-alpha antibody after i.p.v. challenges suggest that TNF- alpha may not be as important in the pathogenesis of lethal peritonitis than after lethal acute bacteremia.
Abstract: The production of TNF-alpha, IL-1, and IL-6 was measured in mice after bolus i.v. Escherichia coli O111 LPS injections and during bacteremia induced either by bolus i.v. or by i.p. challenges of live E. coli O111. High but transient TNF-alpha peaks were observed after bolus i.v. LPS or bacterial challenges. In contrast, the levels during lethal peritonitis increased progressively to values 50- to 100-fold lower than the peak values observed after i.v. injections, and remained sustained until death. Whereas after i.v. challenge with 1000 LD50 of LPS, anti-TNF-alpha antibody fully protected mice from death and reduced serum IL-1 and IL-6 levels, anti-TNF-alpha antibody did not improve the survival of mice nor reduced serum IL-1 and IL-6 levels after i.p. bacterial challenge. In contrast to anti-TNF-alpha antibodies, anti-LPS antibodies were protective in the peritonitis model. Protection was accompanied by a striking reduction of bacterial numbers and of TNF-alpha, IL-1, and IL-6 levels in the serum, but the levels of these cytokines were only marginally affected in the peritoneal lavage fluid. This latter observation demonstrates that the local peritoneal cytokines did not diffuse readily into the circulation, thus suggesting that at least part of the circulating cytokines are produced systemically. In conclusion, the striking differences between cytokine profiles as well as the divergent efficacy of anti-TNF-alpha antibody after i.v. bolus and after i.p. challenges suggest that TNF-alpha may not be as important in the pathogenesis of lethal peritonitis than after lethal acute bacteremia.
242 citations
TL;DR: The regulatory unit of Bacillus subtilis strain 168 encompassing the structural genes of the N-acetylmuramoyl-L-alanine amidase and of its modifier has been sequenced, and found to be a divergon consisting of divergently transcribed operons lytABC and lytR.
Abstract: The regulatory unit of Bacillus subtilis strain 168 encompassing the structural genes of the N-acetylmuramoyl-L-alanine amidase and of its modifier has been sequenced, and found to be a divergon consisting of divergently transcribed operons lytABC and lytR. Proteins LytA, LytB and LytC are endowed with export signal peptides. Mature LytA is a 9.4 kDa, highly acidic polypeptide whose deduced amino acid sequence points to a lipoprotein. LytB and LytC, the modifier and the amidase, are highly basic. After cleavage of the signal sequence their molecular masses are 74.1 and 49.9 kDa, respectively. These two proteins share considerable homology in their N-terminal moieties and have three GSNRY consensus motifs, characteristic of nearly all amidases. The C-terminal moiety of LytB exhibits homology to the product of spollD. LytR is a 35 kDa protein which acts as an attenuator of the expression of both lytABC and lytR operons. Transcription of the lytABC operon proceeds from two promoters: PD, identified as P28–7 (Gilman et al., 1984), and an upstream PA. The former only is subject to LytR attenuation. Translational initiation of lytB and lytC is directed by UUG start codons, suggesting that lytA, B and C undergo coupled translation. Transcription of lytR is initiated at two start sites, one of which corresponds to a highly intense PA promoter whereas the other does not seem to share much homology with any of the known promoter consensus sequences. Both promoters are attenuated by LytR. It is confirmed that the synthesis of the amidase is controlled at least in part by SigD, i.e. that it belongs to the fla regulon and that its activity, or part of it, is co-regulated with flagellar motility. The role of the mutations conferring the Sin, Fla and Ifm phenotypes in the expression of the lytABC operon is discussed.
241 citations
TL;DR: In this paper, the number of light neutrino species is found to be Nv=3.30% CL with the constraints of the standard electroweak model, which rules out the possibility of a fourth type of LN at 98% CL.
234 citations
TL;DR: In this paper, a new amplitude-modulated radio-frequency pulses are proposed that allow one to achieve selective excitation, de-excitation, inversion, and refocusing of spin-1/2 systems in NMR.
