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Biomedical subjects

C Hofmann

Publications and source records attributed to C Hofmann.

At least 55 records · Page 3Linked to original sources
PubMed1999

Comparison of upper esophageal sphincter opening in healthy asymptomatic young and elderly volunteers.

Deglutitive upper esophageal sphincter opening (UES) in the elderly has been incompletely studied. Our aim was to determine in the elderly the temporal and dimensional characteristics of deglutitive UES opening; anterior and superior hyoid and laryngeal excursions as measures of distracting forces imparted on the UES; and hypopharyngeal intrabolus pressure (IBP). Fourteen healthy elderly and 14 healthy young volunteers were studied by concurrent videofluoroscopy and hypopharyngeal manometry during swallowing of 5- and 10-mL barium boluses. The anteroposterior UES diameter, as well as the anterior hyoid bone and laryngeal excursion, was significantly smaller in the elderly compared to the young (p < .05) for 5-mL barium boluses, but not for 10-mL boluses. The lateral diameter of UES opening was similar between groups for all boluses. The IBP for 5- and 10-mL swallows in the elderly was significantly higher than that in the young (p < .05). We conclude that anteroposterior deglutitive UES opening and hyoid bone and thyroid cartilage anterior excursion are reduced in the elderly. These changes are associated with increased IBP, suggesting a higher pharyngeal outflow resistance in the elderly compared to the young.

Adult↗
PubMed1999

Protection of baculovirus-vectors against complement-mediated inactivation by recombinant soluble complement receptor type 1.

Baculovirus-based vectors are efficient means for gene transfer into hepatocytes in vitro. However, gene transfer in vivo is hampered by inactivation of baculovirus by the complement system. In this study, we demonstrate protection of baculovirus vectors against complement-mediated inactivation through recombinant soluble complement receptor type 1 (sCR1). Blocking of only the alternative complement pathway by a mutant of sCR1 did not result in baculovirus survival in human serum. The data suggest the use of sCR1 as a potent drug to facilitate baculovirus-mediated gene transfer into hepatocytes in vivo.

Animals↗
PubMed1999

Glucocorticoid fast feedback is not altered in rats prenatally exposed to ethanol.

Animals exposed in utero to ethanol exhibit hormonal hyperresponsiveness to stressors in adulthood. One possible mechanism for this hyperresponsiveness is a deficit in negative feedback regulation of the hypothalamic-pituitary-adrenal axis. The present study tested the hypothesis that a deficit in the fast feedback time domain may play a role in the hormonal hyperresponsiveness in ethanol-exposed rats. Sprague-Dawley offspring from prenatal ethanol (E), pair-fed (PF), and ad lib-fed control (C) groups were tested in two experiments. Experiment 1 used a swim stress paradigm and tested animals at the trough of the corticosterone (CORT) circadian rhythm. Experiment 2 used ether stress and tested animals at the peak of the circadian rhythm. Animals were injected subcutaneously with CORT or saline and were immediately subjected to either a 5-min swim stress or a 1-min ether stress. Half the animals were terminated immediately after stress (5-min postinjection), and the rest were terminated 25 min later. Plasma levels of CORT and ACTH were assayed to determine whether E animals differed from control animals in showing a CORT-induced blunting of the ACTH response to the stressor, indicating alterations in fast feedback regulation. Injection of CORT significantly blunted the ACTH response to swim stress (experiment 1) in E, PF, and C females and males, compared with their saline-injected counterparts. There were no significant differences among groups. Similarly, CORT-injected males in E, PF, and C groups all exhibited a significantly blunted ACTH response to ether stress (experiment 2). CORT-injected C females also exhibited a significantly blunted ACTH response to ether stress, whereas E females showed an obvious CORT decrease that approached significance. However, PF females showed a clear deficit in fast feedback regulation. Together, these data suggest that: (1) CORT injection can serve as a fast feedback signal that can blunt the ACTH response to a stressor; and (2) prenatal ethanol exposure does not produce a deficit in hypothalamic-pituitary-adrenal feedback regulation in the fast feedback time domain.

