Nasal carriage of Staphylococcus aureus.
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Biomedical subjects
Publications and source records attributed to U Glück.
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OBJECTIVES: The alkaline single cell gel electrophoresis or "comet" assay allows measurement of DNA damage in single cells with a high degree of sensitivity, e.g., for investigations of the effect of environmental agents with DNA-damaging potential. This study aimed to adapt this test to respiratory cells of the human nasal mucosa to examine the genotoxic effect of air pollution (cigarette smoke). STUDY DESIGN: In a prospective study, nasal epithelia of 16 cigarette smokers were examined by the adapted comet assay and the results were correlated with the results of the Papanicolaou-stained nasal cytology, carried out in a blinded fashion. The control group comprised 20 non-smoking men. All subjects under investigation were healthy office workers. METHODS: Nasal epithelia were harvested from the maxilloturbinates. One part of cells was Papanicolaou stained and evaluated by cytopathologists. The comet assay was performed on the other part of the cells. The examiners were blinded to the study and control groups. RESULTS: Among cigarette smokers, a significant correlation between cytopathological cell nucleus changes (metaplasia and dysplasia) and the DNA migration (tail lengths) in the comet assay was found as a sign of DNA damage. This was not found in nonsmoking control persons. CONCLUSIONS: These results confirm the sensitivity of the comet assay and the hypothesis that cell nucleus changes in conventional nasal cytology are associated with DNA damage.
UNLABELLED: The difference between the spectra of potential bacterial pathogens (PBPs) in the nasal vestibule and cavity has not been taken into account in clinical studies. PURPOSE: Since one can anticipate different flora in different kinds of mucosae, the authors compared bacterial species in the vestibule with those of the cavity. SUBJECTS AND METHOD: A total of 534 healthy male clerical workers in a downtown Lucerne office building were examined with fractionated swabs. RESULTS: PBPs, notably Staphylococcus aureus, were found in 412 subjects and surprisingly, differences in flora of the two sites were noted in 130 of them: PBPs were observed in the vestibule and not in the cavity in 85 of the subjects, and in 45 of them, the reverse was true. CONCLUSION: The practical implications of these findings are considerable regarding infection control in patients at increased infection risk.
Virosomal vaccines were prepared by extracting hemagglutinin (HA) and neuraminidase from influenza virus and incorporating it in the membranes of liposomes composed of phosphatidylcholine. Two intranasal spray vaccine series were prepared: one series comprised 7.5 micrograms of HA of each of three strains recommended by the World Health Organization and 1 microgram of Escherichia coli heat-labile toxin (HLT), and the other contained the HA without HLT. In addition, a third vaccine preparation contained 15 micrograms of HA and 2 micrograms of HLT. The parenteral virosomal vaccine contained 15 micrograms of HA without additional adjuvant. The immunogenicity of a single spray vaccination (15 micrograms of HA and 2 micrograms of HLT) was compared with that of two vaccinations (7.5 micrograms of HA with or without 1 microgram of HLT) with an interval of 1 week in 60 healthy working adults. Twenty volunteers received one parenteral virosomal vaccine. Two nasal spray vaccinations with HLT-adjuvanted virosomal influenza vaccine induced a humoral immune response which was comparable to that with a single parenteral vaccination. A significantly higher induction of influenza virus-specific immunoglobulin A was noted in the saliva after two nasal applications. The immune response after a single spray vaccination was significantly lower. It could be shown that the use of HLT as a mucosal adjuvant is necessary to obtain a humoral immune response comparable to that with parenteral vaccination. All vaccines were well tolerated.
Compared with the lower respiratory tract, the nose reacts with greater physiological sensitivity to environmental stimuli by means of secretion, obstruction and sneezing. When a certain level of nasal reaction is exceeded, we have what is called vasomotoric rhinopathy. Systemic illnesses can also be reflected in the nose. Timely recognition can prevent life-threatening situations such as arise in Wegener's granulomatosis or rhinoliquorrhoea. In rhinitic complaints thought should also be given to the possible side effects of medication. Antihypertensive products and hormonal contraceptives are those most frequently responsible. The suffering experienced by a patient with chronically blocked nasal breathing is often underestimated. A variety of possible causes are reviewed.