224 citations
TL;DR: Ethanol, either added to the diet or substituted for other foods, increases 24-hour energy expenditure and decreases lipid oxidation.
Abstract: Background. Ethanol can account for up to 10 percent of the energy intake of persons who consume moderate amounts of ethanol. Its effect on energy metabolism, however, is not known. Methods. We studied the effect of ethanol on 24-hour substrate-oxidation rates in eight normal men during two 48-hour sessions in an idirect-calorimetry chamber. In each session, the first 24 hours served as the control period. On the second day of one session, an additional 25 percent of the total energy requirement was added as ethanol (mean [±SD], 96±4 g per day); during the other session, 25 percent of the total energy requirement was replaced by ethanol, which was isocalorically substituted for lipids and carbohydrates. Results. Both the addition of ethanol and the isocaloric substitution of ethanol for other foods reduced 24-hour lipid oxidation. The respective mean (±SE) decreases were 49.4±6.7 and 44.1 ±9.3 g per day (i.e., reductions of 36±3 percent and 31 ±7 percent from the oxidation rate during the control...
TL;DR: It is concluded that changes in fat mass significantly affect fat oxidation and that this process may contribute to the long-term regulation of fat and energy balance in obese individuals.
TL;DR: This observation, taken together with the fact that dibutyryl-cAMP application also results in enhanced glycogen resynthesis, strongly suggests that the long-term effect of VIP or NA is mediated by the cAMP second-messenger pathway.
Abstract: Vasoactive intestinal peptide (VIP) and noradrenaline (NA) have been previously shown to promote glycogenolysis in mouse cerebral cortex (Magistretti, 1990). This action, which is fully expressed within a few minutes, is exerted on astrocytes (Sorg and Magistretti, 1991). In the present article, we report a second, temporally delayed, action of VIP or NA in primary cultures of mouse cerebral cortical astrocytes; thus, following glycogenolysis, an induction of glycogen resynthesis is observed, resulting, within 9 hr, in glycogen levels that are 6-10 times higher than those measured before the application of either neurotransmitter. This effect of VIP or NA is concentration dependent and, for NA, is mediated by adrenergic receptors of the beta subtype. The continued presence of the neurotransmitter is not necessary for this long-term effect, since pulses as short as 1 min result in the doubling of glycogen levels 9 hr later. The induction of glycogen resynthesis triggered by VIP or NA is dependent on protein synthesis, since both cycloheximide and actinomycin D abolish it entirely. The ability to elicit glycogenolysis is not sufficient per se to trigger the induction of glycogen resynthesis. Thus, two glycogenolytic agents such as methoxamine, an alpha 1-adrenergic agonist, and phorbol 12,13-dibutyrate, both acting via protein kinase C activation, are unable to induce glycogen resynthesis. This observation, taken together with the fact that dibutyryl-cAMP application also results in enhanced glycogen resynthesis, strongly suggests that the long-term effect of VIP or NA is mediated by the cAMP second-messenger pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: It is shown that mice immunized with peptides or oligosaccharides conjugated to the 70‐kDa hsp produced high titers of IgG antibodies in the absence of any previous priming with BCG, and that preimmunization with the 65‐k da hsp could substitute for BCG in providing effective priming for the induction of anti‐(NANP) antibodies.