Adrenal Cortex Hormones↗
PubMed1999

[Propofol for sedation in gastroscopy--a randomized comparison with midazolam].

UNLABELLED: Midazolam, a benzodiazepine with amnestic and sedative effects is the drug of choice for sedation of patients undergoing upper gastrointestinal endoscopy. Propofol, a phenolic derivate, is a short-acting anesthetic producing a more rapid onset sedation amnesia and a shorter recovery than midazolam: In higher doses it acts as hypnotic. The aim of this study was to evaluate both drugs in a prospective randomized trial for sedation of patients undergoing esophagogastroduodenoscopy (EGD). METHODS: 60 patients undergoing EGD were randomized to receive either propofol (n = 30) or midazolam (n = 30). No other analgetic or sedative drugs were used. 3 l oxygen were given routinely by nose. Blood pressure, oxygen saturation (pulse oxymetry) and heart rate was monitored continuously. The sedation quality was determined from the endoscopist and patient separately by use of a scale as either good, fair or insufficient. RESULTS: Changes of the heart rate and oxygen saturation showed no differences in both groups (> 0.05). The blood pressure decreased significant by using propofol (p < 0.01). The sedation quality was good in both groups without significant differences. The recovery time was shorter if propofol was administered (p < 0.01). CONCLUSIONS: Propofol is an alternative drug for sedation in upper endoscopy. It showed same sedation quality as midazolam with the advantage of a short recovery time. Because of a possible decrease of the blood pressure continuous monitoring is recommended.

Adult↗
PubMed1998

Saccharomyces cerevisiae Duo1p and Dam1p, novel proteins involved in mitotic spindle function.

In this paper, we describe the identification and characterization of two novel and essential mitotic spindle proteins, Duo1p and Dam1p. Duo1p was isolated because its overexpression caused defects in mitosis and a mitotic arrest. Duo1p was localized by immunofluorescence, by immunoelectron microscopy, and by tagging with green fluorescent protein (GFP), to intranuclear spindle microtubules and spindle pole bodies. Temperature-sensitive duo1 mutants arrest with short spindles. This arrest is dependent on the mitotic checkpoint. Dam1p was identified by two-hybrid analysis as a protein that binds to Duo1p. By expressing a GFP-Dam1p fusion protein in yeast, Dam1p was also shown to be associated with intranuclear spindle microtubules and spindle pole bodies in vivo. As with Duo1p, overproduction of Dam1p caused mitotic defects. Biochemical experiments demonstrated that Dam1p binds directly to microtubules with micromolar affinity. We suggest that Dam1p might localize Duo1p to intranuclear microtubules and spindle pole bodies to provide a previously unrecognized function (or functions) required for mitosis.

Antibodies, Fungal↗
PubMed1998

Spontaneous calcium oscillations in embryonic stem cell-derived primitive endodermal cells.

In vitro differentiation of mouse embryonic stem cells within three-dimensional cell aggregates called embryoid bodies parallels the development of postimplantation embryos at the egg cylinder stage, where visceral and parietal endoderm diverge from the primitive endoderm. We have investigated spontaneous [Ca2+]i oscillations by means of confocal laser-scanning microscopy in primitive endodermal cell layers of embryoid bodies during their differentiation to parietal and visceral endoderm. The frequency of [Ca2+]i oscillations increased from day 4 to day 19 of development, whereas their duration decreased from day 3 to days 16-17. Oscillations depended on both extracellular Ca2+ and Ca2+ release from intracellular stores as they were abolished in Ca(2+)-free solution and in the prescence of Ni2+ and thapsigargin. Signal transduction operated via the phospholipase C (PLC)-mediated inositol 1,4,5-triphosphate (InsP3) pathway with a negative feedback loop via protein kinase C (PKC) as U73,122, a blocker of PLC; bisindolylmaleimide 1, staurosporine, and H-7, blockers of PKC; and 10 mM caffeine totally inhibited [Ca2+]i spiking. Thimerosal, which hypersensitizes the InsP3 receptor, as well as vasopressin and bradykinin, which act via the InsP3 pathway, increased the frequency of [Ca2+]i spikes. In the prescence of brefeldin A (50 microM) or monensin (20 microM), which both inhibit endo/exocytotic vesicle pathways, an immediate transient increase in spiking activity was followed by a decline within 1 to 2 h. In the presence of brefeldin A or thapsigargin or in the absence of extracellular Ca2+, endocytotic vesicles were absent, suggesting that oscillating [Ca2+]i transients are involved in the exo/endocytotic vesicle shuttle.