BACKGROUND: Control of the nuclear localization of specific proteins is an important mechanism for regulating many signal transduction pathways. Upon activation of the Wnt signaling pathway, beta-catenin localizes into the nucleus and interacts with TCF/LEF-1 (T-cell factor/lymphocyte enhancer factor-1) transcription factors, triggering activation of downstream genes. The role of regulated nuclear localization in beta-catenin signaling is still unclear. Beta-catenin has no nuclear localization sequence (NLS). Although it has been reported that beta-catenin can piggyback into the nucleus by binding to TCF/LEF-1, there is evidence that its import is independent of TCF/LEF-1 in vivo. Therefore, the mechanism for beta-catenin nuclear localization remains to be established. RESULTS: We have analyzed beta-catenin nuclear import in an in vitro assay using permeabilized cells. Beta-catenin docks specifically onto the nuclear envelope in the absence of other cytosolic factors. Docking is not inhibited by an NLS peptide and does not require importins/karyopherins, the receptors for classical NLS substrates. Rather, docking is specifically competed by importin-beta/beta-karyopherin, indicating that beta-catenin and importin-beta/beta-karyopherin both interact with common nuclear pore components. Nuclear translocation of beta-catenin is energy dependent and is inhibited by nonhydrolyzable GTP analogs and by a dominant-negative mutant form of the Ran GTPase. Cytosol preparations contain inhibitory activities for beta-catenin import that are distinct from the competition by importin-beta/beta-karyopherin and may be involved in the physiological regulation of the pathway. CONCLUSIONS: Beta-catenin is imported into the nucleus by binding directly to the nuclear pore machinery, similar to importin-beta/beta-karyopherin or other importin-beta-like import factors, such as transportin. These findings provide an explanation for how beta-catenin localizes to the nucleus without an NLS and independently of its interaction with TCF/LEF-1. This is a new and unusual mechanism for the nuclear import of a signal transduction protein. The lack of beta-catenin import activity in the presence of normal cytosol suggests that its import may be regulated by upstream events in the Wnt signaling pathway.
Modern toxicological studies have prompted us to rethink the role of olfaction and odours in our world. Our sense of smell is able to discriminate between an almost unlimited number of compounds of different chemical composition at extremely low threshold levels. Olfaction is classified as a chemical sense because of the bimolecular excitation process between the stimulant and receptor molecule. Receptor molecules of the olfactory epithelium have a variable region of the molecule which can differentiate between an unlimited number of aromatics. The sense of smell--the oldest phylogenetic sense--is therefore in very intensive contact with the "chemical" environment. Virtually all of the aromatic products which we are exposed to are highly complex chemical mixtures of numerous individual components which have a toxic potential little investigated to date. The perception of odours can be interpreted as a warning--a protective mechanism necessary for survival. At the same time, however, the exaggerated use of perfumes is held to be indicative of a highly cultured status. Unlike any other sense, that of smell is directly connected to archaic areas of the paleocortex region of the cerebral hemisphere, so that an odour will fill us with joy or abhorrence outside of our control. Odours cannot, therefore, be analyzed rationally without eliciting instinctive reactions, positive or negative, which result in acceptance or rejection. The highly developed memory for odour types is believed to be coupled to the route of the olfactory tract. The use of olfactometry today enables odours to be reliably quantified and characterized in a reproducible manner.
Actin filaments are major determinants of cell shape, motility and adhesion, which control important biological processes including embryonic development and wound healing. These processes are associated with changes in actin assembly, which is regulated by controlling the balance between polymerized and non-polymerized actin. To maintain a significant pool of non-polymerized actin, mechanism(s) linking actin synthesis to its state of polymerization were proposed. We have studied this relationship between actin synthesis and organization by modulating actin assembly using different drugs. Unassembled actin was increased in 3T3 cells using either the Clostridium botulinum C2 toxin, which ADP-ribosylates actin, or by latrunculin A, a Red Sea sponge product, which binds monomeric actin. The synthesis of actin was dramatically reduced in these cells owing to a concomitant decrease in actin RNA level. Similar results were obtained with HeLa cells grown in both monolayer and in suspension, suggesting that cell shape changes associated with drug treatment are not the primary cause for the effect on actin synthesis. In contrast, the scrape-loading of 3T3 cells with phalloidin, a stabilizer of polymerized actin that increased the level of assembled actin, resulted in elevated actin synthesis and RNA content. The expression of vinculin, a major component of adhesion plaques and cell-cell junctions, which is involved in actin-membrane associations, was altered in parallel with that of actin in cells treated with these drugs. The decrease in actin RNA resulted from destabilization of actin mRNA in cells where unassembled actin level was elevated. This is suggested by the unchanged transcription of actin in isolated nuclei from drug-treated cells, and by demonstrating that actin mRNA was degraded faster in cells after C2 toxin treatment than in control cells. This feedback control mechanism is mainly confined to the cytoplasm, as it remained active in enucleated cells. The results suggest the existence of an autoregulatory pathway for the expression of actin and other microfilament-associated proteins which is linked to the state of actin polymerization in the cell.
The long-term sequelae on kidney function and blood pressure of renal shock wave treatment were studied in normotensive Wistar rats, contralaterally nephrectomized Wistar rats and borderline hypertensive F1-hybrids bred from stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats. Renal shock wave treatment raised arterial blood pressure in borderline hypertensive, but not in normotensive, rats. A concomitant impairment of ipsilateral renal function or perfusion was not seen despite macroscopic and microscopic evidence of a loss of functioning parenchyma. We conclude that extracorporeal shock wave treatment, by way of its detrimental effects on the kidney, has the potential to provoke arterial hypertension in rats, provided that a genetic predisposition exists.