Abstract: In a recent work, we have shown that mycobacterial heat-shock proteins (hsp) of 65-kDa (GroEL-type) and 70-kDa (DnaK-type) acted as carrier molecules in mice, previously primed with Mycobacterium tuberculosis var. bovis (bacillus Calmette-Guerin, BCG), for the induction of high and long-lasting titers of IgG against the repetitive malaria synthetic peptide (NANP)40. Anti-peptide antibodies were induced when the malaria peptide, conjugated to the mycobacterial hsp, was given in the absence of any adjuvants (Lussow et al., Eur. J. Immunol. 1991. 87:2960). In this report, we show that mice immunized with peptides or oligosaccharides conjugated to the 70-kDa hsp produced high titers of IgG antibodies in the absence of any previous priming with BCG. The anti-peptide antibody response persisted for at least 1 year. This adjuvant-free carrier effect of the 70-kDa hsp was T cell dependent, since no anti-peptide nor anti-70-kDa IgG antibodies were induced in athymic nu/nu mice. Previous immunization of mice with the 65-kDa or 70-kDa hsp did not have any negative effect on the induction of anti-peptide IgG antibodies after immunization with hsp-peptide conjugates in the absence of adjuvants. Furthermore, preimmunization with the 65-kDa hsp could substitute for BCG in providing an effective priming for the induction of anti-(NANP) antibodies. Finally, both the 65-kDa and 70-kDa hsp acted as carrier molecules for the induction of IgG antibodies to group C meningococcal oligosaccharides, in the absence of adjuvants. These findings strongly suggest that the use of hsp as carriers in conjugated constructs for the induction of anti-peptide and anti-oligosaccharide antibodies could be of value in the design of new vaccines for eventual use in humans.
TL;DR: The cluster-like physical organization of these genes and concerted regulation during hematopoietic differentiation suggests that they are located in a developmentally activated chromatin domain promoting high-level, cell-specific expression in the monocyte-myelocyte lineage.
Abstract: The human neutrophil and monocyte-derived serine protease homologues neutrophil elastase (NE), proteinase 3 (PR3), and azurocidin (AZU) are involved in a variety of immune defense reactions. NE and PR3 assist in the destruction of phagocytosed microorganisms, cleave the important connective-tissue protein elastin, and generate chemotactic activities by forming alpha 1-proteinase inhibitor complexes and elastin peptides. AZU is cytotoxic to certain microorganisms and chemotactic for monocytes. All three proteins are produced and packaged into azurophil granules in large quantities during neutrophil differentiation. We have isolated several cosmid clones each of which contains the functional genes for AZU, PR3, and NE in this order. The PR3 gene is separated by 8 kilobases from the 3' end of the AZU gene and by 3 kilobases from the 5' end of the NE gene. We report a physical map of the gene cluster, its location on chromosome 19pter, and the exon-intron organization of the AZU and PR3 genes. Our fluorescence in situ hybridization studies disprove the previous chromosomal assignment of the human NE gene to 11q14. The five exons of AZU and PR3 are organized like those of NE and other granule-associated serine proteases of hematopoietic cells. NE, PR3, and AZU are coordinately downregulated in the premonocytic cell line U937 during induced terminal differentiation. The cluster-like physical organization of these genes and concerted regulation during hematopoietic differentiation suggests that they are located in a developmentally activated chromatin domain promoting high-level, cell-specific expression in the monocyte-myelocyte lineage.
Journal Article•
TL;DR: Synthetic constructs assembled as multiple Ag peptide systems containing repetitive sequences of Plasmodium falciparum and PlasModium berghei may represent possible candidates for a malaria vaccine.
Abstract: Synthetic constructs were assembled as multiple Ag peptide systems containing repetitive sequences of Plasmodium falciparum and Plasmodium berghei, the causative agents of human and murine malaria respectively, and two universal human tetanus toxin T cell epitopes 830-843 and 947-967. These constructs were tested for antibody production in mice and for their capacity to stimulate human PBL and tetanus toxin-specific T cell clones. A high antibody titer can be obtained in mice when multiple Ag peptide systems are injected in various adjuvants or in PBS alone. Furthermore, all constructs can activate PBL from every donor tested. However, a variable response was obtained when different clones specific for the two tetanus toxin universal epitopes were used. These constructs may represent possible candidates for a malaria vaccine.
TL;DR: It is concluded that the TBM alpha 1 isoform is necessary and sufficient to confer the ouabain resistant phenotype and some specific sequence of the beta subunit can modulate the activation of the Na,K-pump by extracellular potassium ions.