Animals↗
PubMed1998

Inhibitory action of BMPs on Pax1 expression and on shoulder girdle formation during limb development.

Pax1 expression in vertebrate limb buds is confined to cells in a discrete anterior proximal domain (Timmons et al. [1994] Development 120:2773-2785; Ebensperger et al. [1995] Anat. Embryol. 191:297-310). In dorsoventral patterning of Drosophila, expression of pox meso, an insect gene with high sequence similarity to Pax1, is repressed by decapentaplegic (dpp) in dorsal mesoderm and, thus, is restricted to a discrete ventral domain (Staehling-Hampton et al. [1994] Nature 372:783-786). In the chick wing, cells expressing a vertebrate homolog of dpp, bone morphogenetic protein 4 (Bmp4), abut the Pax1 domain, suggesting a similar relationship between homologous genes in both vertebrates and invertebrates. Here, we show that two BMPs (BMP4, and BMP2, also highly related to dpp) can repress Pax1 in the developing chick wing. Chick wing bud cells expressing Pax1 give rise to the shoulder girdle. Cells in an equivalent position in the mouse forelimb also express Pax1, and Pax1 mutant mice display shoulder girdle defects. Similarly in chick embryos, girdle defects are produced by treatments with signalling molecules that lead to expression of BMPs, which subsequently reduce Pax1 expression in the limb bud. Recently, BMP4 has been shown to inhibit Pax1 expression in the developing trunk (Monsoro-Burq et al. [1996] Development 122:3607-3616) and Pax9 expression in developing teeth (Neubüser et al. [1997] Cell 90:247-255). Thus, a property of BMPs appears to be to regulate pox meso homologs negatively and, thus, limit their expression domains.

Animals↗
PubMed1998

Intussusception in adults: CT diagnosis.

PURPOSE: Intussusception in adults is nowadays usually diagnosed on computed tomography (CT), as CT is often the first modality for the investigation of prolonged abdominal pain from which these patients suffer. We wish to present the CT, clinical and pathological findings of 16 adult patients with intussusception seen over a 5-year period. MATERIALS AND METHODS: The abdominal scans of 16 patients with intussusception were reviewed. Special attention was directed to the location of the mass, its shape and fat content, possible underlying pathology and dilatation of the bowel proximally. The findings were correlated with clinical and pathological data. RESULTS: Eight men and eight women, aged 34-81 years, were studied. The most frequent indication for CT was prolonged abdominal pain. CT findings included an inhomogeneous soft tissue mass, target or sausage-shaped, depending on the angle of the CT beam vs. the intussusception, with a fatty component in 14 of the 16. Intussusception was enteroenteric (six), ileocolic (three), or colocolic (seven). Complete small bowel obstruction was present only in one case and some bowel dilatation in three. The underlying pathology could be diagnosed on CT in only two cases of lipoma. Nine patients had an underlying malignant process, eight of them unsuspected. Of the other five, two had coeliac disease, two were classified as idiopathic and one had a necrotic polyp of undetermined pathology. CONCLUSION: Intussusception on CT presented a characteristic mass lesion containing fat stripes in almost all patients. Obstruction was rarely seen. Malignant lesions were the most common cause and therefore early diagnosis and prompt intervention are essential.

Abdominal Pain↗
PubMed1998

Baculovirus-mediated gene transfer in the presence of human serum or blood facilitated by inhibition of the complement system.