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alpha-Actinin is an abundant actin crosslinking protein, also localized at adherens type junctions. In adhesion plaques, alpha-actinin can link the actin filaments to integrin via vinculin and talin, or directly by binding to the cytoplasmic domain of beta 1-integrin. The expression of alpha-actinin is rapidly elevated in growth-activated quiescent cells, and is reduced in SV40-transformed 3T3 cells and various differentiating cell types (reviewed by Glück, U., Kwiatkowski, D. J. and Ben-Ze'ev, A. Proc. Nat. Acad. Sci. USA 90, 383-387, 1993). To study the effect of changes in alpha-actinin levels on cell behavior, alpha-actinin expression was elevated in 3T3 cells by transfection with a full-length human nonmuscle alpha-actinin cDNA. To suppress alpha-actinin levels, 3T3 cells were transfected with an antisense alpha-actinin cDNA construct. Cells overexpressing alpha-actinin by 40-60% displayed a significant reduction in cell motility, as demonstrated by their slower locomotion into an artificial wound, and by forming shorter phagokinetic tracks on colloidal gold-coated substrata. 3T3 cells in which the expression of alpha-actinin was reduced to 25-60% of control levels, after antisense alpha-actinin transfection, had an increased cell motility. Moreover, such alpha-actinin-deficient 3T3 cells formed tumors upon injection into nude mice. The results demonstrate that modulations in alpha-actinin expression can affect, in a major way, the motile and tumorigenic properties of cells, and support the view that decreased alpha-actinin expression could be a common regulatory pathway to malignant transformation of 3T3 cells.
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Eighty-four patients with clinical findings of hyperactive rhinopathy and no significant septal deviations were treated for 4 weeks with topical applications of capsaicin, which is the pungent substance in hot peppers. A neutral solution of low-dose capsaicin allowed patients to administer self-therapy without the need for local anesthesia. The majority of the patients showed a marked reduction in symptoms without significant side effects. Patients with (additional) allergic or medication-related rhinopathy seemed to show fewer therapeutic effects when compared to patients with only hyperactive rhinopathy.
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Human cytoskeletal alpha-actinin cDNA was transfected into highly malignant simian virus 40-transformed BALB/c 3T3 (SVT2) cells that express 6-fold lower levels of alpha-actinin than nontransformed BALB/c 3T3 cells. SVT2 clones expressing various levels of alpha-actinin were isolated and their structure and tumorigenic properties were determined. Transfected SVT2 clones expressing alpha-actinin at levels found in nontumorigenic 3T3 cells displayed a flatter phenotype, a decreased ability to grow in suspension culture in soft agar, and a marked reduction in their ability to form tumors in syngeneic BALB/c mice and in athymic nude mice. Clones overexpressing alpha-actinin at the highest level (about 2-fold higher than 3T3 cells) were completely suppressed in their ability to form tumors in syngeneic BALB/c mice. The results suggest that alpha-actinin, an actin-crosslinking protein that is also localized in cell junctions, may have an effective suppressive ability on the transformed phenotype.
The evolution of the larynx from its first appearance in lung fish up to the stage of its more elaborate structure in mammals is reviewed. Each step of development is illustrated by examples from animals. The function of the larynx has been described since the beginning of its evolution as that of preventing the entrance into the pulmonary air tract of any substances except air. In addition to this primitive and all-important function, in the course of the time the larynx, having the physical properties of an organ-pipe, has acquired the secondary function of sound production as an important means of communication.
Mouse endothelial-adipocyte cell line (14F1.1), which induces proliferation of mouse stem cells in culture, is also capable of supporting long-term survival in culture of human myeloid progenitor cells; colony forming unit-granulocyte/macrophage (CFU-GM) was recovered from cultures incubated with the 14F1.1 cell line after over a month of incubation. The CFU-GM population increased beyond the input number, whereas, in control cultures initiated without stromal cells, the number of progenitors gradually declined. Addition of a relatively low concentration of human colony-stimulating factors (CSFs) into the cultures promoted the formation of "cobblestone areas," where mouse stroma and human hemopoietic cells closely interacted. 14F1.1 supernatant alone did not support the survival of human CFU-GM but synergized with the function of human granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate adherent macrophage proliferation.
The expression of the adherens junction proteins vinculin, alpha-actinin, and talin was compared in serum-stimulated 3T3 cells and in regenerating rat liver following partial hepatectomy. The levels of vinculin RNA and protein synthesis were rapidly and transiently elevated in growth-activated fibroblasts (peaking at 2-3 h) and in regenerating liver (at 4-8 h), preceding the replicative stage. alpha-Actinin expression was also induced, but more slowly (peaking at 6-8 h in 3T3 cells and at 28 h in regenerating liver), and remained elevated when DNA synthesis was proceeding in both systems. The expression of talin RNA was only slightly elevated in 3T3 cells following serum stimulation, and it remained largely unchanged in regenerating liver. The levels of RNA coding for fibronectin and for the beta 1-integrin subunit were transiently and extensively induced during liver regeneration (fibronectin with a peak at 8 h and beta 1-integrin at 12 h). The uvomorulin RNA level, and the expression of the liver-specific genes albumin and transthyretin, decreased in regenerating liver. The results suggest a physiologically significant regulation in the expression of structural components which link the extracellular matrix to the microfilament system in growth-activated fibroblasts and in regenerating liver.