TL;DR: In demineralized sections, the collagen fibers of the bone matrix tended to be somewhat thinner and occasionally less densely packed in the vicinity of the implant surface, but they extended all the way to the titanium surface, without any intervening fibril-free layer.
Abstract: This experiment was aimed at studying the intact tissue/implant interface of non-submerged dental implants with a titanium surface. Epoxy-resin replicas were fabricated from 3.05 x 8 mm cylindrical titanium implants with a plasma-sprayed apical portion and a smooth coronal collar. The replicas were coated with a 90-120-nm-thick layer of pure titanium and autoclaved. The coated replicas were inserted as non-submerged endosseous implants in the edentulous premolar region of dog mandibles and allowed to heal for three months. Jaw sections containing the implants were processed for light and electron microscopic study of the intact tissue/implant interface with and without prior demineralization. Gingival connective tissue fibers were closely adapted to the titanium layer, in an orientation more or less parallel to the implant surface. There was no evidence of any fiber insertions into the surface irregularities of the smooth or rough titanium surface. Undemineralized bone was intimately adapted to the titanium surface without any intervening space. In demineralized sections, the collagen fibers of the bone matrix tended to be somewhat thinner and occasionally less densely packed in the vicinity of the implant surface. However, they extended all the way to the titanium surface, without any intervening fibril-free layer.
TL;DR: The knowledge of the primary structure of several elements of the aldosterone response system allows us to understand abnormal regulation of Na+ balance at the molecular level and, potentially, to identify genetic alterations responsible for these defects.
Abstract: Aldosterone, like other steroid hormones, initiates its effects by binding to intracellular receptors; these receptors are then able to control the transcription of several genes. The products of these genes eventually modulate the activity of ionic transport systems located in the apical and the basolateral membrane of specialized epithelial cells, thereby modulating the excretion of Na+ and K+ ions. Considerable progress has been made recently in understanding these mechanisms and the structure of the proteins involved in these processes. A novel principle has been discovered to explain the selective effect of aldosterone on its target epithelia. These tissues exclude competing glucocorticoid hormones by the activity of the 11 beta-hydroxysteroid dehydrogenase to allow aldosterone, an enzyme-resistant steroid, to bind to its receptors. Aldosterone induces numerous changes in the activity of membrane ion transport systems and enzymes and cell morphology. Although the enhancement of Na,K-ATPase synthesis and the increase of the number of active Na+ channels in the apical membrane appear as both direct and primary effects, the mechanisms of the other effects remain to be determined. The knowledge of the primary structure of several elements of the aldosterone response system (e.g., mineralocorticoid receptor and Na,K-ATPase) allows us to understand abnormal regulation of Na+ balance at the molecular level and, potentially, to identify genetic alterations responsible for these defects.
TL;DR: The incorporation of serine as oxazolidine protected “pseudo proline “in a host peptide results in the disruption of secondary structure formation thus increasing the solvation of the peptide chain.
TL;DR: The chapter focuses on the relatively high Km for glucose of GLUT-2, which is necessary for its specific transport functions in the tissues in which it is expressed, such as the liver, intestine, kidney, and pancreatic islet β cells.
Abstract: Publisher Summary This chapter discusses the molecular and cellular physiology of GLUT-2, which is the liver/β-cell glucose transporter. The chapter focuses on the relatively high Km for glucose of GLUT-2, which is necessary for its specific transport functions in the tissues in which it is expressed, such as the liver, intestine, kidney, and pancreatic islet β cells. The chapter also examines the involvement of this high-Km transporter in the control of glucose-induced insulin secretion by the pancreatic β cells and its role in the development of β-cell dysfunction characteristic of insulinomas and diabetic rat islets. The cloning of the liver glucose transporter is achieved by screening rat and human liver cDNA libraries with a cDNA probe for GLUT-1 using reduced stringency conditions. This technique also yields cDNA clones for all the other transporter isoforms cloned. The liver glucose transporter—GLUT-2—is 55% identical in amino acid sequence to GLUT-1. The characterization of GLUT-2 as a glucose carrier is completed by expressing the transporter in bacteria. GLUT-2 is expressed in a restricted set of organs that are of critical importance for the control of glucose homeostasis.