Baculovirus vectors are efficient tools for gene transfer into hepatocytes in vitro. However, gene transfer is strongly reduced in the presence of native sera, providing an explanation for the failure of direct application of the virus in vivo. In this study, we define the role of the complement (C) system (C) as a major cause for baculovirus inactivation in human serum. Baculoviruses most likely activate the classical pathway of the C system and assembly of very late C components is required for inactivation of the vector. We demonstrate the survival of baculovirus vectors in human serum through treatment with a functional blocking antibody against C component 5. Inactivation of baculovirus in human plasma and whole blood was prevented by treatment with cobra venom factor. The data reveal various interactions of baculovirus vectors with the C system and will lead to facilitation of baculovirus-mediated gene transfer into hepatocytes in vivo by protection of the vector from C inactivation.

Antibodies, Monoclonal↗
PubMed1998

Pharyngeal acid reflux events in patients with vocal cord nodules.

OBJECTIVE: Gastroesophageal reflux has been implicated in the pathogenesis of vocal cord nodules. However, a cause-and-effect relationship has not been established. Because documentation of pharyngeal acid reflux events makes this correlation more plausible, the aim of the present study was to determine the frequency of pharyngeal acid reflux events in patients with vocal cord nodules. METHODS: Eleven patients with vocal cord nodules (mean age, 42 +/- 6 years) and eleven healthy volunteers (mean age, 45 +/- 6 years) were studied. Patients underwent barium esophagram and ambulatory 24-hour simultaneous three-site pharyngoesophageal pH monitoring. Controls only had ambulatory 24-hour simultaneous three-site pH monitoring. In the ambulatory pH monitoring studies, pH was recorded from the manometrically determined sites of pharynx (2 cm above upper esophageal sphincter), proximal esophagus (10 cm distal to pharyngeal site), and distal esophagus (5 cm above the lower esophageal sphincter). Pharyngeal acid reflux event was deemed acceptable if all three sites recorded a decrease in pH below 4 which was not related to meal or drinking. RESULTS: Pharyngeal acid reflux events occurred in seven of 11 patients with vocal cord nodules (1-4 episodes) and two of 11 controls (1-2 episodes) (P < .05). In both groups all pharyngeal acid reflux events occurred in upright position and were not associated with belching or coughing. Barium studies documented hiatal hernia in two patients and gastroesophageal reflux in five of 11 patients. However, none of the esophageal reflux events reached the pharynx on barium esophagram. CONCLUSIONS: Prevalence of pharyngeal acid reflux events is significantly higher in patients with vocal cord nodules compared with normal controls and suggests a contributory role for gastroesophagopharyngeal acid reflux in the pathogenesis of some vocal cord nodules.

Adolescent↗
PubMed1998

Synthesis, biological effects and pathophysiological implications of the novel arachidonic acid metabolite 5-oxo-eicosatetraenoic acid (Review).

Arachidonic acid is rapidly metabolized by several distinct enzymes including the 5-lipoxygenase generating leukotrienes and 5-hydroxyeicosatetraenoic acid (5-HETE). These well studied metabolites cause a variety of physiological and pathophysiological effects in different tissues. Recently, oxidation of 5-HETE to 5-oxo-eicosatetraenoic acid (5-oxo-ETE) by an NADP+-dependent dehydrogenase has been demonstrated. Calcium ionophors and protein kinase C activators stimulate the synthesis of 5-oxo-ETE in neutrophils, eosinophils and monocytes. This novel arachidonic acid metabolite has a potent chemotactic activity for neutrophils and eosinophils. It stimulates adhesion of neutrophils and induces reactive oxygen metabolites in eosinophils. There is evidence that 5-oxo-ETE and 5-HETE interact with a specific G-protein coupled receptor. Since in contrast to 5-oxo-ETE much higher concentrations of 5-HETE are needed to provoke cell responses, 5-oxo-ETE might be the physiological relevant ligand for this putative receptor. Further downstream signalling pathways of this ligand include calcium transients, actin polymerization, activation of phosphatidylinositol-3-kinase and MAP-kinase. 5-oxo-ETE has been extracted from scales of psoriatic patients and injection of 5-oxo-ETE into rabbit subcutis causes a severe edema with an inflammatory cell infiltrate resembling an urticarial lesion. These findings indicate, that 5-oxo-ETE might play a role in different cutaneous inflammatory diseases.

