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Biomedical subjects

U Glück

Publications and source records attributed to U Glück.

At least 19 recordsLinked to original sources

[The power of odors--pathogenic or unpleasant].

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.

Humans

The state of actin assembly regulates actin and vinculin expression by a feedback loop.

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.

3T3 Cells

Extracorporeal shock wave treatment raises blood pressure in borderline hypertensive rats.

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.

Animals

Modulation of alpha-actinin levels affects cell motility and confers tumorigenicity on 3T3 cells.

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.

3T3 Cells

[Clinical experiences with local capsaicin treatment of chronic rhinopathy].

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.

Administration, Intranasal

Suppression of tumorigenicity in simian virus 40-transformed 3T3 cells transfected with alpha-actinin cDNA.

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.

3T3 Cells

[Phylogenesis of the human larynx].

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.

Animals

Long-term survival of human myeloid progenitor cells induced by a mouse bone marrow stromal cell line.

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.

Animals

Regulation of adherens junction protein expression in growth-activated 3T3 cells and in regenerating liver.

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.

3T3 Cells

[The history of bronchial asthma].

'Panta rhei': everything flows. The significance of bronchial asthma is currently changing to no less a degree than medicine itself. In order to know where we are, we must know where we have come from. The historical course of bronchial asthma to some extent reflects the history of medicine itself: the Hellenic systems were followed by Byzantine, Galenic teaching methods, while Humanism and the Renaissance were followed by the considerable fireworks of early modern medicine. This continued with Magendie's experimental revolution in the 19th century and, finally, analytic medical research up to today.

Asthma

[Neglected allergens].

The atopic symptoms manifest themselves mainly in hay fever or bronchial asthma. In a not inconsiderable number of cases, the question of oral complaints, connected with the intake of certain foodstuffs, is ignored in the medical anamnesis. Here, we are dealing with what is known as food-associated allergy syndrome, which is largely based on a cross reaction between certain types of pollen (birch, alder, hazel and mugwort) and food allergens (drupes, pomes, nuts, vegetables such as celery, carrots and fennel, etc.). Whereas following the intake of fruit the complaints are usually restricted solely to the oral cavity and the throat (aphthas, stomatitis, swelling of the lips and/or tongue, irritation of the hard palate, hoarseness and compulsive clearing of the throat), nuts and celery among others from the family Compositae often cause acute, allergic attacks with sometimes serious general symptoms such as laryngeal oedema, bronchial asthma, urticaria and even anaphylactic shock. In the sensitization against animal allergens, it must not be forgotten that the most powerful immunogens are to be found, for example, in the urine of small rodents (mice and rats). In the manufacture or application of fish food with red gnat larvae, people who are disposed to this will often react with an attack of bronchial asthma.

Allergens

[The physiological significance of paranasal sinuses in man: speculations for 1800 years].

The function of the paranasal sinuses has been a controversial subject since the time of Galen (130-201 AD). A review of the literature reveals quite different beliefs about their biological purpose, and eight hypotheses have received particular attention: 1) They lighten the bones of the skull; 2) improve the resonance of the voice; 3) humidify and warm inspired air; 4) increase the area of the olfactory membrane; 5) serve as shock absorbers in mechanical impacts; 6) act as thermal insulators of the brain; 7) promote facial growth and architecture; and 8) persist as evolutionary relics or faults. Scrutiny of these hypotheses shows that none has a scientific basis.

Body Temperature Regulation

[Pollinosis and oral allergy syndrome].

Allergic diseases are frequent, affecting 10%-15% of the population. The atopic symptoms manifest mainly as pollinosis or bronchial asthma. Many of the atopic patients have an additional food-related allergy, often due to a cross-reactivity between pollen allergens (birch, hazelnut, alder, mugwort) and food allergens. The foods which most frequently elicit oral, gastro-intestinal or anaphylactic symptoms are fruits such as apples, peaches, cherries or apricots, but also nuts and vegetables from the botanic group of the compositae (celery, carrots, fennel, sunflower kernels, camomile, parsley, etc.). While fruits mainly cause oral symptoms (aphthae, stomatitis, swelling of the lips or tongue, pharyngitis, hoarseness and laryngeal oedema), nuts and celery can often also induce acute generalized symptoms, such as severe laryngeal oedema, bronchial asthma, urticaria or allergic shock. In our experience these patients tend to minimize their oral symptoms and the practitioner has often to ask about them specifically.

Anaphylaxis

[The antimicrobial effect of lysozyme on nasal mucosa].

We tested the effect of lysozyme on the nasal mucosa in a controlled double-blind in vivo study. The administration of non-pathogenic vaccine strains of living measles virus and of living Vivotif bacteria (attenuated Salmonella typhi) to 14 healthy subjects showed that lysozyme possesses a clear antimicrobial and antiviral effect.

Administration, Intranasal

Long-term proliferation of human leukemia cells induced by mouse stroma.

Acute lymphocytic leukemias (ALL) of infants and children were found to preferentially survive in coculture with a cloned cell line of endothelial adipose cells (14F1.1) from mouse bone marrow. One of these ALLs expressed a phenotype compatible with an early stage of differentiation (HLA-DR+, CD19+, and CD34+) and exhibited extensive growth in the presence of the mouse stromal cells during a period greater than 25 weeks following seeding. These ALL cells were strictly dependent upon the mouse stromal clone 14F1.1 and failed to proliferate in the absence of the endothelial adipocytes or with a variety of "feeder cells." Throughout the culture period the cells died if removed from the stroma. No similarly proliferative cell population with strict dependence upon stromal cells was found among a variety of other leukemias including hairy cell, acute myeloid, and chronic lymphocytic leukemia. The 14F1.1 clone has been previously found to promote the renewal of mouse and human stem cells. It is therefore possible that leukemias with a stem cell-like phenotype depend upon stromal cell factors similar to those affecting the growth of normal stem cells. These factors appear to operate across genetic barriers.

Antibodies, Monoclonal