TL;DR: Mild alkaline hydrolysis reveals that the lipid components of GPI anchors are heterogeneous in that both base‐sensitive and base‐resistant lipid moieties can be found on most proteins.
Abstract: Numerous glycoproteins of Saccharomyces cerevisiae are anchored in the lipid bilayer by a glycophosphatidylinositol (GPI) anchor. Mild alkaline hydrolysis reveals that the lipid components of these anchors are heterogeneous in that both base-sensitive and base-resistant lipid moieties can be found on most proteins. The relative abundance of base-resistant lipid moieties is different for different proteins. Strong alkaline or acid hydrolysis of the mild base-resistant lipid component liberates C18-phytosphingosine indicating the presence of a ceramide. Two lines of evidence suggest that proteins are first attached to a base-sensitive GPI anchor, the lipid moiety of which subsequently gets exchanged for a base-resistant ceramide: (i) an early glycolipid intermediate of GPI biosynthesis only contains base-sensitive lipid moieties; (ii) after a pulse with [3H]myo-inositol the relative abundance of base-sensitive GPI anchors decreases significantly during chase. This decrease does not take place if GPI-anchored proteins are retained in the ER.
TL;DR: The overall results demonstrate the feasibility of tumor immunophotodiagnosis at the clinical level and confirm the specificity of tumor localization by the conjugate.
Abstract: Based on previous experiments in nude mice, showing that fluoresceinated monoclonal antibodies against carcinoembryonic antigen localized specifically in human carcinoma xenografts and could be detected by laser-induced fluorescence, we performed a feasibility study to determine whether this immunophotodiagnosis method could be applied in the clinic. Six patients, with known primary colorectal carcinoma, received an i.v. injection of 4.5 or 9 mg of mouse-human chimeric anti-carcinoembryonic antigen monoclonal antibody coupled with 0.10-0.28 mg of fluorescein (molar ratio 1/10 to 1/14). The monoclonal antibody was also labeled with 0.2-0.4 mCi of 125I (1 Ci = 37 GBq). Photodetection of the tumor was done ex vivo on surgically resected tissues for the six patients and in vivo by fluorescence rectosigmoidoscopy for the sixth patient. Upon laser irradiation, clearly detectable heterogeneous green fluorescence from the dye-antibody conjugate was visually observed on all six tumors; almost no such fluorescence was detectable on normal mucosa. The yellowish tissue autofluorescence, which was emitted from both tumor and normal mucosa, could be subtracted by real-time image processing. Radioactivity measurements confirmed the specificity of tumor localization by the conjugate; tissue concentrations of up to 0.059% injected dose per g of tumor and 10 times less (0.006%) per g of normal mucosa were found. The overall results demonstrate the feasibility of tumor immunophotodiagnosis at the clinical level.
TL;DR: Molecules from the parasite that can induce, and are the target of, the protective T-cell response are being characterized and appear to play a role in protective immunity.
TL;DR: In situ laser extraction techniques have been developed for determining the stable isotope ratios in carbonates, silicates, oxides and sulfides with high spatial resolution as discussed by the authors, and these methods use the laser as a heat source to extract the appropriate gas.
Abstract: In situ laser extraction techniques have been developed for determining the stable isotope ratios in carbonates, silicates, oxides and sulfides with high spatial resolution. All of these methods use the laser as a heat source to extract the appropriate gas. Carbonate analyses are made by decomposing the carbonate at elevated temperatures to liberate CO2. Oxygen is extracted from silicates by heating the sample surface in a halogen fluoride atmosphere, and sulfur is extracted from sulfides by heating in either an O2 or halogen fluoride atmosphere. The analytical precision for carbonate analyses isσ = ±0.2‰and±0.1‰ forδ18C andδ18O, respectively. Higher scatter in some samples is probably due to sample heterogeneities. In situ silicate analyses have a precision ofσ = ±0.1‰0.6‰ depending upon sample material and heterogeneity. The measured isotopic ratio may be different from the accepted value, but is insensitive to changing operating conditions. Published results for in situ analyses of sulfides have a precision of< ±0.3‰ (1σ). Theδ34S-values obtained with the laser method are less than accepted values, and vary according to the sulfide.