Journal Article↗
PubMed1998

The hormonal effects of alcohol use on the mother and fetus.

During pregnancy, the hormonal systems of the mother and fetus are intricately interconnected to ensure normal fetal development. Accordingly, maternal alcohol consumption during pregnancy can interfere with fetal development, not only directly, through adverse effects exerted by alcohol that crosses the placenta and enters the fetal bloodstream, but also indirectly, by disturbing the functions and interactions of maternal and fetal hormones. In both the mother and the fetus, alcohol exposure can impair the functioning of the hypothalamic-pituitary-adrenal axis, which regulates the body's response to stress; the hypothalamic-pituitary-gonadal axis, which controls reproductive functions; and the hypothalamic-pituitary-thyroid axis, which regulates the metabolism of almost all tissues. In addition, alcohol can interfere with the activities of growth hormone and insulin-like growth factors, which promote body growth and activity. Some of the effects of maternal alcohol consumption on fetal hormone systems may contribute to the adverse effects observed in children with fetal alcohol syndrome and related disorders.

Alcohol Drinking↗
PubMed1997

The monocyte chemotactic protein-4 induces oxygen radical production, actin reorganization, and CD11b up-regulation via a pertussis toxin-sensitive G-protein in human eosinophils.

The novel human CC-chemokine monocyte chemotactic protein-4 (MCP-4) is a chemotaxin for eosinophils. Here, the biological activities and the activation profile of MCP-4 was further characterized in eosinophils and compared to other activators such as platelet activating factor (PAF), Eotaxin and RANTES. As demonstrated by lucigenin-dependent chemiluminescence and superoxide dismutase-inhibitable cytochrome C reduction MCP-4 stimulated the production of reactive oxygen metabolites. Furthermore, MCP-4 induced up-regulation of the integrin CD11b. Flow cytometric studies revealed rapid and transient actin polymerization upon stimulation with MCP-4. At optimal concentrations the changes induced by MCP-4 were weaker than the effects after stimulation with PAF and comparable to those obtained by RANTES and Eotaxin. Cell responses elicited by MCP-4 were inhibited by pertussis toxin indicating involvement of Gi-proteins in this signal pathway. These findings point to a role of MCP-4 in the pathogenesis of eosinophilic inflammation as chemotaxin as well as activator of pro-inflammatory effector functions.

Actins↗
PubMed1997

Evidence for the involvement of phosphatidylinositol 4,5-bisphosphate 3-kinase in CD18-mediated adhesion of human neutrophils to fibrinogen.

The CD18 integrin mediates chemotaxin-induced adhesion of neutrophils to fibrinogen. In neutrophils chemotaxins activate different intracellular pathways, which metabolize phosphatidylinositol 4,5-bisphosphate. To analyse the functional role of phosphatidylinositol 4,5-bisphosphate 3-kinase in the adhesion response, studies with the fungal metabolite wortmannin and the chemically unrelated compound LY 294002 were performed. These compounds inhibited with similar concentration dependency chemotaxin-induced formation of [32P]phosphatidylinositol 3,4,5-trisphosphate and CD18-mediated adhesion of neutrophils to fibrinogen, but did not influence expression of CD18 molecules at the cell surface. These data suggest involvement of phosphatidylinositol 4,5-bisphosphate 3-kinase in chemokine-induced avidity changes of CD18 integrins.

Androstadienes↗
PubMed1997

Down-regulation of tissue specific tumor necrosis factor-alpha in the liver and lung after burn injury and endotoxemia.

Burn injury and endotoxin lead to the development of a systemic inflammatory response. Because tumor necrosis factor-alpha (TNF-alpha) is a component of the proinflammatory response, we have determined the effect of burn injury and endotoxin in a murine model of thermal on tissue specific TNF-alpha levels in the liver and lung. Male mice were divided into four groups and injected with endotoxin (ETX) (2.5 mg/kg intraperitoneally) or saline (CNTL) or subjected to a 16% full-thickness scald burn (B), or ETX administration 72 hours after burn injury (B+ETX). Animals were killed at 0 to 24 hours after ETX or CNTL, 0 to 72 hours after B, and 72 to 96 hours after B+ETX (ETX administration 72 hours after B). TNF-alpha mRNA by Northern blot and protein analysis by enzyme-linked immunosorbent assay were determined and protein expressed as nanogram per gram of tissue. Statistical analysis was performed using analysis of variance with significance at p < 0.05. Burn injury did not result in detectable levels of liver or lung TNF protein or mRNA. Endotoxin administration resulted in a near six-fold rise in liver TNF protein compared with controls at 1, 2, and 6 hours after ETX (p < 0.05 to p < 0.001). Liver mRNA remained elevated from 20 minutes to 24 hours after ETX versus CNTL (p < 0.05). Endotoxin injection produced a persistent lung TNF protein elevation reaching significance at 1 and 2 hours (p < 0.001) and a rise in mRNA at 40 minutes to 6 hours (p < 0.05) versus CNTL. The liver showed a trend of reduced mRNA after B+ETX versus ETX (p = NS), whereas protein levels were reduced by 50 to 60% at 1 and 2 hours (p < 0.01). Lung mRNA values after B+ETX were only 40% compared with ETX at nearly all time points (p < 0.001) but were 15 times above CNTL values at 2 hours (p < 0.05). Based on these results, we conclude that burn injury did not cause an increase in liver or lung tissue specific TNF-alpha. However, the presence of a preexisting burn injury dramatically altered the response to endotoxin and the primary point of regulation appears to be at the posttranscriptional level.

Animals↗
PubMed1997

Augmentation of deglutitive upper esophageal sphincter opening in the elderly by exercise.

Earlier studies have shown that the cross-sectional area of the deglutitive upper esophageal sphincter (UES) opening in healthy asymptomatic elderly individuals is reduced compared with healthy young volunteers. The aim of this study was to determine the effect of a head-raising exercise on swallow-induced UES opening and hypopharyngeal intrabolus pressure in the elderly. We studied a total of 31 asymptomatic healthy elderly subjects by videofluoroscopy and manometry before and after real (19 subjects) and sham (12 subjects) exercises. A significant increase was found in the magnitude of the anterior excursion of the larynx, the maximum anteroposterior diameter, and the cross-sectional area of the UES opening after the real exercise (P < 0.05). These changes were associated with a significant decrease in the hypopharyngeal intrabolus pressure studied in 12 (real-exercise) and 6 (sham-exercise) subjects (P < 0.05). A similar effect was not found in the sham-exercise group. In normal elderly subjects, deglutitive UES opening is amenable to augmentation by exercise aimed at strengthening the UES opening muscles. This augmentation is accompanied by a significant decrease in hypopharyngeal intrabolus pressure, indicating a decrease in pharyngeal outflow resistance. This approach may be helpful in some patients with dysphagia due to disorders of deglutitive UES opening.

Aged↗
PubMed1996

Gene transfer into hepatocytes and human liver tissue by baculovirus vectors.

Gene therapy of liver diseases requires the development of efficient vectors for gene transfer in vivo. Retroviral and adenoviral vectors have been shown to deliver genes efficiently into hepatocytes in vitro and in vivo. However, these vectors do not allow for exclusive infection of the liver which would be highly advantageous for in vivo gene therapy strategies. We have recently demonstrated that genetically modified baculoviruses (Autographa californica nuclear polyhedrosis virus) efficiently deliver genes into cultured cells and have a strong preference for hepatocytes of different origin. Baculoviral gene transduction efficiency into human hepatocytes was determined to approach 100% and expression levels are high, provided that gene expression is controlled by mammalian promoters. In this report, we present further properties of baculoviruses regarding their use for hepatocyte gene transfer. Baculovirus-mediated gene expression declines rapidly in the hepatocellular carcinoma cell line Huh7 and more slowly in primary cultures of mouse hepatocytes. Direct application of baculoviruses for gene delivery to the liver in vivo is hampered by serum components, presumably by complement. However, we demonstrate here that baculoviral gene transfer is feasible in ex vivo perfused human liver tissue. This result suggests the development of a strategy using baculoviral vectors for liver-directed gene therapy.

Animals↗