A new level of spatial resolution is possible with the in situ laser methods. Oxygen isotope variations of10‰ are found to exist at a scale of< 1mm in greenschist-grade quartz veins. Carbon and oxygen isotopic ratios may be quite heterogeneous in hydrothermal calcites and low-grade marbles. High-grade marbles are isotopically homogeneous. Determinations of isotopic variations at the sub-millimeter scale may be used as an indicator of fluid sources and mechanisms of isotopic exchange.
TL;DR: In this paper, the effects of blocking intraocular axoplasmic transport (with colchicine) or action potentials (by means of TTX) on the optic tecta of day 16 chick embryos were investigated.
Abstract: We have investigated how neurons in the optic tecta of embryonic day 16 chick embryos depend for survival on their afferents from the retina. To distinguish between activity-mediated effects and other, "trophic," ones, we compared the effects on the tectal neurons of blocking intraocular axoplasmic transport (with colchicine) or action potentials (by means of TTX). Both interventions rapidly induced the appearance of dying (pyknotic) neurons in the tectum, with major increases in their number occurring within 13 hr post-colchicine and within 9 hr post-TTX. Following both drugs, the dying neurons were morphologically similar, and in both cases the cell death depended on protein synthesis. However, the effects of colchicine and of TTX could be dissociated, since the most superficial tectal neurons became pyknotic only in response to colchicine, and, with a sufficiently short survival time (9 hr), the deep cells of the stratum griseum centrale became pyknotic only in response to TTX. We hence argue that the survival of the tectal neurons depends on their ongoing maintenance by substances released from retinotectal axon terminals, the release being activity dependent in the case of the deep neurons but independent of activity in the case of the superficial ones.
TL;DR: It is suggested that total calorie intake and other dietary factors potentially linked with benign gallbladder conditions are involved in the aetiology ofgallbladder cancer.
Abstract: A population-based case-control study of gallbladder cancer was conducted in the south-west of Poland, within the frame-work of the SEARCH Programme of the International Agency for Research on Cancer. A total of 73 cases and 186 controls were interviewed using a questionnaire including demographic and socio-economic factors, education, smoking, alcohol, tea and coffee consumption, and past medical history. A validated diet history was used to estimate the daily intake of calories, fats, carbohydrates, proteins, cholesterol, fibres and vitamins C and E. Gallbladder disease was the major determinant of subsequent gallbladder cancer: 41 cases (56%) vs. 15 (8%) controls had a past history of gallbladder disease, corresponding to an odds ratio (OR) of 12.5 (95% confidence interval, 5.8 to 26.6), and the OR was 12.1 for gallbladder problems dating back 20 years or more in the past. There was an inverse relationship with education, the OR being 0.3 (95% CI 0.1 to 1.2) for 13 years of education or more vs. less than 7. Gallbladder cancer risk was positively associated with total calorie intake, with ORs of 1.4, 1.5, 4.1 for the 3 upper quartiles compared with the lowest one (trend, p less than 0.01). Weaker direct associations were observed for proteins, carbohydrates and cholesterol. There was some suggestion of inverse associations with fibre intake, and a more consistent one with vitamins C and E. These results further quantify the role of gallstones, and suggest that total calorie intake and other dietary factors potentially linked with benign gallbladder conditions are involved in the aetiology of gallbladder cancer.
TL;DR: The structure of the M cell, its function in promoting the immune response and its exploitation by invading pathogens are described and the other immunological function of epithelia, secretion of polymeric IgA, is reviewed.
TL;DR: In this paper, a transtensive phase of diffuse crustal extension is recognized in many intra-continental rifts, followed by a pre-oceanic rifting phase during which extensional strain was concentrated on the axial rift zone.